Vol 3, No 3 (2025): Current Issue (Volume 3, Issue 3), 2025
Editorial
From Resource-Limited to Research-Rich: Unlocking the Scientific Potential of Developing Nations
Zuhair Dahham Hammood
For too long, the scientific narrative has been dominated by voices from wealthier nations. While their contributions are invaluable, the imbalance has left a vast reservoir of untapped knowledge and innovation in the developing world. Today, the time has come to shift the paradigm—from viewing developing countries as mere recipients of scientific progress to recognizing them as active producers of valuable, context-specific knowledge.
From Resource-Limited to Research-Rich is not a rhetorical flourish—it is a vision, a goal, and a challenge. It reflects a belief that scientific excellence is not the exclusive property of nations with abundant financial resources, but rather, a pursuit driven by curiosity, commitment, and community.
Developing countries, despite limited infrastructure and funding, are home to some of the most pressing health challenges—from endemic infectious diseases and rising non-communicable burdens to unique environmental and sociopolitical contexts. These challenges demand local insight, homegrown data, and context-sensitive solutions. The answers will not come from imported models alone. They must arise from within [1].
In this transformation, medical journals have a profound responsibility—not just as gatekeepers of knowledge, but as platforms for empowerment. Barw Medical Journal stands committed to this mission: to provide a voice to researchers working under constraints, to mentor and guide early-career scientists, and to uphold the integrity and quality of regional scholarship.
Success stories are already emerging. Across Africa, Asia, the Middle East, and Latin America, we are witnessing a rise in high-quality research led by local scientists. These efforts, often fueled by personal passion more than institutional support, prove that scientific ingenuity thrives even where resources are scarce [2].
However, more must be done. Governments must prioritize funding for health research. International agencies must listen more and dictate less. And academic partnerships must be based on equity, not extraction.
The path from resource-limited to research-rich is not paved overnight. It requires intentional investment, strategic collaboration, and relentless belief in the intellectual power of every nation. As we look ahead, let us remember: the next breakthrough in global health may very well come from a modest lab, in a hospital like ours, led by minds that simply needed a chance to be heard.
At Barw Medical Journal, we are here to amplify those voices.
Original Articles

The Effect of Clinical Knee Measurement in Children with Genu Varus
Kamal Jamil, Chong YT, Ahmad Fazly Abd Rasid, Abdul Halim Abdul Rashid, Lawand Ahmed
Abstract
Introduction
Children with genu varus needs frequent assessment and follow up that may need several radiographies. This study investigates the effectiveness of the clinical assessment of genu varus in comparison to the radiological assessment.
Methods
In this study, relationship between clinical and radiographic assessments of genu varus (bow leg) in children, focusing on the use of intercondylar distance (ICD) and clinical tibiofemoral angle (cTFA) as clinical measures, compared to the mechanical tibiofemoral angle (mTFA) obtained via scanogram, the radiographic gold standard for assessing lower limb deformity. Clinical measurements (ICD and cTFA) were gathered along with the mTFA from scanogram radiographs. Reliability was tested between two observers, and Spearman’s correlation coefficient was used to evaluate the relationships between the clinical and radiographic measurements.
Results
The study involved 36 children with an average age of 6.3 years. There were strong intra-rater reliability for both observers (ICC 0.87 for observer 1, ICC 0.97 for observer 2) and excellent inter-observer agreement (ICC 0.97). Positive correlations were found between cTFA and mTFA (r² = 0.67, p < 0.001), between ICD and cTFA (r² = 0.53, p < 0.001), and between ICD and mTFA (r² = 0.62, p < 0.001).
Conclusion
This study suupports the idea that clinical methods may be sufficient for evaluation, minimizing the need for radiation exposure and offering a reliable alternative to radiography.
Introduction
Genu varus, also known as bow-leggedness is defined as any separation of the medial surfaces of the knees when the medial malleoli are in contact, and the patient is standing in the anatomical position [1]. The prevalence of genu varus ranges from 11.4% to 14.5% [2,3]. It is found to be more prevalent in boys than in girls [2]. Genu varus may be physiological or pathological. There are multiple ways to aid in the screening and diagnosis of genu varus, which include clinical and radiological methods. Clinical methods such as intercondylar distance (ICD) and tibiofemoral angle measurement have been used to screen and assess the degree of genu varus. However, imaging modality such as a long-leg AP radiograph or scanogram is considered the gold standard assessment for lower limb deformity.
Many studies on genu varus in children have utilized either the clinical or radiological lower limb measurements to describe the tibiofemoral angle progression in normal children, data of normal ranges of knee angle in relation to age, and transition time from varus to valgus of different populations and ethnic groups [4-10].In a recent systematic review, it is proposed that children above the age of 18 months with genu varus should be closely monitored clinically using ICD or cTFA, whereby an ICD of more than 4 cm needed to be investigated for pathologic cause [11]. However, reliability has not been confirmed.
Hence, serial assessment might be needed to manage children with genu varus. Clinical methods of assessment are preferrable due to no exposure to radiation as compared to a radiograph but may be inaccurate or unreliable [12]. We are interested to find out the correlation between the radiological and clinical assessments.
Methods
Study design and setting
This was a single center cohort study. The study was conducted in an orthopaedic clinic of a tertiary hospital. Children with age ranging from 1 to 17 years old who were diagnosed as genu varus by orthopaedic specialists and has long leg radiograph done, were included. We excluded children who have previous history of fracture of the lower limb, had any knee swelling, tumour or contracture. Consent was taken from the parents before enrolment to the study. This study was conducted in accordance with the Declaration of Helsinki and was approved by the Universiti Kebangsaan Malaysia Institutional Ethical Committee (JEP-2020-194).
Procedure
The baseline data such as age, gender, weight/height and underlying diagnosis were taken. The knee intercondylar distance was measured using a measuring tape, with the child standing, and both medial malleoli touching. The centre of the medial femoral condyles was identified by palpation of the most prominent part of the distal femur. The measurement between the condyles was performed following the method described by Heath et al [13]. The reading was measured in centimetres as the intercondylar distance. The clinical tibiofemoral angle (cTFA) was measured with a goniometer, following the method described by Arazi et al [14]. With the child in standing, the anterior superior iliac spine, centre of the patella, and midpoint of the ankle joint were marked with a pen. After the marking of the tibiofemoral axis, the angle was measured and recorded. The angle was expressed in degrees. Illustrates the method of measurements on a patient (Figure 1).
A standardized long-leg anterior-posterior radiograph (scanogram) of lower limbs was obtained from hospital radiological database. The angle formed between the mechanical axis of the femur and the mechanical axis of tibia was recorded as mechanical tibiofemoral angle (mTFA). The mTFA was determined from digital X-Ray by using the measuring tool from Medweb (Medweb, Inc, San Francisco, CA) software. In bilateral cases, the limb with the worst angle measured was chosen for analysis.
The clinical and radiological measurements were performed by a single researcher (CYT), who was trained on the measurement technique. For the radiographic measurements, a prior intra- and inter-observer reliability study was performed on 10 radiographs by two main researchers (CYT and KJ) on the same children at two different intervals.
Data analysis
The intra- and inter-observer reliability of tibiofemoral angle measurement was measured using with 95% confidence intervals to gauge the precisions of the ICCs [15]. Correlations between clinical tibiofemoral angle (cTFA), mechanical tibiofemoral angle (mTFA) and intercondylar distance (ICD) were tested using Spearman’s Correlation test. Differences between cTFA and mTFA were investigated using paired sample t-test and Bland Altman 95% limits of agreement. All statistical analysis was performed using SPSS (v24, IBM, NY, USA). Statistical significance was set at a cut-off of p<0.05.
Results
There were 36 children included with the mean age of 6.3 years. Thirty-two were Malay (88.8%), while the remaining participants were three Indians (8.3 %) and one Chinese (2.7%) by ethnicity. Twenty-two children were male (61%) and 14 female (38%). There were five unilateral and 31 bilateral genu varus. Eleven children had Blount disease; 13 cases had rickets while the remaining 12 was managed as physiological genu varus.
Reliability study performed between two observers for the tibiofemoral angle measurements revealed Good intra-rater reliability for observer 1 (ICC 0.87) and Excellent intra-rater reliability for observer 2 (ICC 0.97). Excellent inter-observer agreement (ICC 0.97) was also shown.
All thirty-six children (mean age 6.6 ± 5.7) were examined in standing position. The association between the radiological mTFA and clinical TFA measurements was assessed. Our findings revealed that there was a moderate correlation between cTFA and mTFA (r2=0.67, p< 0.001) (Figure 2).
Subsequently, the association between the ICD and clinical TFA and between ICD and radiological mTFA measurements were assessed. We also found a moderate positive correlation between ICD and cTFA, (r2=0.53, p< 0.001) and between ICD and mTFA, (r2=0.62, p< 0.001), respectively (Figure 3).
Paired t- test revealed a mean difference of -4.67 degrees between the cTFA and mTFA. The difference was statistically significant of p= 0.00. The limits of agreement revealed were a lower limit of -7.02 degrees and an upper limit of -2.34 degrees (Figure 4).
Discussion
We examined the correlation between clinical and radiographic TFA measurements of the lower extremities in 36 children with genu varus who has been referred to our centre. We found a significant correlation between radiological mTFA and clinical TFA. This result is in parallel with other studies by [16,17]. Navali et al concluded that goniometer measurement appears to be valid alternatives to the mechanical axis on full-leg radiograph for determining frontal plane knee alignment [17]. Kraus et al also concluded knee alignment assessed clinically by goniometer or measured on a knee radiograph is correlated with the angle measured on the full-limb radiograph [17]. However, both studies were carried out in adults’ population with osteoarthritis knee. Our study determined the correlation between radiological and clinical TFA specifically in paediatric population with genu varus.
Another significant finding in this study is ICD has moderate correlation with cTFA and mTFA. There are several correlation studies that were reported on ICD. Saini et al found that a fair degree of correlation was established between ICD and tibiofemoral angle (TFA), measured clinically by a goniometer [8]. A similar finding between ICD and TFA was seen in other studies [6-11]. This suggested that both measurements can complement each other in monitoring genu varus. The importance of ICD measurement was highlighted by other authors. Cahuzac et al in 1995 has established a data for the normal values of varus profile of the legs in normal children between 10 and 16 years of age, whereby a measurement of ICD of more than 5 cm is considered abnormal [18]. This is supported by other investigators [14-19]. For younger children aged of at least 18 months, ICD of 4cm should be closely monitored [11].
The different degrees of correlation in various studies might be influenced by the different method of measurements. Mathew et al had found the clinical measurement of using ICD to have minimal intra-observer variability [6]. However, a standardized way of measurement and positioning of the patients is important to get a consistent finding. Obtaining a proper standing radiograph in a young child can proved to be challenging, so other measures such as footprint drawn on the floor have been suggested [11].
We also found that the difference of agreement between cTFA and mTFA measurement were significant. mTFA consistently produced a higher value with the mean difference around 5 degrees indicating that the angles were not similar between the two techniques. However, as mentioned earlier both measurements correlated with each other. This means that although not totally accurate as measured on radiograph (mTFA), clinical method can still show similar trend of deformity therefore useful for monitoring change or progress.
There were some limitations in our study. Firstly, our sample population was relatively small with a wide age range (1-17 years). Secondly, we only performed observer reliability study for the radiographic measurement. However, the clinical measurements were done by a single researcher, who was trained to perform the measurement following the standard protocol.
Conclusion
Clinical measurement of tibiofemoral angle and ICD to good correlation with radiological measurement, when performed with the child in standing position. Therefore, for monitoring purposes or serial alignment assessment, these methods are adequate.
Declarations
Conflicts of interest: The author(s) have no conflicts of interest to disclose.
Ethical approval: The study's ethical approval was obtained from the Universiti Kebangsaan Malaysia Institutional Ethical Committee (JEP-2020-194).
Patient consent (participation and publication): Verbal informed consent was obtained from patients for publication.
Source of Funding: Universiti Kebangsaan Malaysia
Role of Funder: The funder remained independent, refraining from involvement in data collection, analysis, or result formulation, ensuring unbiased research free from external influence.
Acknowledgements: None to be declared.
Authors' contributions: KJ and CYT conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. CYT designed the data collection instruments, collected data and carried out the initial analyses. AFAR and AHAR coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Use of AI: AI was not used in the drafting of the manuscript, the production of graphical elements, or the collection and analysis of data.
Data availability statement: Note applicable.

Exploring Large Language Models Integration in the Histopathologic Diagnosis of Skin Diseases: A Comparative Study
Talar Sabir Ahmed, Rawa M. Ali, Ari M. Abdullah, Hadeel A. Yasseen, Ronak S. Ahmed, Ameer M....
Abstract
Introduction
The exact manner in which large language models (LLMs) will be integrated into pathology is not yet fully comprehended. This study examines the accuracy, benefits, biases, and limitations of LLMs in diagnosing dermatologic conditions within pathology.
Methods
A pathologist compiled 60 real histopathology case scenarios of skin conditions from a hospital database. Two other pathologists reviewed each patient’s demographics, clinical details, histopathology findings, and original diagnosis. These cases were presented to ChatGPT-3.5, Gemini, and an external pathologist. Each response was classified as complete agreement, partial agreement, or no agreement with the original pathologist’s diagnosis.
Results
ChatGPT-3.5 had 29 (48.4%) complete agreements, 14 (23.3%) partial agreements, and 17 (28.3%) none agreements. Gemini showed 20 (33%), 9 (15%), and 31 (52%) complete agreement, partial agreement, and no agreement responses, respectively. Additionally, the external pathologist had 36(60%), 17(28%), and 7(12%) complete agreements, partial agreements, and no agreements responses, respectively, in relation to the pathologists’ diagnosis. Significant differences in diagnostic agreement were found between the LLMs and the pathologist (P < 0.001).
Conclusion
In certain instances, ChatGPT-3.5 and Gemini may provide an accurate diagnosis of skin pathologies when presented with relevant patient history and descriptions of histopathological reports. However, their overall performance is insufficient for reliable use in real-life clinical settings.
Introduction
The healthcare sector is undergoing significant transformation with the emergence of large language models (LLMs), which have the potential to revolutionize patient care and outcomes. In November 2022, OpenAI introduced a natural language model called Chat Generative Pre-Trained Transformer (ChatGPT). It is renowned for its ability to generate responses that approximate human interaction in various tasks. Gemini, developed by Google, is a text-based AI conversational tool that utilizes machine learning and natural language understanding to address complex inquiries. These models generate new data by identifying structures and patterns from existing data, demonstrating their versatility in producing content across different domains. Generative LLMs rely on sophisticated deep learning methodologies and neural network architectures to scrutinize, comprehend, and produce content that closely resembles human-created outputs. Both ChatGPT and Gemini have gained global recognition for their unprecedented ability to emulate human conversation and cognitive abilities [1-3].
ChatGPT offers a notable advantage in medical decision-making due to its proficiency in analyzing complex medical data. It is a valuable resource for healthcare professionals, providing quick insights derived from patient records, medical research, and clinical guidelines [1,4]. Moreover, ChatGPT can play a crucial role in the differential diagnostic process by synthesizing information from symptoms, medical history, and risk factors, and comprehensively processing this data to present a range of potential medical diagnoses, thereby assisting medical practitioners in their assessments. This has the potential to improve diagnostic accuracy and reduce instances of misdiagnosis or delays [4].
The integration of ChatGPT and Gemini into the medical decision-making landscape has generated interest from various medical specialties. Multiple disciplines have published articles highlighting the significance and potential applications of ChatGPT and Gemini in their respective fields [2,5]. Despite the growing number of these models used in diagnostics, patient management, preventive medicine, and genomic analysis across medicine, the integration of LLMs in dermatology remains limited. This study emphasizes the exploration of large language models, highlighting their less common yet promising role in advancing dermatologic diagnostics and patient care [6]
This study aims to explore the role of LLMs and its decision-making capabilities in the field of pathology, specifically in dermatologic conditions. It focuses on ChatGPT 3.5 and Gemini and compares their accuracy and concordance with the diagnoses of human pathologists. The study also investigates the potential advantages, biases, and constraints of integrating LLM tools into pathology decision-making processes.
Methods
Case Selection
A pathologist selected 60 real case scenarios, with half being neoplastic conditions and the other half non-neoplastic, from a hospital’s medical database. The cases involved patients who had undergone biopsy and histopathological examination for skin conditions. The records included information on age, sex, and the chief complaint of the patients, in addition to a detailed description of the histopathology reports (clinical and microscopic description without the diagnosis).
Consensus Diagnosis
Two additional board-certified pathologists reviewed each case, reaching a collaborative consensus diagnosis through a meticulous review of clinical and microscopic descriptions. This process ensured diagnostic accuracy and reliability while minimizing individual biases.
Eligibility Criteria
The study included cases that had complete and relevant histopathological reports and comprehensive patient demographic information. Specifically, cases were included if they provided a definitive diagnosis in the histopathological report and contained detailed patient data such as age, gender, and clinical history. Cases were excluded if the histopathological report was incomplete, lacked critical patient information, or if the diagnosis could not be definitively made based solely on the textual description.
Sampling Method
The selection process involved a systematic review of available cases from the hospital's medical database to ensure a representative sample of different dermatologic diagnoses. A random sampling method was employed to minimize selection bias and to ensure the sample was representative of the broader population of dermatologic conditions within the database. The selected cases span a range of common and less common dermatologic conditions, enhancing the generalizability of the study’s findings.
Evaluation by AI Systems and External Pathologist
In March 2023, these cases were evaluated using two LLM systems, namely ChatGPT-3.5 and Gemini. In addition, an external board-certified pathologist was tested similarly to the AI systems, receiving only the necessary histopathology report descriptions (without histopathological images) to ensure a fair comparison between the LLM systems and the external pathologist.
Pathologists’ Experience
The Pathologists involved in the study had a minimum of eight years of experience in their respective specialties, handling an average of 30 cases per month. This level of experience ensured a deep familiarity with a wide range of case scenarios. Crucially, the pathologists conducted their assessments were fully informed of the study design, including the comparative analysis with AI systems. Their expertise and understanding were vital in upholding the integrity and reliability of the diagnostic evaluations throughout the study
AI Prompting Strategy
The LLM systems were initially greeted with a prompt saying “Hello,” followed by standardized inquiries presented as: “Please provide the most accurate diagnoses from the texts that will be given below.” Each case was individually presented by copy-pasting it from a Word document and requesting each system to provide a diagnosis of the case scenario based on the information presented. The first response of each system to the inquiry was documented. If no diagnosis was given, the prompt was repeated as such: “Please, based on the histopathological report information given above, provide the most likely disease that causes it.” Until a diagnosis was obtained. In some cases, after a diagnosis was provided, an additional question was asked to specify the histologic subtype of the condition (e.g., if the diagnosis was “seborrheic keratosis”, the system was asked to specify the histologic subtype). Furthermore, the board-certified external pathologist was tested with the same questions, and the correct diagnosis was inquired.
Response Categorization
The responses from both systems and the external pathologist were categorized into three subtypes: complete agreement with the original diagnosis by the human pathologists, partial agreement, or none agreement. The criteria for categorizing agreement levels into "complete," "partial," and "none agreement" are based on the distinction between general and specific diagnostic classifications. For instance, when the original diagnosis provides a detailed type and subtype (e.g., "Seborrheic keratosis, irritated type"), an AI tool's or external pathologist's response was classified as demonstrating "complete agreement" if it accurately identifies both the general diagnosis ("Seborrheic keratosis") and the specific subtype ("irritated type"). This classification acknowledges that accurate identification of both components reflects a thorough understanding and alignment with the original diagnosis. Conversely, an assessment was categorized as "partial agreement" if the response correctly identifies the general diagnosis but inaccurately specifies the subtype. Furthermore, a diagnosis was classified as demonstrating "no agreement" when both the general diagnosis and subtype provided by the AI tool or external pathologist are incorrect. These classification criteria draw upon established methodologies in diagnostic agreement studies, emphasizing the importance of distinguishing between different levels of agreement based on the precision and correctness of diagnostic outputs [7].
Data Processing and Statistical Analysis
The initial processing of the acquired data involved several steps before statistical analysis. First, the data were inputted into Microsoft Excel 2019. Subsequently, they were transferred to Statistical Package for the Social Sciences software (SPSS) 27.0 and the DATA tab for further analysis. Fleiss kappa was utilized to measure agreement among Chat GPT, the external pathologist, and Gemini. Additionally, Chi-square tests were applied to investigate associations between the two LLMs and the external pathologist. In this study, significance was defined as a p-value of < 0.05. A literature review was performed for the study, selectively considering papers from reputable journals while excluding those from predatory sources based on established criteria [8].
Results
ChatGPT-3.5 provided 29 (48.4%) complete agreement, 14 (23.3%) partial agreement, and 17 (28.3%) none agreement responses for the scenarios presented. In contrast, Gemini offered 20 (33%), 9(15%), and 31 (52%) complete agreement, partial agreement, and none agreement responses, respectively, for the same scenarios. Moreover, the external pathologist provided 36 (60%) complete agreement, 17 (28%) partial agreement, and 7 (12%) none agreement responses (Table 1). The complete details of the scenarios, including the diagnosis from the pathologists, ChatGPT’s, Gemini’s, and the external pathologist diagnoses are available in (Supplement 1).
Variables |
Frequency/percentage |
Pathological classification Neoplastic Non-neoplastic |
30 (50%) 30 (50%) |
Neoplastic Benign Malignant |
19 (31.7%) 11 (18.3%) |
Non-neoplastic Dermatosis Infectious, pilosebaceous Connective tissue disease Infectious Granulomatous Vascular Epidermal maturation/keratinization disorder Dermatosis, pilosebaceous Pilosebaceous Panniculitis, Dermatosis, infectious Dermatosis, pigmentation disorder Granulomatous, panniculitis Bullous |
9 (15%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 1 (3.3%) 1 (1.7%) 1 (1.7%) 1 (1.7%) 1 (1.7%) |
External Pathologist Complete agreement Partial agreement None agreement |
36 (60%) 17 (28%) 7 (12%) |
ChatGPT Complete agreement Partial agreement None agreement |
29 (48.4%) 14 (23.3%) 17 (28.3%) |
Gemini Complete agreement Partial agreement None agreement |
20 (33%) 9 (15%) 31 (52%) |
The agreement between Chat GPT, the external pathologist, and Gemini was assessed using Fleiss' kappa, which indicated a statistically significant at a level of <0.001, demonstrating slight to moderate agreement with respect to the original diagnosis made by the pathologists. Out of the 29 questions where Chat GPT agreed with the original diagnosis, only 12 (41.4%) instances also received complete agreement from both Gemini and the external pathologist (Table 2).
Variables | External pathologist |
Measurement of Agreement (Fleiss) |
Significance level |
|||
Complete agreement |
Partial agreement |
None agreement |
||||
Gemini |
Complete agreement |
12 (41.4%) |
1(7.1%) |
2 (11.8%) |
0.25 | <0.001 |
Partial agreement |
3 (10.4%) |
1(7.1%) |
0 (0.0%) |
|||
None agreement |
1(3.4%) |
0(0.0%) |
0 (0.0%) |
|||
Complete agreement |
2 (7%) |
3(21.4%) |
0 (0.0%) |
|||
Partial agreement |
1(3.4%) |
3(21.4%) |
0 (0.0%) |
|||
None agreement |
5(17.2%) |
2(14.4%) |
9 (53%) |
|||
Total |
29 |
14 |
17 |
When assessing the agreement between Chat GPT, the external pathologist, and Gemini, using the external pathologist as the reference, the external pathologist showed complete agreement with the original diagnosis in 36 cases. Among these, Chat GPT achieved complete agreement in 19 cases (52.7%), while Gemini achieved complete agreement in 15 cases (41.7%). Additionally, the external pathologist showed none agreement with the original diagnosis in only 7 cases. Among these, Chat GPT achieved none agreement in 5 cases (71.4%), while Gemini achieved none agreement in 6 cases (85.7%). Statistical analysis indicated significant differences in agreement levels between AI tools (ChatGPT and Gemini) and the external pathologist, with a P-value of <0.001 (Table 3).
AI tools | ChatGPT |
P-value |
|||
Complete agreement |
Partial agreement |
None agreement |
|||
ChatGPT |
Complete agreement |
19(52.7%) |
8(47.1%) |
2(28.6%) |
<0.001 |
Partial agreement |
6(16.7%) |
8(47.1%) |
0(0%) |
||
None agreement |
11(30.6%) |
1(5.8%) |
5(71.4%) |
||
Gemini |
Complete agreement |
15(41.7%) |
4(23.5%) |
1(14.3%) |
<0.001 |
Partial agreement |
5(13.9%) |
4(23.5%) |
0(0%) |
||
None agreement |
16(44.4%) |
9(53%) |
6(85.7%) |
||
Total |
36(100%) |
17(100%) |
7(100%) |
In addition, the agreement between the external pathologist, ChatGPT, and Gemini was assessed for both neoplastic and non-neoplastic cases. Statistical analysis revealed significant differences in the agreement levels between the LLMs and the external pathologist, with a P-value of <0.001, highlighting the statistically significant disparity in agreement rates between the AI tools and the external pathologist (Table 4 and 5).
AI tools | External pathologist | P-value | |||
Complete agreement |
Partial agreement |
None agreement |
|||
ChatGPT |
Complete agreement |
11(61.1%) |
2(40%) |
4(57.1%) |
<0.001 |
Partial agreement |
3(16.7%) |
3(60%) |
1(14.3%) |
||
None agreement |
4(22.2%) |
0(0%) |
2(28.6%) |
||
Gemini |
Complete agreement |
9(50%) |
1(20%) |
1(14.3%) |
<0.001 |
Partial agreement |
7(38.9%) |
4(80%) |
4(57.1%) |
||
None agreement |
2(11.1%) |
0(0%) |
2(28.6%) |
||
Total non-neoplastic cases |
18(100%) |
5(100%) |
7(100%) |
AI tools | External pathologist | P-value | |||
Complete agreement |
Partial agreement |
None agreement |
|||
ChatGPT |
Complete agreement |
8(44.4%) |
0(40%) |
4(40%) |
<0.001 |
Partial agreement |
8(44.4%) |
2(1000%) |
0(0%) |
||
None agreement |
2(11.1%) |
0(0%) |
6(60%) |
||
Gemini |
Complete agreement |
6(33.3%) |
0(20%) |
3(30%) |
<0.001 |
Partial agreement |
9(50%) |
2(100%) |
5(50%) |
||
None agreement |
3(16.7%) |
0(0%) |
2(20%) |
||
Total neoplastic cases |
18(100%) |
2(100%) |
10(100%) |
Discussion
Despite being in existence for over five decades, LLM has recently garnered substantial attention in the public sphere. The increased focus on LLMs in the medical field has led to speculation about the potential replacement of doctors by these systems. However, LLMs are more likely to serve as a complementary tool, aiding clinicians in efficiently processing data and making clinical decisions. This is substantiated by the fact that LLMs can "learn" from extensive collections of medical data. Modern systems are also noted for their self-correcting capabilities. As electronic medical records become more prevalent, there is a growing reservoir of stored patient data. While having access to more data is undoubtedly advantageous, scanning through patient charts can be challenging. Algorithms have been developed to sift through patient notes and detect individuals with specific risk factors, diagnoses, or outcomes. This capability is particularly valuable because, in theory, a LLM system could be developed to review and extract data from medical charts, including pathology reports, and promptly identify patients at highest risk for conditions that could cause significant morbidity or mortality if missed by the physician [6,9].
The field of pathology is no exception to the adaptation of LLMs and the utilization of these technological advancements. Various in recent years have assessed LLM’s accuracy, potential use, and associated limitations. For instance, a study by Vaidyanathaiyer et al., evaluated ChatGPT's proficiency in pathology through thirty clinical case scenarios. These cases were evenly distributed across three primary subcategories: hematology, histopathology, and clinical pathology, with ten cases from each category. The researchers reported that ChatGPT received high grade of “A” on nearly three-quarters of the questions; in the remaining questions, and “B” grades on remaining questions. They found that ChatGPT demonstrated moderate proficiency in these subcategories, excelling in rapid data analysis and providing fundamental insights, though it had limitations in generating thorough and elaborate information [10]. Furthermore, Passby et al. demonstrated capacity of ChatGPT to address multiple-choice inquiries in the Specialty Certificate Examination of dermatology, with ChatGPT-4 outperforming ChatGPT-3.5, scoring 90% versus 63%, respectively, compared to an approximate passing score of 70% [11]. In an investigation by Delsoz et al., twenty corneal pathologies with their respective case descriptions were provided to ChatGPT-3.5 and ChatGPT-4. ChatGPT-4 performed better, correctly answering 85% of the questions, whereas ChatGPT-3.5 answered only 60% correctly [12]. The current study found that ChatGPT-3.5 performed similarly in the percentage of correct responses. However, this study further evaluated the LLM responses and found that nearly 23.3% and 15% of ChatGPT and Gemini answers, respectively, were fair but still had inaccuracies. This highlight areas where these systems can improve, as they sometimes almost answer correctly but not fully. For instance, when a histopathology report of squamous cell carcinoma in situ was given to ChatGPT-3.5, it answered with squamous cell carcinoma. On further prompting, the system favored an invasive squamous cell carcinoma over an in-situ one, even when the suggestion was made to it whether an in-situ lesion was more appropriate for that scenario. similarly, in the case of guttate psoriasis, Gemini answered with only “psoriasis” did not specify the type, while ChatGPT-3.5 responded with “psoriasis vulgaris”. In a study by Rahsepar et al. on pulmonary malignancies, Google Bard (the former name of Gemini) provided 9.2% partially correct answers, similar to Gemini's 15% partially correct responses in this study. However, ChatGPT-3.5 answered 17.5% of lung cancer questions incorrectly, whereas in the present study, ChatGPT-3.5’s incorrect answers were nearly twice as frequent. This may be due to ChatGPT broader access to data and medical information on lung cancer compared to the dermatological conditions tested in this study, highlighting the limitations and risks of relying on these systems for rarer diseases [13].
Although existing language models have access to extensive medical data, they often lack a nuanced understanding of individual diseases or specific patient cases. They have not undergone specialized training for medical tasks, relying solely on the provided data and information. The unclear methodology behind the LLM's diagnostic process leads to skepticism regarding the reliability of LLM-generated diagnoses. Consequently, their ability to accurately diagnose complex or unique cases may be limited, as demonstrated in the current study on skin histopathology cases. Notably, in a few cases, LLMs declined to provide a diagnosis on the initial prompt, citing concerns about giving medical advice, and only issued a diagnosis after repeated prompting with the same scenario. Despite their ability to offer insights based on existing knowledge, LLMs may lack a complete understanding of the intricate details and visual indicators crucial for pathologists' diagnosis. In the current study, the pathologist initially examined the histopathology slides and then provided the report to the AI systems. Another issue is that preserving the integrity of LLMs and safeguarding the confidentiality of associated data from unauthorized access is critical, particularly in scenarios involving sensitive patient information [14,15]. The case scenarios in this study did not include specific patient identifiers. Additionally, failure to evolve the LLM tools utilized in the pathological assessment alongside advancements in clinical practice and treatment poses the risk of stagnation and adherence to outdated methodologies. Although it is possible to manually update LLM algorithms to align with new protocols, their efficacy depends heavily on the availability of pertinent data, which might not be readily accessible during transitional periods. Such adaptations could introduce errors, particularly in pathology, through misclassifications of entities as classification and staging systems undergo revisions. Another concern is automation bias, which refers to the tendency of clinicians to regard LLM-based predictions as flawless or to adhere to them without questioning their validity. This bias often emerges soon after exposure to new technology and may stem from concerns about the legal consequences of disregarding an algorithm's output. Research across various fields has shown that automation bias can reduce clinician accuracy, affecting areas such as electrocardiogram interpretation and dermatologic diagnoses. Clinicians at all proficiency levels, including experts, are susceptible to this phenomenon [3,14-16].
The LLM has numerous applications in the medical field, with various technologies being developed at an unprecedented pace. For example, in the field of epilepsy, Empatica has created a wearable monitor called Embrace, which detects the onset of seizures in patients with epilepsy and notifies designated family members or trusted physicians. This innovation enhances safety and facilitates early management of such cases and received FDA approval six years ago [17]. Additionally, one of the earliest uses of LLM was for the detection of atrial fibrillation. AliveCor mobile application, which facilitates ECG monitoring and atrial fibrillation detection using a mobile phone, was FDA-approved. Recent findings from the REHEARSE-AF study indicated that traditional care methods are less effective at detecting atrial fibrillation in ambulatory individuals compared to remote ECG monitoring using Kardia [17,18]. Another example is the artificial immune recognition system, which has demonstrated remarkable accuracy in diagnosing tuberculosis by using support vector machine classifiers. These advanced systems significantly outperform traditional methods, making them a robust tool in identifying tuberculosis cases with high reliability. This underscores the potential of these models to enhance diagnostic processes in infectious diseases [19]. The advancements across various medical disciplines render the application of LLMs in histopathological diagnostics increasingly viable and anticipated for future clinical implementation. This progress motivates further research by scientists and numerous companies, as the focus has shifted from questioning whether LLM will be used in pathology or not to when and how these models will be utilized precisely.
One limitation of this study is that the aforementioned LLM systems were not evaluated for their ability and accuracy in directly reaching a diagnosis from histopathological images. Instead, the study relied on providing necessary information from the histopathological reports in text form, which imposes practical constraints and still requires an expert pathologist. Future studies focusing on both histopathological images and texts are necessary to further evaluate the comprehensive capabilities of LLM tools in this domain.
Conclusion
In certain instances, ChatGPT-3.5 and Gemini may provide an accurate diagnosis of skin conditions when provided with pertinent patient history and descriptions of histopathological reports. Specifically, Gemini showed higher accuracy in diagnosing non-neoplastic cases, while ChatGPT-3.5 demonstrated better performance in neoplastic cases. However, despite these strengths, the overall performance of both models is insufficient for reliable use in real-life clinical settings.
Declarations
Conflicts of interest: The author(s) have no conflicts of interest to disclose.
Ethical approval: Not applicable.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: RMA and AMA were significant contributors to the conception of the study and the literature search for related studies. DSH and SHM involved in the literature review, study design, and manuscript writing. TSA, HAY, RSA, and AMS were involved in the literature review, the study's design, the critical revision of the manuscript, and data collection. RMA and DSH confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the introduction section. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Defining the Scientist: A Consensus-Based Approach
João Gama, Marko Mladineo, Shelina Bhamani, Behzad Shahmoradi, Victoria Samanidou, Alexander S....
Abstract
Introduction
The term “scientist” lacks a universally accepted definition, reflecting the evolving, interdisciplinary nature of scientific work and posing challenges for recognition, communication, and policy. This study aims to develop consensus-based definitions of the term “scientist” by engaging experienced scholars across diverse fields.
Methods
This study involved 156 scholars, each with at least 1,000 citations, recruited via convenience sampling. Fourteen scientist definitions, derived from literature and expert input, were assessed using a nine-point Likert scale via a structured google forms survey. The sample size was calculated using G*power (effect size = 0.5, power = 0.95), requiring at least 80 participants. Content Validity Index (CVI) was used for analysis. Definitions scoring ≥0.78 were accepted and included for final analysis, 0.70–0.78 were revised and re-evaluated, and <0.70 were excluded. Participation was voluntary and anonymous, ensuring ethical compliance and confidentiality.
Results
Of the 14 proposed definitions, six (42.9%) were excluded (CVI < 0.70), seven (50.0%) were accepted (CVI > 0.78), and one (7.1%) underwent revision (CVI 0.70–0.78). The highest-rated definitions were refined into two consensus-based versions: a short definition (“A scientist is a person who conducts research”) and a detailed one emphasizing hypothesis formulation and knowledge dissemination. Final validation yielded CVIs of 0.82 and 0.84, respectively, confirming strong expert agreement on both definitions.
Conclusion
This study developed two validated definitions of “scientist” emphasizing systematic research and knowledge dissemination. These definitions clarify the concept of scientific identity, providing a flexible yet rigorous framework applicable across academic, interdisciplinary, and policy-making contexts.
Introduction
The term "scientist" has undergone significant transformation since its inception, reflecting the dynamic nature of scientific inquiry and the evolving landscape of knowledge. This lack of clarity stems from the diverse roles and contributions of individuals in scientific fields, the evolving nature of research, and the interdisciplinary scope of modern science. Historically, figures such as Galileo and Newton were regarded as natural philosophers, a reflection of an earlier framework for knowledge production that has evolved alongside modern scientific advancements. Before twentieth century, the term "scientist" was commonly referred to as a "man of science," "natural philosopher," or by various other designations [1,2].
In contemporary contexts, scientists operate across a broad spectrum of fields, including medicine, biology, chemistry, physics, and social sciences, each employing methodologies tailored to their specific inquiries. For instance, biologists may design experiments to test hypotheses about living organisms, while social scientists might use qualitative methods to explore human behavior [3]. The Science Council defines a scientist as an individual who methodically collects and applies research and evidence to develop hypotheses, performs experiments, and shares results to advance knowledge in their field [4]. While National Cancer Institute defines a scientist as an individual with a background in science, particularly someone actively engaged in a specific area of research [5]. This diversity in practices underscores the challenge of defining "scientist" in a way that captures the breadth of their contributions.
The plurality of definitions extends to global organizations and frameworks. For example, the United Nations Educational, Scientific, and Cultural Organization highlights the critical role of scientists in addressing global challenges and promoting sustainable development. This definition broadens the scope to include individuals working in multidisciplinary teams or applying scientific knowledge to public policy and societal issues. Similarly, some academic discussions focus on the characteristics of a scientist, such as curiosity, skepticism, and a commitment to evidence-based conclusions, rather than formal qualifications or job titles [6].
Unlike well-defined professions such as medicine or engineering, where specific educational pathways and professional titles (e.g., "doctor" or "engineer") confer clear identities, the term "scientist" lacks a universally recognized credentialing system. This absence can lead to underrepresentation or misrepresentation of scientific expertise, especially in interdisciplinary and collaborative contexts [7]. For example, the growing integration of data science in biology or physics illustrates the importance of understanding who qualifies as a scientist to ensure effective communication and collaboration among stakeholders. The absence of a standardized definition poses practical challenges for scientific communication, policymaking, and inclusivity. This study aims to address this gap by engaging scholars across disciplines to develop a consensus-based definition of "scientist." By recognizing the diverse and interdisciplinary contributions of scientists, such a definition could enhance collaboration, improve public understanding, and inform policies that support the scientific community.
Methods
Study design and participants
A total of 156 scholars (out of 300 invited) participated in this study. Eligibility was determined based on the scholars' substantial academic expertise, evidenced by the achievement of at least 1,000 citations within their respective fields. This criterion ensured that participants had significant research experience and were highly qualified to contribute to the formulation of a consensus-based definition of "scientist." Participants were recruited through a convenience sampling method, and data were collected via a structured survey administered through google forms. While convenience sampling was used due to the accessibility of high-citation scholars, efforts were made to ensure disciplinary diversity to mitigate potential bias. Personalized invitations were sent via email to each scholar to facilitate their inclusion in the study.
Sample size determination
The sample size was determined using G*power statistical software (version 3.1.9.7), employing a two-tailed goodness of fit test with an effect size of 0.5, an alpha error probability of 0.05, and a statistical power of 0.95. According to the calculations, a minimum of 80 participants were required to achieve statistically valid results. Consequently, 156 scholars were recruited to participate in the study, ensuring robust representation and adequate statistical power.
Data collection
Fourteen proposed definitions of "scientist," curated from existing literature and expert contributions, were presented to the enrolled scholars for evaluation (Table 1). Each definition included a Likert scale with nine response options, ranging from "strongly agree" to "strongly disagree." Responses were systematically recorded and compiled in an Excel sheet for subsequent analysis. This process facilitated the systematic capture of scholarly consensus on each definition.
Proposed Definitions | Options | ||||||||
A person studying or has expert knowledge of one or more natural or physical sciences. (Oxford Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
An expert who studies or works in one of the sciences. (Cambridge Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person learned in science and especially natural science. (Merriam-Webster Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A scientist is someone who systematically gathers and uses research and evidence, to make hypotheses and test them, to gain and share understanding and knowledge. (Science Council) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A scientist is someone who has studied science and whose job is to teach or do research in science. (Collins Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
An expert in science, especially one of the physical or natural sciences. (Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A scientist is a person with some kind of knowledge or expertise in any of the sciences. (Vocabulary dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person who is trained in a science and whose job involves doing scientific research or solving scientific problems. (Britannica Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person who has studied science, especially one who is active in a particular field of investigation. (National Cancer Institute) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
Someone who works or is trained in science. (Longman Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person whose profession is investigating in one of the natural sciences. (Your Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person who is engaged in and has expert knowledge of a science. (Free Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
Someone whose job or education is about science. (LanGeek Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A scientist is a person who researches to advance knowledge in an area of the natural sciences. (Wikipedia) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
Data analysis
The Content Validity Index (CVI) was employed to assess the relevance and agreement of the definitions. Definitions with a CVI below 0.70 were excluded, as they failed to meet the minimum threshold for consensus. Definitions with a CVI between 0.70 and 0.78 underwent a second round of evaluation, with refined wording sent back to the same scholars for further review. Definitions achieving a CVI above 0.78 were deemed sufficiently valid for inclusion in the final analysis [8]. These definitions formed the foundation for the development of a unified, consensus-based definition of "scientist."
Ethical considerations
Participation in the study was entirely voluntary, and all responses were anonymized to preserve participant confidentiality.
Results
Initially, out of the 14 proposed definitions of the term "scientist," six (42.9%) received a CVI score below the threshold of 0.70 and were consequently excluded from further consideration. In contrast, seven definitions (50.0%) demonstrated strong content validity with CVI scores equal to or exceeding 0.78 and were therefore retained for subsequent synthesis and analysis. Only one definition (7.1%) fell within the intermediate range, with a CVI between 0.70 and 0.78 (Table 2).
Proposed Definition |
Agree |
Disagree |
Undecided |
CVI |
Status |
Science Council Definition |
146 |
8 |
2 |
0.94 |
Accepted |
Britannica Dictionary Definition |
136 |
16 |
4 |
0.87 |
Accepted |
Cambridge Dictionary |
130 |
20 |
6 |
0.83 |
Accepted |
Wikipedia Definition |
125 |
27 |
4 |
0.80 |
Accepted |
Free Dictionary Definition |
124 |
25 |
7 |
0.79 |
Accepted |
National Cancer Institute Definition |
124 |
25 |
7 |
0.79 |
Accepted |
Collins Dictionary Definition |
122 |
31 |
3 |
0.78 |
Accepted |
Oxford Dictionary Definition |
120 |
31 |
5 |
0.77 |
Revised |
Longman Dictionary Definition |
104 |
42 |
10 |
0.67 |
Excluded |
Your Dictionary Definition |
103 |
48 |
5 |
0.66 |
Excluded |
Dictionary (generic) Definition |
91 |
52 |
13 |
0.58 |
Excluded |
Vocabulary dictionary Definition |
88 |
58 |
10 |
0.56 |
Excluded |
Merriam-Webster Dictionary Definition |
81 |
64 |
11 |
0.52 |
Excluded |
LanGeek Dictionary Definition |
79 |
67 |
10 |
0.51 |
Excluded |
CVI: Content Validity Index, CVI Thresholds: Accepted: ≥ 0.78, Revised: 0.70–0.78, Excluded: < 0.70 |
Through a rigorous, iterative evaluation process involving expert feedback, the definitions with the highest CVI scores (those above 0.78) were integrated and refined into two distinct, consensus-based definitions of the term "scientist." The first was a concise definition: “A scientist is a person who conducts research.” The second was a more comprehensive and elaborated definition: “A scientist is someone who systematically conducts or gathers and uses research to formulate hypotheses and test them, in order to gain and disseminate understanding and knowledge.”
These two final definitions were subsequently circulated among the panel of scholars for a second round of evaluation, during which they were asked to rate the definitions for content validity. The short definition received a CVI of 0.82, while the more detailed definition attained a slightly higher CVI of 0.84, reflecting strong agreement among the experts. Although no additional formal qualitative feedback was solicited at this stage; minor wording adjustments were made based on informal suggestions received during this validation round.
Discussion
The role of a scientist extends far beyond the stereotypical image of an individual in a white coat working exclusively in a laboratory setting. Careers grounded in scientific expertise are remarkably diverse, encompassing domains such as research, education, industry, and regulatory affairs. The Science Council categorizes scientists into 10 different types, highlighting the diversity of scientific roles beyond the stereotypical lab-based researcher. It includes types such as experimental scientists, theoretical scientists, data scientists, and more, reflecting the broad spectrum of scientific work today [9]. Definitions of the term “scientist” vary, yet they generally converge on the principles of systematic inquiry, evidence-based investigation, and the pursuit of knowledge across various disciplines. For instance, the Oxford Advanced Learner’s Dictionary and the Britannica Dictionary emphasize formal training and research functions, typically within the natural sciences such as biology, chemistry, or physics [10,11]. In contrast, contemporary perspectives, such as those discussed by the American Association for the Advancement of Science in 2024, recognize a broader spectrum of scientific engagement, encompassing both professional researchers and individuals committed to understanding the world through observation, experimentation, and analysis [12]. In light of this diversity, the present study aimed to clarify and formalize the definition of a "scientist" through expert consensus. Two definitions were developed: a concise definition “A scientist is a person who conducts research”, and a comprehensive definition “A scientist is someone who systematically conducts or gathers and uses research to formulate hypotheses and test them, in order to gain and disseminate understanding and knowledge.” These definitions encapsulate the core activities and guiding principles of scientific inquiry, emphasizing both methodological rigor and the essential role of knowledge dissemination across disciplines.
A key finding of this study lies in its recognition of the evolving tension between disciplinary specialization and the increasing importance of interdisciplinary collaboration. As highlighted in contemporary analyses of interdisciplinary research and development, scientists now frequently operate at the intersection of multiple fields, such as nanomedicine, where the diversity and dissimilarity of collaborators’ knowledge can significantly enhance research productivity [13]. The concise definition, "A scientist is a person who conducts research" captures this shift by avoiding constraints tied to specific disciplinary boundaries. In contrast, the more detailed definition explicitly incorporates the systematic formulation and testing of hypotheses, along with the dissemination of knowledge, thereby reinforcing the structured and communicative nature of scientific inquiry. These elements align closely with UNESCO’s 2019 call for stronger science-society engagement and underscore the ethical responsibilities inherent in modern scientific practice [14].
The study’s findings also contribute to ongoing debates surrounding professional identity within the scientific community. In contrast to regulated professions such as medicine, the absence of a universal credentialing system for scientists complicates formal recognition, particularly in non-academic and interdisciplinary contexts. This ambiguity is reflected in the National Cancer Institute’s pragmatic definition of a scientist, which emphasizes active participation in research rather than reliance on formal titles or qualifications [15]. By anchoring the term “scientist” in core research activities rather than occupational labels, the consensus-based definitions proposed in this study offer a more inclusive framework. This approach accommodates emerging roles in fields such as data science and applied research, thereby addressing the risk of under recognition in collaborative and cross-sector environments.
The dual definitions, concise and comprehensive, offer flexibility for different contexts, a strategy aligned with the Science Council’s emphasis on methodological diversity [4]. The detailed definition’s focus on systematic inquiry and dissemination aligns with studies of interdisciplinary science, where “impassioned commitment” to shared goals drives innovation [13]. Simultaneously, the availability of a concise definition enhances clarity in public discourse and science communication, while the more detailed version provides the specificity necessary for institutional contexts such as policy development, research funding, and professional accreditation.
Notably, the study’s findings also challenge enduring stereotypes of the “lone genius” scientist by highlighting the inherently collaborative and iterative nature of scientific practice. Contemporary frameworks, such as those emerging from computational biology, suggest that scientific identity is increasingly dynamic, pluralistic, and shaped by collective knowledge production [16]. The process undertaken in this study, involving successive refinement and expert validation of definitions, closely mirrors the recursive logic of the scientific method itself. This methodological alignment is particularly salient in fields like nutritional epidemiology, where the replication of findings remains a persistent challenge and iterative inquiry is essential for refining evidence [17].
Despite the methodological rigor and expert involvement, several limitations should be acknowledged. First, the study employed convenience sampling, which may introduce selection bias and limit the generalizability of the findings. Although participants were selected based on a minimum citation threshold to ensure scholarly expertise, this criterion may have inadvertently excluded emerging researchers or experts with significant practical contributions who have not yet achieved high citation metrics. Second, the use of an online survey format may have constrained participant engagement, as scholars with limited availability or preference for alternative formats may have been underrepresented. Additionally, response bias cannot be ruled out, as those with a particular interest in the topic or in defining scientific identity may have been more inclined to participate, potentially skewing the results. Future refinements of the definition should also consider voices from non-academic scientific contexts including those in industry, policy, and community-based science who are increasingly central to addressing complex global challenges.
Conclusion
By engaging experienced scholars across disciplines, this study establishes two validated definitions of “scientist” that emphasize systematic research activity and knowledge dissemination. These definitions offer a structured yet adaptable framework for understanding scientific identity, balancing clarity with flexibility. They help address the ambiguity surrounding the term “scientist,” providing a foundation for improved communication, interdisciplinary collaboration, and evidence-informed policy development. Importantly, they remain open to future refinement as scientific practice continues to evolve.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: JG, MM, SB, BS, VS, ASN, SHM, HAH, AGH, ADS, RAK, WRR, AB, GB, SS, SN, CJ, PL, MSS, ZK, MC, AM, SK, FCT, FB, FRK, MAM, AA, VK, DH, PM, VRM, MSA, EA, and RV were significant contributors to the conception of the study, voting for the items. FHK, BAA, and AMM were involved in the literature review, manuscript writing, and data analysis and interpretation. FHK and AMM Confirmation of the authenticity of all the raw data. All authors have read and approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Management of Lower Limb Varicose Veins Using Endovenous Laser Ablation, Micro-Phlebectomy, and Sclerotherapy Using Multimodal Analgesia
Fahmi H. Kakamad, Fuad E. Fuad, Soran H. Tahir, Ayoob A. Mohammed, Rezheen J. Rashid, Hiwa O....
Abstract
Introduction
Previously, the conventional surgical procedure of high-ligation and saphenous stripping was commonly used to treat varicose veins (VVs). However, contemporary advancements have led to the rapid evolution of VV management. This study shares a single center's experience in treating patients with lower limb VVs through endovenous laser ablation in combination with phlebectomy and sclerotherapy using multimodal analgesia.
Methods
This case series study included consecutive patients diagnosed with lower limb VVs. The inclusion criteria encompassed VVs categorized from score C1 to C6 (clinical, etiologic, anatomic, and pathophysiological), saphenofemoral incompetence, and patients aged between 18 and 75.
Results
A total of 153 patients were enrolled. The majority were female (73.0%), resulting in a female-to-male ratio of 2.73:1. The age of patients ranged from 18 to 73 years, with a mean age of 40.8 ± 11.7 years. Regarding post-procedural complications, wounds developed in 25 patients (16.3%), making it the most common complication, while thrombophlebitis occurred in 15 cases (9.8%), skin discoloration in nine cases (5.9%), and recanalization and DVT each in a case (0.7%). Due to extensive varicose veins, 31 patients (20.0%) required a sclerotherapy session six weeks after the operation. Patients could return to routine daily activities within 4 to 10 hours. Overall, the patient satisfaction rate (complete and partial) was 85%. Only a case of recurrence (0.7%) was reported after a one-year follow-up.
Conclusion
Endovenous laser ablation, in combination with phlebectomy and sclerotherapy using multimodal analgesia, may yield a satisfactory outcome in patients with moderate to severe VVs.
Introduction
Varicose veins (VVs) are abnormally twisted and dilated blood vessels, typically located in the lower limbs. They originate from damaged or faulty venous valves, which may subsequently give rise to painful swelling and the potential formation of blood clots [1]. It is the most commonly encountered among vascular diseases, affecting up to one-third of the population and profoundly impacting the quality of life [2]. Increased age, female gender, multiparity, obesity, a history of deep venous thrombosis (DVT), and engagement in occupations involving extended periods of standing are all recognized as significant risk factors associated with the onset of VVs [3]. Historically, VVs were often viewed as a cosmetic problem, and patient preferences largely influenced treatment decisions. However, advancements in medical imaging, particularly duplex ultrasonography, revolutionized the understanding of VVs by providing a more precise assessment of venous reflux and allowing healthcare professionals to accurately diagnose the underlying venous insufficiency contributing to VVs [4]. Previously, the conventional surgical procedure of high-ligation and saphenous stripping was commonly used for the treatment of VVs. However, contemporary advancements have led to the rapid evolution of VV management, offering minimally invasive interventions such as radiofrequency (RFA), laser ablations, foam, liquid sclerotherapy, and microphlebectomy [5]. Endovenous laser ablation (EVLA) uses laser energy to occlude impaired veins, rerouting blood circulation toward healthier venous pathways. Microphlebectomy presents another alternative therapeutic modality involving the surgical removal of superficial veins via small puncture incisions. Sclerotherapy entails the injection of a sclerosing agent into afflicted veins, resulting in their closure and redirection of blood flow [6]. This study aims to share the experience of a single center in treating patients with lower limb VVs through EVLA in combination with phlebectomy and sclerotherapy under multimodal analgesia. The study avoided citing suspicious data by checking for predatory behavior among the referenced studies [7].
Methods
Study design
The study was a single-center case series encompassing consecutive patients diagnosed with lower limb VVs and treated at the Thoracic and Vascular Surgery Department of Smart Health Tower from January 2020 to September 2023. Patients provided consent to participate in the study and to authorize the publication of any related data.
Data collection
Following data de-identification, the necessary information was retrospectively gathered from patients' profiles within the department's database. This included patient demographics, chief complaint, clinical score, affected side, severity of the condition, ultrasound examination results, and treatment outcomes.
Eligibility criteria
The inclusion criteria encompassed VVs categorized from score C1 to C6 (clinical, etiologic, anatomic, and pathophysiological) (CEAP), presence of saphenofemoral incompetence, and patients aged between 18 and 75 years. The exclusion criteria comprised any prior treatment of VVs, suspicion or confirmation of DVT or occlusion, contraindications to anesthesia, and refusal to undergo the treatment procedure.
Intervention
In the pre-operative phase, approximately 30 minutes before the operation, patients received a combination of medications, including pethidine (50 mg subcutaneously), ketorolac (30 mg intramuscularly), and ondansetron (8 mg), if there were no contraindications. In the operating theater, intravenous pethidine was administered after properly marking the varicose vein sites by injecting normal saline, patient positioning, and monitoring. This was followed by a slow tramadol infusion (100 mg) and paracetamol (1000 mg). Continuous administration of dexmedetomidine (100 –150 µg in 100 ml of normal saline) was initiated, with oxygen supplementation adjusted as necessary. Antiemetic drugs, aside from ondansetron, were administered during the procedure unless contraindicated. In rare cases of anxiety or the requirement for minimal sedation, fentanyl (50 µg), midazolam (1mg), or a combination of both were included.
The EVLA procedure started with a Doppler ultrasound by a radiologist to guide a needle to access the great saphenous vein (GSV). Then, a guide wire was carefully inserted into the vein, followed by the placement of an introducer sheath, which might include a dilator. Just below knee level was the preferred entry point for the insufficient GSV due to its larger size, straight course, and lower risk of nerve injury. The laser (1470 nm) was inserted into the varicose vein after verifying the laser's tip position by observing the red standby light through the skin with a diameter between 200 and 600 mm (dependent on the varicose vein and the laser parameters). The laser's settings were customized as necessary, and it was carefully withdrawn through the vein using a technique suited to the specific situation. The laser power was calibrated according to the vein size, with a minimum setting of 42 watts. The power was determined by multiplying the vein diameter by a factor of 7. After major vein ablation, micro-avulsion was done for the visible varicose veins using a particular instrument (Drawsh) (Figure 1). The reticular and telangiectasia were injected with a foamy solution consisting of two ml of polidocanol and eight ml of atmospheric air (1:4) as the sclerosing agent.
Statistical analysis
The data organization was conducted using Microsoft Excel 2019. Descriptive analysis was performed using the Statistical Package for the Social Sciences (SPSS) Version 25 for qualitative data synthesis. The data were presented as medians, means, standard deviations, frequencies, percentages, and ranges.
Results
A total of 153 patients were enrolled in this study. The majority were female (73.0%), resulting in a female-to-male ratio of 2.73:1. The age of patients ranged from 18 to 73 years, with a mean age of 40.8 ± 11.7 years. Over half of the cases were overweight (54.9%), and the mean BMI was 26.3 ± 4.2. The major chief complaint was pain (17.7%), followed by swelling (15.0%) and lower limb discoloration (5.2%). The disease was asymptomatic in 59.5% of the cases. The disease presented as VVs (C2) in most cases (73.9%), although 21 (13.7%) presented with reticular veins (C1) and 10 (6.5%) with telangiectasia (C1). Disease severity was moderate in over half of the cases (53.6%), followed by severe in 51 cases (33.3%). The majority of patients (61.4%) had bilateral lower limb involvement, while the remaining patients had unilateral involvement, with 22.2% affected in the left lower limb and 16.3% in the right lower limb. The mean diameters of the GSV undergoing treatment were 9 mm.
The mean reflux duration of the affected veins was 1.1 seconds, ranging from 0.6 to 2.5 seconds, with the procedure duration ranging from 45 to 220 minutes. Regarding post-procedural complications, wounds developed at the site of sclerosant injection in 25 patients (16.3%), making it the most common complication, while thrombophlebitis occurred in 15 cases (9.8%), skin discoloration in nine cases (5.9%), and recanalization and DVT each in a case (0.7%). The thrombophlebitis cases were treated with an anti-inflammatory agent. Wounds healed with proper dressing within two to three weeks. Due to extensive VVs, 31 patients (20.0%) required sclerotherapy six weeks after the operation. Additionally, all instances of skin discoloration resolved spontaneously. Patients could return to routine daily activities within 4 to 10 hours. Overall, 54.3% of the patients were completely satisfied with the outcome. Meanwhile, 30.7% were partially satisfied, and 15.0% were not satisfied with the procedure. Only a case of recurrence was reported during the one-year follow-up (Table 1).
Variables |
Frequency / Percentage |
Demographics |
|
Age range (median, mean ± SD), years |
18 – 73 (40, 40.8 ± 11.7) |
BMI (mean± SD), kg/m2 Underweight Normal Overweight Obesity |
26.3 ± 4.2 3 (2.0%) 52 (34.0%) 84 (54.9%) 14 (9.1%) |
Gender Male Female |
41 (27.0%) 112 (73.0%) |
Chief complaint Pain Swelling Lower limb discoloration Itching Extensive varicose vein impending rupture |
27 (17.7%) 23 (15.0%) 8 (5.2%) 4 (2.6%) 91 (59.5%) |
CEAP classification C1 C2 C3 C4 C5 C6 |
21 (13.7%) 113 (73.9%) 8 (5.2%) 6 (3.9%) 5 (3.3%) 0 (0.0%) |
Severity status Mild Moderate Severe |
20 (13.1%) 82 (53.6%) 51 (33.3%) |
Affected site Right lower limb Left lower limb Both lower limbs |
25 (16.3%) 34 (22.2%) 94 (61.4%) |
Reflux duration (seconds), mean (range) |
1.1 (0.6-2.5) |
Diameter of GSV (mm), mean (range) |
9 (6-22) |
Operation time (minutes), mean (range) |
70 (45-220) |
Returning to routine daily activity (hours), mean (range) |
6 (4-10) |
Satisfaction level Completely satisfied Partially satisfied Not satisfied |
47 (30.7%) 23 (15.0%) |
Post-procedure complications Wounds at the site of injections Thrombophlebitis Skin discoloration Recanalization Deep vein thrombosis |
25 (16.3%) 15 (9.8%) 9 (5.9%) 1 (0.7%) 1 (0.7%) |
Post laser injection (sclerotherapy) Yes No |
122 (80.0%) |
Recurrence |
1 (0.7%) |
Discussion
The VVs represent a prevalent condition, with occurrence rates typically ranging from 29.5% to 39.0% in women and 10.4% to 23.0% in men [1]. Annually, the condition manifests in approximately 2.6% of women and 1.9% of men. Its prevalence consistently rises with age, a trend often associated with increased height, weight, and body mass [1,8]. Chronic venous disease exacerbates the severity of symptoms, progressing from telangiectasia, characterized by the formation of threadlike patterns on the skin (referred to as spider veins), to VVs. This progression often imposes a substantial negative impact on the patient's quality of life [9]. In the current study, consistent with the genuine literature, females were predominantly affected, with a female-to-male ratio of 2.73:1. The mean age of patients, 40.8 years, aligns with previous findings [1,8]. The primary manifestation of the disease was VVs in the majority of cases (73.9%), indicating significant disease progression. Among the cases, the severity was moderate in 53.6% and severe in 33.3%.
Aligned with technological advancements, continual investigation has been undertaken to explore therapeutic approaches for treating VVs through endovenous methodologies [10]. A pivotal milestone occurred in 2001 when Navarro et al. reported the inaugural utilization of thermal endovenous ablation employing an 810 nm diode laser [11]. Subsequently, a consistent evolution in laser technology has ensued, accompanied by many studies employing diverse wavelengths and laser modalities [10,12,13]. At present, the Food and Drug Administration (FDA) has approved lasers of various wavelengths, including 810, 940, 980, and 1470 nm diode lasers, alongside 1319 and 1320 nm neodymium-doped yttrium aluminum garnet (Nd: YAG) lasers. Simultaneously, the progression of laser technology has stimulated research into thermal ablation techniques for the GSV using radiofrequency energy. The FDA endorsement for the application of radiofrequency energy in endovenous ablation procedures was granted in 1999 [10]. In 2002, Weiss et al. published the initial cases wherein patients underwent thermal ablation employing radiofrequency energy [14]. The current clinical practice guidelines advocate for ablation (EVLA and RFA) as the primary treatment for superficial venous insufficiency while recommending phlebectomy or sclerotherapy for addressing varicosities [15]. In the present study, EVLA (1470 nm) was employed in combination with phlebectomy and sclerotherapy to manage VVs in 153 patients.
A meta-analysis of 119 studies found success rates of 94% for EVLA and 84% for RFA from data on 12,320 legs [16]. Puggioni et al. reported one-month follow-up success rates of 100% for EVLA and 96% for RFA [17]. Bozoglan et al. reported no significant complications such as DVT, pulmonary embolism, or skin burns in either EVLA or RFA. Minor complications included induration (20.7% in EVLA and 31% in RFA), ecchymosis (31% in EVLA and 27.6% in RFA), and edema (27.6% in EVLA and 65.5% in RFA). They claimed that most minor complications, such as hematoma and ecchymosis, were attributed to the use of tumescent anesthesia rather than the procedures themselves. They reported a recanalization rate of 6.8% in the RFA group, while no instances of recanalization were noted in the EVLA group. Patient satisfaction levels were significantly higher with EVLA at 51.7% compared to the 31.0% satisfaction rate observed for RFA. Only 17.2% of patients reported satisfaction with both procedures. Individuals in the EVLA group typically returned to daily activities within 0.9 days, while those in the RFA group took an average of 1.3 days to resume regular activities. The mean duration of procedures was 31.2 minutes for EVLA and 32.7 minutes for RFA [10]. Another study involving 148 patients undergoing EVLA reported pain in over 50% of patients, hematoma in 40.5%, superficial vein thrombosis in 6.8%, induration in 6.8%, hyperpigmentation in 3.4%, infection and dysesthesia in less than 2%, and nerve damage occurring in less than 1% of cases [18]. Additionally, a meta-analysis reported the incidence of thrombophlebitis and hematoma at 4.9% and 4.4%, respectively [19]. Kawai et al. performed EVLA with and without phlebectomy and found hematoma in 26.6% of cases with phlebectomy and 23.2% of cases without phlebectomy. They reported no instances of DVT [15]. Because sclerotherapy plays a significant role in managing and diminishing the appearance of VVs, which have reached a severe stage [1], they needed additional sclerotherapy in 8 cases (3.2%) in the phlebectomy group and 26 cases (3.7%) in the non-phlebectomy group. The operation time ranged from 27 to 40 minutes in the EVLA with the phlebectomy group and 19 to 31 minutes in the counterpart group. Recanalization was observed in four cases (1.6%) in the EVLA with the phlebectomy group and in 25 cases (3.6%) in the latter group [15]. In this study, developing wounds was the most prevalent complication (16.3%), followed by thrombophlebitis (9.8%) and skin discoloration (5.9%). Thrombophlebitis was treated with an anti-inflammatory agent, skin discoloration resolved spontaneously, and wounds healed within a few weeks with dressing. The duration of the operation in the present study ranged from 45 to 220 minutes, with a mean of 70 minutes. The recanalization rate (0.7%) was lower than the rate reported by Kawai et al. [15] but higher than that reported by Bozoglan et al [10]. Patients returned to daily activities within 4 to 10 hours, and the overall treatment satisfaction (partial and complete) reached 85%, surpassing Bozoglan et al.'s [10]. There was a case of DVT, and sclerotherapy was required in 20% of cases due to the severity of the disease.
Regarding the working principle, EVLA enables veins to absorb energy for heat generation, leading to vein obliteration. The energy utilized during the procedure significantly impacts the outcome. It has been discovered that energy delivery directly influences recurrence, with lower energy levels yielding poorer outcomes than higher energy levels [20]. The recurrence rate for up to 10 years was found to be 66% in EVLA, and 36% of the patients needed reintervention [21]. To mitigate the risk of recurrence, a laser wavelength of 1470 nm was employed in the procedures of the current study. After one year of follow-up, only a case of recurrence was reported. This study has some drawbacks, including a retrospective design that means crucial data may be overlooked for discussion and a short follow-up period to properly indicate the recurrence rate.
Conclusion
Endovenous laser ablation, in combination with phlebectomy and sclerotherapy using multimodal analgesia, may yield a satisfactory outcome in patients with moderate to severe VVs.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable.
Patient consent (participation and publication): Patients provided consent to participate in the study and to authorize the publication of any related data.
Source of Funding: Smart Health Tower.
Role of Funder: The funder remained independent, refraining from involvement in data collection, analysis, or result formulation, ensuring unbiased research free from external influence.
Acknowledgements: None to be declared.
Authors' contributions: FHK was a major contributor to the study's conception and to the literature search for related studies. SHT, AAM, and RJR were the radiologists who provided access to the cases. HOA, BAA, and MNH were involved in the literature review, study design, and writing of the manuscript. FEF, KAS, and BYA were the anesthesiologists who anaesthetized the cases. DHMS, FJA, NSS, PMK, BAA, AMM and SJJ were involved in the literature review, the study's design, the critical revision of the manuscript, and the table processing. All authors have read and approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.
Review Articles

Chest Wall Hydatid Cysts: A Systematic Review
Fahmi H. Kakamad, Harem K. Ahmed, Ali H. Hasan, Ahmed H. Ahmed, Ayoob A. Mohammed, Dindar H....
Abstract
Introduction
Given the rarity of chest wall hydatid disease, information on this condition is primarily drawn from case reports. Hence, this study systematically reviews the disease's manifestation and management.
Methods
Google Scholar was searched with the following keywords: (hydatid OR hydatidosis OR tapeworms OR echinococcosis OR echinococcus OR granulosus AND chest OR wall OR thoracic OR thorax OR rib OR sternum OR sternal OR cartilage OR intercostal OR extra-pulmonary). Inclusion criteria involved a confirmed diagnosis of chest wall hydatid cyst. Only English-language studies published in legitimate journals were included.
Results
The reported cases were primarily from Turkey (41.5%). The mean age of the patients was 39.7 ± 17.1 years, with a male predominance (56.9%). The most common clinical presentations were swelling (47.1%) and chest or abdominal pain (45.1%). Only 10 cases (19.6%) had reported a history of animal contact. Among those with documented residency (35.3%), 16 (31.4%) resided in rural areas. The average mass size on the CT scan was 7.5 ± 2.4 cm. Surgery was the treatment of choice, with thoracotomy performed in 37.3% of cases, video-assisted thoracoscopy in 1.9%, and the surgical technique not specified in 60.8% of cases. The mean hospital stay was 8.6 ± 4.4 days, and no recurrences were reported.
Conclusion
Despite its rarity, chest wall hydatid cyst may have a good prognosis with few complications. Given its often-nonspecific presentation, reviewing the patient's medical history may help establish an accurate provisional diagnosis.
Introduction
Hydatid disease, caused by tapeworm parasites, is prevalent in sheep-rearing regions, including the Middle East, Mediterranean areas, Africa, South America, and Australia [1,2]. In humans, three types of echinococcosis are known to occur: cystic echinococcosis caused by Echinococcus granulosus, alveolar echinococcosis caused by Echinococcus multilocularis, and polycystic echinococcosis due to Echinococcus Vogeli or Echinococcus oligarthrus [3]. The most common causative organism of human hydatid disease is Echinococcus granulosus [1]. The parasite is a tapeworm with an approximate length of 2 to 7 mm [4]. Hydatid disease or echinococcosis is an old and well-known helminthic disease known since Hippocrates [5]. Rudolphi, in 1808, first used the term hydatid cyst [HC] to describe human echinococcosis [2]. Dogs are the definitive hosts, while farm animals are intermediate hosts. Although humans are not involved in the parasite's life cycle, they may be affected accidentally, either by direct contact with a dog or by ingesting contaminated food and fluid from parasite eggs [6]. After oral ingestion, the cyst hatches in the duodenum and initially spreads to the liver through the portal vein via hematogenous or occasionally lymphogenous routes. It then reaches the lungs through the venous system, and from the lungs, it can disseminate to other organs via the arterial system [7]. The disease can be seen in different body parts, like the thyroid, bladder, heart, and pulmonary artery [7-10]. The chest wall is a very uncommon localization for this disease [6,11]. Therefore, the literature has limited information regarding chest wall HCs. This study aims to systematically review the manifestation and management of the disease.
Methods
Study design
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Data sources and search strategy
Google Scholar was searched with the following keywords: [hydatid OR hydatidosis OR tapeworms OR echinococcosis OR echinococcus OR granulosus AND chest OR wall OR thoracic OR thorax OR rib OR sternum OR sternal OR cartilage OR intercostal OR extra-pulmonary].
Eligibility Criteria
Inclusion criteria involved a confirmed diagnosis of chest wall HC. Only English-language studies published in legitimate journals were included [12].
Data items
One author screened the studies to select those that met the eligibility criteria, and another rechecked his work. Key data, including the first author's name, study design, country and year of publication, sample size, patient demography, clinical presentation, management strategies, and outcomes, were extracted from the included studies.
Data analysis and synthesis
The data were collected in a Microsoft Excel sheet (2021), and descriptive statistics were performed using the Statistical Package for the Social Sciences (SPSS) version 27. The data were presented as frequencies, percentages, means, and standard deviations.
Results
Study Selection
A systematic search identified a total of 432 articles. After the initial screening, 29 studies presenting only abstracts, two duplicates, and three non-English publications were excluded, resulting in 398 articles for further evaluation. Title and abstract screening excluded 329 studies due to irrelevance, leaving 69 articles for full-text review. Of these, seven were excluded due to irrelevancy, eight due to unretrieved data, and two for being letters to the editor. During the final screening, 11 studies were removed due to publishing in predatory journals. Finally, 41 studies [1–3,5,6,11,13–26,28-48] met the inclusion criteria and were included in the review (Figure 1). The raw data for each included study are detailed in Tables 1, 2, and 3.
Author/reference |
Year |
Type of Study |
Country |
No. of Case |
Age |
Gender |
Residency |
Contact with Animal |
PMH |
PSH |
Origin |
Althobaity et al. [1] |
2023 |
Case report |
Saudi Arabia |
1 |
22 |
Male |
N\A |
Yes |
Insignificant |
N\A |
Primary |
Goyal et al. [2] |
2010 |
Case report |
India |
1 |
30 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
Godazandeh et al. [3] |
2020 |
Case report |
Iran |
1 |
40 |
Male |
Urban |
No |
N\A |
No |
Primary |
Basit et al. [5] |
2021 |
Case report |
Afghanistan |
1 |
65 |
Male |
Rural |
N\A |
N\A |
No |
Primary |
Salih et al. [6] |
2017 |
Case report |
Iraq |
1 |
20 |
Female |
Rural |
Yes |
N\A |
N\A |
N\A |
Döner et al. [11] |
2019 |
Case report |
Turkey |
1 |
31 |
Female |
N\A |
N\A |
N\A |
N\A |
Primary |
MohIeldeen et al. [13] |
2013 |
Case report |
Iraq |
1 |
42 |
Male |
Rural |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
Secondary |
Akkas et al. [14] |
2016
|
Case report |
Turkey
|
2 |
32 |
Male |
N\A |
N\A |
Hepatic hydatid cyst 2 years ago |
N\A |
Secondary |
24 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
Alloubi et al. [15] |
2012 |
Case report |
Morocco |
1 |
57 |
Male |
Rural |
N\A |
N\A |
N\A |
N\A |
Al-Qudah et al. [16] |
2000 |
Case report |
Jordan |
1 |
24 |
Male |
N\A |
N\A |
N\A |
N\A |
Primary |
Afghani et al. [17] |
2017 |
Case report |
Iran |
1 |
35 |
Female |
N\A |
N\A |
N\A |
N\A |
Primary |
Yekeler et al. [18] |
2010 |
Case report |
Turkey |
1 |
57 |
Male |
Rural |
Yes |
Insignificant |
N\A |
N\A |
Ulger et al. [19] |
2013 |
Case report |
Turkey |
1 |
62 |
Male |
N\A |
N\A |
Hydatid cyst |
Hydatid cyst surgery |
N\A |
Tulay et al. [20] |
2015 |
Case report |
Turkey |
1 |
48 |
Male |
N\A |
N\A |
Insignificant |
No |
Primary |
Tomos et al. [21] |
2005 |
Case report |
Greece |
1 |
26 |
Female |
N\A |
N\A |
Hydatid cyst |
Pulmonary and hepatic hydatid cyst surgery |
Secondary |
Tezcan et al. [22] |
2014 |
Case report |
Turkey |
1 |
55 |
Male |
N\A |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
Secondary |
Tadasa et al. [23] |
2023 |
Case report |
Ethiopia |
1 |
65 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
Sevinc et al. [24] |
2014 |
Case report |
Turkey |
1 |
31 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
Sarkar et al. [25] |
2015 |
Case report |
India |
1 |
58 |
Female |
Rural |
Yes |
N\A |
N\A |
Primary |
Sabzi et al. [26] |
2023 |
Case report |
Iran |
1 |
53 |
Male |
Rural |
Yes |
N\A |
N\A |
Secondary |
Roman et al. [28] |
2015 |
Case report |
Romania |
1 |
25 |
Male |
Rural |
Yes |
History of trauma |
N\A |
N\A |
Redington et al. [29] |
2001 |
Case report |
United Kingdom |
1 |
72 |
Male |
N\A |
N\A |
History of trauma |
N\A |
N\A |
Raut et al. [30] |
2004 |
Case report |
India |
1 |
28 |
Male |
Rural |
Yes |
N\A |
N\A |
N\A |
Ninos et al. [31] |
2010 |
Case report |
Greece |
1 |
50 |
Male |
N\A |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
Primary |
Kiliç et al. [32] |
2003 |
Case report |
Turkey |
1 |
54 |
Male |
Rural |
N\A |
Insignificant |
N\A |
Primary |
Karapolat et al. [33] |
2012 |
Case report |
Turkey |
1 |
69 |
Female |
N\A |
N\A |
N\A |
N\A |
Primary |
Karaoğlanoğlu et al. [34] |
2001 |
Case report |
Turkey |
1 |
63 |
Male |
Rural |
Yes |
N\A |
N\A |
N\A |
Kaplanoğlu et al. [35] |
2017 |
Case report |
Turkey |
1 |
27 |
Female |
N\A |
N\A |
N\A |
No |
N\A |
Honda et al. [36] |
2010 |
Case report
|
Japan |
1 |
9 |
Female |
Rural |
N\A |
Insignificant |
N\A |
Secondary |
Han et al. [37] |
2004 |
Case report |
Turkey |
1 |
N\A |
Female |
N\A |
N\A |
Insignificant |
N\A |
N\A |
Gezer et al. [38] |
2006 |
Case report |
Turkey |
1 |
57 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
Foroulis et al. [39] |
2003 |
Case report |
Greece |
1 |
28 |
Female |
Urban |
N\A |
N\A |
N\A |
Primary |
Findikcioglu et al. [40] |
2010 |
Case report |
Turkey |
1 |
48 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
Faber et al. [41] |
2010 |
Case report |
Israel |
1 |
18 |
Female |
Rural |
N\A |
Thoracic outlet syndrome |
N\A |
N\A |
Demir et al. [42] |
2010 |
Case report |
Turkey |
1 |
9 |
Male |
Rural |
Yes |
N\A |
N\A |
Primary |
Chafik et al. [43] |
2009 |
Case report |
Morocco |
1 |
35 |
Male |
N\A |
N\A |
History of trauma |
Undiagnosed swelling drainage |
N\A |
Sinberg et al. [44] |
1936 |
Case report |
United States |
1 |
15 |
Male |
Rural |
Yes |
Insignificant |
N/A |
Primary |
Rose et al. [45] |
1893 |
Case report |
United Kingdom |
1 |
25 |
Female |
N\A |
N/A |
Bronchitis |
N/A |
Primary |
Machboua et al. [46]
|
2023 |
Case series
|
Morocco |
5 |
26 |
Male |
Rural |
N\A |
N\A |
N\A |
N\A |
32 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
28 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
57 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
63 |
Female |
N\A |
N\A |
Hydatid cyst |
Pulmonary and hepatic hydatid cyst surgery |
Secondary |
|||||
Özdemir et al. [47] |
1994 |
Case series |
Turkey |
6 |
40 |
Female |
N\A |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
N\A |
38 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
26 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
35 |
Male |
N\A |
N\A |
Hydatid cyst |
Hepatic hydatid cyst surgery |
Secondary |
|||||
35 |
Female |
N\A |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
Secondary |
|||||
Avci et al. [48] |
2005 |
Case report |
Turkey |
1 |
72 |
Female |
N\A |
N\A |
History of trauma |
No |
Primary |
N/A: non-available, PMH: past medical history, PSH: past surgical history |
Author/reference |
Year
|
No. of Case |
Presentation
|
Duration (months) |
Size of the mass on CT scan (cm) |
Hydatid serology
|
Provisional diagnosis
|
Pre-operative medication |
Althobaity et al. [1] |
2023 |
1 |
Chest pain |
36 |
N\A |
N\A |
Hydatid disease |
Albendazole |
Goyal et al. [2] |
2010 |
1 |
Swelling, Chest pain |
N\A |
N\A |
N\A |
N\A |
No |
Godazandeh et al. [3] |
2020 |
1 |
Swelling |
5 |
N\A |
Negative |
N\A |
No |
Basit et al. [5] |
2021 |
1 |
Chest pain |
0.66* |
N\A |
N\A |
Chest wall tumor |
No |
Salih et al. [6] |
2017 |
1 |
Swelling, Chest pain |
60 |
N\A |
N\A |
N\A |
No |
Döner et al. [11] |
2019 |
1 |
Swelling, Chest pain |
N\A |
4 |
N\A |
Hydatid disease |
No |
MohIeldeen et al. [13] |
2013 |
1 |
Chest pain, Numbness |
4 |
N\A |
N\A |
Hydatid disease |
No |
Akkas et al. [14] |
2016
|
2 |
Chest pain |
N\A |
10 |
N\A |
N\A |
No |
N\A |
N\A |
10 |
N\A |
N\A |
No |
|||
Alloubi et al. [15] |
2012 |
1 |
Chest pain |
3 |
9 |
N\A |
Chest wall tumor |
No |
Al-Qudah et al. [16] |
2000 |
1 |
Dyspnea, Cough, Fever, Shoulder pain |
12 |
N\A |
Negative |
N\A |
No |
Afghani et al. [17] |
2017 |
1 |
Swelling, Chest pain |
N\A |
N\A |
Negative |
Hydatid disease |
Albendazole |
Yekeler et al. [18] |
2010 |
1 |
N\A |
N\A |
N\A |
Positive |
Hydatid disease |
No |
Ulger et al. [19] |
2013 |
1 |
Chest pain |
70 |
N\A |
N\A |
Hydatid disease |
Albendazole |
Tulay et al. [20] |
2015 |
1 |
Swelling |
5 |
10 |
N/A |
N\A |
No |
Tomos et al. [21] |
2005 |
1 |
Chest pain |
N\A |
N\A |
Negative |
N\A |
No |
Tezcan et al. [22] |
2014 |
1 |
Cough, Dyspnea, Shoulder pain |
N\A |
8 |
N\A |
N\A |
No |
Tadasa et al. [23] |
2023 |
1 |
Cough, Back pain, Heaviness, Paresthesia |
12 |
N\A |
N\A |
Hydatid disease |
Albendazole |
Sevinc et al. [24] |
2014 |
1 |
Swelling |
N\A |
5 |
N\A |
Hydatid disease |
No |
Sarkar et al. [25] |
2015 |
1 |
Swelling |
36 |
N\A |
Positive |
Hydatid disease |
Albendazole |
Sabzi et al. [26] |
2023 |
1 |
Swelling, Chest pain |
24 |
N\A |
Negative |
Hydatid disease |
No |
Roman et al. [28] |
2015 |
1 |
Chest pain |
N\A |
3 |
N\A |
Hydatid disease |
No |
Redington et al. [29] |
2001 |
1 |
Dizziness, Sweating, Horsness of voice, Swelling, Chest pain |
24 |
7 |
Negative |
Hydatid disease |
Albendazole |
Raut et al. [30] |
2004 |
1 |
Back pain, Paraparesis |
6 |
N\A |
N\A |
Hydatid disease |
No |
Ninos et al. [31] |
2010 |
1 |
Swelling |
N\A |
N\A |
Negative |
Hydatid disease |
Albendazole |
Kiliç et al. [32] |
2003 |
1 |
Swelling, Chest pain |
3 |
N\A |
N\A |
N\A |
No |
Karapolat et al. [33] |
2012 |
1 |
Abdominal pain |
48 |
9 |
N\A |
Chest wall tumor |
No |
Karaoğlanoğlu et al. [34] |
2001 |
1 |
Cough |
144 |
N\A |
Negative |
N\A |
No |
Kaplanoğlu et al. [35] |
2017 |
1 |
Swelling |
6 |
N\A |
N\A |
N\A |
No |
Honda et al. [36] |
2010 |
1 |
Fever, General fatigue, Nausea |
N\A |
6 |
Positive |
N\A |
No |
Han et al. [37] |
2004 |
1 |
Swelling |
8 |
N\A |
Positive |
N\A |
No |
Gezer et al. [38] |
2006 |
1 |
Shoulder pain, Numbness, Arm weakness |
3 |
N\A |
N\A |
N\A |
No |
Foroulis et al. [39] |
2003 |
1 |
Swelling |
N\A |
N\A |
Positive |
N\A |
Albendazole |
Findikcioglu et al. [40] |
2010 |
1 |
Swelling |
N\A |
N\A |
N\A |
N\A |
No |
Faber et al. [41] |
2010 |
1 |
Shoulder pain, Swelling |
12 |
N\A |
N\A |
Aneurysmal bone cyst |
No |
Demir et al. [42] |
2010 |
1 |
Chest pain |
1 |
N\A |
Positive |
Ewing sarcoma |
No |
Chafik et al. [43] |
2009 |
1 |
Swelling |
N\A |
N\A |
Negative |
N\A |
No |
Sinberg et al. [44] |
1936 |
1 |
Swelling, Chest pain |
18 |
N\A |
N/A |
N\A |
No |
Rose et al. [45] |
1893 |
1 |
Swelling |
N\A |
N\A |
N/A |
N\A |
No |
Machboua et al. [46]
|
2023 |
5 |
Chest pain, Back pain, Lower limb paresthesia |
N\A |
N\A |
Positive |
N\A |
No |
Chest pain, Back pain, Dyspnea |
N\A |
N\A |
Positive |
N\A |
No |
|||
Chest pain, Dyspnea |
N\A |
N\A |
N\A |
N\A |
No |
|||
Swelling, Chest pain |
N\A |
N\A |
Positive |
N\A |
No |
|||
Chest pain |
N\A |
N\A |
N\A |
N\A |
No |
|||
Özdemir et al. [47] |
1994 |
6 |
Swelling |
N\A |
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
N\A |
N\A |
No |
|||
N\A |
N\A |
N\A |
N\A |
N\A |
No |
|||
Empyema |
N\A |
N\A |
N\A |
N\A |
No |
|||
Swelling |
N\A |
N\A |
N\A |
N\A |
No |
|||
Swelling, Shoulder pain |
N\A |
N\A |
N\A |
N\A |
No |
|||
Avci et al. [48] |
2005 |
1 |
Chest pain |
N\A |
9 |
N\A |
Hematoma |
No |
* Less than a month |
Author/reference |
Year |
No. of Case |
Surgical approach
|
Scolicidal agent |
Site of involvement |
Post-operative medication |
Complication |
Recurrence |
Follow-up (month) |
Althobaity et al. [1] |
2023 |
1 |
Video-assisted thoracoscopy [VATS] |
Hypertonic saline |
N\A |
Albendazole |
Pneumothorax |
No |
5 |
Goyal et al. [2] |
2010 |
1 |
Thoracotomy |
Hypertonic saline |
Rib and intercostal muscle |
No |
No |
N\A |
N\A |
Godazandeh et al. [3] |
2020 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
No |
24 |
Basit et al. [5] |
2021 |
1 |
N\A |
Hypertonic saline |
N\A |
Albendazole |
No |
N\A |
N\A |
Salih et al. [6] |
2017 |
1 |
N\A |
N\A |
N\A |
N\A |
No |
No |
3 |
Döner et al. [11] |
2019 |
1 |
N\A |
N\A |
Intercostal muscle |
Albendazole |
No |
N\A |
N\A |
MohIeldeen et al. [13] |
2013 |
1 |
N\A |
N\A |
8th rib |
Albendazole |
No |
No |
24 |
Akkas et al. [14] |
2016
|
2 |
Thoracotomy |
N\A |
Intercostal muscle |
Albendazole |
No |
No
|
36 |
Thoracotomy |
N\A |
N\A |
Albendazole |
No |
No |
18 |
|||
Alloubi et al. [15] |
2012 |
1 |
Thoracotomy |
N\A |
6th and 7th ribs |
Albendazole |
No |
No |
6 |
Al-Qudah et al. [16] |
2000 |
1 |
Thoracotomy |
N\A |
1st rib |
No |
No |
N\A |
N\A |
Afghani et al. [17] |
2017 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
No |
24 |
Yekeler et al. [18] |
2010 |
1 |
Thoracotomy |
N\A |
6th rib |
Albendazole |
No |
No |
10 |
Ulger et al. [19] |
2013 |
1 |
N\A |
N\A |
Sternum |
No |
N\A |
No |
12 |
Tulay et al. [20] |
2015 |
1 |
N\A |
Hypertonic saline |
N\A |
Albendazole |
N\A |
No |
6 |
Tomos et al. [21] |
2005 |
1 |
Thoracotomy |
N\A |
6th rib |
No |
N\A |
N\A |
N\A |
Tezcan et al. [22] |
2014 |
1 |
N\A |
N\A |
Sternum |
No |
No |
N\A |
N\A |
Tadasa et al. [23] |
2023 |
1 |
No |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
Sevinc et al. [24] |
2014 |
1 |
N\A |
Hypertonic saline |
N\A |
Albendazole |
No |
N\A |
N\A |
Sarkar et al. [25] |
2015 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
No |
12 |
Sabzi et al. [26] |
2023 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
N\A |
N\A |
Roman et al. [28] |
2015 |
1 |
Thoracotomy |
Formalin |
8th rib |
Albendazole, Chemotherapy |
No |
No |
1 |
Redington et al. [29] |
2001 |
1 |
No |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
Raut et al. [30] |
2004 |
1 |
N\A |
N\A |
9th rib |
Albendazole |
No |
N\A |
N\A |
Ninos et al. [31] |
2010 |
1 |
N\A |
N\A |
Intercostal muscle |
Albendazole |
N\A |
No |
12 |
Kiliç et al. [32] |
2003 |
1 |
Thoracotomy |
N\A |
5th, 6th and 7th ribs |
Albendazole |
No |
N\A |
N\A |
Karapolat et al. [33] |
2012 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
No |
12 |
Karaoğlanoğlu et al. [34] |
2001 |
1 |
N\A |
N\A |
5th and 6th ribs, Serratus anterior muscle, Latissimus dorsi muscle |
Albendazole |
No |
No |
6 |
Kaplanoğlu et al. [35] |
2017 |
1 |
N\A |
N\A |
Intercostal muscle |
No |
N\A |
No |
12 |
Honda et al. [36] |
2010 |
1 |
N\A |
Hypertonic saline |
N\A |
Albendazole |
N\A |
No |
16 |
Han et al. [37] |
2004 |
1 |
N\A |
N\A |
7th rib |
Albendazole |
N\A |
N\A |
N\A |
Gezer et al. [38] |
2006 |
1 |
Thoracotomy |
N\A |
1st rib |
Albendazole |
No |
No |
15 |
Foroulis et al. [39] |
2003 |
1 |
Thoracotomy |
Hypertonic saline |
10th vertebra, 9th and 10th ribs |
Albendazole |
No |
No |
48 |
Findikcioglu et al. [40] |
2010 |
1 |
Thoracotomy |
N\A |
Riband vertebra |
No |
N\A |
N\A |
N\A |
Faber et al. [41] |
2010 |
1 |
N\A |
N\A |
1st rib |
No |
No |
N\A |
N\A |
Demir et al. [42] |
2010 |
1 |
N\A |
N\A |
N\A |
Albendazole |
N\A |
N\A |
N\A |
Chafik et al. [43] |
2009 |
1 |
Thoracotomy |
N\A |
N\A |
Albendazole |
No |
N\A |
N\A |
Sinberg et al. [44] |
1936 |
1 |
N\A |
Hypertonic saline |
Sternum |
No |
Slight superficial infection |
N\A |
N\A |
Rose et al. [45] |
1893 |
1 |
N\A |
N\A |
N\A |
No |
Hemorrhage |
N\A |
N\A |
Machboua et al. [46]
|
2023 |
5 |
Thoracotomy |
N\A |
N\A |
No |
Pleurocutaneous fistula, Disabling parietal pain and neurological pain, Disorder of the Shoulder Girdle. |
No |
24 |
Thoracotomy |
N\A |
Rib and vertebra |
No |
No |
N\A
|
N\A |
|||
N\A |
N\A |
N\A |
No |
No |
N\A
|
N\A |
|||
Thoracotomy |
N\A |
N\A |
No |
No |
N\A
|
N\A |
|||
Thoracotomy |
N\A |
N\A |
No |
N\A |
N\A
|
N\A |
|||
Özdemir et al. [47] |
1994 |
6 |
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
|||
Thoracotomy |
N\A |
N\A |
No |
N\A |
N\A
|
N\A |
|||
Thoracotomy |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
|||
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
|||
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
|||
Avci et al. [48] |
2005 |
1 |
N\A |
N\A |
N\A |
No |
No |
N\A |
N\A |
N/A:non-available |
Main findings
The reported cases were primarily from Turkey (41.5%). The mean age of the patients was 39.7 ± 17.1 years, with a male predominance (56.9%). The past medical history for HC was positive in 10 cases (19.6%). The most common clinical presentations were swelling in 24 cases (47.1%) and chest or abdominal pain in 23 cases (45.1%). Only 10 cases (19.6%) had reported a history of animal contact, while one patient (2%) reported no such history. Data on the history of animal contact was unavailable in 78.4% of cases. Among those with documented residency (35.3%), 16 (31.4%) resided in rural areas, while two (3.9%) were from urban settings. The disease was primary in sixteen cases (31.4%), and in nine (17.6%), it was secondary. The disease origin was unknown in 26 cases (51%). The average mass size on the CT scan was 7.5 ± 2.4 cm. Hydatid serology was performed in 18 patients, yielding positive results in nine (50%). A provisional diagnosis of hydatid disease was considered in 14 cases (27.5%). Pre-operative treatment with albendazole was administered to eight patients (15.7%). Surgery was the treatment of choice, with thoracotomy performed in 37.3% of cases, video-assisted thoracoscopy (VATS) in 1.9%, and the surgical technique not specified in 60.8% of cases. The average hospital stay was 8.6 ± 4.4 days. The ribs (31.4%) were the primary involved sites, followed by the muscles (11.8%). Postoperative medication included albendazole in 25 cases (49%) and albendazole with chemotherapy in one case (1.9%). Twenty-four cases (47.1%) had received no postoperative treatment. Only four cases (7.8%) faced complications. No recurrence was reported after a mean follow-up period of 14.1± 10.3 months (Table 4).
Variables | Frequency/percentage |
Mean Age (years) |
39.7 ± 17.1 |
Sex Male Female |
29 (56.9%) 22 (43.1%) |
Country of study Turkey Morocco Greece India Iran Iraq United Kingdom Afghanistan Ethiopia Israel Japan Jordan Romania Saudi Arabia United States |
17 (41.5%) 3 (7.3%) 3 (7.3%) 3 (7.3%) 3 (7.3%) 2 (5.0%) 2 (5.0%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) |
Past medical history of hydatid cyst Positive Negative |
10 (19.6%) 41 (80.4%) |
Contact with an animal Yes No N\A |
10 (19.6%) 1 (2.0%) 40 (78.4%) |
Residency Rural Urban N\A |
16 (31.4%) 2 (3.9%) 33 (64.7%) |
Origin Primary Secondary N\A |
16 (31.4%) 9 (17.6%) 26 (51.0%) |
Size of the mass on CT scan | 7.5 ± 2.4 cm |
Presentation Swelling Chest/Abdominal pain Dyspnea Cough Shoulder/back pain Numbness Others N\A |
24 (47.1%) 23 (45.1%) 4 (7.8%) 4 (7.8%) 9 (17.6%) 5 (9.8%) 6 (11.8%) 4 (7.8%) |
Hydatid serology test Positive Negative N\A |
9 (17.6%) 9 (17.6%) 33 (64.7%) |
Provisional diagnosis Hydatid disease Chest wall tumor Aneurysmal bone cyst Ewing sarcoma Hematoma N\A |
14 (27.5%) 3 (5.9%) 1 (1.9%) 1 (1.9%) 1 (1.9%) 31 (60.8%) |
Pre-operative medication Albendazole No |
8 (15.7%) 43 (84.3%) |
Surgical approach Thoracotomy Video-assisted thoracoscopy N\A |
19 (37.3%) 1 (1.9%) 31 (60.8%) |
Injection of scolicidal agent with surgery Hypertonic saline Formalin No |
8 (15.7%) 1 (1.9%) 42 (82.4%) |
Site of involvement Rib Muscle Sternum Vertebra N\A |
16 (31.4%) 6 (11.8%) 3 (5.9%) 3 (5.9%) 28 (54.9%) |
Post-operative medication Albendazole Albendazole and chemotherapy No N/A |
25 (49.0%) 1 (1.9%) 24 (47.1%) 1 (1.9%) |
Mean postoperative hospital stay (days)* |
8.6 ± 4.4 |
Outcome of surgery Recovered with no complication Recovered with complication N\A |
29 (56.9%) 4 (7.8%) 18 (35.3%) |
Average duration of follow-up (months) |
14.1± 10.3 |
Recurrence Yes No N\A |
0 (0.0%) 21 (41.0%) 30 (59.0%) |
N/A: non-available, CT: computed tomography. *For 12 patients out of 51 patients who underwent surgery. #For 23 patients out of 51 patients who underwent surgery. |
Discussion
Human echinococcosis, a prevalent parasitic infection, presents a considerable health and economic burden to society, yet it remains largely neglected as a disease [49]. The findings of this study provide a comprehensive review of chest wall HC, with the majority of the studies conducted in Turkey (41.5%), followed by Morocco (7.3%), Greece (7.3%), India (7.3%), and Iran (7.3%). The higher incidence in these countries may reflect the endemic nature of hydatid disease, likely due to closer contact with livestock and domestic animals [50]. However, it has become a pressing global health issue, primarily attributed to increasing immigration rates and travel activities [7].
The mean age of 39.7 years, with a slight male predominance (56.9%), suggests that both demographic groups are at risk. However, occupational or environmental exposure factors could contribute to the observed gender disparity.
Clinically, the most common presentation was swelling (47.1%), followed by chest or abdominal pain (45.1%). This indicates that chest wall HCs may present as localized symptoms rather than systemic manifestations [51]. The relatively low percentage (19.6%) of patients with a history of animal contact suggests that direct exposure may not always be reported or remembered, or that indirect exposure through contaminated water or food could also be significant transmission routes [26,27]. In addition, a review by Possenti and colleagues suggested that the primary route of human cystic echinococcosis transmission may be the direct or indirect contamination of hands with Echinococcus granulosus eggs excreted by dogs [52].
Schantz et al. indicated that individuals who own livestock are three times more likely to be diagnosed with this disease compared to those who do not own livestock [53]. In accordance with this finding, 16 (88.9%) of the 18 cases with known residency were from rural areas.
Ten cases (19.6%) had a positive history for HC at other sites, and the primary origin of cysts in 31.4% of patients and secondary origin in 17.6% highlights the importance of considering both primary infection or possible spread from other sites, such as the liver or lungs, as the diagnosis and treatment strategies may be different [1].
In the present study, the average cyst size on the CT scan was 7.5 cm, reflecting potentially large cysts that could cause significant local pressure effects or complications; this might be because the course of infection is slow, and most infected individuals remain either asymptomatic for years or exhibit non-specific symptoms leading to accidental diagnosis [54]. Parasite eggs can remain viable from several months up to a few years in the environment, and diverse conditions [55].
Only nine (50%) out of 18 patients with available data in this systematic review had positive hydatid serology, suggesting that serological tests alone may not be sufficient for diagnosis and imaging, particularly CT scans, plays a crucial role in the diagnostic process [56]. The provisional diagnosis of hydatid disease in only 27.5% of the cases underscores the diagnostic challenges faced by clinicians, especially when the clinical presentation is atypical or when imaging findings are inconclusive [57].
The importance and priority of infection prevention by practicing several preventive actions, especially in developing countries, has been proposed. The most significant of them included self-hygiene practices, proper washing and cooking of foods, and avoiding eating raw foods or groceries [27]. Regarding management, surgical intervention was the primary treatment modality [1,2,7,58]. A study indicated that while VATS has been successfully applied in managing pulmonary HCs, its adoption remains limited. It has been pointed out that many surgeons are still hesitant to use VATS due to a lack of familiarity with the technique and concerns about potential complications, such as cyst rupture or spillage of infectious material [59]. In this review, authors came across similar findings, such as thoracotomy being performed in 37.3% of cases and VATS being performed in 1.9%. This may depend on cyst size and location. Furthermore, the low utilization of minimally invasive approaches like thoracoscopy may suggest either a preference for traditional open techniques or a lack of resources or expertise in minimally invasive surgery in some settings. The postoperative outcomes were generally favorable, with only 7.8% of patients facing complications, and no recurrence was reported, emphasizing the effectiveness of surgical management.
Machboua et al. on intra-thoracic extra-pulmonary hydatidosis noted that the average duration of hospitalization was only seven days, which is similar to what was found in this study (8.58 ± 4.44 days) [46].
The administration of post-operative albendazole alone (49%) or in combination with other medications (1.9%) may appear to be a standard practice to prevent recurrence, even though no recurrences were reported in this study. This could reflect a preventive strategy against the possible dissemination of HCs during surgery [1,14,15,17,18]. Overall, the study may provide valuable insights into the epidemiology, clinical presentation, diagnostic strategies, and management outcomes of chest wall HCs; however, the lack of essential data in a number of reviewed studies might generate biased or non-conclusive findings.
Conclusion
Despite its rarity, chest wall HC may have a good prognosis with few complications. Given its often-nonspecific presentation, reviewing the patient's medical history may help establish an accurate provisional diagnosis.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable, as systematic reviews do not require ethical approval.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: FHK and BAA were significant contributors to the conception of the study and the literature search for related studies. HOA and DHH involved in the literature review, study design, and manuscript writing. HKA, AHH, AHA, AAM, SMA, SOK, FA, SSA, and SHM were involved in the literature review, the study's design, the critical revision of the manuscript, and data collection. FHK and HOA confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Are Cervical Ribs Indicators of Childhood Cancer? A Narrative Review
Fahmi H. Kakamad, Lawand Ahmed Sharif, Ahmed H. Ahmed, Sakar O. Arif, Omed M. Hussein, Azad S....
Abstract
A cervical rib (CR), also known as a supernumerary or extra rib, is an additional rib that forms above the first rib, resulting from the overgrowth of the transverse process of a cervical vertebra. Increasingly recognized as a potential marker of developmental disruptions and genetic instability, CRs are believed to arise from mutations in homeobox (Hox) genes that influence axial skeletal development. While often asymptomatic, CRs have been linked to thoracic outlet syndrome and a higher prevalence in individuals with certain childhood cancers. Studies have reported associations between CRs and malignancies such as neuroblastoma, brain tumors, leukemia, sarcomas, Wilms tumor, and germ cell tumors, suggesting possible shared embryological pathways or genetic predispositions. However, conflicting research findings highlight inconsistencies in these associations, underscoring the need for further investigation. This review aims to assess the association between CRs and childhood cancers by examining prevalence rates, exploring genetic and developmental links, evaluating inconsistencies in existing research, and identifying gaps for future study to clarify the clinical significance of CRs in cancer risk assessment.
Introduction
A Cervical rib (CR), also known as a "neck rib" or "supernumerary rib," is an extra rib that forms above the first rib, near the collarbone. It develops due to an overgrowth of the transverse process of a cervical spine vertebra. It is thought to result from mutations in homeobox (Hox) genes, which play a role in shaping the axial skeleton in humans and vertebrates. This rib can occur on either side and may be unattached (floating) or fused with the first rib. It can range from a fully formed bone to a delicate fibrous strand [1].
The CRs are present in about 2% of the general adult population. The prevalence is higher in women, who are about twice as likely to have CRs as men. Additionally, ethnic differences have been observed, with one study finding that CRs are more common in African Americans than in whites [2].
Typically, CR is discovered incidentally through radiographic imaging unless it causes symptoms [3]. In some cases, CR can contribute to thoracic outlet syndrome by narrowing the interscalene triangle, leading to pain, weakness, numbness, or cold sensitivity in the affected limb [1, 4, 5]. The first documented clinical signs of neurovascular compression associated with CRs were reported by Cooper in 1818 [6].
Studies have demonstrated a higher prevalence of CRs in individuals with childhood cancers. This association may stem from disruptions in embryonic development during critical stages of blastogenesis, which can simultaneously lead to cervical segmentation defects and increase cancer susceptibility [7, 8].
Moreover, CRs are often regarded as markers of adverse developmental events or genetic instability. Their higher prevalence in stillborn fetuses and individuals with chromosomal abnormalities further underscores their potential role as indicators of systemic vulnerabilities that may contribute to malignancy risk. These findings highlight the importance of understanding rib anomalies (RAs) as anatomical curiosities and potential markers for identifying individuals at increased risk for certain cancers [9]. This study aims to review the association between CRs and cancer, with all referenced articles assessed for eligibility [10].
Studies Linking Rib Anomalies to Childhood Cancers
Despite growing awareness of a possible connection between RAs and malignancies, research on this topic remains limited. Only four studies have examined this association, each providing valuable insights into the potential link.
The earliest study by Schumacher et al. (1995) investigated the relationship between RAs and childhood malignancies by reviewing chest X-rays of 1,000 children with cancer and 200 control patients with non-malignant conditions. They found a significantly higher prevalence of RAs, particularly CRs, in children with certain malignancies compared to controls. This suggested that these skeletal abnormalities might be linked to altered morphogenesis in tumor development [7].
A decade later, Merks et al. (2005) conducted a more extensive study analyzing chest radiographs of 906 children with cancer and 881 healthy Caucasian pediatric controls. Their findings confirmed previous reports, demonstrating a higher occurrence of specific RAs in children with certain malignancies. They emphasized the potential role of genetic predisposition in cancer development and suggested that skeletal anomalies could serve as markers for underlying genetic abnormalities [8].
Loder et al. (2007) expanded on these findings by focusing on rib number variations in 218 children with malignancies and 200 control children who had been admitted for polytrauma or suspected child abuse. Their study highlighted a significant difference in rib counts between children with cancer and healthy controls. They speculated that genes involved in vertebral and rib development might also play a role in cancer predisposition, suggesting the possibility of using skeletal anomalies as a screening tool for early cancer detection [11].
Finally, Zierhut et al. (2011) reinforced the association between RAs and childhood cancers through a hospital-based case-control study of 459 pediatric cancer patients and 1,135 controls who had undergone chest X-rays for non-cancer-related reasons. Their research confirmed that children with cancer were more likely to have RAs, particularly those diagnosed with specific malignancies. They underscored the need for further studies to determine the biological mechanisms linking RAs to cancer development [12].
Cancers Linked to Cervical Ribs
Neuroblastoma
Neuroblastoma is a highly aggressive tumor that develops from neural crest cells and is the most common cancer in infants under one year old worldwide [13]. It represents about 10% of all pediatric cancers and primarily affects children within their first five years of life [14].
A defining characteristic of neuroblastoma is its highly variable clinical behavior. In approximately 50% of affected infants, the tumor regresses spontaneously, whereas in others, it advances into an aggressive, metastatic disease that is often resistant to standard treatments like chemoradiotherapy, stem cell transplantation, and immunotherapy [15]. This unpredictability complicates treatment, especially for high-risk patients who experience chemo-resistant relapse, with survival rates remaining below 40% [14].
The initiation and progression of neuroblastoma are driven by genetic abnormalities that interfere with cell division, proliferation, and apoptosis [15]. Significant genetic factors include MYCN amplification, TP53 deletions, ALK mutations or amplifications, TERT rearrangements, ATRX deletions or mutations, and segmental chromosomal aberrations. However, whole-genome sequencing studies have identified only a limited number of recurrent somatic mutations, making the development of targeted therapies challenging. Consequently, a precise understanding of the biological complexity and diversity of neuroblastoma is crucial for improving diagnostic and treatment approaches [15].
Schumacher et al. (1992) identified a strong correlation between neuroblastoma and CRs, reporting that 33% of children with neuroblastoma had CRs, a markedly higher prevalence than in the general population. This notable disparity suggests a potential developmental or genetic connection between neuroblastoma and skeletal anomalies. Furthermore, neuroblastoma was the only malignancy in their study to exhibit a significantly increased incidence of rib bifurcation (4.5%), a rate nearly four times higher than expected, reinforcing the possibility of disrupted skeletal development linked to the disease [7].
In contrast, Merks et al. (2005) analyzed 61 neuroblastoma patients and found that 9.8% had CRs, compared to 6.1% in the control group. While this suggests a slightly increased prevalence, the difference was not statistically significant (p = 0.252). This discrepancy with Schumacher et al. (1992) may be due to differences in sample size, diagnostic criteria, or population characteristics [7, 8].
Loder et al. (2007) took a broader approach by grouping neuroblastoma with other neural malignancies. Their findings showed a higher incidence of RAs (35%) in children with neural tumors compared to those with other malignancies. However, they did not specifically find an association between neuroblastoma and CRs. Among the eight neuroblastoma patients in their study, RAs were present, but no cases of CRs were observed. Instead, the most common skeletal abnormality was a reduced rib count, with affected children having 22 or 23 ribs instead of the typical 24. This suggests that while RAs may be linked to neuroblastoma, the specific presence of CRs may not be a defining characteristic [11].
Similarly, Zierhut et al. (2011) analyzed 31 neuroblastoma cases and found that 6.4% had RAs. However, the study did not report how many of these cases involved CRs specifically. The statistical analysis yielded an odds ratio (OR) of 1.46 (95% CI: 0.34–6.30) for any rib anomaly in neuroblastoma patients, indicating a slightly higher occurrence of skeletal abnormalities but without statistical significance. The lack of a significant association between RAs and neuroblastoma may be due to the study’s small sample size, which could have limited its ability to detect a stronger relationship [12].
Overall, while Schumacher et al. (1992) identified a strong association between neuroblastoma and CRs, subsequent studies, including those by Merks et al. (2005), Loder et al. (2007), and Zierhut et al. (2011), reported weaker or non-significant links [7, 8, 11, 12]. The inconsistencies across studies highlight the need for further research with larger sample sizes and more detailed skeletal analyses to determine whether CRs represent a meaningful developmental marker for neuroblastoma or if their observed association is due to broader skeletal anomalies.
Brain Tumors
A brain tumor forms when cells grow irregularly and multiply uncontrollably. These tumors may arise from brain cells, the meninges (the membranes surrounding the brain), glands, or nerves. They can cause direct damage to brain cells and elevate pressure within the skull, resulting in harmful effects [16].
Due to their severity, brain tumors are classified into different grades. Grade 1 tumors are the least aggressive, typically associated with more prolonged survival. They grow slowly, resemble normal cells under a microscope, and can often be effectively treated with surgical removal. Examples include pilocytic astrocytoma, ganglioglioma, and gangliocytoma. Grade 2 tumors also grow slowly but appear abnormal under a microscope. Some may invade nearby tissues and tend to recur, occasionally progressing to a higher grade [16].
Grade 3 tumors are malignant and share similarities with grade 2 tumors but are more likely to recur as grade 4 tumors. Grade 4 tumors are the most aggressive, growing rapidly and appearing highly abnormal under a microscope. They invade surrounding brain tissue, form new blood vessels, and contain areas of dead cells at their core. Glioblastoma Multiforme is a well-known example of a grade 4 tumor [16].
Brain tumors develop due to a combination of genetic, environmental, and molecular factors. Genetic predisposition plays a key role, with inherited syndromes such as neurofibromatosis and Li-Fraumeni syndrome increasing the risk. Environmental exposures, particularly ionizing radiation, are well-established contributors, while occupational exposure to chemicals and electromagnetic fields remains inconclusive. Viral infections, immune dysfunction, and chronic inflammation may also influence tumor development [17, 18].
The study by Schumacher et al. (1992) found that 27.4% of children with brain tumors had CRs, compared to only 5.5% in the control group (p < 0.001). This substantial difference suggests a potential developmental link between CRs and brain tumors, possibly due to shared embryological pathways affecting both skeletal and neural development. The high prevalence reported in this study indicates that CRs might serve as an anatomical marker for underlying genetic or developmental disruptions associated with brain tumor formation [7].
Merks et al. (2005) further supported this hypothesis by identifying a significant association between CR anomalies and astrocytomas. Their study reported that 18.2% of childhood cancer patients with astrocytomas had CRs, compared to 6.1% in the control group. This finding suggests that certain subtypes of brain tumors, particularly astrocytomas, may have a stronger developmental association with CR anomalies [8].
However, Loder et al. (2007) did not find a strong link between brain tumors and CRs. While RAs were more frequent in children with neural malignancies (35%), none of these anomalies were identified as CRs. Instead, children with neural malignancies were found to be 6.23 times more likely to have an abnormal rib count compared to the control group. This suggests that while skeletal anomalies may be associated with neural tumors in general, CRs specifically may not be a consistent marker [11].
Zierhut et al. (2011) also provided a more tempered perspective. Their study examined 34 pediatric cases of central nervous system tumors, including brain tumors, and found that 8.8% (n = 3) had some form of rib anomaly. However, they did not identify a statistically significant association between CRs and brain tumors. This finding further weakens the case for a direct link and suggests that broader skeletal anomalies may be involved rather than CRs specifically [12].
Overall, while Schumacher et al. (1992) and Merks et al. (2005) suggest a possible association between CRs and brain tumors, the findings from Loder et al. (2007) and Zierhut et al. (2011) cast doubt on the specificity of this relationship [7, 8, 11, 12]. The inconsistencies across studies highlight the need for further research to determine whether CRs are a true marker for brain tumor risk or if their association is due to broader developmental abnormalities affecting multiple organ systems.
Leukemia
Leukemia is a frequently occurring cancer in both children and adults. It results from disruptions in normal cell regulation that lead to the uncontrolled growth of hematopoietic stem cells in the bone marrow. It is more commonly found in males and individuals of white ethnicity, with its prevalence increasing with age. On average, about one in 70 people will develop leukemia during their lifetime. The four main types of leukemia, each with unique characteristics, are acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia, and chronic myelogenous leukemia [19].
Leukemia occurs worldwide, with a higher prevalence and overall mortality in more developed countries. However, the mortality rate tends to be greater in developing nations [20]. The development of leukemia results from a complex interaction between genetic predisposition and environmental influences, with neither factor alone provides a complete explanation. While significant strides have been made in identifying risk factors and potential disease mechanisms, the exact causes of most leukemia cases remain uncertain. Known risk factors include genetic syndromes, chromosomal abnormalities, radiation exposure, specific chemicals, certain viral infections, and prior cancer treatments, but these account for only a fraction of cases [20, 21].
The study by Schumacher et al. (1992) found a significant association between CRs and leukemia, with 26.8% (n = 227) of leukemia patients exhibiting CRs compared to only 5.5% (n = 11) in the control group (p < 0.001). This finding suggests a potential developmental or genetic link between skeletal anomalies and leukemia, possibly due to disruptions in early embryonic development affecting both hematopoietic and skeletal systems [7].
Similarly, Merks et al. (2005) identified a significant association between CR anomalies and ALL, with a prevalence of 12.1% in ALL patients compared to 6.1% in controls (p = 0.011). This reinforces the idea that skeletal anomalies may serve as a marker for certain pediatric malignancies, though the underlying mechanisms remain unclear [8].
Loder et al. (2007) further examined RAs in leukemia patients. Among 218 children with malignancies, 75 had leukemia (64 with ALL and 11 with AML) [11]. The incidence of abnormal rib counts in children with lymphoproliferative malignancies (which includes leukemia and lymphoma) was 15%, compared to 8% in the control group. Logistic regression analysis revealed that children with leukemia and other lymphoproliferative malignancies were twice as likely to have an abnormal rib count compared to controls. While this supports a broader association between RAs and leukemia, the study did not specifically focus on CRs, making direct comparisons with Schumacher et al. (1992) and Merks et al. (2005) more challenging [7, 8].
In contrast, Zierhut et al. (2011) provided a more nuanced perspective. While their study confirmed an overall link between RAs and an increased risk of childhood cancers, the specific association between CRs and leukemia did not reach statistical significance. Notably, children with AML had a significantly higher likelihood of RAs, with an adjusted OR of 2.29 (95% CI: 1.02–5.13). However, when CRs were analyzed separately, the association weakened (adjusted OR = 1.63, 95% CI: 0.55–4.80), failing to reach statistical significance. This suggests that while RAs in general may be linked to leukemia, CRs alone may not be a consistent marker for the disease [12].
Overall, the studies by Schumacher et al. (1992) and Merks et al. (2005) suggest a potential association between CRs and leukemia [7, 8, 11]. However, Zierhut et al. (2011) cast doubt on the specificity of this relationship, indicating that while RAs may be more common in leukemia patients, CRs alone may not be a reliable marker [12]. Further research is needed to clarify whether CRs are a developmental indicator of leukemia risk or if their observed association is due to broader skeletal anomalies linked to pediatric malignancies.
Sarcomas
Sarcomas comprise a diverse group of mesenchymal tumors, with over 100 distinct diagnostic types. This variability is evident through both light microscopy and gene expression analysis. Even within the same histological category, there can be substantial differences in biological behavior [22].
Sarcomas are generally classified into two main types: soft tissue sarcomas and primary bone sarcomas, each requiring unique staging and treatment strategies. Soft tissue sarcomas are typically categorized based on genetic alterations and microscopic examination of hematoxylin-eosin–stained tissue, where morphological features resembling normal tissues are identified. Additionally, sarcomas are further assessed by histologic grade. The three key prognostic factors are the tumor’s grade, size, and primary location [22].
Sarcomas usually arise spontaneously, but certain risk factors have been identified. Exposure to ionizing radiation, often from cancer treatments, increases the likelihood of sarcomas, typically appearing 7-10 years after exposure. Other risk factors include chronic lymphedema, exposure to chemicals like vinyl chloride, and infection with human herpesvirus 8, which is linked to Kaposi sarcoma [22].
Several genetic syndromes also elevate sarcoma risk. Neurofibromatosis type 1 leads to benign and malignant nerve sheath tumors, while neurofibromatosis type 2 is associated with meningiomas and cranial nerve schwannomas. Gardner syndrome increases the risk of desmoid tumors, and hereditary retinoblastoma raises the likelihood of osteosarcoma and soft tissue sarcomas later in life. Li-Fraumeni syndrome, caused by TP53 mutations, also predisposes individuals to sarcomas [22].
Schumacher et al. (1992) found a significant association between CRs and sarcomas, reporting their presence in 24.5% of patients with soft tissue sarcomas (p < 0.001) and 17.1% of those with Ewing sarcoma (p < 0.01), compared to only 5.5% in the control group. These findings suggest a potential developmental or genetic link between CR anomalies and sarcomas, possibly due to early mesodermal development disruptions, which influences skeletal and soft tissue formation [7].
However, later studies did not consistently replicate these findings. Merks et al. (2005) found much lower rates of CRs in sarcoma patients, with 7.4% of rhabdomyosarcoma cases (5/68, p = 0.687), 6.3% of osteosarcoma cases (3/48, p = 0.973), and 7.7% of Ewing sarcoma cases (3/39, p = 0.692). None of these differences were statistically significant, suggesting that the initial association reported by Schumacher et al. (1992) may have been due to sample variation or other confounding factors. The stark contrast between these two studies raises questions about whether the observed link is truly biologically relevant or if it was an artifact of study design or population differences [8].
Loder et al. (2007) examined RAs in solid tumors, including osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma, finding that 13% of cases exhibited RAs. However, this association was not statistically significant (p = 0.15), suggesting that while RAs may be more common in children with cancer, they do not appear to be strongly associated with sarcomas specifically [11].
Similarly, Zierhut et al. (2011) identified a general link between RAs and childhood cancers but did not find a significant correlation between CRs and sarcomas. This further weakens the hypothesis that CRs are a marker for sarcoma risk [12].
Overall, while the Schumacher et al. (1992) study initially suggested a strong association between CRs and sarcomas, more recent studies, including those by Merks et al. (2005), Loder et al. (2007), and Zierhut et al. (2011), have not confirmed this relationship [7, 8, 11, 12]. The inconsistencies in findings suggest that if a link does exist, it may be weaker than initially thought or influenced by confounding factors. Further research with larger sample sizes and refined methodologies is needed to clarify whether CRs have any true predictive value for sarcoma development.
Wilms tumor
Wilms tumor (WT), or nephroblastoma, is a malignant solid tumor that arises from the primitive renal bud. It is the most common primary renal tumor in the urogenital tract of children and typically occurs unilaterally in 90–95% of cases. However, it can also present bilaterally or multicentrically, particularly in cases associated with genetic factors, occurring either simultaneously (synchronously) or at different times (metachronously). WT accounts for approximately 2% to 6% of all childhood cancers [23].
Both genetic and environmental factors influence the development of WT. Genetic mutations play a crucial role, particularly in the WT1 and WT2 genes, which are vital for kidney development [23]. WT1 mutations are linked to syndromic forms of WT, such as WAGR and Denys-Drash syndromes, while WT2 abnormalities are associated with Beckwith-Wiedemann syndrome. Additionally, mutations in CTNNB1 (β-catenin), TP53, and microRNAs contribute to tumor development. Environmental factors, including parental exposure to pesticides before conception or during pregnancy, may increase the risk, though their precise impact remains unclear. WT is frequently associated with congenital syndromes involving developmental abnormalities [23].
Schumacher et al. (1992) identified a significant association between CRs and WT, reporting that 23.5% of children with WT had CRs, compared to only 5.5% in the control group (p < 0.001). This strong statistical significance suggests a potential developmental link between skeletal anomalies and WT [7].
However, Merks et al. (2005) found that 9.8% of children with WT had CRs, compared to 6.1% in the control group, but the difference was not statistically significant (p = 0.115). This suggests that while CRs may be more common in WT patients, the association is not robust enough to be considered a reliable marker [8]. Similarly, Zierhut et al. (2011) reported a statistically significant increase in overall RAs among children with renal tumors, including WT. However, when analyzing CRs specifically, they did not find a significant association, further casting doubt on their role as a consistent indicator of WT [12].
Loder et al. (2007) provided additional support for a general link between RAs and pediatric malignancies but did not specifically analyze CRs in WT patients. This broader pattern suggests that skeletal anomalies may be associated with childhood cancers but does not confirm a direct link between CRs and WT [11].
These findings indicate that while there is some evidence of a relationship between skeletal anomalies and WT, the inconsistent association with CRs suggests that other factors may be at play. Additional research is needed to explore the genetic and developmental mechanisms underlying these observations, which could provide further insights into the etiology of WT and its potential links to congenital anomalies.
Germ Cell Tumors
Germ cell tumors (GCTs) are the most diverse childhood neoplasms. The majority are benign teratomas, presenting as heterogeneous masses with cystic and solid components. However, approximately 20% of GCTs are malignant, accounting for 3% of pediatric cancers. Malignant GCTs can occur at any age but follow a bimodal distribution, primarily affecting infants and adolescents [24].
These tumors can develop in various anatomical locations, including the gonads, sacrococcygeal region, mediastinum, retroperitoneum, and other para-axial sites. They are believed to originate from a common progenitor germ cell but exhibit diverse histologies, such as endodermal sinus tumor (yolk sac tumor), germinoma (dysgerminoma or seminoma), embryonal carcinoma, and choriocarcinoma. Different histological types often coexist within a single tumor, with approximately 25% of pediatric GCTs containing multiple histologic components [24].
Malignant GCTs have specific genetic predispositions, and genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) in genes such as KITLG, SPRY4, DMRT1, and TERT, which are linked to the development of testicular GCTs [25].
Schumacher et al. (1992) investigated the relationship between CR anomalies and yolk sac tumors, a type of GCT, but did not find a significant association. The prevalence of RAs in patients with yolk sac tumors was 3.4%, which was not significantly different from the normal population (5.5%). This finding suggests that, unlike other pediatric malignancies, GCTs may not share a strong developmental link with skeletal anomalies [7].
In contrast, Merks et al. (2005) reported a statistically significant association between CR anomalies and GCTs, with 14.7% of GCT patients exhibiting CRs compared to 6.1% in controls (p = 0.046). This suggests a potential genetic or developmental link between GCTs and skeletal anomalies, though the mechanisms underlying this association remain unclear. The higher prevalence observed in this study raises the possibility that certain genetic mutations or disruptions in embryonic development may predispose individuals to both conditions [8].
Loder et al. (2007) did not specifically analyze CRs in relation to GCT. However, their study demonstrated a broader statistically significant association between RAs and childhood malignancies. Children with cancer had a higher prevalence of RAs (18%) compared to the control group (8%), with a p-value of 0.003. While this finding supports a general link between skeletal anomalies and pediatric cancers, it does not establish a direct connection between CRs and GCTs [11].
Similarly, Zierhut et al. (2011) did not specifically report a link between CR and GCTs. The absence of a reported association with GCTs suggests that these tumors may not be as strongly linked to skeletal anomalies as other childhood malignancies [12].
Overall, while some studies indicate a potential link between CR anomalies and GCTs, the evidence remains inconsistent. Merks et al. (2005) provided the most substantial support for an association, but findings from Schumacher et al. (1992) and Zierhut et al. (2011) did not confirm this relationship [7, 8, 12]. Additional research is needed to determine whether CR anomalies can serve as a marker for GCTs or if the observed association is due to other underlying developmental factors.
Other Rib Anomalies Associated with Cancer
Numerical RAs, such as having fewer than 24 ribs, were also found to be more common in children with malignancies. Loder et al. (2007) reported that 18% of children with malignancies had an abnormal rib number compared to 8% of controls. Among specific cancer types, neural tumors had the highest incidence of abnormal rib counts (35%), followed by lymphoproliferative malignancies (15%) and solid tumors (13%) [11]. Similarly, Zierhut et al. (2011) found that children with AML, renal tumors, and hepatoblastoma had a significantly higher likelihood of having an abnormal rib count (p = 0.008) [12].
Rib bifurcations, which involve rib splitting into two separate structures, have also been linked to certain malignancies. Schumacher et al. (1992) reported that 4.5% of neuroblastoma patients exhibited rib bifurcations, a rate four times higher than that of the normal population (1.07%). This suggests that developmental abnormalities affecting rib segmentation may be related to tumorigenesis in neural crest-derived cancers such as neuroblastoma [7].
Rib synostosis, or rib fusion, has also been observed in childhood malignancies. Though relatively rare, this anomaly was documented in some studies. Schumacher et al. (1992) found that 0.5% of cancer patients had rib synostosis compared to none in the control group, while Merks et al. (2005) identified synostosis in 0.2% of cancer patients. Notably, leukemia and brain tumor patients were more likely to present with this anomaly [7, 8].
Additionally, rib hypoplasia (underdeveloped ribs) and aplasia (missing ribs) have been reported in association with various malignancies. Loder et al. (2007) found that children with malignancies were more likely to have fewer ribs, with 44 cases of 22 ribs and 10 cases of 23 ribs, compared to just 16 cases in the control group (p = 0.003) [11]. Schumacher et al. (1992) also reported that 1.2% of cancer patients had rib aplasia or hypoplasia, compared to 0.5% in controls (Table 1) [7].
Study |
Year |
Sample Size |
Key Findings |
Cancer Types |
Types of Rib Anomalies |
Conclusion |
Schumacher et al. [7] |
1992 |
1000 cancer, 200 controls |
Rib anomalies more common in cancer patients (21.8% vs. 5.5% in controls). Neuroblastoma had the highest rate (33%). |
Neuroblastoma, Brain tumors, Leukemia, Soft tissue sarcoma, Wilms' tumor, Ewing sarcoma |
CRs, Bifurcations, Synostoses, Aplasia/Hypoplasia |
Rib anomalies may be linked to tumor development. Further research needed. |
Merks et al. [8] |
2005 |
906 cancer, 881 controls |
CRs were more common in cancer patients (8.6% vs. 6.1% in controls), particularly in leukemia and astrocytoma. |
ALL, Astrocytoma, Germ Cell Tumors |
CRs, Bifid ribs, Rib synostosis |
Rib anomalies could indicate genetic mutations linked to cancer. |
Loder et al. [11] |
2007 |
218 cancer, 200 controls |
Rib anomalies were more frequent in cancer patients (18% vs. 8%). Neural tumors had the highest incidence (35%). |
Neural tumors, Lymphoproliferative malignancies, Solid tumors |
Fewer than 24 ribs, Rib fusions, Bifurcations |
Possible link between rib anomalies and homeobox gene mutations. |
Zierhut et al. [12] |
2011 |
625 cancer, 1499 controls |
Significant association found between rib anomalies and leukemia, renal tumors, and hepatoblastoma. |
AML, Renal tumors, Hepatoblastoma |
Fewer or more than 24 ribs, CRs, Bifurcations |
Rib anomalies could be a marker for cancer predisposition. More research needed. |
ALL: Acute Lymphoblastic Leukemia, AML: Acute Myelogenous Leukemia, CR: Cervical rib |
Future Perspectives
Future research should focus on large-scale, multicenter studies to validate these findings and establish whether RAs, particularly numerical variations, bifurcations, synostoses, and hypoplasia, can be predictive markers for specific cancers. Advances in imaging technologies, such as high-resolution computed tomography and magnetic resonance imaging, may enhance the accuracy of rib anomaly detection and contribute to more precise correlations with cancer risk.
Genetic and molecular studies are also needed to explore the role of Hox genes and other developmental pathways in skeletal formation and oncogenesis. Identifying genetic mutations contributing to RAs and tumor development could lead to novel insights into cancer predisposition syndromes. Additionally, investigating the role of environmental and epigenetic factors in the occurrence of RAs and malignancies may provide a more comprehensive understanding of their shared etiology.
From a clinical perspective, integrating rib anomaly screening into routine pediatric check-ups for high-risk populations could help in early cancer detection. However, before implementing such screening, further studies must determine the predictive value of RAs and whether they can be used as independent risk markers.
Ultimately, interdisciplinary collaboration between geneticists, radiologists, oncologists, and developmental biologists will be crucial in advancing understanding of the link between RAs and childhood cancer. As research continues, these efforts may pave the way for novel diagnostic strategies and targeted therapies for pediatric malignancies.
Conclusion
CRs may serve as valuable indicators of underlying genetic and developmental abnormalities linked to pediatric cancers. Understanding these connections could ultimately contribute to improved cancer screening, early diagnosis, and personalized treatment strategies for children at risk.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: FHK and BAA were significant contributors to the conception of the study and the literature search for related studies. HAN and MNH involved in the literature review, study design, and manuscript writing. SKA, AKG, WNS, HSN, LJM, ASH, OMH, SOA, AHA, LAS and ADS were involved in the literature review, data collection, the study's design, and the critical revision of the manuscript. FHK and BAA confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: Perplexity (Deep Research) and ChatGPT (GPT-4.5) were used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Presentation and Management of Cervical Thoracic Duct Cyst: A Systematic Review of the Literature
Fahmi H. Kakamad, Dilan S. Hiwa, Aland S. Abdullah, Hiwa O. Baba, Aso S. Muhialdeen, Sarwat T....
Abstract
Introduction
Thoracic duct cysts are an uncommon phenomenon, especially within the cervical region. Due to its limited reported cases, very little is known about its etiology, presentation, and management. This systematic review is conducted to shed light on the ways the cyst presents and the outcomes of different treatment regimens.
Methods
The EMBASE, CINAHL, PubMed/MEDLINE, Cochrane Library, and Web of Science databases were thoroughly screened to identify any studies published in English up to March 24th, 2024.
Results
The average age of the patients was 47.8 years, with 9 (56.3%) females in the study population. The mean size of the cysts was 5.99 cm, and the most common symptom was pain, present in 5 (31.3%) patients. The most common management approach chosen for 6 (37.5%) patients was simple follow-up and observation, followed by surgical excision in 5 (31.3%) patients.
Conclusion
Patients with thoracic duct cervical cysts may be asymptomatic or present with pain. Both surgical excision and conservative management may yield satisfactory outcomes.
Introduction
The thoracic duct runs 38 to 45 centimeters from the cysterna chyli at L2 vertebral level to the lower cervical spine [1]. The duct is 2 to 5 millimeters wide, and it carries lymph ingested with fat from the vascular bed of the gastrointestinal system and drains into the central veins of the neck [1,2]. Very rarely, a cyst develops from the thoracic duct, also called a lymphocele of the thoracic duct [3]. The pathology is very uncommon, even more so in the cervical segment, since among the limited reported cases, the majority have been documented as either a thoracic or an abdominal thoracic duct cyst [4]. Although not established, theories suggest that congenital thoracic duct weakness and inflammation-mediated degeneration of the duct can predispose to cyst formation [5]. Due to the limited number of cases reported, no gold standard treatment has been established for cervical thoracic duct cysts; however, both surgical and conservative management have been proposed. To our knowledge, this is the first review in the literature about cervical thoracic duct cysts. This study aims to contribute to the literature by summarizing presentations, management, and outcomes of reported cases of cervical thoracic duct cysts.
Methods
Study design
The guideline followed in this systematic review was that of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Any study with a reported case of a cervical thoracic cyst was included, provided that necessary information was given on the patient and the mass.
Data sources and search strategy
EMBASE, CINAHL, PubMed/MEDLINE, Cochrane Library, and Web of Science databases were all screened using the following ("Thoracic duct" AND Cyst OR Cysts AND Neck OR Cervical) keywords.
Eligibility criteria
Any study with a reported case of thoracic duct cyst found within the cervical region and published in English was deemed eligible. Information on the patient, as well as the characteristics of the cyst, was required. To avoid bias, any study published in predatory journals, identified using Kscien’s list, was excluded from this systematic review [6].
Study selection process
The titles and abstracts of the enrolled studies were screened by two different researchers, attempting to identify papers based on the study's eligibility criteria. A third researcher was recruited to resolve any disagreements that might arise between the initial two researchers.
Data items
Data was collected on mean age, sex, type of study, country of study, presentation, type of symptoms, location of the cyst, size of the cyst, management, and outcome of each management.
Statistical analysis
Microsoft Excel Workbook sheet was used to record the extracted data. The Statistical Package for Social Sciences (SPSS) 26.0 software was used in further quantitative analysis. The data is presented as frequencies and percentages.
Results
Study selection
The systematic search first brought 39 papers. Out of the initial 39, three only-abstract studies were excluded without further screening. The remaining 36 papers had their titles and abstracts screened, which resulted in 25 papers being removed due to irrelevancy. No paper was excluded due to wrong designs. The remaining 11 [4,7-16] studies were checked for wrong outcomes and predatory publishing; however, none were found. This left 11 papers at last to be included in this systematic review. The PRISMA flow chart highlights more details (Figure 1).
Characteristics of the included studies
Among the 11 included studies, 10 (91%) were case reports, with only one (9%) study being a case series. The United States, with four (36.3%), and France, with two (18.2%) studies, contributed the most, followed by Greece, China, Finland, Norway, and Canada, each with one study.
Main findings
A total of 16 patients were included in this systematic review. The average age of the patients was 47.8 ± 17.8 years. There were nine (56.3%) females compared to six (37.5%) males, leaving one (6.2%) patient unspecified. Half of the patients were symptomatic, and pain was the sole symptom in four (25%) patients. Details on the baseline observation and follow-up of the cyst were done for six (37.5%) patients, followed by surgical excision in five (31.4%) patients, a low-fat diet for two (12.5%) patients, aspiration performed in one (6.2%) patient, and lastly, one (6.2%) patient who underwent both surgical excision and had also received a low-fat diet modification regimen. All (100%) patients had their mass in the left supraclavicular region. The outcome of 12 (75%) patients was to be discharged without complications, whereas one (6.2%) patient was observed to have a persistent mass, and three (18.8%) patients did not have their outcome mentioned (Tables 2 and 3).
Author/ year of publication |
Type of Study |
Country of study |
Age (years) |
Sex |
Presentation |
Type of symptoms |
Brauchle et al. 2003 [4] |
Case report |
United States |
41 |
Male |
Asymptomatic |
N/A |
Mattila et al. 1999 [7] |
Case report |
Finland |
49 |
Female |
Asymptomatic |
N/A |
Metaxas et al. 2021 [8] |
Case report |
Greece |
42 |
Male |
Symptomatic |
Pain |
Wang et al. 2009 [9] |
Case report |
China |
28 |
Female |
Asymptomatic |
N/A |
Veziant et al. 2015 [10] |
Case report |
France |
49 |
Female |
Symptomatic |
Pain and Dyspnea |
Planchette et al. 2021 [11] |
Case series |
France |
50 |
Male |
Asymptomatic |
N/A |
74 |
Female |
Asymptomatic |
N/A |
|||
45 |
Female |
Symptomatic |
Pain |
|||
65 |
Female |
Asymptomatic |
N/A |
|||
64 |
Female |
Symptomatic |
Pain |
|||
62 |
Female |
Symptomatic |
Pain |
|||
Bhalla et al. 2017 [12] |
Case report |
United States |
0.67 |
Male |
Symptomatic |
Dyspnea |
Steinberg 1964 [13] |
Case report |
United States |
56 |
Female |
Symptomatic |
Migraine headaches |
Steinberg & Watson 1966 [14] |
Case report |
United States |
28 |
N/A |
Symptomatic |
Soreness |
Kolbenstvedt et al. 1986 [15] |
Case report |
Norway |
55 |
Male |
Asymptomatic |
N/A |
Wax et al. 1992 [16] |
Case report |
Canada |
56 |
Male |
Asymptomatic |
N/A |
Author/ year of publication |
Age (years) |
Location of cyst |
Size of cyst |
Management |
Outcome |
Brauchle et al. 2003 [4] |
41 |
Left supraclavicular |
4 cm |
Aspiration |
Patient was discharged |
Mattila et al. 1999 [7] |
49 |
Left supraclavicular |
3.8 cm |
Surgical Excision |
Patient was discharged |
Metaxas et al. 2021 [8] |
42 |
Left Neck |
N/A |
Surgical Excision |
Patient was discharged |
Wang et al. 2009 [9] |
28 |
Left supraclavicular |
10 cm |
Surgical Excision |
Patient was discharged |
Veziant et al. 2015 [10] |
49 |
Left supraclavicular |
3 cm |
Surgical Excision |
Patient was discharged |
Planchette et al. 2021 [11] |
50 |
Left supraclavicular |
N/A |
Follow up |
Patient was discharged |
74 |
Left supraclavicular |
N/A |
Follow up |
Patient was discharged |
|
45 |
Left supraclavicular |
N/A |
Follow up |
Patient was discharged |
|
65 |
Left supraclavicular |
N/A |
Follow up |
N/A |
|
64 |
Left supraclavicular |
N/A |
Low fat diet |
Patient was discharged |
|
62 |
Left supraclavicular |
N/A |
Low fat diet |
Patient was discharged |
|
Bhalla et al. 2017 [12] |
0.67 |
Left supraclavicular |
13.1 cm |
Surgical drainage and low fat diet |
Patient was discharged |
Steinberg 1964 [13] |
56 |
Left supraclavicular |
3 cm |
N/A |
N/A |
Steinberg & Watson 1966 [14] |
28 |
Left supraclavicular |
3 cm |
Follow up |
N/A |
Kolbenstvedt et al. 1986 [15] |
55 |
Left supraclavicular |
3 cm |
Follow up |
Mass persistence |
Wax et al. 1992 [16] |
56 |
Left supraclavicular |
10 cm |
Surgical Excision |
Patient was discharged |
Variables |
Frequency/percentage |
Age (mean ± SD) |
47.8 ± 17.8 years |
Sex Male Female N/A |
Number of patients (16) 6 (37.5%) 9 (56.3%) 1 (6.2%) |
Country of study United States France Greece China Finland Norway Canada |
Number of studies (11) 4 (36.3%) 2 (18.2%) 1 (9.1%) 1 (9.1%) 1 (9.1%) 1 (9.1%) 1 (9.1%) |
Type of Study Case report Case series |
Number of studies (11) 10 (90.1%) 1 (9.9%) |
Presentation Symptomatic Asymptomatic |
Number of patients (16) 8 (50%) 8 (50%) |
Type of symptoms Pain Pain and dyspnea Dyspnea Migraine Soreness N/A |
Number of patients (16) 4 (25%) 1 (6.2%) 1 (6.2%) 1 (6.2%) 1 (6.2%) 8 (50%) |
Size of cyst (mean ± SD) |
5.99 ± 3.99 cm |
Management Aspiration Surgical Excision Follow up Low-fat diets Surgical excision & low-fat diet N/A |
Number of patients (16) 1 (6.2%) 5 (31.4%) 6 (37.5%) 2 (12.5%) 1 (6.2%) 1 (6.2%) |
Outcome Patient was discharged Mass persisted N/A |
Number of patients (16) 12 (75%) 1 (6.2%) 3 (18.8%) |
* N/A: Not applicable |
Discussion
Apart from the right side of the upper extremity, the right side of the thorax, and the right side of the neck, the thoracic duct drains the lymphatics of the rest of the body [1]. An uncommon phenomenon related to the duct is a thoracic duct cyst, also called a lymphocele of the thoracic duct [3]. Theoretically, the cyst can arise throughout the length of the entire duct; however, it usually arises within either the thorax or the abdomen. A thoracic lymphocele of the cervical region is the rarest form [4]. A cervical thoracic duct cyst will present as a lateral neck mass arising from the supraclavicular fossa. In this systematic review, all 16 patients presented with a mass, either painful or not, within the left supraclavicular fossa. Bhalla et al. reported the youngest patient recorded in the literature with a thoracic duct lymphocele presenting in an 8-month-old boy [12]. According to Abelarado et al., the cyst tends to occur more frequently in females, and the average age among the patients presenting with the cyst is 49.8 years [15]. This is in accordance with the current study’s findings, as the average age was 47.8 ± 17.8 years, and the majority were females. No single factor has been identified as a cause of this pathology; however, inflammation-mediated degeneration of the duct wall and congenital weakness have been suggested, as well as any possible traumas [3].
As previously mentioned, since the duct drains the left side of the neck, the cyst will present as a left-sided supraclavicular mass. Most patients with a thoracic duct lymphocele are asymptomatic [5]. Half of the patients in this systematic review were symptomatic, and the other half had no complaints. Symptoms are generally due to the compressive effect of the mass on adjacent structures and can include pain, dysphagia,
cyanosis, and even respiratory distress [7]. In this study, four (25%) patients presented with pain alone, making it the most common symptom. Others, such as migraine headaches, dyspnea, and soreness, were also reported, with one patient suffering from both pain and dyspnea. Lymphoscintigraphy used to be considered the gold standard for diagnosis; however, with the advent of new high-resolution imaging techniques, this tool has become less popular [17]. Confirmation of the diagnosis is usually conducted during surgery, as histological analysis of the specimen can be beneficial. One way this is done is by staining the endothelial cells lining the thoracic duct to verify that the cyst is, in fact, a thoracic duct cyst [4,18]. According to Mattila et al., another way to diagnose a thoracic duct cyst is via puncture and subsequence analysis. Following aspiration, the aspirate will manifest as a milky fluid showing excess triglyceride in laboratory investigations and lymphocytes, neutrophils, and macrophages, among others [7].
Regarding management, no single gold standard has been established. This is attributed to the low number of cases that have been recorded. As previously mentioned, aspiration, although usually performed for diagnosis purposes, can be sufficient to deal with the mass. In this review, only one of the patients had aspiration alone. Surgical excision of the thoracic duct cyst is another common way to manage the mass [7]. This was performed for five (31.4%) patients in this review. Interestingly, in some instances, and especially after deeming the mass nonneoplastic, patients are followed up and observed after they either refuse surgery or the physician doesn’t consider it necessary. This has been highlighted in six (37.5%) patients within this study’s population. Furthermore, patients were managed through diet modification and, more specifically, transitioning to a low-fat diet. This yielded a satisfactory outcome in the two patients who only received diet modification and in the one patient who underwent surgical excision followed by a transition to a low-fat diet. All different management methods yielded satisfactory outcomes, with patients discharged without complications in three-quarters of the cases. This was apart from one patient whose mass persisted since they underwent no management and were observed.
Conclusion
Patients with thoracic duct cervical cysts may be asymptomatic or present with pain. Both surgical excision and conservative management may yield satisfactory outcomes.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable, as systematic reviews do not require ethical approval.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: FHK and BAA were significant contributors to the conception of the study and the literature search for related studies. DSH and ASA involved in the literature review, study design, and manuscript writing. AJQ, RJR, MLF, STSA, ASM, and HOB were involved in the literature review, the study's design, the critical revision of the manuscript, and data collection. FHK and DSH confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.
Case Reports

Renal Ewing Sarcoma: A Case Report and Literature Review
Rebaz M. Ali, Bnar Sardar Saida, Saman S. Fakhralddin, Ari M. Abdullah, Hadeel Adnan Yasseen,...
Abstract
Introduction
Primary renal Ewing sarcoma is an extremely rare and aggressive tumor, representing less than 1% of all renal tumors. This case report contributes valuable insights into the challenges of diagnosing and managing this rare malignancy, particularly when it presents with atypical symptoms.
Case presentation
A 30-year-old female presented with intermittent grassy green-colored urine, later turning into red, with a headache and no abdominal pain. Clinical examination revealed elevated blood pressure. Imaging studies, including ultrasound and computed tomography scans, identified a large, heterogeneous mass in the left kidney with invasion into the renal vein and lymph nodes, leading to a staging of T3N1M0. The patient underwent a left radical nephrectomy, with pathology confirming a Grade 2 primary Ewing sarcoma / primitive neuroectodermal tumor of the kidney. Despite aggressive treatment with adjuvant chemotherapy, stable metastatic deposits persisted, indicating ongoing active disease.
Literature review
Ewing sarcoma typically occurs in bones but can occasionally arise in solid organs such as the kidney. Most patients present with non-specific symptoms, and the disease often remains undiagnosed until it has metastasized. Current treatment involves multimodal therapy, including surgery and chemotherapy, but prognosis remains poor, especially in cases with metastasis.
Conclusion
This case underscores the complexity of diagnosing and treating primary renal Ewing sarcoma. Persistent metastasis despite treatment highlights the need for vigilant monitoring. Further genetic profiling could enhance understanding and management of this rare condition.
Introduction
Sarcomas are a diverse group of malignant tumors originating from mesenchymal tissues, and they can arise in virtually any part of the body, often posing diagnostic and therapeutic challenges due to their rarity and varied presentation. Recent reports have highlighted unusual locations and rare co-occurrences of sarcomas, emphasizing the need for heightened clinical suspicion when encountering atypical masses [1,2].
Ewing sarcoma (EWS) is a highly aggressive tumor typically found in the bones of children and young adults. However, it can occasionally originate from solid organs that contain neuroendocrine cells, such as the kidney, lungs, heart, bladder, small intestine and parotid glands, with approximately 6% of cases being extraosseous [3-5]. Ewing sarcoma is classified as a small round cell sarcoma characterized by gene fusions between a member of the Ewing Sarcoma Breakpoint Region 1 (EWSR1) gene family and a member of the E26 transformation-specific sequence (ETS) family of transcription factors [6]. Primary EWS of the kidney is an extremely rare tumor, comprising less than 1% of all renal tumors, with fewer than 200 cases reported globally. However, the precise number of cases is challenging to determine, as these tumors are not always accurately diagnosed. [3,7]. It is a highly aggressive tumor that primarily affects young individuals, with a particular prevalence among males [8]. Patients typically present with an abdominal mass or renal symptoms such as abdominal pain and hematuria. Due to its hidden intra-abdominal location, the tumor often grows to a significant size before being detected [9]. Primary kidney EWS metastasizes to the bone, lungs, and lymph nodes. Its clinical presentation is not specific, and it can resemble other renal tumors in histologic appearance [10]. In this case, a 30-year-old female presented with primary renal EWS, exhibiting unusual symptoms such as grassy green to red urine. The references’ eligibility has been verified [11]. The report is structured in accordance with CaReL guidelines and includes a recent review of the literature [12].
Case Presentation
Patient information
A 30-year-old female presented with a chief complaint of intermittent grassy green-colored urine, which later became red. She also experienced headaches but reported no fever, vomiting, or abdominal pain. Her past medical history was unremarkable, though she had undergone the removal of an ovarian cyst on the left side just one month prior to her diagnosis.
Clinical findings
On clinical examination, there was no abdominal tenderness or other systemic abnormalities. Her vital signs were normal except for elevated blood pressure, recorded at 120/100 mmHg.
Diagnostic approach
Diagnostic investigations included abdominal ultrasonography, which revealed an enlarged and irregularly shaped left kidney with mild pelvicalyceal system dilation. A large heterogeneous iso to hyper-echoic mass measuring 11x10x8 cm was identified, extending from the mid to lower pole of the kidney and displaying internal vascularity. A subsequent computed tomography (CT) scan of the abdomen confirmed the presence of a large heterogeneous solid lesion at the lower pole of the left kidney, measuring approximately 12x10x8.5 cm. The mass showed heterogeneous enhancement after contrast administration and extended into the renal pelvis and lower calyx, with associated mild dilation. The scan also revealed invasion of the retroaortic right renal vein and two enlarged locoregional lymph nodes, the largest measuring 6 mm in short axis. These findings were indicative of a malignant renal tumor, staged as T3N1M0 (Figure 1).
Therapeutic interventions
The patient underwent a left radical nephrectomy. Histopathological examination confirmed the diagnosis of a primary EWS /primary neuroectodermal tumor of the kidney, classified as Grade 2, with a mitotic activity of 6-8 per 10 high-power fields (Figure 2). The tumor, which measured 10 cm at its greatest dimension, was located in the lower pole of the left kidney and was unifocal.
There was no evidence of tumor necrosis, lymphovascular invasion, or positive surgical margins, though one out of eight examined lymph nodes tested positive for metastasis. The final pathological stage was pT1pN1M0. Immunohistochemistry showed that the tumor cells were positive for CD99, while other markers such as AE1/AE3, CD45, desmin, S100, synaptophysin, CD31, and WT1 were negative. The patient subsequently received adjuvant chemotherapy with the VAC-IE regimen (vincristine, doxorubicin, cyclophosphamide-ifosfamide, etoposide).
Follow-up
One month after the operation, a magnetic resonance imaging (MRI) of the abdomen revealed a 50x20 mm elongated, well-defined area of bright signal on T1 and T2 imaging, with no diffusion-weighted imaging restriction or enhancement, overlapping the left psoas muscle. This finding was suggestive of a postoperative hematoma. A high-resolution CT scan of the chest was normal. Three months later, a fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed multifocal areas of FDG avidity extending from the lateral aspect of the crus of the left hemidiaphragm and left psoas muscle, with a maximum standardized uptake value of 6.53. The largest hypermetabolic lesion measured 1.2x1.1 cm. A laparoscopic biopsy of a nodule on the small bowel serosa and psoas muscle showed benign findings with no evidence of malignancy.
Over the course of the follow-up, two additional FDG-PET scans were performed, three months apart. The latest scan revealed a stable metastatic deposit in the left nephrectomy bed along the left psoas muscle with a slight decrease in FDG uptake (less than 30%). The disease was considered interval stable, and although radiation treatment was recommended, it was ultimately deemed unnecessary. The patient continued to be monitored, with two additional abdominal MRIs conducted four months apart. The most recent MRI showed a non-enhancing lesion measuring 67x29x20 mm, consistent with previous findings.
Discussion
Most cases of EWS develop in the bones, with the lower extremities and pelvis being the most common sites of occurrence. However, it is extremely rare for EWS to appear as a primary tumor in the kidney. The cells responsible for EWS are believed to originate from neural crest cells or mesenchymal stem cells [9, 13]. Approximately 66% of patients have distant metastasis at the time of diagnosis, with the lungs being the most common site, followed by the liver and bones [4]. The median age for this condition is 27 years, with a slight predominance in males. The symptoms are non-specific and include flank pain in 84% of cases, a palpable mass in 60%, and hematuria in 38% [6]. The review of 19 cases of EWS of the kidney in this study (Table 1) revealed a mean age of 24.5 years, with females accounting for 57.9% of the cases. The most common symptoms were flank pain (47.36%), followed by hematuria (42.1%) and abdominal pain (36.8%). The average tumor size was 12.27 cm. In contrast, the current case involved a 30-year-old female who presented with intermittent grassy green-colored urine and a headache, but no abdominal pain.
Diagnosis can be assisted using radiological techniques such as MRI and CT scans, in determining the tumor's size, location, and the extent of both local and distant metastasis [9]. The definitive diagnosis of renal EWS relies on pathological, immunohistochemical, and molecular testing. Microscopically, the majority of cases consist of uniform small round cells with round nuclei, finely stippled chromatin, subtle nucleoli, scant clear or eosinophilic cytoplasm, and indistinct cytoplasmic membranes [6]. The protein K2.2 plays a role in regulating gene expression within the neuroendocrine and glial differentiation pathways, and NKX2.2 serves as a specific marker for identifying the EWS/FLI1 fusion protein, exhibiting a high sensitivity of 93% and a specificity of 89% [6]. In the current case, abdominal ultrasonography revealed an enlarged, irregularly shaped left kidney with a large mass sized 10 cm that was confirmed by CT scan, which was smaller than ten and larger than seven of the cases in this literature review (Table 1).
Author and Year | No. of Cases |
Age Gender |
Clinical Presentation |
Medical & Surgical History | Diagnostic Method |
Size and Site of Tumor |
Treatment | Outcome | |
Conservative | Surgical | ||||||||
Aithal et al., 2024[4] |
1 |
40 F |
Painless hematuria |
None reported |
MRI, CECT, Histo, IHC |
7x5.5x5 cm, Lower pole, LK |
Chemotherapy |
Nephrectomy |
N/A |
Alahmadi et al., 2020[8] |
1 |
16 M |
Hematuria, flank pain |
Schizophrenia |
CECT, Histo, IHC |
19 × 15 × 12 cm, RK |
Chemotherapy |
Nephrectomy |
Remission |
Bradford et al., 2020[14] |
Case 1 |
16 M |
Abdominal pain |
N/A |
IHC |
RK |
VDC/IE; |
Partial Nephrectomy |
Died |
Case 2 |
11 M |
Flank and testicle pain, fever |
N/A |
Ultrasound, CT, IHC |
28×17×7.3 cm, LK |
VDC/IE; auto SCT; everolimus, Chemotherapy |
Nephrectomy |
Alive with disease |
|
Case 3 |
18 F |
Hematuria, right flank pain |
N/A |
PET, CT |
6.8×6.2×6.0 cm, RK |
VDC/IE |
Radical nephrectomy, IVC tumor removal |
Remission |
|
Case 4 |
17 F |
N/A |
N/A |
PET |
N/A |
Chemotherapy, VDC/IE |
Tumor resection |
Remission |
|
Case 5 |
16 F |
N/A |
N/A |
N/A |
25×18×19 cm, LK |
VDC/IE |
Gross total resection |
Remission |
|
Case 6 |
13 F |
Abdominal pain, spinal cord compression |
N/A |
MRI, PET, Histo |
6.8×14×13 cm, LK |
VDC/IE |
Nephrectomy, following neoadjuvant chemotherapy |
Died |
|
Case 7 |
15 F |
Abdominal pain, ataxia, elevated urate and creatinine |
N/A |
N/A |
21 cm, LK |
Chemotherapy, VDC/IE switched to VDC/CE for ifosfamide nephrotoxicity |
Radical nephrectomy, partial ureterectomy, IVC thrombectomy |
Died |
|
Bray et al., 2023[13] |
1 |
31 F |
Macroscopic hematuria, flank pain |
unremarkable |
CT, MRI, Ultrasound |
11.6 cm, RK |
VDC/IE Chemotherapy |
laparoscopic radical Nephrectomy |
Remission |
Cheng et al., 2020[15] |
1 |
31 F |
Hematuria, flank pain, palpable mass |
unremarkable |
CT, 3D imaging, PET, Histo, IHC |
18×14.5×14 cm, LK |
Chemotherapy |
Nephrectomy |
Metastasis |
El Mohtarim et al., 2024[6] |
1 |
14 F |
Flank swelling, abdominal pain weight loss |
2 mo of abdominal pain |
MRI, CT, Histo, IHC |
20×16×14 cm, RK |
Chemotherapy, VDC/IE |
Nephrectomy |
Remission |
Ilhan et al., 2023[7] |
1 |
54 M |
Flank pain, hematuria |
Smoker, Alcohol consumption |
Ultrasound, CT, Histo, IHC |
7.4×6.3 cm, RK |
Chemotherapy (VAC-IE) |
Nephrectomy |
Remission |
Khudair et al., 2024[9] |
1 |
38 F |
Abdominal pain, flank Pain |
Constipation, vomiting, morbid obesity |
Ultrasound, CT, Histo |
25×18×18 cm, RK |
Chemotherapy |
N/A |
Died |
Patra et al., 2022[10] |
Case 1 |
33 F |
Abdominal pain |
N/A |
CECT, biopsy, Histo, IHC |
7.4 cm, RK |
Chemotherapy |
Nephrectomy |
Died |
Case 2 |
35 M |
Palpable lump |
N/A |
CECT, biopsy, Histo, IHC |
4.5 cm, LK |
Chemotherapy |
Nephrectomy |
Remission |
|
Case 3 |
19 M |
Palpable lump, hematuria |
N/A |
CECT, biopsy, Histo, IHC |
19 cm, RK |
NACT |
Nephrectomy |
Alive with disease |
|
Case 4 |
28 M |
Abdominal pain |
N/A |
CECT, biopsy, Histo, IHC |
6.4 cm, LK |
NACT |
Nephrectomy |
Alive with disease |
|
Sardana et al., 2021[3] |
1 |
49 M |
Gross hematuria, flank pain |
GERD, asthma, hyperlipidemia |
MRI, CT, Histo, IHC |
7.0×6.2×5.8 cm, RK |
Chemotherapy, Radiotherapy |
Nephrectomy |
Remission |
F: female M: male N/A: not applicable mo: months MRI: magnetic resonance imaging CECT: contrast enhanced computed tomography Histo: histopathology IHC: immunohistochemistry PET: positron emission tomography LK: left kidney RK: right kidney NACT: Neoadjuvant chemotherapy IVC: inferior vena cava VDC/IE: vincristine, doxorubicin, and cyclophosphamide/ ifosfamide, etoposide y: year |
To establish a definitive diagnosis, the patient underwent a left radical nephrectomy. Similarly, in the cases by Patra et al., histopathological examination confirmed the tumor as a Grade 2 primary EWS /PNET of the kidney [10]. Despite its aggressive nature, there was no evidence of distant metastasis in the present patient, and she received adjuvant chemotherapy, which was in line with the cases by Ilhan et al. and Bradford et al. [7,14]. In contrast, Cheng et al. reported metastatic spread to multiple sites, including lymph nodes, adrenal glands, and lungs, requiring a switch to apatinib, with the patient surviving 18 months postoperatively [15].
The most common treatment approach currently involves multimodal therapy, which includes surgery and adjuvant chemotherapy for localized EWS of the kidney [7]. The current patient underwent a left radical nephrectomy to remove the primary tumor. The surgery was successful in excising the tumor. The pathological examination revealed no tumor necrosis, lymphovascular invasion, or positive surgical margins, but one out of eight examined lymph nodes tested positive for metastasis, leading to a final pathological stage of pT1pN1M0.
Immunohistochemical analysis confirmed the diagnosis of EWS/PNET, with the tumor cells showing positivity for CD99, a marker commonly associated with EWS. Other markers, including AE1/AE3, CD45, desmin, S100, synaptophysin, CD31, and WT1, showed negatively, and Ki67 showed a proliferation index of 20%. In contrast, Cheng et al. reported positive results for AE1/AE3, CD99, CD56, and synaptophysin [15]. Following surgery, the patient received adjuvant chemotherapy using the VAC-IE regimen similar to Ilhan et al., which includes vincristine, doxorubicin, cyclophosphamide (VAC), ifosfamide, and etoposide (IE). This multimodal chemotherapy approach was implemented to target any remaining microscopic disease and to lower the risk of tumor recurrence [7].
The current case did not achieve full remission due to stable metastatic deposits, indicating active cancer. In contrast, the patients in the studies of both Ilhan et al. and Bray et al. remained in remission with no disease progression, reflecting more
favorable outcomes [7,13]. The prognosis of EWS depends on various factors, including tumor location and size, presence of metastatic disease, and treatment plans. However, the impact of age on disease outcomes remains uncertain [3]. In the present report, while the disease is stable, the persistence of metastasis suggests ongoing risk, requiring continuous monitoring. Detailed genetic profiling of the tumor was not included, which could have provided deeper insights into the disease's molecular mechanisms and influenced treatment strategies.
Conclusion
The current case highlights that EWS of the kidney can present with grassy green-colored urine and hematuria. Radical nephrectomy with the VAC-IE regimen may result in good outcomes with continuous monitoring required in cases of metastatic deposits.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable
Patient consent (participation and publication): Written informed consent was obtained from the patient for publication.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: RMA and SMA were significant contributors to the conception of the study and the literature search for related studies. MAG, DSH and JSA were involved in the literature review, study design, and manuscript writing. ZNH, HAY, AMA, SSF, BSS and AKG were involved in the literature review, the study's design, and the critical revision of the manuscript, and they participated in data collection. SHT was the radiologist who performed the assessment of the case. RMA was the pathologist who performed the diagnostic of the case. RMA and MAG confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Note applicable.

Suture-Induced Tubo-Ovarian Abscess: A Case Report with Literature Review
Huda M. Muhammad, Nahida Hama Ameen Ahmed, Sawen M. Ahmed, Zhiyan M. Mohammed, Meer M....
Abstract
Introduction
Suture is an underreported cause for tubo-ovarian abscess (TOA) that can cause significant morbidity. This report describes a case of TOA arising from a silk suture three years after bilateral tubal ligation.
Case presentation
A 38-year-old woman with a history of tubal ligation presented with persistent pelvic pain and fever. Imaging revealed a suspicious left adnexal mass with features concerning for malignancy or abscess. Surgical exploration revealed a TOA adherent to surrounding structures, containing a retained silk suture from prior surgery. The abscess and suture were removed, and histopathology confirmed chronic inflammation without malignancy. The patient underwent additional procedures for thorough management, including polypectomy and contralateral tubal ligation.
Literature Review
A total of nine cases of TOAs and suture-induced abscesses were reviewed. Of these, seven were TOAs, six of which occurred postoperatively. Three cases developed following tubal ligation procedures. The abscesses ranged in size from 1 to 7.6 cm. The interval between the presumed inciting event and abscess detection varied widely, with one case presenting more than three decades after surgery. Isolated microorganisms included Escherichia coli, Streptococcus pyogenes, and Peptostreptococcus anaerobius. All patients underwent surgical intervention via various approaches, and several also received adjunctive antibiotic therapy.
Conclusion
Suture-induced TOA following sterilization may result in considerable morbidity, and surgical intervention may provide favorable outcomes.
Introduction
Pelvic inflammatory disease (PID) is a polymicrobial infection resulting from the ascent of pathogens from the cervix or vagina to the upper genital tract. It is most commonly caused by Chlamydia trachomatis and Neisseria gonorrhoeae, which together are responsible for approximately 60–75% of cases. Once these pathogens ascend, they can infect the endometrium, fallopian tubes, ovaries, and surrounding pelvic structures, triggering an inflammatory response [1].
A tubo-ovarian abscess (TOA) is a severe complication of PID, characterized by the formation of a purulent abscess involving the uterus, fallopian tubes, and ovaries [2]. This condition primarily affects women of reproductive age, with the highest incidence occurring in the fourth decade of life. Approximately 4.4% of sexually active women have a history of PID, placing them at increased risk for TOA development [3]. Given its non-specific clinical presentation, TOA can be challenging to diagnose, often requiring differentiation from other acute abdominal and pelvic conditions. The differential diagnosis includes ovarian torsion, ectopic pregnancy, appendicitis, gastroenteritis, constipation, and urinary tract infection, all of which can present with overlapping symptoms such as pelvic pain, fever, nausea, and gastrointestinal discomfort [2].
Although TOAs are commonly associated with PID, they can also develop from less common etiologies, such as the presence of surgical sutures. Reports of TOAs linked to surgical sutures remain scarce in the literature. This report highlights a unique case of a TOA that developed due to a silk suture three years after the patient had undergone bilateral tubal ligation, a procedure intended for permanent female sterilization. This case underscores the need for awareness of non-infectious etiologies in the differential diagnosis of TOAs, particularly in patients without a recent history of PID. The report was written according to the CaReL guidelines, and unreliable sources were excluded [4,5].
Case Presentation
Patient information
A 38-year-old female presented with a one-month history of worsening, persistent pelvic pain. Her medical history was unremarkable, and her surgical history included bilateral tubal ligation performed three years earlier.
Clinical findings
Physical examination revealed a high temperature, tenderness in the left suprapubic area, and the presence of an immobile pelvic mass upon palpation.
Diagnostic assessment
A pelvic ultrasound (US) showed a left-sided heterogeneous lesion measuring 44 x 30 mm. The mass was a vascular solid lesion with calcifications, exhibiting indistinct margins and evidence of invasion into the adjacent peritoneum and the left rectus abdominis muscle. Doppler imaging demonstrated high vascularity, with a score of 3-4. These characteristics were highly suspicious for a desmoid tumor or a primary peritoneal tumor; however, direct invasion of the left ovary could not be excluded (Figure 1). Computed tomography (CT) with IV contrast revealed a 6 x 4 x 3 cm, multilocular mass located in the left lower abdomen, arising from the left adnexa and attached to both the uterus and left ovary. The mass extended into the posterior aspect of the left rectus muscle. It was in proximity to the left inferior epigastric artery and a loop of small intestine, though no direct invasion was observed. Surrounding fat stranding raised the possibility of infection, such as a TOA, though malignancy could not be excluded. Mild pelvic free fluid was noted, and no suspicious lymph nodes were identified. The other abdominal organs, including the liver, spleen, pancreas, kidneys, and adrenal glands, appeared normal. The laboratory results revealed the following: Carcinoembryonic Antigen (CEA) was 0.471 ng/ml (normal range: 0-5 ng/ml), Cancer Antigen 125 (Ca125) was 33.6 IU/ml (normal range: <35 IU/ml), and Carbohydrate Antigen 19-9 (CA 19-9) was 5.73 IU/ml (normal range: <33 IU/ml), all of which fell within the normal reference ranges. Serum C-reactive protein (CRP) level was slightly elevated at 8.38 mg/L, above the normal range of <5.0 mg/L.
Therapeutic intervention
To ensure accurate diagnosis and appropriate management, consultations were held with oncology and gastrointestinal surgery specialists. After a thorough evaluation, an explorative laparoscopy was planned. During the procedure, a TOA was found, firmly adherent to the omentum and anterior abdominal wall. The abscess was carefully aspirated using suction, and a biopsy was taken for frozen section analysis. The preliminary histopathology report indicated inflammation and fibrosis, confirming the lesion's nature. As the surgery progressed, an unexpected finding was discovered: an unabsorbable silk suture embedded within the abscess. This suture, most likely a remnant from her previous procedure, was carefully excised along with the surrounding fibrotic tissue and sent for further histopathological analysis. To reduce the risk of recurrence, the contralateral fallopian tube was also removed and securely ligated. In addition to addressing the abscess and suture, a hysteroscopy and polypectomy were performed to ensure thorough treatment. The procedure was completed successfully, with all abscess material and pathological tissues removed. The histopathological examination revealed a hyperplastic endometrial polyp with background secretory changes consistent with progestin exposure, without evidence of atypia or malignancy. The left tubal mass showed chronic nonspecific salpingitis, and the attached omentum exhibited severe acute-on-chronic inflammation with fibrosis, consistent with an abscess wall. The right fallopian tube revealed para-tubal cysts and Walthard cell rests, while the right ovarian cyst was identified as a hemorrhagic corpus luteum. No malignancy was detected in any of the submitted specimens.
Follow-up
Post-operative treatment included intravenous Flagyl (Metronidazole) and Claforan (Cefotaxime), and there were no complications. After six months of follow-up, no significant complication was observed.
Discussion
The development of PID and TOAs has long been considered a rare complication of tubal sterilization. The most frequently isolated pathogens of these abscesses include Escherichia coli and Bacteroides species. Additional identified organisms in these abscesses comprise Peptostreptococcus, Peptococcus, and aerobic Streptococcus species [1]. Although rare, infections involving Staphylococcus species and Burkholderia pseudomallei have also been reported in the literature [6,7]. Among the reviewed cases, six patients developed TOAs following surgical procedures. Among the cases in which microbiological data were reported, Escherichia coli was identified in two patients, Streptococcus pyogenes in another two, and Peptostreptococcus anaerobius in one (Table 1) [1,2,8-12].
Author/year |
Age |
Sex |
Pregnancy |
Gynecological history |
Surgical history |
Comorbidities |
Symptoms |
Location |
Mass size (cm)* |
Treatment |
Presence of Foreign Body |
Identified pathogens |
Pathological findings |
Outcome |
Sun et al./2024 [9] |
18 |
M |
N/A |
N/A |
Mucocele excision |
None |
Soft and tender nodule |
Lower lip |
1 |
Total excision of the lesion |
Silk suture |
N/A |
Acute and chronic inflammation & multinucleated foreign body giant cells |
Recovery |
Linck et al./2023 [16] |
51 |
F |
3 |
Abnormal uterine bleeding |
D&C hysteroscopy & polypectomy |
None |
Heavy menstrual bleeding, fever & abdominal pain |
Right posterior pelvic area |
5.1 |
Antibiotic, Interventional radiology percutaneous drainage, laparotomy, total hysterectomy & bilateral salpingo-oophorectomy |
None |
Escherichia coli |
Acute inflammation & acute serositis |
Recovery |
Campbell et al./2021 [2] |
15 |
F |
None |
Unremarkable |
Appendectomy |
None |
Abdominal pain |
Right adnexa |
7.1 |
Laparoscopy, drainage of the right pyosalpinx, removal of the stump appendix & antibiotics |
Stump appendix |
None |
Necrotic material with acute inflammatory debris |
Recovery |
Zein et al./2021 [13] |
58 |
M |
N/A |
N/A |
Retinal detachment repair |
HIV infection |
Swollen conjunctivae, bulbar injection, and tearing |
Left eye |
1 |
Corticosteroids, excision of the lesion, & Amniotic membrane transplantation |
Silk suture |
None |
Chronic inflammation |
Recovery |
Naredi et al./2021 [15] |
45 |
F |
2 |
Unremarkable |
|
Hypertension & obesity |
Lower abdominal pain |
Left adnexa |
7.6 |
Intravenous antibiotics, drainage, laparotomy & left salpingo-ophrectomy |
N/A |
N/A |
Inflammation |
Recovery |
Solt et al./2010 [1] |
24 |
F |
3 |
Menarche at 12 & irregular menstrual cycles |
Colectomy, appendectomy, cesarean deliveries, elective abortion, lami nectomy, breast augmentation & Essure placement |
Mitochondrial neurogastrointestinal encephalopathy, progressive gastrointestinal dysmotility, symmetric polyneuropathy, asymptomatic leukoencephalopathy, asthma, antiphospholipid syndrome, supraventricular tachycardia, renal lithiasis, and bipolar disorder. |
Right lower quadrant pain, nausea, and vomiting |
Right adnexa |
N/A |
Laparoscopy, total abdominal hysterectomy & antibiotics |
Essure microinserts |
Streptococcus pyogenes |
N/A |
Developed acute peritonitis |
Weinberger et al./1996 [12] |
34 |
F |
3 |
PID |
Bilateral tubal ligation |
None |
Lower abdominal pain, fever |
Right adnexa |
6.1 |
Antibiotics, adhesiolysis, total abdominal hysterectomy, right salpingo-oophorectomy, & vaginal T-tube drain placement |
Silastic band |
Peptostreptococcus anaerobius |
Acute necrotizing oophoritis |
Recovery |
37 |
F |
2 |
Unremarkable |
Bilateral tubal ligation |
None |
bilateral lower quadrant pain, fever, tenderness, vaginal spotting & discharge |
Left adnexa |
4 |
Laparoscopy, laparotomy, bilateral salpingectomies, right oophorectomy, endometrial biopsy, incidental appendectomy & antibiotics |
None |
Streptococcus pyogenes |
Acute suppurative salpingitis, ovarian cortex hemorrhage. Proliferative phase endometrium |
Recovery |
|
38 |
F |
2 |
Unremarkable |
Tubal fulguration, kidney transplant |
Systemic lupus erythematosus, immunocompromised |
bilateral lower quadrant pain, fever, tenderness & yellow discharge |
Ovaries |
4.4 |
Laparotomy, bilateral distal salpingectomy & antibiotics. |
None |
Escherichia coli |
Acute suppurative salpingitis & paratubal abscess formation |
Recovery |
|
M: Male, F: Female, N/A: Not Available, D&C: Dilation and curettage, HIV: Human immunodeficiency virus, PID: Pelvic inflammatory disease *Only the largest dimension is reported in the table. |
Although the exact incidence of upper genital tract infections following surgical sterilization remains unknown, traditional gynecologic literature emphasizes that such occurrences are exceedingly rare. However, other data suggest that the upper genital tract may remain vulnerable to infection even after sterilization. A study found that 6% of hospitalized PID cases involved patients with prior sterilization, with symptoms including systemic toxicity and requiring surgical evaluation in some instances [13].
The postoperative infection in the current patient was caused by the use of silk sutures for tubal ligation. This resulted in the development of a suture abscess, which is a type of foreign body reaction that forms in response to the presence of exogenous suture material introduced during surgery. When this foreign material becomes contaminated with bacterial or fungal organisms, it can lead to the formation of an abscess at the site of the previous surgical procedure [8].
The use of absorbable sutures is preferred for tubal ligations, as they allow the ligated ends to separate naturally over time, thereby reducing the risk of infections and enhancing the effectiveness and permanence of the sterilization [14]. Silk and other multifilament suture materials, on the other hand, permit capillary penetration of bacteria and fluids into the spaces between the filaments, creating an environment that promotes inflammation and increases the risk of both acute and latent infections [15]. This is what is suspected to have happened with the current patient. Post-sterilization infections can manifest within weeks of the procedure or years later. In the present case, the patient developed a TOA three years after undergoing sterilization. Similarly, Weinberger et al. reported three cases of delayed TOA, occurring 8, 15, and 9 years post-sterilization [9]. Suture-related abscesses can present in an even more delayed manner, as demonstrated by Zein et al., who reported a case in which a suture abscess developed 37 years after the original surgical procedure [10].
Efforts to identify predictors for surgical versus antibiotic treatment of TOAs have focused on factors like abscess size, laterality, age, and inflammation severity. Yagur et al. found that bilateral TOAs were more likely to require surgery than unilateral ones, despite no size difference between the two groups. This contrasts with earlier studies, which linked larger abscess size to increased surgical intervention [14]. Among the reviewed cases of TOA, similar to the current patient, surgical intervention was performed in all instances, irrespective of the lesion's laterality or size [1,2,9,11,12]. Currently, the management of TOA typically involves the administration of parenteral broad-spectrum antibiotics. Early diagnosis combined with prompt antibiotic therapy has led to successful medical management in approximately 70–75% of cases. However, the remaining 25–30% of patients require surgical drainage, often utilizing minimally invasive techniques such as laparoscopic drainage or ultrasound-guided transvaginal aspiration and drainage [11]. When managing TOAs, clinicians need to obtain a comprehensive surgical and gynecological history to guide the appropriate therapeutic approach. In cases where a foreign body is suspected or confirmed preoperatively, surgical intervention may offer improved long-term outcomes. A notable limitation of this case report was the absence of microbiological testing. Empirical postoperative treatment was administered based solely on clinical symptoms, which may have limited the ability to definitively identify the underlying pathogen.
Conclusion
Suture-induced TOAs following sterilization may result in considerable morbidity. In these cases, surgical intervention may provide favorable outcomes.
Declarations
Patient consent (participation and publication): Written informed consent was obtained from the patient for publication.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: HMM and NHAA were significant contributors to the conception of the study and the literature search for related studies. SMA, ZMM, OHGH, AGHH, ADS, SOA, LAA, SJJ, and MAA were involved in the literature review, the study's design, and the critical revision of the manuscript, and they participated in data collection. MMA and RMA were involved in the literature review, study design, and manuscript writing. NSS was the radiologist who assessed the case. HMM and MMA confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.
Letter to the Editor
Annotations on Indeterminate Cytology of Thyroid Nodules in Thyroidology: Novi Sub Sole?
Ilker Sengul, Demet Sengul
Letter to the Editor
Dear Editor,
Indeterminate cytology (IC) remains the most challenging issue for health professionals working in thyroidology, thyroidologists [1-4]. We read a great deal of the article by Ali et al [5]. entitled "Clinicopathological Features of Indeterminate Thyroid Nodules: A Single-center Cross-sectional Study," published in 3rd volume, Barw Medical Journal. This study addresses a challenging and crucial issue by examining the characteristics and malignancy rates of thyroid nodules with IC, the most controversial category for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The authors evaluated the clinicopathological features of the thyroid nodules with Category III, TBSRTC, in a single-center cross-sectional study [5].
One of the strengths of the article is its focus on the challenges in managing IC. Ali and colleagues [5] thoroughly examine comprehensive data, including demographic details, medical history, laboratory tests, preoperative imaging, cytologic evaluation, and histopathological diagnosis. The results indicate a notable malignancy rate in Category III, TBSRTC. Furthermore, the study points out that malignancy tended to be younger, while benign nodules were significantly larger than malignant ones. The study also found a significant association between malignant nodules and Thyroid Imaging Reporting and Data System (TI-RADS) categories 4 and 5 and benign with TI-RADS 2 and 3, which findings align with some existing literature, providing valuable insights into the clinical assessment of IC.
However, several limitations of the study warrant consideration. Firstly, its single-center and retrospective design may limit the generalizability of the findings to diverse populations and settings. As the authors acknowledge, the retrospective data collection might have resulted in missing crucial information. While TI-RADS scoring was provided, more specific ultrasound features of thyroid nodules could have been beneficial. Of note, does including or excluding noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), which has been considered a low-risk entity by the current understanding, affect and/or alter the overall results and the assessment of diagnostic performance and study outcome(s)? [2-4] Furthermore, which caliber of the needle had been utilized throughout the study with or without local and/or topical anesthetic agent(s), and would the utilization of thicker or finer needles in order to obtain cytologic samples with or without any local and/or topical anesthesia alter the outcome(s) of this study? [2] Moreover, which edition of TBSRTC has been used for the work and would stress the up-to-date 3rd edition of TBSRTC [3], considering both the novel and crucial subdivisions of category III might affect the study’s relevant outcome(s)? [3,4] Another point of attention is the relatively short data collection period compared to the publication. Finally, while the discussion section compares the findings with various studies in the literature, a more in-depth exploration of the methodological differences and potential discrepancies in results could have been provided. For instance, the conflicting views in the literature regarding the relationship between nodule size and malignancy risk could have been further contrasted with the study's findings. The authors also acknowledge the small sample size as a limitation. For future research, multi-center and prospective studies with detailed imaging, such as elastography and contrast-enhanced sonography, and investigations into the role of molecular markers in thyroid nodules with Category III could improve diagnostic accuracy and potentially reduce unnecessary surgical interventions.
In conclusion, this study significantly contributes to the evaluation of IC in thyroidology despite its limitations. However, considering the noted limitations, further research with more comprehensive and methodologically robust studies in this area is warranted. This issue merits further investigation.
Sincerely,
The Barw Medical Journal is an online multidisciplinary, open-access journal with an extensive and transparent peer review process that covers a wide range of medical aspects. This Journal offers a distinct and progressive service to assist scholars in publishing high-quality works across a wide range of medical disciplines and aspects, as well as delivering the most recent and reliable scientific updates to the readers.
To maintain the quality of the Barw Medical Journal’s contents, a double-blind, unbiased peer-review process has been established and followed to only publish works that adhere to the scientific, technical, ethical, and standard guidelines. Barw Medical Journal focuses especially on the research output from developing countries and encourages authors from these regions of the world to contribute actively and effectively to the construction of medical literature.
We accept original articles, systematic reviews, meta-analyses, review articles, case reports and case series, editorials, letter to editors, and brief reports/commentaries/perspectives/short communications/correspondence. The journal mainly focuses on the following areas:
- Evidence-based medicine.
- public health and healthcare policies.
- Current diseases’ diagnosis and management.
- Biomedicine, including physiology, genetics, molecular biology, pharmacology, pathology, and pathophysiology.
- Clinical and applied studies like surgery and innovated techniques, internal medicine, gastroenterology, obstetrics, gynecology, pediatrics, and otorhinolaryngology.
The Barw Medical Journal is an online multidisciplinary, open-access medical journal with an extensive and transparent peer review process that covers a wide range of medical aspects including clinical and basic science.
Latest Articles

Defining the Scientist: A Consensus-Based Approach
João Gama, Marko Mladineo, Shelina Bhamani, Behzad Shahmoradi, Victoria Samanidou, Alexander S....
Abstract
Introduction
The term “scientist” lacks a universally accepted definition, reflecting the evolving, interdisciplinary nature of scientific work and posing challenges for recognition, communication, and policy. This study aims to develop consensus-based definitions of the term “scientist” by engaging experienced scholars across diverse fields.
Methods
This study involved 156 scholars, each with at least 1,000 citations, recruited via convenience sampling. Fourteen scientist definitions, derived from literature and expert input, were assessed using a nine-point Likert scale via a structured google forms survey. The sample size was calculated using G*power (effect size = 0.5, power = 0.95), requiring at least 80 participants. Content Validity Index (CVI) was used for analysis. Definitions scoring ≥0.78 were accepted and included for final analysis, 0.70–0.78 were revised and re-evaluated, and <0.70 were excluded. Participation was voluntary and anonymous, ensuring ethical compliance and confidentiality.
Results
Of the 14 proposed definitions, six (42.9%) were excluded (CVI < 0.70), seven (50.0%) were accepted (CVI > 0.78), and one (7.1%) underwent revision (CVI 0.70–0.78). The highest-rated definitions were refined into two consensus-based versions: a short definition (“A scientist is a person who conducts research”) and a detailed one emphasizing hypothesis formulation and knowledge dissemination. Final validation yielded CVIs of 0.82 and 0.84, respectively, confirming strong expert agreement on both definitions.
Conclusion
This study developed two validated definitions of “scientist” emphasizing systematic research and knowledge dissemination. These definitions clarify the concept of scientific identity, providing a flexible yet rigorous framework applicable across academic, interdisciplinary, and policy-making contexts.
Introduction
The term "scientist" has undergone significant transformation since its inception, reflecting the dynamic nature of scientific inquiry and the evolving landscape of knowledge. This lack of clarity stems from the diverse roles and contributions of individuals in scientific fields, the evolving nature of research, and the interdisciplinary scope of modern science. Historically, figures such as Galileo and Newton were regarded as natural philosophers, a reflection of an earlier framework for knowledge production that has evolved alongside modern scientific advancements. Before twentieth century, the term "scientist" was commonly referred to as a "man of science," "natural philosopher," or by various other designations [1,2].
In contemporary contexts, scientists operate across a broad spectrum of fields, including medicine, biology, chemistry, physics, and social sciences, each employing methodologies tailored to their specific inquiries. For instance, biologists may design experiments to test hypotheses about living organisms, while social scientists might use qualitative methods to explore human behavior [3]. The Science Council defines a scientist as an individual who methodically collects and applies research and evidence to develop hypotheses, performs experiments, and shares results to advance knowledge in their field [4]. While National Cancer Institute defines a scientist as an individual with a background in science, particularly someone actively engaged in a specific area of research [5]. This diversity in practices underscores the challenge of defining "scientist" in a way that captures the breadth of their contributions.
The plurality of definitions extends to global organizations and frameworks. For example, the United Nations Educational, Scientific, and Cultural Organization highlights the critical role of scientists in addressing global challenges and promoting sustainable development. This definition broadens the scope to include individuals working in multidisciplinary teams or applying scientific knowledge to public policy and societal issues. Similarly, some academic discussions focus on the characteristics of a scientist, such as curiosity, skepticism, and a commitment to evidence-based conclusions, rather than formal qualifications or job titles [6].
Unlike well-defined professions such as medicine or engineering, where specific educational pathways and professional titles (e.g., "doctor" or "engineer") confer clear identities, the term "scientist" lacks a universally recognized credentialing system. This absence can lead to underrepresentation or misrepresentation of scientific expertise, especially in interdisciplinary and collaborative contexts [7]. For example, the growing integration of data science in biology or physics illustrates the importance of understanding who qualifies as a scientist to ensure effective communication and collaboration among stakeholders. The absence of a standardized definition poses practical challenges for scientific communication, policymaking, and inclusivity. This study aims to address this gap by engaging scholars across disciplines to develop a consensus-based definition of "scientist." By recognizing the diverse and interdisciplinary contributions of scientists, such a definition could enhance collaboration, improve public understanding, and inform policies that support the scientific community.
Methods
Study design and participants
A total of 156 scholars (out of 300 invited) participated in this study. Eligibility was determined based on the scholars' substantial academic expertise, evidenced by the achievement of at least 1,000 citations within their respective fields. This criterion ensured that participants had significant research experience and were highly qualified to contribute to the formulation of a consensus-based definition of "scientist." Participants were recruited through a convenience sampling method, and data were collected via a structured survey administered through google forms. While convenience sampling was used due to the accessibility of high-citation scholars, efforts were made to ensure disciplinary diversity to mitigate potential bias. Personalized invitations were sent via email to each scholar to facilitate their inclusion in the study.
Sample size determination
The sample size was determined using G*power statistical software (version 3.1.9.7), employing a two-tailed goodness of fit test with an effect size of 0.5, an alpha error probability of 0.05, and a statistical power of 0.95. According to the calculations, a minimum of 80 participants were required to achieve statistically valid results. Consequently, 156 scholars were recruited to participate in the study, ensuring robust representation and adequate statistical power.
Data collection
Fourteen proposed definitions of "scientist," curated from existing literature and expert contributions, were presented to the enrolled scholars for evaluation (Table 1). Each definition included a Likert scale with nine response options, ranging from "strongly agree" to "strongly disagree." Responses were systematically recorded and compiled in an Excel sheet for subsequent analysis. This process facilitated the systematic capture of scholarly consensus on each definition.
Proposed Definitions | Options | ||||||||
A person studying or has expert knowledge of one or more natural or physical sciences. (Oxford Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
An expert who studies or works in one of the sciences. (Cambridge Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person learned in science and especially natural science. (Merriam-Webster Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A scientist is someone who systematically gathers and uses research and evidence, to make hypotheses and test them, to gain and share understanding and knowledge. (Science Council) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A scientist is someone who has studied science and whose job is to teach or do research in science. (Collins Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
An expert in science, especially one of the physical or natural sciences. (Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A scientist is a person with some kind of knowledge or expertise in any of the sciences. (Vocabulary dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person who is trained in a science and whose job involves doing scientific research or solving scientific problems. (Britannica Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person who has studied science, especially one who is active in a particular field of investigation. (National Cancer Institute) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
Someone who works or is trained in science. (Longman Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person whose profession is investigating in one of the natural sciences. (Your Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A person who is engaged in and has expert knowledge of a science. (Free Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
Someone whose job or education is about science. (LanGeek Dictionary) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
A scientist is a person who researches to advance knowledge in an area of the natural sciences. (Wikipedia) |
Strongly Disagree |
Moderately Disagree |
Disagree |
Slightly Disagree |
Undecided |
Slightly Agree
|
Moderately Agree |
Agree |
Strongly Agree |
Data analysis
The Content Validity Index (CVI) was employed to assess the relevance and agreement of the definitions. Definitions with a CVI below 0.70 were excluded, as they failed to meet the minimum threshold for consensus. Definitions with a CVI between 0.70 and 0.78 underwent a second round of evaluation, with refined wording sent back to the same scholars for further review. Definitions achieving a CVI above 0.78 were deemed sufficiently valid for inclusion in the final analysis [8]. These definitions formed the foundation for the development of a unified, consensus-based definition of "scientist."
Ethical considerations
Participation in the study was entirely voluntary, and all responses were anonymized to preserve participant confidentiality.
Results
Initially, out of the 14 proposed definitions of the term "scientist," six (42.9%) received a CVI score below the threshold of 0.70 and were consequently excluded from further consideration. In contrast, seven definitions (50.0%) demonstrated strong content validity with CVI scores equal to or exceeding 0.78 and were therefore retained for subsequent synthesis and analysis. Only one definition (7.1%) fell within the intermediate range, with a CVI between 0.70 and 0.78 (Table 2).
Proposed Definition |
Agree |
Disagree |
Undecided |
CVI |
Status |
Science Council Definition |
146 |
8 |
2 |
0.94 |
Accepted |
Britannica Dictionary Definition |
136 |
16 |
4 |
0.87 |
Accepted |
Cambridge Dictionary |
130 |
20 |
6 |
0.83 |
Accepted |
Wikipedia Definition |
125 |
27 |
4 |
0.80 |
Accepted |
Free Dictionary Definition |
124 |
25 |
7 |
0.79 |
Accepted |
National Cancer Institute Definition |
124 |
25 |
7 |
0.79 |
Accepted |
Collins Dictionary Definition |
122 |
31 |
3 |
0.78 |
Accepted |
Oxford Dictionary Definition |
120 |
31 |
5 |
0.77 |
Revised |
Longman Dictionary Definition |
104 |
42 |
10 |
0.67 |
Excluded |
Your Dictionary Definition |
103 |
48 |
5 |
0.66 |
Excluded |
Dictionary (generic) Definition |
91 |
52 |
13 |
0.58 |
Excluded |
Vocabulary dictionary Definition |
88 |
58 |
10 |
0.56 |
Excluded |
Merriam-Webster Dictionary Definition |
81 |
64 |
11 |
0.52 |
Excluded |
LanGeek Dictionary Definition |
79 |
67 |
10 |
0.51 |
Excluded |
CVI: Content Validity Index, CVI Thresholds: Accepted: ≥ 0.78, Revised: 0.70–0.78, Excluded: < 0.70 |
Through a rigorous, iterative evaluation process involving expert feedback, the definitions with the highest CVI scores (those above 0.78) were integrated and refined into two distinct, consensus-based definitions of the term "scientist." The first was a concise definition: “A scientist is a person who conducts research.” The second was a more comprehensive and elaborated definition: “A scientist is someone who systematically conducts or gathers and uses research to formulate hypotheses and test them, in order to gain and disseminate understanding and knowledge.”
These two final definitions were subsequently circulated among the panel of scholars for a second round of evaluation, during which they were asked to rate the definitions for content validity. The short definition received a CVI of 0.82, while the more detailed definition attained a slightly higher CVI of 0.84, reflecting strong agreement among the experts. Although no additional formal qualitative feedback was solicited at this stage; minor wording adjustments were made based on informal suggestions received during this validation round.
Discussion
The role of a scientist extends far beyond the stereotypical image of an individual in a white coat working exclusively in a laboratory setting. Careers grounded in scientific expertise are remarkably diverse, encompassing domains such as research, education, industry, and regulatory affairs. The Science Council categorizes scientists into 10 different types, highlighting the diversity of scientific roles beyond the stereotypical lab-based researcher. It includes types such as experimental scientists, theoretical scientists, data scientists, and more, reflecting the broad spectrum of scientific work today [9]. Definitions of the term “scientist” vary, yet they generally converge on the principles of systematic inquiry, evidence-based investigation, and the pursuit of knowledge across various disciplines. For instance, the Oxford Advanced Learner’s Dictionary and the Britannica Dictionary emphasize formal training and research functions, typically within the natural sciences such as biology, chemistry, or physics [10,11]. In contrast, contemporary perspectives, such as those discussed by the American Association for the Advancement of Science in 2024, recognize a broader spectrum of scientific engagement, encompassing both professional researchers and individuals committed to understanding the world through observation, experimentation, and analysis [12]. In light of this diversity, the present study aimed to clarify and formalize the definition of a "scientist" through expert consensus. Two definitions were developed: a concise definition “A scientist is a person who conducts research”, and a comprehensive definition “A scientist is someone who systematically conducts or gathers and uses research to formulate hypotheses and test them, in order to gain and disseminate understanding and knowledge.” These definitions encapsulate the core activities and guiding principles of scientific inquiry, emphasizing both methodological rigor and the essential role of knowledge dissemination across disciplines.
A key finding of this study lies in its recognition of the evolving tension between disciplinary specialization and the increasing importance of interdisciplinary collaboration. As highlighted in contemporary analyses of interdisciplinary research and development, scientists now frequently operate at the intersection of multiple fields, such as nanomedicine, where the diversity and dissimilarity of collaborators’ knowledge can significantly enhance research productivity [13]. The concise definition, "A scientist is a person who conducts research" captures this shift by avoiding constraints tied to specific disciplinary boundaries. In contrast, the more detailed definition explicitly incorporates the systematic formulation and testing of hypotheses, along with the dissemination of knowledge, thereby reinforcing the structured and communicative nature of scientific inquiry. These elements align closely with UNESCO’s 2019 call for stronger science-society engagement and underscore the ethical responsibilities inherent in modern scientific practice [14].
The study’s findings also contribute to ongoing debates surrounding professional identity within the scientific community. In contrast to regulated professions such as medicine, the absence of a universal credentialing system for scientists complicates formal recognition, particularly in non-academic and interdisciplinary contexts. This ambiguity is reflected in the National Cancer Institute’s pragmatic definition of a scientist, which emphasizes active participation in research rather than reliance on formal titles or qualifications [15]. By anchoring the term “scientist” in core research activities rather than occupational labels, the consensus-based definitions proposed in this study offer a more inclusive framework. This approach accommodates emerging roles in fields such as data science and applied research, thereby addressing the risk of under recognition in collaborative and cross-sector environments.
The dual definitions, concise and comprehensive, offer flexibility for different contexts, a strategy aligned with the Science Council’s emphasis on methodological diversity [4]. The detailed definition’s focus on systematic inquiry and dissemination aligns with studies of interdisciplinary science, where “impassioned commitment” to shared goals drives innovation [13]. Simultaneously, the availability of a concise definition enhances clarity in public discourse and science communication, while the more detailed version provides the specificity necessary for institutional contexts such as policy development, research funding, and professional accreditation.
Notably, the study’s findings also challenge enduring stereotypes of the “lone genius” scientist by highlighting the inherently collaborative and iterative nature of scientific practice. Contemporary frameworks, such as those emerging from computational biology, suggest that scientific identity is increasingly dynamic, pluralistic, and shaped by collective knowledge production [16]. The process undertaken in this study, involving successive refinement and expert validation of definitions, closely mirrors the recursive logic of the scientific method itself. This methodological alignment is particularly salient in fields like nutritional epidemiology, where the replication of findings remains a persistent challenge and iterative inquiry is essential for refining evidence [17].
Despite the methodological rigor and expert involvement, several limitations should be acknowledged. First, the study employed convenience sampling, which may introduce selection bias and limit the generalizability of the findings. Although participants were selected based on a minimum citation threshold to ensure scholarly expertise, this criterion may have inadvertently excluded emerging researchers or experts with significant practical contributions who have not yet achieved high citation metrics. Second, the use of an online survey format may have constrained participant engagement, as scholars with limited availability or preference for alternative formats may have been underrepresented. Additionally, response bias cannot be ruled out, as those with a particular interest in the topic or in defining scientific identity may have been more inclined to participate, potentially skewing the results. Future refinements of the definition should also consider voices from non-academic scientific contexts including those in industry, policy, and community-based science who are increasingly central to addressing complex global challenges.
Conclusion
By engaging experienced scholars across disciplines, this study establishes two validated definitions of “scientist” that emphasize systematic research activity and knowledge dissemination. These definitions offer a structured yet adaptable framework for understanding scientific identity, balancing clarity with flexibility. They help address the ambiguity surrounding the term “scientist,” providing a foundation for improved communication, interdisciplinary collaboration, and evidence-informed policy development. Importantly, they remain open to future refinement as scientific practice continues to evolve.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: JG, MM, SB, BS, VS, ASN, SHM, HAH, AGH, ADS, RAK, WRR, AB, GB, SS, SN, CJ, PL, MSS, ZK, MC, AM, SK, FCT, FB, FRK, MAM, AA, VK, DH, PM, VRM, MSA, EA, and RV were significant contributors to the conception of the study, voting for the items. FHK, BAA, and AMM were involved in the literature review, manuscript writing, and data analysis and interpretation. FHK and AMM Confirmation of the authenticity of all the raw data. All authors have read and approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Suture-Induced Tubo-Ovarian Abscess: A Case Report with Literature Review
Huda M. Muhammad, Nahida Hama Ameen Ahmed, Sawen M. Ahmed, Zhiyan M. Mohammed, Meer M....
Abstract
Introduction
Suture is an underreported cause for tubo-ovarian abscess (TOA) that can cause significant morbidity. This report describes a case of TOA arising from a silk suture three years after bilateral tubal ligation.
Case presentation
A 38-year-old woman with a history of tubal ligation presented with persistent pelvic pain and fever. Imaging revealed a suspicious left adnexal mass with features concerning for malignancy or abscess. Surgical exploration revealed a TOA adherent to surrounding structures, containing a retained silk suture from prior surgery. The abscess and suture were removed, and histopathology confirmed chronic inflammation without malignancy. The patient underwent additional procedures for thorough management, including polypectomy and contralateral tubal ligation.
Literature Review
A total of nine cases of TOAs and suture-induced abscesses were reviewed. Of these, seven were TOAs, six of which occurred postoperatively. Three cases developed following tubal ligation procedures. The abscesses ranged in size from 1 to 7.6 cm. The interval between the presumed inciting event and abscess detection varied widely, with one case presenting more than three decades after surgery. Isolated microorganisms included Escherichia coli, Streptococcus pyogenes, and Peptostreptococcus anaerobius. All patients underwent surgical intervention via various approaches, and several also received adjunctive antibiotic therapy.
Conclusion
Suture-induced TOA following sterilization may result in considerable morbidity, and surgical intervention may provide favorable outcomes.
Introduction
Pelvic inflammatory disease (PID) is a polymicrobial infection resulting from the ascent of pathogens from the cervix or vagina to the upper genital tract. It is most commonly caused by Chlamydia trachomatis and Neisseria gonorrhoeae, which together are responsible for approximately 60–75% of cases. Once these pathogens ascend, they can infect the endometrium, fallopian tubes, ovaries, and surrounding pelvic structures, triggering an inflammatory response [1].
A tubo-ovarian abscess (TOA) is a severe complication of PID, characterized by the formation of a purulent abscess involving the uterus, fallopian tubes, and ovaries [2]. This condition primarily affects women of reproductive age, with the highest incidence occurring in the fourth decade of life. Approximately 4.4% of sexually active women have a history of PID, placing them at increased risk for TOA development [3]. Given its non-specific clinical presentation, TOA can be challenging to diagnose, often requiring differentiation from other acute abdominal and pelvic conditions. The differential diagnosis includes ovarian torsion, ectopic pregnancy, appendicitis, gastroenteritis, constipation, and urinary tract infection, all of which can present with overlapping symptoms such as pelvic pain, fever, nausea, and gastrointestinal discomfort [2].
Although TOAs are commonly associated with PID, they can also develop from less common etiologies, such as the presence of surgical sutures. Reports of TOAs linked to surgical sutures remain scarce in the literature. This report highlights a unique case of a TOA that developed due to a silk suture three years after the patient had undergone bilateral tubal ligation, a procedure intended for permanent female sterilization. This case underscores the need for awareness of non-infectious etiologies in the differential diagnosis of TOAs, particularly in patients without a recent history of PID. The report was written according to the CaReL guidelines, and unreliable sources were excluded [4,5].
Case Presentation
Patient information
A 38-year-old female presented with a one-month history of worsening, persistent pelvic pain. Her medical history was unremarkable, and her surgical history included bilateral tubal ligation performed three years earlier.
Clinical findings
Physical examination revealed a high temperature, tenderness in the left suprapubic area, and the presence of an immobile pelvic mass upon palpation.
Diagnostic assessment
A pelvic ultrasound (US) showed a left-sided heterogeneous lesion measuring 44 x 30 mm. The mass was a vascular solid lesion with calcifications, exhibiting indistinct margins and evidence of invasion into the adjacent peritoneum and the left rectus abdominis muscle. Doppler imaging demonstrated high vascularity, with a score of 3-4. These characteristics were highly suspicious for a desmoid tumor or a primary peritoneal tumor; however, direct invasion of the left ovary could not be excluded (Figure 1). Computed tomography (CT) with IV contrast revealed a 6 x 4 x 3 cm, multilocular mass located in the left lower abdomen, arising from the left adnexa and attached to both the uterus and left ovary. The mass extended into the posterior aspect of the left rectus muscle. It was in proximity to the left inferior epigastric artery and a loop of small intestine, though no direct invasion was observed. Surrounding fat stranding raised the possibility of infection, such as a TOA, though malignancy could not be excluded. Mild pelvic free fluid was noted, and no suspicious lymph nodes were identified. The other abdominal organs, including the liver, spleen, pancreas, kidneys, and adrenal glands, appeared normal. The laboratory results revealed the following: Carcinoembryonic Antigen (CEA) was 0.471 ng/ml (normal range: 0-5 ng/ml), Cancer Antigen 125 (Ca125) was 33.6 IU/ml (normal range: <35 IU/ml), and Carbohydrate Antigen 19-9 (CA 19-9) was 5.73 IU/ml (normal range: <33 IU/ml), all of which fell within the normal reference ranges. Serum C-reactive protein (CRP) level was slightly elevated at 8.38 mg/L, above the normal range of <5.0 mg/L.
Therapeutic intervention
To ensure accurate diagnosis and appropriate management, consultations were held with oncology and gastrointestinal surgery specialists. After a thorough evaluation, an explorative laparoscopy was planned. During the procedure, a TOA was found, firmly adherent to the omentum and anterior abdominal wall. The abscess was carefully aspirated using suction, and a biopsy was taken for frozen section analysis. The preliminary histopathology report indicated inflammation and fibrosis, confirming the lesion's nature. As the surgery progressed, an unexpected finding was discovered: an unabsorbable silk suture embedded within the abscess. This suture, most likely a remnant from her previous procedure, was carefully excised along with the surrounding fibrotic tissue and sent for further histopathological analysis. To reduce the risk of recurrence, the contralateral fallopian tube was also removed and securely ligated. In addition to addressing the abscess and suture, a hysteroscopy and polypectomy were performed to ensure thorough treatment. The procedure was completed successfully, with all abscess material and pathological tissues removed. The histopathological examination revealed a hyperplastic endometrial polyp with background secretory changes consistent with progestin exposure, without evidence of atypia or malignancy. The left tubal mass showed chronic nonspecific salpingitis, and the attached omentum exhibited severe acute-on-chronic inflammation with fibrosis, consistent with an abscess wall. The right fallopian tube revealed para-tubal cysts and Walthard cell rests, while the right ovarian cyst was identified as a hemorrhagic corpus luteum. No malignancy was detected in any of the submitted specimens.
Follow-up
Post-operative treatment included intravenous Flagyl (Metronidazole) and Claforan (Cefotaxime), and there were no complications. After six months of follow-up, no significant complication was observed.
Discussion
The development of PID and TOAs has long been considered a rare complication of tubal sterilization. The most frequently isolated pathogens of these abscesses include Escherichia coli and Bacteroides species. Additional identified organisms in these abscesses comprise Peptostreptococcus, Peptococcus, and aerobic Streptococcus species [1]. Although rare, infections involving Staphylococcus species and Burkholderia pseudomallei have also been reported in the literature [6,7]. Among the reviewed cases, six patients developed TOAs following surgical procedures. Among the cases in which microbiological data were reported, Escherichia coli was identified in two patients, Streptococcus pyogenes in another two, and Peptostreptococcus anaerobius in one (Table 1) [1,2,8-12].
Author/year |
Age |
Sex |
Pregnancy |
Gynecological history |
Surgical history |
Comorbidities |
Symptoms |
Location |
Mass size (cm)* |
Treatment |
Presence of Foreign Body |
Identified pathogens |
Pathological findings |
Outcome |
Sun et al./2024 [9] |
18 |
M |
N/A |
N/A |
Mucocele excision |
None |
Soft and tender nodule |
Lower lip |
1 |
Total excision of the lesion |
Silk suture |
N/A |
Acute and chronic inflammation & multinucleated foreign body giant cells |
Recovery |
Linck et al./2023 [16] |
51 |
F |
3 |
Abnormal uterine bleeding |
D&C hysteroscopy & polypectomy |
None |
Heavy menstrual bleeding, fever & abdominal pain |
Right posterior pelvic area |
5.1 |
Antibiotic, Interventional radiology percutaneous drainage, laparotomy, total hysterectomy & bilateral salpingo-oophorectomy |
None |
Escherichia coli |
Acute inflammation & acute serositis |
Recovery |
Campbell et al./2021 [2] |
15 |
F |
None |
Unremarkable |
Appendectomy |
None |
Abdominal pain |
Right adnexa |
7.1 |
Laparoscopy, drainage of the right pyosalpinx, removal of the stump appendix & antibiotics |
Stump appendix |
None |
Necrotic material with acute inflammatory debris |
Recovery |
Zein et al./2021 [13] |
58 |
M |
N/A |
N/A |
Retinal detachment repair |
HIV infection |
Swollen conjunctivae, bulbar injection, and tearing |
Left eye |
1 |
Corticosteroids, excision of the lesion, & Amniotic membrane transplantation |
Silk suture |
None |
Chronic inflammation |
Recovery |
Naredi et al./2021 [15] |
45 |
F |
2 |
Unremarkable |
|
Hypertension & obesity |
Lower abdominal pain |
Left adnexa |
7.6 |
Intravenous antibiotics, drainage, laparotomy & left salpingo-ophrectomy |
N/A |
N/A |
Inflammation |
Recovery |
Solt et al./2010 [1] |
24 |
F |
3 |
Menarche at 12 & irregular menstrual cycles |
Colectomy, appendectomy, cesarean deliveries, elective abortion, lami nectomy, breast augmentation & Essure placement |
Mitochondrial neurogastrointestinal encephalopathy, progressive gastrointestinal dysmotility, symmetric polyneuropathy, asymptomatic leukoencephalopathy, asthma, antiphospholipid syndrome, supraventricular tachycardia, renal lithiasis, and bipolar disorder. |
Right lower quadrant pain, nausea, and vomiting |
Right adnexa |
N/A |
Laparoscopy, total abdominal hysterectomy & antibiotics |
Essure microinserts |
Streptococcus pyogenes |
N/A |
Developed acute peritonitis |
Weinberger et al./1996 [12] |
34 |
F |
3 |
PID |
Bilateral tubal ligation |
None |
Lower abdominal pain, fever |
Right adnexa |
6.1 |
Antibiotics, adhesiolysis, total abdominal hysterectomy, right salpingo-oophorectomy, & vaginal T-tube drain placement |
Silastic band |
Peptostreptococcus anaerobius |
Acute necrotizing oophoritis |
Recovery |
37 |
F |
2 |
Unremarkable |
Bilateral tubal ligation |
None |
bilateral lower quadrant pain, fever, tenderness, vaginal spotting & discharge |
Left adnexa |
4 |
Laparoscopy, laparotomy, bilateral salpingectomies, right oophorectomy, endometrial biopsy, incidental appendectomy & antibiotics |
None |
Streptococcus pyogenes |
Acute suppurative salpingitis, ovarian cortex hemorrhage. Proliferative phase endometrium |
Recovery |
|
38 |
F |
2 |
Unremarkable |
Tubal fulguration, kidney transplant |
Systemic lupus erythematosus, immunocompromised |
bilateral lower quadrant pain, fever, tenderness & yellow discharge |
Ovaries |
4.4 |
Laparotomy, bilateral distal salpingectomy & antibiotics. |
None |
Escherichia coli |
Acute suppurative salpingitis & paratubal abscess formation |
Recovery |
|
M: Male, F: Female, N/A: Not Available, D&C: Dilation and curettage, HIV: Human immunodeficiency virus, PID: Pelvic inflammatory disease *Only the largest dimension is reported in the table. |
Although the exact incidence of upper genital tract infections following surgical sterilization remains unknown, traditional gynecologic literature emphasizes that such occurrences are exceedingly rare. However, other data suggest that the upper genital tract may remain vulnerable to infection even after sterilization. A study found that 6% of hospitalized PID cases involved patients with prior sterilization, with symptoms including systemic toxicity and requiring surgical evaluation in some instances [13].
The postoperative infection in the current patient was caused by the use of silk sutures for tubal ligation. This resulted in the development of a suture abscess, which is a type of foreign body reaction that forms in response to the presence of exogenous suture material introduced during surgery. When this foreign material becomes contaminated with bacterial or fungal organisms, it can lead to the formation of an abscess at the site of the previous surgical procedure [8].
The use of absorbable sutures is preferred for tubal ligations, as they allow the ligated ends to separate naturally over time, thereby reducing the risk of infections and enhancing the effectiveness and permanence of the sterilization [14]. Silk and other multifilament suture materials, on the other hand, permit capillary penetration of bacteria and fluids into the spaces between the filaments, creating an environment that promotes inflammation and increases the risk of both acute and latent infections [15]. This is what is suspected to have happened with the current patient. Post-sterilization infections can manifest within weeks of the procedure or years later. In the present case, the patient developed a TOA three years after undergoing sterilization. Similarly, Weinberger et al. reported three cases of delayed TOA, occurring 8, 15, and 9 years post-sterilization [9]. Suture-related abscesses can present in an even more delayed manner, as demonstrated by Zein et al., who reported a case in which a suture abscess developed 37 years after the original surgical procedure [10].
Efforts to identify predictors for surgical versus antibiotic treatment of TOAs have focused on factors like abscess size, laterality, age, and inflammation severity. Yagur et al. found that bilateral TOAs were more likely to require surgery than unilateral ones, despite no size difference between the two groups. This contrasts with earlier studies, which linked larger abscess size to increased surgical intervention [14]. Among the reviewed cases of TOA, similar to the current patient, surgical intervention was performed in all instances, irrespective of the lesion's laterality or size [1,2,9,11,12]. Currently, the management of TOA typically involves the administration of parenteral broad-spectrum antibiotics. Early diagnosis combined with prompt antibiotic therapy has led to successful medical management in approximately 70–75% of cases. However, the remaining 25–30% of patients require surgical drainage, often utilizing minimally invasive techniques such as laparoscopic drainage or ultrasound-guided transvaginal aspiration and drainage [11]. When managing TOAs, clinicians need to obtain a comprehensive surgical and gynecological history to guide the appropriate therapeutic approach. In cases where a foreign body is suspected or confirmed preoperatively, surgical intervention may offer improved long-term outcomes. A notable limitation of this case report was the absence of microbiological testing. Empirical postoperative treatment was administered based solely on clinical symptoms, which may have limited the ability to definitively identify the underlying pathogen.
Conclusion
Suture-induced TOAs following sterilization may result in considerable morbidity. In these cases, surgical intervention may provide favorable outcomes.
Declarations
Patient consent (participation and publication): Written informed consent was obtained from the patient for publication.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: HMM and NHAA were significant contributors to the conception of the study and the literature search for related studies. SMA, ZMM, OHGH, AGHH, ADS, SOA, LAA, SJJ, and MAA were involved in the literature review, the study's design, and the critical revision of the manuscript, and they participated in data collection. MMA and RMA were involved in the literature review, study design, and manuscript writing. NSS was the radiologist who assessed the case. HMM and MMA confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Renal Ewing Sarcoma: A Case Report and Literature Review
Rebaz M. Ali, Bnar Sardar Saida, Saman S. Fakhralddin, Ari M. Abdullah, Hadeel Adnan Yasseen,...
Abstract
Introduction
Primary renal Ewing sarcoma is an extremely rare and aggressive tumor, representing less than 1% of all renal tumors. This case report contributes valuable insights into the challenges of diagnosing and managing this rare malignancy, particularly when it presents with atypical symptoms.
Case presentation
A 30-year-old female presented with intermittent grassy green-colored urine, later turning into red, with a headache and no abdominal pain. Clinical examination revealed elevated blood pressure. Imaging studies, including ultrasound and computed tomography scans, identified a large, heterogeneous mass in the left kidney with invasion into the renal vein and lymph nodes, leading to a staging of T3N1M0. The patient underwent a left radical nephrectomy, with pathology confirming a Grade 2 primary Ewing sarcoma / primitive neuroectodermal tumor of the kidney. Despite aggressive treatment with adjuvant chemotherapy, stable metastatic deposits persisted, indicating ongoing active disease.
Literature review
Ewing sarcoma typically occurs in bones but can occasionally arise in solid organs such as the kidney. Most patients present with non-specific symptoms, and the disease often remains undiagnosed until it has metastasized. Current treatment involves multimodal therapy, including surgery and chemotherapy, but prognosis remains poor, especially in cases with metastasis.
Conclusion
This case underscores the complexity of diagnosing and treating primary renal Ewing sarcoma. Persistent metastasis despite treatment highlights the need for vigilant monitoring. Further genetic profiling could enhance understanding and management of this rare condition.
Introduction
Sarcomas are a diverse group of malignant tumors originating from mesenchymal tissues, and they can arise in virtually any part of the body, often posing diagnostic and therapeutic challenges due to their rarity and varied presentation. Recent reports have highlighted unusual locations and rare co-occurrences of sarcomas, emphasizing the need for heightened clinical suspicion when encountering atypical masses [1,2].
Ewing sarcoma (EWS) is a highly aggressive tumor typically found in the bones of children and young adults. However, it can occasionally originate from solid organs that contain neuroendocrine cells, such as the kidney, lungs, heart, bladder, small intestine and parotid glands, with approximately 6% of cases being extraosseous [3-5]. Ewing sarcoma is classified as a small round cell sarcoma characterized by gene fusions between a member of the Ewing Sarcoma Breakpoint Region 1 (EWSR1) gene family and a member of the E26 transformation-specific sequence (ETS) family of transcription factors [6]. Primary EWS of the kidney is an extremely rare tumor, comprising less than 1% of all renal tumors, with fewer than 200 cases reported globally. However, the precise number of cases is challenging to determine, as these tumors are not always accurately diagnosed. [3,7]. It is a highly aggressive tumor that primarily affects young individuals, with a particular prevalence among males [8]. Patients typically present with an abdominal mass or renal symptoms such as abdominal pain and hematuria. Due to its hidden intra-abdominal location, the tumor often grows to a significant size before being detected [9]. Primary kidney EWS metastasizes to the bone, lungs, and lymph nodes. Its clinical presentation is not specific, and it can resemble other renal tumors in histologic appearance [10]. In this case, a 30-year-old female presented with primary renal EWS, exhibiting unusual symptoms such as grassy green to red urine. The references’ eligibility has been verified [11]. The report is structured in accordance with CaReL guidelines and includes a recent review of the literature [12].
Case Presentation
Patient information
A 30-year-old female presented with a chief complaint of intermittent grassy green-colored urine, which later became red. She also experienced headaches but reported no fever, vomiting, or abdominal pain. Her past medical history was unremarkable, though she had undergone the removal of an ovarian cyst on the left side just one month prior to her diagnosis.
Clinical findings
On clinical examination, there was no abdominal tenderness or other systemic abnormalities. Her vital signs were normal except for elevated blood pressure, recorded at 120/100 mmHg.
Diagnostic approach
Diagnostic investigations included abdominal ultrasonography, which revealed an enlarged and irregularly shaped left kidney with mild pelvicalyceal system dilation. A large heterogeneous iso to hyper-echoic mass measuring 11x10x8 cm was identified, extending from the mid to lower pole of the kidney and displaying internal vascularity. A subsequent computed tomography (CT) scan of the abdomen confirmed the presence of a large heterogeneous solid lesion at the lower pole of the left kidney, measuring approximately 12x10x8.5 cm. The mass showed heterogeneous enhancement after contrast administration and extended into the renal pelvis and lower calyx, with associated mild dilation. The scan also revealed invasion of the retroaortic right renal vein and two enlarged locoregional lymph nodes, the largest measuring 6 mm in short axis. These findings were indicative of a malignant renal tumor, staged as T3N1M0 (Figure 1).
Therapeutic interventions
The patient underwent a left radical nephrectomy. Histopathological examination confirmed the diagnosis of a primary EWS /primary neuroectodermal tumor of the kidney, classified as Grade 2, with a mitotic activity of 6-8 per 10 high-power fields (Figure 2). The tumor, which measured 10 cm at its greatest dimension, was located in the lower pole of the left kidney and was unifocal.
There was no evidence of tumor necrosis, lymphovascular invasion, or positive surgical margins, though one out of eight examined lymph nodes tested positive for metastasis. The final pathological stage was pT1pN1M0. Immunohistochemistry showed that the tumor cells were positive for CD99, while other markers such as AE1/AE3, CD45, desmin, S100, synaptophysin, CD31, and WT1 were negative. The patient subsequently received adjuvant chemotherapy with the VAC-IE regimen (vincristine, doxorubicin, cyclophosphamide-ifosfamide, etoposide).
Follow-up
One month after the operation, a magnetic resonance imaging (MRI) of the abdomen revealed a 50x20 mm elongated, well-defined area of bright signal on T1 and T2 imaging, with no diffusion-weighted imaging restriction or enhancement, overlapping the left psoas muscle. This finding was suggestive of a postoperative hematoma. A high-resolution CT scan of the chest was normal. Three months later, a fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed multifocal areas of FDG avidity extending from the lateral aspect of the crus of the left hemidiaphragm and left psoas muscle, with a maximum standardized uptake value of 6.53. The largest hypermetabolic lesion measured 1.2x1.1 cm. A laparoscopic biopsy of a nodule on the small bowel serosa and psoas muscle showed benign findings with no evidence of malignancy.
Over the course of the follow-up, two additional FDG-PET scans were performed, three months apart. The latest scan revealed a stable metastatic deposit in the left nephrectomy bed along the left psoas muscle with a slight decrease in FDG uptake (less than 30%). The disease was considered interval stable, and although radiation treatment was recommended, it was ultimately deemed unnecessary. The patient continued to be monitored, with two additional abdominal MRIs conducted four months apart. The most recent MRI showed a non-enhancing lesion measuring 67x29x20 mm, consistent with previous findings.
Discussion
Most cases of EWS develop in the bones, with the lower extremities and pelvis being the most common sites of occurrence. However, it is extremely rare for EWS to appear as a primary tumor in the kidney. The cells responsible for EWS are believed to originate from neural crest cells or mesenchymal stem cells [9, 13]. Approximately 66% of patients have distant metastasis at the time of diagnosis, with the lungs being the most common site, followed by the liver and bones [4]. The median age for this condition is 27 years, with a slight predominance in males. The symptoms are non-specific and include flank pain in 84% of cases, a palpable mass in 60%, and hematuria in 38% [6]. The review of 19 cases of EWS of the kidney in this study (Table 1) revealed a mean age of 24.5 years, with females accounting for 57.9% of the cases. The most common symptoms were flank pain (47.36%), followed by hematuria (42.1%) and abdominal pain (36.8%). The average tumor size was 12.27 cm. In contrast, the current case involved a 30-year-old female who presented with intermittent grassy green-colored urine and a headache, but no abdominal pain.
Diagnosis can be assisted using radiological techniques such as MRI and CT scans, in determining the tumor's size, location, and the extent of both local and distant metastasis [9]. The definitive diagnosis of renal EWS relies on pathological, immunohistochemical, and molecular testing. Microscopically, the majority of cases consist of uniform small round cells with round nuclei, finely stippled chromatin, subtle nucleoli, scant clear or eosinophilic cytoplasm, and indistinct cytoplasmic membranes [6]. The protein K2.2 plays a role in regulating gene expression within the neuroendocrine and glial differentiation pathways, and NKX2.2 serves as a specific marker for identifying the EWS/FLI1 fusion protein, exhibiting a high sensitivity of 93% and a specificity of 89% [6]. In the current case, abdominal ultrasonography revealed an enlarged, irregularly shaped left kidney with a large mass sized 10 cm that was confirmed by CT scan, which was smaller than ten and larger than seven of the cases in this literature review (Table 1).
Author and Year | No. of Cases |
Age Gender |
Clinical Presentation |
Medical & Surgical History | Diagnostic Method |
Size and Site of Tumor |
Treatment | Outcome | |
Conservative | Surgical | ||||||||
Aithal et al., 2024[4] |
1 |
40 F |
Painless hematuria |
None reported |
MRI, CECT, Histo, IHC |
7x5.5x5 cm, Lower pole, LK |
Chemotherapy |
Nephrectomy |
N/A |
Alahmadi et al., 2020[8] |
1 |
16 M |
Hematuria, flank pain |
Schizophrenia |
CECT, Histo, IHC |
19 × 15 × 12 cm, RK |
Chemotherapy |
Nephrectomy |
Remission |
Bradford et al., 2020[14] |
Case 1 |
16 M |
Abdominal pain |
N/A |
IHC |
RK |
VDC/IE; |
Partial Nephrectomy |
Died |
Case 2 |
11 M |
Flank and testicle pain, fever |
N/A |
Ultrasound, CT, IHC |
28×17×7.3 cm, LK |
VDC/IE; auto SCT; everolimus, Chemotherapy |
Nephrectomy |
Alive with disease |
|
Case 3 |
18 F |
Hematuria, right flank pain |
N/A |
PET, CT |
6.8×6.2×6.0 cm, RK |
VDC/IE |
Radical nephrectomy, IVC tumor removal |
Remission |
|
Case 4 |
17 F |
N/A |
N/A |
PET |
N/A |
Chemotherapy, VDC/IE |
Tumor resection |
Remission |
|
Case 5 |
16 F |
N/A |
N/A |
N/A |
25×18×19 cm, LK |
VDC/IE |
Gross total resection |
Remission |
|
Case 6 |
13 F |
Abdominal pain, spinal cord compression |
N/A |
MRI, PET, Histo |
6.8×14×13 cm, LK |
VDC/IE |
Nephrectomy, following neoadjuvant chemotherapy |
Died |
|
Case 7 |
15 F |
Abdominal pain, ataxia, elevated urate and creatinine |
N/A |
N/A |
21 cm, LK |
Chemotherapy, VDC/IE switched to VDC/CE for ifosfamide nephrotoxicity |
Radical nephrectomy, partial ureterectomy, IVC thrombectomy |
Died |
|
Bray et al., 2023[13] |
1 |
31 F |
Macroscopic hematuria, flank pain |
unremarkable |
CT, MRI, Ultrasound |
11.6 cm, RK |
VDC/IE Chemotherapy |
laparoscopic radical Nephrectomy |
Remission |
Cheng et al., 2020[15] |
1 |
31 F |
Hematuria, flank pain, palpable mass |
unremarkable |
CT, 3D imaging, PET, Histo, IHC |
18×14.5×14 cm, LK |
Chemotherapy |
Nephrectomy |
Metastasis |
El Mohtarim et al., 2024[6] |
1 |
14 F |
Flank swelling, abdominal pain weight loss |
2 mo of abdominal pain |
MRI, CT, Histo, IHC |
20×16×14 cm, RK |
Chemotherapy, VDC/IE |
Nephrectomy |
Remission |
Ilhan et al., 2023[7] |
1 |
54 M |
Flank pain, hematuria |
Smoker, Alcohol consumption |
Ultrasound, CT, Histo, IHC |
7.4×6.3 cm, RK |
Chemotherapy (VAC-IE) |
Nephrectomy |
Remission |
Khudair et al., 2024[9] |
1 |
38 F |
Abdominal pain, flank Pain |
Constipation, vomiting, morbid obesity |
Ultrasound, CT, Histo |
25×18×18 cm, RK |
Chemotherapy |
N/A |
Died |
Patra et al., 2022[10] |
Case 1 |
33 F |
Abdominal pain |
N/A |
CECT, biopsy, Histo, IHC |
7.4 cm, RK |
Chemotherapy |
Nephrectomy |
Died |
Case 2 |
35 M |
Palpable lump |
N/A |
CECT, biopsy, Histo, IHC |
4.5 cm, LK |
Chemotherapy |
Nephrectomy |
Remission |
|
Case 3 |
19 M |
Palpable lump, hematuria |
N/A |
CECT, biopsy, Histo, IHC |
19 cm, RK |
NACT |
Nephrectomy |
Alive with disease |
|
Case 4 |
28 M |
Abdominal pain |
N/A |
CECT, biopsy, Histo, IHC |
6.4 cm, LK |
NACT |
Nephrectomy |
Alive with disease |
|
Sardana et al., 2021[3] |
1 |
49 M |
Gross hematuria, flank pain |
GERD, asthma, hyperlipidemia |
MRI, CT, Histo, IHC |
7.0×6.2×5.8 cm, RK |
Chemotherapy, Radiotherapy |
Nephrectomy |
Remission |
F: female M: male N/A: not applicable mo: months MRI: magnetic resonance imaging CECT: contrast enhanced computed tomography Histo: histopathology IHC: immunohistochemistry PET: positron emission tomography LK: left kidney RK: right kidney NACT: Neoadjuvant chemotherapy IVC: inferior vena cava VDC/IE: vincristine, doxorubicin, and cyclophosphamide/ ifosfamide, etoposide y: year |
To establish a definitive diagnosis, the patient underwent a left radical nephrectomy. Similarly, in the cases by Patra et al., histopathological examination confirmed the tumor as a Grade 2 primary EWS /PNET of the kidney [10]. Despite its aggressive nature, there was no evidence of distant metastasis in the present patient, and she received adjuvant chemotherapy, which was in line with the cases by Ilhan et al. and Bradford et al. [7,14]. In contrast, Cheng et al. reported metastatic spread to multiple sites, including lymph nodes, adrenal glands, and lungs, requiring a switch to apatinib, with the patient surviving 18 months postoperatively [15].
The most common treatment approach currently involves multimodal therapy, which includes surgery and adjuvant chemotherapy for localized EWS of the kidney [7]. The current patient underwent a left radical nephrectomy to remove the primary tumor. The surgery was successful in excising the tumor. The pathological examination revealed no tumor necrosis, lymphovascular invasion, or positive surgical margins, but one out of eight examined lymph nodes tested positive for metastasis, leading to a final pathological stage of pT1pN1M0.
Immunohistochemical analysis confirmed the diagnosis of EWS/PNET, with the tumor cells showing positivity for CD99, a marker commonly associated with EWS. Other markers, including AE1/AE3, CD45, desmin, S100, synaptophysin, CD31, and WT1, showed negatively, and Ki67 showed a proliferation index of 20%. In contrast, Cheng et al. reported positive results for AE1/AE3, CD99, CD56, and synaptophysin [15]. Following surgery, the patient received adjuvant chemotherapy using the VAC-IE regimen similar to Ilhan et al., which includes vincristine, doxorubicin, cyclophosphamide (VAC), ifosfamide, and etoposide (IE). This multimodal chemotherapy approach was implemented to target any remaining microscopic disease and to lower the risk of tumor recurrence [7].
The current case did not achieve full remission due to stable metastatic deposits, indicating active cancer. In contrast, the patients in the studies of both Ilhan et al. and Bray et al. remained in remission with no disease progression, reflecting more
favorable outcomes [7,13]. The prognosis of EWS depends on various factors, including tumor location and size, presence of metastatic disease, and treatment plans. However, the impact of age on disease outcomes remains uncertain [3]. In the present report, while the disease is stable, the persistence of metastasis suggests ongoing risk, requiring continuous monitoring. Detailed genetic profiling of the tumor was not included, which could have provided deeper insights into the disease's molecular mechanisms and influenced treatment strategies.
Conclusion
The current case highlights that EWS of the kidney can present with grassy green-colored urine and hematuria. Radical nephrectomy with the VAC-IE regimen may result in good outcomes with continuous monitoring required in cases of metastatic deposits.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable
Patient consent (participation and publication): Written informed consent was obtained from the patient for publication.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: RMA and SMA were significant contributors to the conception of the study and the literature search for related studies. MAG, DSH and JSA were involved in the literature review, study design, and manuscript writing. ZNH, HAY, AMA, SSF, BSS and AKG were involved in the literature review, the study's design, and the critical revision of the manuscript, and they participated in data collection. SHT was the radiologist who performed the assessment of the case. RMA was the pathologist who performed the diagnostic of the case. RMA and MAG confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Note applicable.

Presentation and Management of Cervical Thoracic Duct Cyst: A Systematic Review of the Literature
Fahmi H. Kakamad, Dilan S. Hiwa, Aland S. Abdullah, Hiwa O. Baba, Aso S. Muhialdeen, Sarwat T....
Abstract
Introduction
Thoracic duct cysts are an uncommon phenomenon, especially within the cervical region. Due to its limited reported cases, very little is known about its etiology, presentation, and management. This systematic review is conducted to shed light on the ways the cyst presents and the outcomes of different treatment regimens.
Methods
The EMBASE, CINAHL, PubMed/MEDLINE, Cochrane Library, and Web of Science databases were thoroughly screened to identify any studies published in English up to March 24th, 2024.
Results
The average age of the patients was 47.8 years, with 9 (56.3%) females in the study population. The mean size of the cysts was 5.99 cm, and the most common symptom was pain, present in 5 (31.3%) patients. The most common management approach chosen for 6 (37.5%) patients was simple follow-up and observation, followed by surgical excision in 5 (31.3%) patients.
Conclusion
Patients with thoracic duct cervical cysts may be asymptomatic or present with pain. Both surgical excision and conservative management may yield satisfactory outcomes.
Introduction
The thoracic duct runs 38 to 45 centimeters from the cysterna chyli at L2 vertebral level to the lower cervical spine [1]. The duct is 2 to 5 millimeters wide, and it carries lymph ingested with fat from the vascular bed of the gastrointestinal system and drains into the central veins of the neck [1,2]. Very rarely, a cyst develops from the thoracic duct, also called a lymphocele of the thoracic duct [3]. The pathology is very uncommon, even more so in the cervical segment, since among the limited reported cases, the majority have been documented as either a thoracic or an abdominal thoracic duct cyst [4]. Although not established, theories suggest that congenital thoracic duct weakness and inflammation-mediated degeneration of the duct can predispose to cyst formation [5]. Due to the limited number of cases reported, no gold standard treatment has been established for cervical thoracic duct cysts; however, both surgical and conservative management have been proposed. To our knowledge, this is the first review in the literature about cervical thoracic duct cysts. This study aims to contribute to the literature by summarizing presentations, management, and outcomes of reported cases of cervical thoracic duct cysts.
Methods
Study design
The guideline followed in this systematic review was that of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Any study with a reported case of a cervical thoracic cyst was included, provided that necessary information was given on the patient and the mass.
Data sources and search strategy
EMBASE, CINAHL, PubMed/MEDLINE, Cochrane Library, and Web of Science databases were all screened using the following ("Thoracic duct" AND Cyst OR Cysts AND Neck OR Cervical) keywords.
Eligibility criteria
Any study with a reported case of thoracic duct cyst found within the cervical region and published in English was deemed eligible. Information on the patient, as well as the characteristics of the cyst, was required. To avoid bias, any study published in predatory journals, identified using Kscien’s list, was excluded from this systematic review [6].
Study selection process
The titles and abstracts of the enrolled studies were screened by two different researchers, attempting to identify papers based on the study's eligibility criteria. A third researcher was recruited to resolve any disagreements that might arise between the initial two researchers.
Data items
Data was collected on mean age, sex, type of study, country of study, presentation, type of symptoms, location of the cyst, size of the cyst, management, and outcome of each management.
Statistical analysis
Microsoft Excel Workbook sheet was used to record the extracted data. The Statistical Package for Social Sciences (SPSS) 26.0 software was used in further quantitative analysis. The data is presented as frequencies and percentages.
Results
Study selection
The systematic search first brought 39 papers. Out of the initial 39, three only-abstract studies were excluded without further screening. The remaining 36 papers had their titles and abstracts screened, which resulted in 25 papers being removed due to irrelevancy. No paper was excluded due to wrong designs. The remaining 11 [4,7-16] studies were checked for wrong outcomes and predatory publishing; however, none were found. This left 11 papers at last to be included in this systematic review. The PRISMA flow chart highlights more details (Figure 1).
Characteristics of the included studies
Among the 11 included studies, 10 (91%) were case reports, with only one (9%) study being a case series. The United States, with four (36.3%), and France, with two (18.2%) studies, contributed the most, followed by Greece, China, Finland, Norway, and Canada, each with one study.
Main findings
A total of 16 patients were included in this systematic review. The average age of the patients was 47.8 ± 17.8 years. There were nine (56.3%) females compared to six (37.5%) males, leaving one (6.2%) patient unspecified. Half of the patients were symptomatic, and pain was the sole symptom in four (25%) patients. Details on the baseline observation and follow-up of the cyst were done for six (37.5%) patients, followed by surgical excision in five (31.4%) patients, a low-fat diet for two (12.5%) patients, aspiration performed in one (6.2%) patient, and lastly, one (6.2%) patient who underwent both surgical excision and had also received a low-fat diet modification regimen. All (100%) patients had their mass in the left supraclavicular region. The outcome of 12 (75%) patients was to be discharged without complications, whereas one (6.2%) patient was observed to have a persistent mass, and three (18.8%) patients did not have their outcome mentioned (Tables 2 and 3).
Author/ year of publication |
Type of Study |
Country of study |
Age (years) |
Sex |
Presentation |
Type of symptoms |
Brauchle et al. 2003 [4] |
Case report |
United States |
41 |
Male |
Asymptomatic |
N/A |
Mattila et al. 1999 [7] |
Case report |
Finland |
49 |
Female |
Asymptomatic |
N/A |
Metaxas et al. 2021 [8] |
Case report |
Greece |
42 |
Male |
Symptomatic |
Pain |
Wang et al. 2009 [9] |
Case report |
China |
28 |
Female |
Asymptomatic |
N/A |
Veziant et al. 2015 [10] |
Case report |
France |
49 |
Female |
Symptomatic |
Pain and Dyspnea |
Planchette et al. 2021 [11] |
Case series |
France |
50 |
Male |
Asymptomatic |
N/A |
74 |
Female |
Asymptomatic |
N/A |
|||
45 |
Female |
Symptomatic |
Pain |
|||
65 |
Female |
Asymptomatic |
N/A |
|||
64 |
Female |
Symptomatic |
Pain |
|||
62 |
Female |
Symptomatic |
Pain |
|||
Bhalla et al. 2017 [12] |
Case report |
United States |
0.67 |
Male |
Symptomatic |
Dyspnea |
Steinberg 1964 [13] |
Case report |
United States |
56 |
Female |
Symptomatic |
Migraine headaches |
Steinberg & Watson 1966 [14] |
Case report |
United States |
28 |
N/A |
Symptomatic |
Soreness |
Kolbenstvedt et al. 1986 [15] |
Case report |
Norway |
55 |
Male |
Asymptomatic |
N/A |
Wax et al. 1992 [16] |
Case report |
Canada |
56 |
Male |
Asymptomatic |
N/A |
Author/ year of publication |
Age (years) |
Location of cyst |
Size of cyst |
Management |
Outcome |
Brauchle et al. 2003 [4] |
41 |
Left supraclavicular |
4 cm |
Aspiration |
Patient was discharged |
Mattila et al. 1999 [7] |
49 |
Left supraclavicular |
3.8 cm |
Surgical Excision |
Patient was discharged |
Metaxas et al. 2021 [8] |
42 |
Left Neck |
N/A |
Surgical Excision |
Patient was discharged |
Wang et al. 2009 [9] |
28 |
Left supraclavicular |
10 cm |
Surgical Excision |
Patient was discharged |
Veziant et al. 2015 [10] |
49 |
Left supraclavicular |
3 cm |
Surgical Excision |
Patient was discharged |
Planchette et al. 2021 [11] |
50 |
Left supraclavicular |
N/A |
Follow up |
Patient was discharged |
74 |
Left supraclavicular |
N/A |
Follow up |
Patient was discharged |
|
45 |
Left supraclavicular |
N/A |
Follow up |
Patient was discharged |
|
65 |
Left supraclavicular |
N/A |
Follow up |
N/A |
|
64 |
Left supraclavicular |
N/A |
Low fat diet |
Patient was discharged |
|
62 |
Left supraclavicular |
N/A |
Low fat diet |
Patient was discharged |
|
Bhalla et al. 2017 [12] |
0.67 |
Left supraclavicular |
13.1 cm |
Surgical drainage and low fat diet |
Patient was discharged |
Steinberg 1964 [13] |
56 |
Left supraclavicular |
3 cm |
N/A |
N/A |
Steinberg & Watson 1966 [14] |
28 |
Left supraclavicular |
3 cm |
Follow up |
N/A |
Kolbenstvedt et al. 1986 [15] |
55 |
Left supraclavicular |
3 cm |
Follow up |
Mass persistence |
Wax et al. 1992 [16] |
56 |
Left supraclavicular |
10 cm |
Surgical Excision |
Patient was discharged |
Variables |
Frequency/percentage |
Age (mean ± SD) |
47.8 ± 17.8 years |
Sex Male Female N/A |
Number of patients (16) 6 (37.5%) 9 (56.3%) 1 (6.2%) |
Country of study United States France Greece China Finland Norway Canada |
Number of studies (11) 4 (36.3%) 2 (18.2%) 1 (9.1%) 1 (9.1%) 1 (9.1%) 1 (9.1%) 1 (9.1%) |
Type of Study Case report Case series |
Number of studies (11) 10 (90.1%) 1 (9.9%) |
Presentation Symptomatic Asymptomatic |
Number of patients (16) 8 (50%) 8 (50%) |
Type of symptoms Pain Pain and dyspnea Dyspnea Migraine Soreness N/A |
Number of patients (16) 4 (25%) 1 (6.2%) 1 (6.2%) 1 (6.2%) 1 (6.2%) 8 (50%) |
Size of cyst (mean ± SD) |
5.99 ± 3.99 cm |
Management Aspiration Surgical Excision Follow up Low-fat diets Surgical excision & low-fat diet N/A |
Number of patients (16) 1 (6.2%) 5 (31.4%) 6 (37.5%) 2 (12.5%) 1 (6.2%) 1 (6.2%) |
Outcome Patient was discharged Mass persisted N/A |
Number of patients (16) 12 (75%) 1 (6.2%) 3 (18.8%) |
* N/A: Not applicable |
Discussion
Apart from the right side of the upper extremity, the right side of the thorax, and the right side of the neck, the thoracic duct drains the lymphatics of the rest of the body [1]. An uncommon phenomenon related to the duct is a thoracic duct cyst, also called a lymphocele of the thoracic duct [3]. Theoretically, the cyst can arise throughout the length of the entire duct; however, it usually arises within either the thorax or the abdomen. A thoracic lymphocele of the cervical region is the rarest form [4]. A cervical thoracic duct cyst will present as a lateral neck mass arising from the supraclavicular fossa. In this systematic review, all 16 patients presented with a mass, either painful or not, within the left supraclavicular fossa. Bhalla et al. reported the youngest patient recorded in the literature with a thoracic duct lymphocele presenting in an 8-month-old boy [12]. According to Abelarado et al., the cyst tends to occur more frequently in females, and the average age among the patients presenting with the cyst is 49.8 years [15]. This is in accordance with the current study’s findings, as the average age was 47.8 ± 17.8 years, and the majority were females. No single factor has been identified as a cause of this pathology; however, inflammation-mediated degeneration of the duct wall and congenital weakness have been suggested, as well as any possible traumas [3].
As previously mentioned, since the duct drains the left side of the neck, the cyst will present as a left-sided supraclavicular mass. Most patients with a thoracic duct lymphocele are asymptomatic [5]. Half of the patients in this systematic review were symptomatic, and the other half had no complaints. Symptoms are generally due to the compressive effect of the mass on adjacent structures and can include pain, dysphagia,
cyanosis, and even respiratory distress [7]. In this study, four (25%) patients presented with pain alone, making it the most common symptom. Others, such as migraine headaches, dyspnea, and soreness, were also reported, with one patient suffering from both pain and dyspnea. Lymphoscintigraphy used to be considered the gold standard for diagnosis; however, with the advent of new high-resolution imaging techniques, this tool has become less popular [17]. Confirmation of the diagnosis is usually conducted during surgery, as histological analysis of the specimen can be beneficial. One way this is done is by staining the endothelial cells lining the thoracic duct to verify that the cyst is, in fact, a thoracic duct cyst [4,18]. According to Mattila et al., another way to diagnose a thoracic duct cyst is via puncture and subsequence analysis. Following aspiration, the aspirate will manifest as a milky fluid showing excess triglyceride in laboratory investigations and lymphocytes, neutrophils, and macrophages, among others [7].
Regarding management, no single gold standard has been established. This is attributed to the low number of cases that have been recorded. As previously mentioned, aspiration, although usually performed for diagnosis purposes, can be sufficient to deal with the mass. In this review, only one of the patients had aspiration alone. Surgical excision of the thoracic duct cyst is another common way to manage the mass [7]. This was performed for five (31.4%) patients in this review. Interestingly, in some instances, and especially after deeming the mass nonneoplastic, patients are followed up and observed after they either refuse surgery or the physician doesn’t consider it necessary. This has been highlighted in six (37.5%) patients within this study’s population. Furthermore, patients were managed through diet modification and, more specifically, transitioning to a low-fat diet. This yielded a satisfactory outcome in the two patients who only received diet modification and in the one patient who underwent surgical excision followed by a transition to a low-fat diet. All different management methods yielded satisfactory outcomes, with patients discharged without complications in three-quarters of the cases. This was apart from one patient whose mass persisted since they underwent no management and were observed.
Conclusion
Patients with thoracic duct cervical cysts may be asymptomatic or present with pain. Both surgical excision and conservative management may yield satisfactory outcomes.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable, as systematic reviews do not require ethical approval.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: FHK and BAA were significant contributors to the conception of the study and the literature search for related studies. DSH and ASA involved in the literature review, study design, and manuscript writing. AJQ, RJR, MLF, STSA, ASM, and HOB were involved in the literature review, the study's design, the critical revision of the manuscript, and data collection. FHK and DSH confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Chest Wall Hydatid Cysts: A Systematic Review
Fahmi H. Kakamad, Harem K. Ahmed, Ali H. Hasan, Ahmed H. Ahmed, Ayoob A. Mohammed, Dindar H....
Abstract
Introduction
Given the rarity of chest wall hydatid disease, information on this condition is primarily drawn from case reports. Hence, this study systematically reviews the disease's manifestation and management.
Methods
Google Scholar was searched with the following keywords: (hydatid OR hydatidosis OR tapeworms OR echinococcosis OR echinococcus OR granulosus AND chest OR wall OR thoracic OR thorax OR rib OR sternum OR sternal OR cartilage OR intercostal OR extra-pulmonary). Inclusion criteria involved a confirmed diagnosis of chest wall hydatid cyst. Only English-language studies published in legitimate journals were included.
Results
The reported cases were primarily from Turkey (41.5%). The mean age of the patients was 39.7 ± 17.1 years, with a male predominance (56.9%). The most common clinical presentations were swelling (47.1%) and chest or abdominal pain (45.1%). Only 10 cases (19.6%) had reported a history of animal contact. Among those with documented residency (35.3%), 16 (31.4%) resided in rural areas. The average mass size on the CT scan was 7.5 ± 2.4 cm. Surgery was the treatment of choice, with thoracotomy performed in 37.3% of cases, video-assisted thoracoscopy in 1.9%, and the surgical technique not specified in 60.8% of cases. The mean hospital stay was 8.6 ± 4.4 days, and no recurrences were reported.
Conclusion
Despite its rarity, chest wall hydatid cyst may have a good prognosis with few complications. Given its often-nonspecific presentation, reviewing the patient's medical history may help establish an accurate provisional diagnosis.
Introduction
Hydatid disease, caused by tapeworm parasites, is prevalent in sheep-rearing regions, including the Middle East, Mediterranean areas, Africa, South America, and Australia [1,2]. In humans, three types of echinococcosis are known to occur: cystic echinococcosis caused by Echinococcus granulosus, alveolar echinococcosis caused by Echinococcus multilocularis, and polycystic echinococcosis due to Echinococcus Vogeli or Echinococcus oligarthrus [3]. The most common causative organism of human hydatid disease is Echinococcus granulosus [1]. The parasite is a tapeworm with an approximate length of 2 to 7 mm [4]. Hydatid disease or echinococcosis is an old and well-known helminthic disease known since Hippocrates [5]. Rudolphi, in 1808, first used the term hydatid cyst [HC] to describe human echinococcosis [2]. Dogs are the definitive hosts, while farm animals are intermediate hosts. Although humans are not involved in the parasite's life cycle, they may be affected accidentally, either by direct contact with a dog or by ingesting contaminated food and fluid from parasite eggs [6]. After oral ingestion, the cyst hatches in the duodenum and initially spreads to the liver through the portal vein via hematogenous or occasionally lymphogenous routes. It then reaches the lungs through the venous system, and from the lungs, it can disseminate to other organs via the arterial system [7]. The disease can be seen in different body parts, like the thyroid, bladder, heart, and pulmonary artery [7-10]. The chest wall is a very uncommon localization for this disease [6,11]. Therefore, the literature has limited information regarding chest wall HCs. This study aims to systematically review the manifestation and management of the disease.
Methods
Study design
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Data sources and search strategy
Google Scholar was searched with the following keywords: [hydatid OR hydatidosis OR tapeworms OR echinococcosis OR echinococcus OR granulosus AND chest OR wall OR thoracic OR thorax OR rib OR sternum OR sternal OR cartilage OR intercostal OR extra-pulmonary].
Eligibility Criteria
Inclusion criteria involved a confirmed diagnosis of chest wall HC. Only English-language studies published in legitimate journals were included [12].
Data items
One author screened the studies to select those that met the eligibility criteria, and another rechecked his work. Key data, including the first author's name, study design, country and year of publication, sample size, patient demography, clinical presentation, management strategies, and outcomes, were extracted from the included studies.
Data analysis and synthesis
The data were collected in a Microsoft Excel sheet (2021), and descriptive statistics were performed using the Statistical Package for the Social Sciences (SPSS) version 27. The data were presented as frequencies, percentages, means, and standard deviations.
Results
Study Selection
A systematic search identified a total of 432 articles. After the initial screening, 29 studies presenting only abstracts, two duplicates, and three non-English publications were excluded, resulting in 398 articles for further evaluation. Title and abstract screening excluded 329 studies due to irrelevance, leaving 69 articles for full-text review. Of these, seven were excluded due to irrelevancy, eight due to unretrieved data, and two for being letters to the editor. During the final screening, 11 studies were removed due to publishing in predatory journals. Finally, 41 studies [1–3,5,6,11,13–26,28-48] met the inclusion criteria and were included in the review (Figure 1). The raw data for each included study are detailed in Tables 1, 2, and 3.
Author/reference |
Year |
Type of Study |
Country |
No. of Case |
Age |
Gender |
Residency |
Contact with Animal |
PMH |
PSH |
Origin |
Althobaity et al. [1] |
2023 |
Case report |
Saudi Arabia |
1 |
22 |
Male |
N\A |
Yes |
Insignificant |
N\A |
Primary |
Goyal et al. [2] |
2010 |
Case report |
India |
1 |
30 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
Godazandeh et al. [3] |
2020 |
Case report |
Iran |
1 |
40 |
Male |
Urban |
No |
N\A |
No |
Primary |
Basit et al. [5] |
2021 |
Case report |
Afghanistan |
1 |
65 |
Male |
Rural |
N\A |
N\A |
No |
Primary |
Salih et al. [6] |
2017 |
Case report |
Iraq |
1 |
20 |
Female |
Rural |
Yes |
N\A |
N\A |
N\A |
Döner et al. [11] |
2019 |
Case report |
Turkey |
1 |
31 |
Female |
N\A |
N\A |
N\A |
N\A |
Primary |
MohIeldeen et al. [13] |
2013 |
Case report |
Iraq |
1 |
42 |
Male |
Rural |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
Secondary |
Akkas et al. [14] |
2016
|
Case report |
Turkey
|
2 |
32 |
Male |
N\A |
N\A |
Hepatic hydatid cyst 2 years ago |
N\A |
Secondary |
24 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
Alloubi et al. [15] |
2012 |
Case report |
Morocco |
1 |
57 |
Male |
Rural |
N\A |
N\A |
N\A |
N\A |
Al-Qudah et al. [16] |
2000 |
Case report |
Jordan |
1 |
24 |
Male |
N\A |
N\A |
N\A |
N\A |
Primary |
Afghani et al. [17] |
2017 |
Case report |
Iran |
1 |
35 |
Female |
N\A |
N\A |
N\A |
N\A |
Primary |
Yekeler et al. [18] |
2010 |
Case report |
Turkey |
1 |
57 |
Male |
Rural |
Yes |
Insignificant |
N\A |
N\A |
Ulger et al. [19] |
2013 |
Case report |
Turkey |
1 |
62 |
Male |
N\A |
N\A |
Hydatid cyst |
Hydatid cyst surgery |
N\A |
Tulay et al. [20] |
2015 |
Case report |
Turkey |
1 |
48 |
Male |
N\A |
N\A |
Insignificant |
No |
Primary |
Tomos et al. [21] |
2005 |
Case report |
Greece |
1 |
26 |
Female |
N\A |
N\A |
Hydatid cyst |
Pulmonary and hepatic hydatid cyst surgery |
Secondary |
Tezcan et al. [22] |
2014 |
Case report |
Turkey |
1 |
55 |
Male |
N\A |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
Secondary |
Tadasa et al. [23] |
2023 |
Case report |
Ethiopia |
1 |
65 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
Sevinc et al. [24] |
2014 |
Case report |
Turkey |
1 |
31 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
Sarkar et al. [25] |
2015 |
Case report |
India |
1 |
58 |
Female |
Rural |
Yes |
N\A |
N\A |
Primary |
Sabzi et al. [26] |
2023 |
Case report |
Iran |
1 |
53 |
Male |
Rural |
Yes |
N\A |
N\A |
Secondary |
Roman et al. [28] |
2015 |
Case report |
Romania |
1 |
25 |
Male |
Rural |
Yes |
History of trauma |
N\A |
N\A |
Redington et al. [29] |
2001 |
Case report |
United Kingdom |
1 |
72 |
Male |
N\A |
N\A |
History of trauma |
N\A |
N\A |
Raut et al. [30] |
2004 |
Case report |
India |
1 |
28 |
Male |
Rural |
Yes |
N\A |
N\A |
N\A |
Ninos et al. [31] |
2010 |
Case report |
Greece |
1 |
50 |
Male |
N\A |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
Primary |
Kiliç et al. [32] |
2003 |
Case report |
Turkey |
1 |
54 |
Male |
Rural |
N\A |
Insignificant |
N\A |
Primary |
Karapolat et al. [33] |
2012 |
Case report |
Turkey |
1 |
69 |
Female |
N\A |
N\A |
N\A |
N\A |
Primary |
Karaoğlanoğlu et al. [34] |
2001 |
Case report |
Turkey |
1 |
63 |
Male |
Rural |
Yes |
N\A |
N\A |
N\A |
Kaplanoğlu et al. [35] |
2017 |
Case report |
Turkey |
1 |
27 |
Female |
N\A |
N\A |
N\A |
No |
N\A |
Honda et al. [36] |
2010 |
Case report
|
Japan |
1 |
9 |
Female |
Rural |
N\A |
Insignificant |
N\A |
Secondary |
Han et al. [37] |
2004 |
Case report |
Turkey |
1 |
N\A |
Female |
N\A |
N\A |
Insignificant |
N\A |
N\A |
Gezer et al. [38] |
2006 |
Case report |
Turkey |
1 |
57 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
Foroulis et al. [39] |
2003 |
Case report |
Greece |
1 |
28 |
Female |
Urban |
N\A |
N\A |
N\A |
Primary |
Findikcioglu et al. [40] |
2010 |
Case report |
Turkey |
1 |
48 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
Faber et al. [41] |
2010 |
Case report |
Israel |
1 |
18 |
Female |
Rural |
N\A |
Thoracic outlet syndrome |
N\A |
N\A |
Demir et al. [42] |
2010 |
Case report |
Turkey |
1 |
9 |
Male |
Rural |
Yes |
N\A |
N\A |
Primary |
Chafik et al. [43] |
2009 |
Case report |
Morocco |
1 |
35 |
Male |
N\A |
N\A |
History of trauma |
Undiagnosed swelling drainage |
N\A |
Sinberg et al. [44] |
1936 |
Case report |
United States |
1 |
15 |
Male |
Rural |
Yes |
Insignificant |
N/A |
Primary |
Rose et al. [45] |
1893 |
Case report |
United Kingdom |
1 |
25 |
Female |
N\A |
N/A |
Bronchitis |
N/A |
Primary |
Machboua et al. [46]
|
2023 |
Case series
|
Morocco |
5 |
26 |
Male |
Rural |
N\A |
N\A |
N\A |
N\A |
32 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
28 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
57 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
63 |
Female |
N\A |
N\A |
Hydatid cyst |
Pulmonary and hepatic hydatid cyst surgery |
Secondary |
|||||
Özdemir et al. [47] |
1994 |
Case series |
Turkey |
6 |
40 |
Female |
N\A |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
N\A |
38 |
Male |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
26 |
Female |
N\A |
N\A |
N\A |
N\A |
N\A |
|||||
35 |
Male |
N\A |
N\A |
Hydatid cyst |
Hepatic hydatid cyst surgery |
Secondary |
|||||
35 |
Female |
N\A |
N\A |
Hydatid cyst |
Pulmonary hydatid cyst surgery |
Secondary |
|||||
Avci et al. [48] |
2005 |
Case report |
Turkey |
1 |
72 |
Female |
N\A |
N\A |
History of trauma |
No |
Primary |
N/A: non-available, PMH: past medical history, PSH: past surgical history |
Author/reference |
Year
|
No. of Case |
Presentation
|
Duration (months) |
Size of the mass on CT scan (cm) |
Hydatid serology
|
Provisional diagnosis
|
Pre-operative medication |
Althobaity et al. [1] |
2023 |
1 |
Chest pain |
36 |
N\A |
N\A |
Hydatid disease |
Albendazole |
Goyal et al. [2] |
2010 |
1 |
Swelling, Chest pain |
N\A |
N\A |
N\A |
N\A |
No |
Godazandeh et al. [3] |
2020 |
1 |
Swelling |
5 |
N\A |
Negative |
N\A |
No |
Basit et al. [5] |
2021 |
1 |
Chest pain |
0.66* |
N\A |
N\A |
Chest wall tumor |
No |
Salih et al. [6] |
2017 |
1 |
Swelling, Chest pain |
60 |
N\A |
N\A |
N\A |
No |
Döner et al. [11] |
2019 |
1 |
Swelling, Chest pain |
N\A |
4 |
N\A |
Hydatid disease |
No |
MohIeldeen et al. [13] |
2013 |
1 |
Chest pain, Numbness |
4 |
N\A |
N\A |
Hydatid disease |
No |
Akkas et al. [14] |
2016
|
2 |
Chest pain |
N\A |
10 |
N\A |
N\A |
No |
N\A |
N\A |
10 |
N\A |
N\A |
No |
|||
Alloubi et al. [15] |
2012 |
1 |
Chest pain |
3 |
9 |
N\A |
Chest wall tumor |
No |
Al-Qudah et al. [16] |
2000 |
1 |
Dyspnea, Cough, Fever, Shoulder pain |
12 |
N\A |
Negative |
N\A |
No |
Afghani et al. [17] |
2017 |
1 |
Swelling, Chest pain |
N\A |
N\A |
Negative |
Hydatid disease |
Albendazole |
Yekeler et al. [18] |
2010 |
1 |
N\A |
N\A |
N\A |
Positive |
Hydatid disease |
No |
Ulger et al. [19] |
2013 |
1 |
Chest pain |
70 |
N\A |
N\A |
Hydatid disease |
Albendazole |
Tulay et al. [20] |
2015 |
1 |
Swelling |
5 |
10 |
N/A |
N\A |
No |
Tomos et al. [21] |
2005 |
1 |
Chest pain |
N\A |
N\A |
Negative |
N\A |
No |
Tezcan et al. [22] |
2014 |
1 |
Cough, Dyspnea, Shoulder pain |
N\A |
8 |
N\A |
N\A |
No |
Tadasa et al. [23] |
2023 |
1 |
Cough, Back pain, Heaviness, Paresthesia |
12 |
N\A |
N\A |
Hydatid disease |
Albendazole |
Sevinc et al. [24] |
2014 |
1 |
Swelling |
N\A |
5 |
N\A |
Hydatid disease |
No |
Sarkar et al. [25] |
2015 |
1 |
Swelling |
36 |
N\A |
Positive |
Hydatid disease |
Albendazole |
Sabzi et al. [26] |
2023 |
1 |
Swelling, Chest pain |
24 |
N\A |
Negative |
Hydatid disease |
No |
Roman et al. [28] |
2015 |
1 |
Chest pain |
N\A |
3 |
N\A |
Hydatid disease |
No |
Redington et al. [29] |
2001 |
1 |
Dizziness, Sweating, Horsness of voice, Swelling, Chest pain |
24 |
7 |
Negative |
Hydatid disease |
Albendazole |
Raut et al. [30] |
2004 |
1 |
Back pain, Paraparesis |
6 |
N\A |
N\A |
Hydatid disease |
No |
Ninos et al. [31] |
2010 |
1 |
Swelling |
N\A |
N\A |
Negative |
Hydatid disease |
Albendazole |
Kiliç et al. [32] |
2003 |
1 |
Swelling, Chest pain |
3 |
N\A |
N\A |
N\A |
No |
Karapolat et al. [33] |
2012 |
1 |
Abdominal pain |
48 |
9 |
N\A |
Chest wall tumor |
No |
Karaoğlanoğlu et al. [34] |
2001 |
1 |
Cough |
144 |
N\A |
Negative |
N\A |
No |
Kaplanoğlu et al. [35] |
2017 |
1 |
Swelling |
6 |
N\A |
N\A |
N\A |
No |
Honda et al. [36] |
2010 |
1 |
Fever, General fatigue, Nausea |
N\A |
6 |
Positive |
N\A |
No |
Han et al. [37] |
2004 |
1 |
Swelling |
8 |
N\A |
Positive |
N\A |
No |
Gezer et al. [38] |
2006 |
1 |
Shoulder pain, Numbness, Arm weakness |
3 |
N\A |
N\A |
N\A |
No |
Foroulis et al. [39] |
2003 |
1 |
Swelling |
N\A |
N\A |
Positive |
N\A |
Albendazole |
Findikcioglu et al. [40] |
2010 |
1 |
Swelling |
N\A |
N\A |
N\A |
N\A |
No |
Faber et al. [41] |
2010 |
1 |
Shoulder pain, Swelling |
12 |
N\A |
N\A |
Aneurysmal bone cyst |
No |
Demir et al. [42] |
2010 |
1 |
Chest pain |
1 |
N\A |
Positive |
Ewing sarcoma |
No |
Chafik et al. [43] |
2009 |
1 |
Swelling |
N\A |
N\A |
Negative |
N\A |
No |
Sinberg et al. [44] |
1936 |
1 |
Swelling, Chest pain |
18 |
N\A |
N/A |
N\A |
No |
Rose et al. [45] |
1893 |
1 |
Swelling |
N\A |
N\A |
N/A |
N\A |
No |
Machboua et al. [46]
|
2023 |
5 |
Chest pain, Back pain, Lower limb paresthesia |
N\A |
N\A |
Positive |
N\A |
No |
Chest pain, Back pain, Dyspnea |
N\A |
N\A |
Positive |
N\A |
No |
|||
Chest pain, Dyspnea |
N\A |
N\A |
N\A |
N\A |
No |
|||
Swelling, Chest pain |
N\A |
N\A |
Positive |
N\A |
No |
|||
Chest pain |
N\A |
N\A |
N\A |
N\A |
No |
|||
Özdemir et al. [47] |
1994 |
6 |
Swelling |
N\A |
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
N\A |
N\A |
No |
|||
N\A |
N\A |
N\A |
N\A |
N\A |
No |
|||
Empyema |
N\A |
N\A |
N\A |
N\A |
No |
|||
Swelling |
N\A |
N\A |
N\A |
N\A |
No |
|||
Swelling, Shoulder pain |
N\A |
N\A |
N\A |
N\A |
No |
|||
Avci et al. [48] |
2005 |
1 |
Chest pain |
N\A |
9 |
N\A |
Hematoma |
No |
* Less than a month |
Author/reference |
Year |
No. of Case |
Surgical approach
|
Scolicidal agent |
Site of involvement |
Post-operative medication |
Complication |
Recurrence |
Follow-up (month) |
Althobaity et al. [1] |
2023 |
1 |
Video-assisted thoracoscopy [VATS] |
Hypertonic saline |
N\A |
Albendazole |
Pneumothorax |
No |
5 |
Goyal et al. [2] |
2010 |
1 |
Thoracotomy |
Hypertonic saline |
Rib and intercostal muscle |
No |
No |
N\A |
N\A |
Godazandeh et al. [3] |
2020 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
No |
24 |
Basit et al. [5] |
2021 |
1 |
N\A |
Hypertonic saline |
N\A |
Albendazole |
No |
N\A |
N\A |
Salih et al. [6] |
2017 |
1 |
N\A |
N\A |
N\A |
N\A |
No |
No |
3 |
Döner et al. [11] |
2019 |
1 |
N\A |
N\A |
Intercostal muscle |
Albendazole |
No |
N\A |
N\A |
MohIeldeen et al. [13] |
2013 |
1 |
N\A |
N\A |
8th rib |
Albendazole |
No |
No |
24 |
Akkas et al. [14] |
2016
|
2 |
Thoracotomy |
N\A |
Intercostal muscle |
Albendazole |
No |
No
|
36 |
Thoracotomy |
N\A |
N\A |
Albendazole |
No |
No |
18 |
|||
Alloubi et al. [15] |
2012 |
1 |
Thoracotomy |
N\A |
6th and 7th ribs |
Albendazole |
No |
No |
6 |
Al-Qudah et al. [16] |
2000 |
1 |
Thoracotomy |
N\A |
1st rib |
No |
No |
N\A |
N\A |
Afghani et al. [17] |
2017 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
No |
24 |
Yekeler et al. [18] |
2010 |
1 |
Thoracotomy |
N\A |
6th rib |
Albendazole |
No |
No |
10 |
Ulger et al. [19] |
2013 |
1 |
N\A |
N\A |
Sternum |
No |
N\A |
No |
12 |
Tulay et al. [20] |
2015 |
1 |
N\A |
Hypertonic saline |
N\A |
Albendazole |
N\A |
No |
6 |
Tomos et al. [21] |
2005 |
1 |
Thoracotomy |
N\A |
6th rib |
No |
N\A |
N\A |
N\A |
Tezcan et al. [22] |
2014 |
1 |
N\A |
N\A |
Sternum |
No |
No |
N\A |
N\A |
Tadasa et al. [23] |
2023 |
1 |
No |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
Sevinc et al. [24] |
2014 |
1 |
N\A |
Hypertonic saline |
N\A |
Albendazole |
No |
N\A |
N\A |
Sarkar et al. [25] |
2015 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
No |
12 |
Sabzi et al. [26] |
2023 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
N\A |
N\A |
Roman et al. [28] |
2015 |
1 |
Thoracotomy |
Formalin |
8th rib |
Albendazole, Chemotherapy |
No |
No |
1 |
Redington et al. [29] |
2001 |
1 |
No |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
Raut et al. [30] |
2004 |
1 |
N\A |
N\A |
9th rib |
Albendazole |
No |
N\A |
N\A |
Ninos et al. [31] |
2010 |
1 |
N\A |
N\A |
Intercostal muscle |
Albendazole |
N\A |
No |
12 |
Kiliç et al. [32] |
2003 |
1 |
Thoracotomy |
N\A |
5th, 6th and 7th ribs |
Albendazole |
No |
N\A |
N\A |
Karapolat et al. [33] |
2012 |
1 |
N\A |
N\A |
N\A |
Albendazole |
No |
No |
12 |
Karaoğlanoğlu et al. [34] |
2001 |
1 |
N\A |
N\A |
5th and 6th ribs, Serratus anterior muscle, Latissimus dorsi muscle |
Albendazole |
No |
No |
6 |
Kaplanoğlu et al. [35] |
2017 |
1 |
N\A |
N\A |
Intercostal muscle |
No |
N\A |
No |
12 |
Honda et al. [36] |
2010 |
1 |
N\A |
Hypertonic saline |
N\A |
Albendazole |
N\A |
No |
16 |
Han et al. [37] |
2004 |
1 |
N\A |
N\A |
7th rib |
Albendazole |
N\A |
N\A |
N\A |
Gezer et al. [38] |
2006 |
1 |
Thoracotomy |
N\A |
1st rib |
Albendazole |
No |
No |
15 |
Foroulis et al. [39] |
2003 |
1 |
Thoracotomy |
Hypertonic saline |
10th vertebra, 9th and 10th ribs |
Albendazole |
No |
No |
48 |
Findikcioglu et al. [40] |
2010 |
1 |
Thoracotomy |
N\A |
Riband vertebra |
No |
N\A |
N\A |
N\A |
Faber et al. [41] |
2010 |
1 |
N\A |
N\A |
1st rib |
No |
No |
N\A |
N\A |
Demir et al. [42] |
2010 |
1 |
N\A |
N\A |
N\A |
Albendazole |
N\A |
N\A |
N\A |
Chafik et al. [43] |
2009 |
1 |
Thoracotomy |
N\A |
N\A |
Albendazole |
No |
N\A |
N\A |
Sinberg et al. [44] |
1936 |
1 |
N\A |
Hypertonic saline |
Sternum |
No |
Slight superficial infection |
N\A |
N\A |
Rose et al. [45] |
1893 |
1 |
N\A |
N\A |
N\A |
No |
Hemorrhage |
N\A |
N\A |
Machboua et al. [46]
|
2023 |
5 |
Thoracotomy |
N\A |
N\A |
No |
Pleurocutaneous fistula, Disabling parietal pain and neurological pain, Disorder of the Shoulder Girdle. |
No |
24 |
Thoracotomy |
N\A |
Rib and vertebra |
No |
No |
N\A
|
N\A |
|||
N\A |
N\A |
N\A |
No |
No |
N\A
|
N\A |
|||
Thoracotomy |
N\A |
N\A |
No |
No |
N\A
|
N\A |
|||
Thoracotomy |
N\A |
N\A |
No |
N\A |
N\A
|
N\A |
|||
Özdemir et al. [47] |
1994 |
6 |
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
|||
Thoracotomy |
N\A |
N\A |
No |
N\A |
N\A
|
N\A |
|||
Thoracotomy |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
|||
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
|||
N\A |
N\A |
N\A |
No |
N\A |
N\A |
N\A |
|||
Avci et al. [48] |
2005 |
1 |
N\A |
N\A |
N\A |
No |
No |
N\A |
N\A |
N/A:non-available |
Main findings
The reported cases were primarily from Turkey (41.5%). The mean age of the patients was 39.7 ± 17.1 years, with a male predominance (56.9%). The past medical history for HC was positive in 10 cases (19.6%). The most common clinical presentations were swelling in 24 cases (47.1%) and chest or abdominal pain in 23 cases (45.1%). Only 10 cases (19.6%) had reported a history of animal contact, while one patient (2%) reported no such history. Data on the history of animal contact was unavailable in 78.4% of cases. Among those with documented residency (35.3%), 16 (31.4%) resided in rural areas, while two (3.9%) were from urban settings. The disease was primary in sixteen cases (31.4%), and in nine (17.6%), it was secondary. The disease origin was unknown in 26 cases (51%). The average mass size on the CT scan was 7.5 ± 2.4 cm. Hydatid serology was performed in 18 patients, yielding positive results in nine (50%). A provisional diagnosis of hydatid disease was considered in 14 cases (27.5%). Pre-operative treatment with albendazole was administered to eight patients (15.7%). Surgery was the treatment of choice, with thoracotomy performed in 37.3% of cases, video-assisted thoracoscopy (VATS) in 1.9%, and the surgical technique not specified in 60.8% of cases. The average hospital stay was 8.6 ± 4.4 days. The ribs (31.4%) were the primary involved sites, followed by the muscles (11.8%). Postoperative medication included albendazole in 25 cases (49%) and albendazole with chemotherapy in one case (1.9%). Twenty-four cases (47.1%) had received no postoperative treatment. Only four cases (7.8%) faced complications. No recurrence was reported after a mean follow-up period of 14.1± 10.3 months (Table 4).
Variables | Frequency/percentage |
Mean Age (years) |
39.7 ± 17.1 |
Sex Male Female |
29 (56.9%) 22 (43.1%) |
Country of study Turkey Morocco Greece India Iran Iraq United Kingdom Afghanistan Ethiopia Israel Japan Jordan Romania Saudi Arabia United States |
17 (41.5%) 3 (7.3%) 3 (7.3%) 3 (7.3%) 3 (7.3%) 2 (5.0%) 2 (5.0%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) |
Past medical history of hydatid cyst Positive Negative |
10 (19.6%) 41 (80.4%) |
Contact with an animal Yes No N\A |
10 (19.6%) 1 (2.0%) 40 (78.4%) |
Residency Rural Urban N\A |
16 (31.4%) 2 (3.9%) 33 (64.7%) |
Origin Primary Secondary N\A |
16 (31.4%) 9 (17.6%) 26 (51.0%) |
Size of the mass on CT scan | 7.5 ± 2.4 cm |
Presentation Swelling Chest/Abdominal pain Dyspnea Cough Shoulder/back pain Numbness Others N\A |
24 (47.1%) 23 (45.1%) 4 (7.8%) 4 (7.8%) 9 (17.6%) 5 (9.8%) 6 (11.8%) 4 (7.8%) |
Hydatid serology test Positive Negative N\A |
9 (17.6%) 9 (17.6%) 33 (64.7%) |
Provisional diagnosis Hydatid disease Chest wall tumor Aneurysmal bone cyst Ewing sarcoma Hematoma N\A |
14 (27.5%) 3 (5.9%) 1 (1.9%) 1 (1.9%) 1 (1.9%) 31 (60.8%) |
Pre-operative medication Albendazole No |
8 (15.7%) 43 (84.3%) |
Surgical approach Thoracotomy Video-assisted thoracoscopy N\A |
19 (37.3%) 1 (1.9%) 31 (60.8%) |
Injection of scolicidal agent with surgery Hypertonic saline Formalin No |
8 (15.7%) 1 (1.9%) 42 (82.4%) |
Site of involvement Rib Muscle Sternum Vertebra N\A |
16 (31.4%) 6 (11.8%) 3 (5.9%) 3 (5.9%) 28 (54.9%) |
Post-operative medication Albendazole Albendazole and chemotherapy No N/A |
25 (49.0%) 1 (1.9%) 24 (47.1%) 1 (1.9%) |
Mean postoperative hospital stay (days)* |
8.6 ± 4.4 |
Outcome of surgery Recovered with no complication Recovered with complication N\A |
29 (56.9%) 4 (7.8%) 18 (35.3%) |
Average duration of follow-up (months) |
14.1± 10.3 |
Recurrence Yes No N\A |
0 (0.0%) 21 (41.0%) 30 (59.0%) |
N/A: non-available, CT: computed tomography. *For 12 patients out of 51 patients who underwent surgery. #For 23 patients out of 51 patients who underwent surgery. |
Discussion
Human echinococcosis, a prevalent parasitic infection, presents a considerable health and economic burden to society, yet it remains largely neglected as a disease [49]. The findings of this study provide a comprehensive review of chest wall HC, with the majority of the studies conducted in Turkey (41.5%), followed by Morocco (7.3%), Greece (7.3%), India (7.3%), and Iran (7.3%). The higher incidence in these countries may reflect the endemic nature of hydatid disease, likely due to closer contact with livestock and domestic animals [50]. However, it has become a pressing global health issue, primarily attributed to increasing immigration rates and travel activities [7].
The mean age of 39.7 years, with a slight male predominance (56.9%), suggests that both demographic groups are at risk. However, occupational or environmental exposure factors could contribute to the observed gender disparity.
Clinically, the most common presentation was swelling (47.1%), followed by chest or abdominal pain (45.1%). This indicates that chest wall HCs may present as localized symptoms rather than systemic manifestations [51]. The relatively low percentage (19.6%) of patients with a history of animal contact suggests that direct exposure may not always be reported or remembered, or that indirect exposure through contaminated water or food could also be significant transmission routes [26,27]. In addition, a review by Possenti and colleagues suggested that the primary route of human cystic echinococcosis transmission may be the direct or indirect contamination of hands with Echinococcus granulosus eggs excreted by dogs [52].
Schantz et al. indicated that individuals who own livestock are three times more likely to be diagnosed with this disease compared to those who do not own livestock [53]. In accordance with this finding, 16 (88.9%) of the 18 cases with known residency were from rural areas.
Ten cases (19.6%) had a positive history for HC at other sites, and the primary origin of cysts in 31.4% of patients and secondary origin in 17.6% highlights the importance of considering both primary infection or possible spread from other sites, such as the liver or lungs, as the diagnosis and treatment strategies may be different [1].
In the present study, the average cyst size on the CT scan was 7.5 cm, reflecting potentially large cysts that could cause significant local pressure effects or complications; this might be because the course of infection is slow, and most infected individuals remain either asymptomatic for years or exhibit non-specific symptoms leading to accidental diagnosis [54]. Parasite eggs can remain viable from several months up to a few years in the environment, and diverse conditions [55].
Only nine (50%) out of 18 patients with available data in this systematic review had positive hydatid serology, suggesting that serological tests alone may not be sufficient for diagnosis and imaging, particularly CT scans, plays a crucial role in the diagnostic process [56]. The provisional diagnosis of hydatid disease in only 27.5% of the cases underscores the diagnostic challenges faced by clinicians, especially when the clinical presentation is atypical or when imaging findings are inconclusive [57].
The importance and priority of infection prevention by practicing several preventive actions, especially in developing countries, has been proposed. The most significant of them included self-hygiene practices, proper washing and cooking of foods, and avoiding eating raw foods or groceries [27]. Regarding management, surgical intervention was the primary treatment modality [1,2,7,58]. A study indicated that while VATS has been successfully applied in managing pulmonary HCs, its adoption remains limited. It has been pointed out that many surgeons are still hesitant to use VATS due to a lack of familiarity with the technique and concerns about potential complications, such as cyst rupture or spillage of infectious material [59]. In this review, authors came across similar findings, such as thoracotomy being performed in 37.3% of cases and VATS being performed in 1.9%. This may depend on cyst size and location. Furthermore, the low utilization of minimally invasive approaches like thoracoscopy may suggest either a preference for traditional open techniques or a lack of resources or expertise in minimally invasive surgery in some settings. The postoperative outcomes were generally favorable, with only 7.8% of patients facing complications, and no recurrence was reported, emphasizing the effectiveness of surgical management.
Machboua et al. on intra-thoracic extra-pulmonary hydatidosis noted that the average duration of hospitalization was only seven days, which is similar to what was found in this study (8.58 ± 4.44 days) [46].
The administration of post-operative albendazole alone (49%) or in combination with other medications (1.9%) may appear to be a standard practice to prevent recurrence, even though no recurrences were reported in this study. This could reflect a preventive strategy against the possible dissemination of HCs during surgery [1,14,15,17,18]. Overall, the study may provide valuable insights into the epidemiology, clinical presentation, diagnostic strategies, and management outcomes of chest wall HCs; however, the lack of essential data in a number of reviewed studies might generate biased or non-conclusive findings.
Conclusion
Despite its rarity, chest wall HC may have a good prognosis with few complications. Given its often-nonspecific presentation, reviewing the patient's medical history may help establish an accurate provisional diagnosis.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable, as systematic reviews do not require ethical approval.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: FHK and BAA were significant contributors to the conception of the study and the literature search for related studies. HOA and DHH involved in the literature review, study design, and manuscript writing. HKA, AHH, AHA, AAM, SMA, SOK, FA, SSA, and SHM were involved in the literature review, the study's design, the critical revision of the manuscript, and data collection. FHK and HOA confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Are Cervical Ribs Indicators of Childhood Cancer? A Narrative Review
Fahmi H. Kakamad, Lawand Ahmed Sharif, Ahmed H. Ahmed, Sakar O. Arif, Omed M. Hussein, Azad S....
Abstract
A cervical rib (CR), also known as a supernumerary or extra rib, is an additional rib that forms above the first rib, resulting from the overgrowth of the transverse process of a cervical vertebra. Increasingly recognized as a potential marker of developmental disruptions and genetic instability, CRs are believed to arise from mutations in homeobox (Hox) genes that influence axial skeletal development. While often asymptomatic, CRs have been linked to thoracic outlet syndrome and a higher prevalence in individuals with certain childhood cancers. Studies have reported associations between CRs and malignancies such as neuroblastoma, brain tumors, leukemia, sarcomas, Wilms tumor, and germ cell tumors, suggesting possible shared embryological pathways or genetic predispositions. However, conflicting research findings highlight inconsistencies in these associations, underscoring the need for further investigation. This review aims to assess the association between CRs and childhood cancers by examining prevalence rates, exploring genetic and developmental links, evaluating inconsistencies in existing research, and identifying gaps for future study to clarify the clinical significance of CRs in cancer risk assessment.
Introduction
A Cervical rib (CR), also known as a "neck rib" or "supernumerary rib," is an extra rib that forms above the first rib, near the collarbone. It develops due to an overgrowth of the transverse process of a cervical spine vertebra. It is thought to result from mutations in homeobox (Hox) genes, which play a role in shaping the axial skeleton in humans and vertebrates. This rib can occur on either side and may be unattached (floating) or fused with the first rib. It can range from a fully formed bone to a delicate fibrous strand [1].
The CRs are present in about 2% of the general adult population. The prevalence is higher in women, who are about twice as likely to have CRs as men. Additionally, ethnic differences have been observed, with one study finding that CRs are more common in African Americans than in whites [2].
Typically, CR is discovered incidentally through radiographic imaging unless it causes symptoms [3]. In some cases, CR can contribute to thoracic outlet syndrome by narrowing the interscalene triangle, leading to pain, weakness, numbness, or cold sensitivity in the affected limb [1, 4, 5]. The first documented clinical signs of neurovascular compression associated with CRs were reported by Cooper in 1818 [6].
Studies have demonstrated a higher prevalence of CRs in individuals with childhood cancers. This association may stem from disruptions in embryonic development during critical stages of blastogenesis, which can simultaneously lead to cervical segmentation defects and increase cancer susceptibility [7, 8].
Moreover, CRs are often regarded as markers of adverse developmental events or genetic instability. Their higher prevalence in stillborn fetuses and individuals with chromosomal abnormalities further underscores their potential role as indicators of systemic vulnerabilities that may contribute to malignancy risk. These findings highlight the importance of understanding rib anomalies (RAs) as anatomical curiosities and potential markers for identifying individuals at increased risk for certain cancers [9]. This study aims to review the association between CRs and cancer, with all referenced articles assessed for eligibility [10].
Studies Linking Rib Anomalies to Childhood Cancers
Despite growing awareness of a possible connection between RAs and malignancies, research on this topic remains limited. Only four studies have examined this association, each providing valuable insights into the potential link.
The earliest study by Schumacher et al. (1995) investigated the relationship between RAs and childhood malignancies by reviewing chest X-rays of 1,000 children with cancer and 200 control patients with non-malignant conditions. They found a significantly higher prevalence of RAs, particularly CRs, in children with certain malignancies compared to controls. This suggested that these skeletal abnormalities might be linked to altered morphogenesis in tumor development [7].
A decade later, Merks et al. (2005) conducted a more extensive study analyzing chest radiographs of 906 children with cancer and 881 healthy Caucasian pediatric controls. Their findings confirmed previous reports, demonstrating a higher occurrence of specific RAs in children with certain malignancies. They emphasized the potential role of genetic predisposition in cancer development and suggested that skeletal anomalies could serve as markers for underlying genetic abnormalities [8].
Loder et al. (2007) expanded on these findings by focusing on rib number variations in 218 children with malignancies and 200 control children who had been admitted for polytrauma or suspected child abuse. Their study highlighted a significant difference in rib counts between children with cancer and healthy controls. They speculated that genes involved in vertebral and rib development might also play a role in cancer predisposition, suggesting the possibility of using skeletal anomalies as a screening tool for early cancer detection [11].
Finally, Zierhut et al. (2011) reinforced the association between RAs and childhood cancers through a hospital-based case-control study of 459 pediatric cancer patients and 1,135 controls who had undergone chest X-rays for non-cancer-related reasons. Their research confirmed that children with cancer were more likely to have RAs, particularly those diagnosed with specific malignancies. They underscored the need for further studies to determine the biological mechanisms linking RAs to cancer development [12].
Cancers Linked to Cervical Ribs
Neuroblastoma
Neuroblastoma is a highly aggressive tumor that develops from neural crest cells and is the most common cancer in infants under one year old worldwide [13]. It represents about 10% of all pediatric cancers and primarily affects children within their first five years of life [14].
A defining characteristic of neuroblastoma is its highly variable clinical behavior. In approximately 50% of affected infants, the tumor regresses spontaneously, whereas in others, it advances into an aggressive, metastatic disease that is often resistant to standard treatments like chemoradiotherapy, stem cell transplantation, and immunotherapy [15]. This unpredictability complicates treatment, especially for high-risk patients who experience chemo-resistant relapse, with survival rates remaining below 40% [14].
The initiation and progression of neuroblastoma are driven by genetic abnormalities that interfere with cell division, proliferation, and apoptosis [15]. Significant genetic factors include MYCN amplification, TP53 deletions, ALK mutations or amplifications, TERT rearrangements, ATRX deletions or mutations, and segmental chromosomal aberrations. However, whole-genome sequencing studies have identified only a limited number of recurrent somatic mutations, making the development of targeted therapies challenging. Consequently, a precise understanding of the biological complexity and diversity of neuroblastoma is crucial for improving diagnostic and treatment approaches [15].
Schumacher et al. (1992) identified a strong correlation between neuroblastoma and CRs, reporting that 33% of children with neuroblastoma had CRs, a markedly higher prevalence than in the general population. This notable disparity suggests a potential developmental or genetic connection between neuroblastoma and skeletal anomalies. Furthermore, neuroblastoma was the only malignancy in their study to exhibit a significantly increased incidence of rib bifurcation (4.5%), a rate nearly four times higher than expected, reinforcing the possibility of disrupted skeletal development linked to the disease [7].
In contrast, Merks et al. (2005) analyzed 61 neuroblastoma patients and found that 9.8% had CRs, compared to 6.1% in the control group. While this suggests a slightly increased prevalence, the difference was not statistically significant (p = 0.252). This discrepancy with Schumacher et al. (1992) may be due to differences in sample size, diagnostic criteria, or population characteristics [7, 8].
Loder et al. (2007) took a broader approach by grouping neuroblastoma with other neural malignancies. Their findings showed a higher incidence of RAs (35%) in children with neural tumors compared to those with other malignancies. However, they did not specifically find an association between neuroblastoma and CRs. Among the eight neuroblastoma patients in their study, RAs were present, but no cases of CRs were observed. Instead, the most common skeletal abnormality was a reduced rib count, with affected children having 22 or 23 ribs instead of the typical 24. This suggests that while RAs may be linked to neuroblastoma, the specific presence of CRs may not be a defining characteristic [11].
Similarly, Zierhut et al. (2011) analyzed 31 neuroblastoma cases and found that 6.4% had RAs. However, the study did not report how many of these cases involved CRs specifically. The statistical analysis yielded an odds ratio (OR) of 1.46 (95% CI: 0.34–6.30) for any rib anomaly in neuroblastoma patients, indicating a slightly higher occurrence of skeletal abnormalities but without statistical significance. The lack of a significant association between RAs and neuroblastoma may be due to the study’s small sample size, which could have limited its ability to detect a stronger relationship [12].
Overall, while Schumacher et al. (1992) identified a strong association between neuroblastoma and CRs, subsequent studies, including those by Merks et al. (2005), Loder et al. (2007), and Zierhut et al. (2011), reported weaker or non-significant links [7, 8, 11, 12]. The inconsistencies across studies highlight the need for further research with larger sample sizes and more detailed skeletal analyses to determine whether CRs represent a meaningful developmental marker for neuroblastoma or if their observed association is due to broader skeletal anomalies.
Brain Tumors
A brain tumor forms when cells grow irregularly and multiply uncontrollably. These tumors may arise from brain cells, the meninges (the membranes surrounding the brain), glands, or nerves. They can cause direct damage to brain cells and elevate pressure within the skull, resulting in harmful effects [16].
Due to their severity, brain tumors are classified into different grades. Grade 1 tumors are the least aggressive, typically associated with more prolonged survival. They grow slowly, resemble normal cells under a microscope, and can often be effectively treated with surgical removal. Examples include pilocytic astrocytoma, ganglioglioma, and gangliocytoma. Grade 2 tumors also grow slowly but appear abnormal under a microscope. Some may invade nearby tissues and tend to recur, occasionally progressing to a higher grade [16].
Grade 3 tumors are malignant and share similarities with grade 2 tumors but are more likely to recur as grade 4 tumors. Grade 4 tumors are the most aggressive, growing rapidly and appearing highly abnormal under a microscope. They invade surrounding brain tissue, form new blood vessels, and contain areas of dead cells at their core. Glioblastoma Multiforme is a well-known example of a grade 4 tumor [16].
Brain tumors develop due to a combination of genetic, environmental, and molecular factors. Genetic predisposition plays a key role, with inherited syndromes such as neurofibromatosis and Li-Fraumeni syndrome increasing the risk. Environmental exposures, particularly ionizing radiation, are well-established contributors, while occupational exposure to chemicals and electromagnetic fields remains inconclusive. Viral infections, immune dysfunction, and chronic inflammation may also influence tumor development [17, 18].
The study by Schumacher et al. (1992) found that 27.4% of children with brain tumors had CRs, compared to only 5.5% in the control group (p < 0.001). This substantial difference suggests a potential developmental link between CRs and brain tumors, possibly due to shared embryological pathways affecting both skeletal and neural development. The high prevalence reported in this study indicates that CRs might serve as an anatomical marker for underlying genetic or developmental disruptions associated with brain tumor formation [7].
Merks et al. (2005) further supported this hypothesis by identifying a significant association between CR anomalies and astrocytomas. Their study reported that 18.2% of childhood cancer patients with astrocytomas had CRs, compared to 6.1% in the control group. This finding suggests that certain subtypes of brain tumors, particularly astrocytomas, may have a stronger developmental association with CR anomalies [8].
However, Loder et al. (2007) did not find a strong link between brain tumors and CRs. While RAs were more frequent in children with neural malignancies (35%), none of these anomalies were identified as CRs. Instead, children with neural malignancies were found to be 6.23 times more likely to have an abnormal rib count compared to the control group. This suggests that while skeletal anomalies may be associated with neural tumors in general, CRs specifically may not be a consistent marker [11].
Zierhut et al. (2011) also provided a more tempered perspective. Their study examined 34 pediatric cases of central nervous system tumors, including brain tumors, and found that 8.8% (n = 3) had some form of rib anomaly. However, they did not identify a statistically significant association between CRs and brain tumors. This finding further weakens the case for a direct link and suggests that broader skeletal anomalies may be involved rather than CRs specifically [12].
Overall, while Schumacher et al. (1992) and Merks et al. (2005) suggest a possible association between CRs and brain tumors, the findings from Loder et al. (2007) and Zierhut et al. (2011) cast doubt on the specificity of this relationship [7, 8, 11, 12]. The inconsistencies across studies highlight the need for further research to determine whether CRs are a true marker for brain tumor risk or if their association is due to broader developmental abnormalities affecting multiple organ systems.
Leukemia
Leukemia is a frequently occurring cancer in both children and adults. It results from disruptions in normal cell regulation that lead to the uncontrolled growth of hematopoietic stem cells in the bone marrow. It is more commonly found in males and individuals of white ethnicity, with its prevalence increasing with age. On average, about one in 70 people will develop leukemia during their lifetime. The four main types of leukemia, each with unique characteristics, are acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia, and chronic myelogenous leukemia [19].
Leukemia occurs worldwide, with a higher prevalence and overall mortality in more developed countries. However, the mortality rate tends to be greater in developing nations [20]. The development of leukemia results from a complex interaction between genetic predisposition and environmental influences, with neither factor alone provides a complete explanation. While significant strides have been made in identifying risk factors and potential disease mechanisms, the exact causes of most leukemia cases remain uncertain. Known risk factors include genetic syndromes, chromosomal abnormalities, radiation exposure, specific chemicals, certain viral infections, and prior cancer treatments, but these account for only a fraction of cases [20, 21].
The study by Schumacher et al. (1992) found a significant association between CRs and leukemia, with 26.8% (n = 227) of leukemia patients exhibiting CRs compared to only 5.5% (n = 11) in the control group (p < 0.001). This finding suggests a potential developmental or genetic link between skeletal anomalies and leukemia, possibly due to disruptions in early embryonic development affecting both hematopoietic and skeletal systems [7].
Similarly, Merks et al. (2005) identified a significant association between CR anomalies and ALL, with a prevalence of 12.1% in ALL patients compared to 6.1% in controls (p = 0.011). This reinforces the idea that skeletal anomalies may serve as a marker for certain pediatric malignancies, though the underlying mechanisms remain unclear [8].
Loder et al. (2007) further examined RAs in leukemia patients. Among 218 children with malignancies, 75 had leukemia (64 with ALL and 11 with AML) [11]. The incidence of abnormal rib counts in children with lymphoproliferative malignancies (which includes leukemia and lymphoma) was 15%, compared to 8% in the control group. Logistic regression analysis revealed that children with leukemia and other lymphoproliferative malignancies were twice as likely to have an abnormal rib count compared to controls. While this supports a broader association between RAs and leukemia, the study did not specifically focus on CRs, making direct comparisons with Schumacher et al. (1992) and Merks et al. (2005) more challenging [7, 8].
In contrast, Zierhut et al. (2011) provided a more nuanced perspective. While their study confirmed an overall link between RAs and an increased risk of childhood cancers, the specific association between CRs and leukemia did not reach statistical significance. Notably, children with AML had a significantly higher likelihood of RAs, with an adjusted OR of 2.29 (95% CI: 1.02–5.13). However, when CRs were analyzed separately, the association weakened (adjusted OR = 1.63, 95% CI: 0.55–4.80), failing to reach statistical significance. This suggests that while RAs in general may be linked to leukemia, CRs alone may not be a consistent marker for the disease [12].
Overall, the studies by Schumacher et al. (1992) and Merks et al. (2005) suggest a potential association between CRs and leukemia [7, 8, 11]. However, Zierhut et al. (2011) cast doubt on the specificity of this relationship, indicating that while RAs may be more common in leukemia patients, CRs alone may not be a reliable marker [12]. Further research is needed to clarify whether CRs are a developmental indicator of leukemia risk or if their observed association is due to broader skeletal anomalies linked to pediatric malignancies.
Sarcomas
Sarcomas comprise a diverse group of mesenchymal tumors, with over 100 distinct diagnostic types. This variability is evident through both light microscopy and gene expression analysis. Even within the same histological category, there can be substantial differences in biological behavior [22].
Sarcomas are generally classified into two main types: soft tissue sarcomas and primary bone sarcomas, each requiring unique staging and treatment strategies. Soft tissue sarcomas are typically categorized based on genetic alterations and microscopic examination of hematoxylin-eosin–stained tissue, where morphological features resembling normal tissues are identified. Additionally, sarcomas are further assessed by histologic grade. The three key prognostic factors are the tumor’s grade, size, and primary location [22].
Sarcomas usually arise spontaneously, but certain risk factors have been identified. Exposure to ionizing radiation, often from cancer treatments, increases the likelihood of sarcomas, typically appearing 7-10 years after exposure. Other risk factors include chronic lymphedema, exposure to chemicals like vinyl chloride, and infection with human herpesvirus 8, which is linked to Kaposi sarcoma [22].
Several genetic syndromes also elevate sarcoma risk. Neurofibromatosis type 1 leads to benign and malignant nerve sheath tumors, while neurofibromatosis type 2 is associated with meningiomas and cranial nerve schwannomas. Gardner syndrome increases the risk of desmoid tumors, and hereditary retinoblastoma raises the likelihood of osteosarcoma and soft tissue sarcomas later in life. Li-Fraumeni syndrome, caused by TP53 mutations, also predisposes individuals to sarcomas [22].
Schumacher et al. (1992) found a significant association between CRs and sarcomas, reporting their presence in 24.5% of patients with soft tissue sarcomas (p < 0.001) and 17.1% of those with Ewing sarcoma (p < 0.01), compared to only 5.5% in the control group. These findings suggest a potential developmental or genetic link between CR anomalies and sarcomas, possibly due to early mesodermal development disruptions, which influences skeletal and soft tissue formation [7].
However, later studies did not consistently replicate these findings. Merks et al. (2005) found much lower rates of CRs in sarcoma patients, with 7.4% of rhabdomyosarcoma cases (5/68, p = 0.687), 6.3% of osteosarcoma cases (3/48, p = 0.973), and 7.7% of Ewing sarcoma cases (3/39, p = 0.692). None of these differences were statistically significant, suggesting that the initial association reported by Schumacher et al. (1992) may have been due to sample variation or other confounding factors. The stark contrast between these two studies raises questions about whether the observed link is truly biologically relevant or if it was an artifact of study design or population differences [8].
Loder et al. (2007) examined RAs in solid tumors, including osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma, finding that 13% of cases exhibited RAs. However, this association was not statistically significant (p = 0.15), suggesting that while RAs may be more common in children with cancer, they do not appear to be strongly associated with sarcomas specifically [11].
Similarly, Zierhut et al. (2011) identified a general link between RAs and childhood cancers but did not find a significant correlation between CRs and sarcomas. This further weakens the hypothesis that CRs are a marker for sarcoma risk [12].
Overall, while the Schumacher et al. (1992) study initially suggested a strong association between CRs and sarcomas, more recent studies, including those by Merks et al. (2005), Loder et al. (2007), and Zierhut et al. (2011), have not confirmed this relationship [7, 8, 11, 12]. The inconsistencies in findings suggest that if a link does exist, it may be weaker than initially thought or influenced by confounding factors. Further research with larger sample sizes and refined methodologies is needed to clarify whether CRs have any true predictive value for sarcoma development.
Wilms tumor
Wilms tumor (WT), or nephroblastoma, is a malignant solid tumor that arises from the primitive renal bud. It is the most common primary renal tumor in the urogenital tract of children and typically occurs unilaterally in 90–95% of cases. However, it can also present bilaterally or multicentrically, particularly in cases associated with genetic factors, occurring either simultaneously (synchronously) or at different times (metachronously). WT accounts for approximately 2% to 6% of all childhood cancers [23].
Both genetic and environmental factors influence the development of WT. Genetic mutations play a crucial role, particularly in the WT1 and WT2 genes, which are vital for kidney development [23]. WT1 mutations are linked to syndromic forms of WT, such as WAGR and Denys-Drash syndromes, while WT2 abnormalities are associated with Beckwith-Wiedemann syndrome. Additionally, mutations in CTNNB1 (β-catenin), TP53, and microRNAs contribute to tumor development. Environmental factors, including parental exposure to pesticides before conception or during pregnancy, may increase the risk, though their precise impact remains unclear. WT is frequently associated with congenital syndromes involving developmental abnormalities [23].
Schumacher et al. (1992) identified a significant association between CRs and WT, reporting that 23.5% of children with WT had CRs, compared to only 5.5% in the control group (p < 0.001). This strong statistical significance suggests a potential developmental link between skeletal anomalies and WT [7].
However, Merks et al. (2005) found that 9.8% of children with WT had CRs, compared to 6.1% in the control group, but the difference was not statistically significant (p = 0.115). This suggests that while CRs may be more common in WT patients, the association is not robust enough to be considered a reliable marker [8]. Similarly, Zierhut et al. (2011) reported a statistically significant increase in overall RAs among children with renal tumors, including WT. However, when analyzing CRs specifically, they did not find a significant association, further casting doubt on their role as a consistent indicator of WT [12].
Loder et al. (2007) provided additional support for a general link between RAs and pediatric malignancies but did not specifically analyze CRs in WT patients. This broader pattern suggests that skeletal anomalies may be associated with childhood cancers but does not confirm a direct link between CRs and WT [11].
These findings indicate that while there is some evidence of a relationship between skeletal anomalies and WT, the inconsistent association with CRs suggests that other factors may be at play. Additional research is needed to explore the genetic and developmental mechanisms underlying these observations, which could provide further insights into the etiology of WT and its potential links to congenital anomalies.
Germ Cell Tumors
Germ cell tumors (GCTs) are the most diverse childhood neoplasms. The majority are benign teratomas, presenting as heterogeneous masses with cystic and solid components. However, approximately 20% of GCTs are malignant, accounting for 3% of pediatric cancers. Malignant GCTs can occur at any age but follow a bimodal distribution, primarily affecting infants and adolescents [24].
These tumors can develop in various anatomical locations, including the gonads, sacrococcygeal region, mediastinum, retroperitoneum, and other para-axial sites. They are believed to originate from a common progenitor germ cell but exhibit diverse histologies, such as endodermal sinus tumor (yolk sac tumor), germinoma (dysgerminoma or seminoma), embryonal carcinoma, and choriocarcinoma. Different histological types often coexist within a single tumor, with approximately 25% of pediatric GCTs containing multiple histologic components [24].
Malignant GCTs have specific genetic predispositions, and genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) in genes such as KITLG, SPRY4, DMRT1, and TERT, which are linked to the development of testicular GCTs [25].
Schumacher et al. (1992) investigated the relationship between CR anomalies and yolk sac tumors, a type of GCT, but did not find a significant association. The prevalence of RAs in patients with yolk sac tumors was 3.4%, which was not significantly different from the normal population (5.5%). This finding suggests that, unlike other pediatric malignancies, GCTs may not share a strong developmental link with skeletal anomalies [7].
In contrast, Merks et al. (2005) reported a statistically significant association between CR anomalies and GCTs, with 14.7% of GCT patients exhibiting CRs compared to 6.1% in controls (p = 0.046). This suggests a potential genetic or developmental link between GCTs and skeletal anomalies, though the mechanisms underlying this association remain unclear. The higher prevalence observed in this study raises the possibility that certain genetic mutations or disruptions in embryonic development may predispose individuals to both conditions [8].
Loder et al. (2007) did not specifically analyze CRs in relation to GCT. However, their study demonstrated a broader statistically significant association between RAs and childhood malignancies. Children with cancer had a higher prevalence of RAs (18%) compared to the control group (8%), with a p-value of 0.003. While this finding supports a general link between skeletal anomalies and pediatric cancers, it does not establish a direct connection between CRs and GCTs [11].
Similarly, Zierhut et al. (2011) did not specifically report a link between CR and GCTs. The absence of a reported association with GCTs suggests that these tumors may not be as strongly linked to skeletal anomalies as other childhood malignancies [12].
Overall, while some studies indicate a potential link between CR anomalies and GCTs, the evidence remains inconsistent. Merks et al. (2005) provided the most substantial support for an association, but findings from Schumacher et al. (1992) and Zierhut et al. (2011) did not confirm this relationship [7, 8, 12]. Additional research is needed to determine whether CR anomalies can serve as a marker for GCTs or if the observed association is due to other underlying developmental factors.
Other Rib Anomalies Associated with Cancer
Numerical RAs, such as having fewer than 24 ribs, were also found to be more common in children with malignancies. Loder et al. (2007) reported that 18% of children with malignancies had an abnormal rib number compared to 8% of controls. Among specific cancer types, neural tumors had the highest incidence of abnormal rib counts (35%), followed by lymphoproliferative malignancies (15%) and solid tumors (13%) [11]. Similarly, Zierhut et al. (2011) found that children with AML, renal tumors, and hepatoblastoma had a significantly higher likelihood of having an abnormal rib count (p = 0.008) [12].
Rib bifurcations, which involve rib splitting into two separate structures, have also been linked to certain malignancies. Schumacher et al. (1992) reported that 4.5% of neuroblastoma patients exhibited rib bifurcations, a rate four times higher than that of the normal population (1.07%). This suggests that developmental abnormalities affecting rib segmentation may be related to tumorigenesis in neural crest-derived cancers such as neuroblastoma [7].
Rib synostosis, or rib fusion, has also been observed in childhood malignancies. Though relatively rare, this anomaly was documented in some studies. Schumacher et al. (1992) found that 0.5% of cancer patients had rib synostosis compared to none in the control group, while Merks et al. (2005) identified synostosis in 0.2% of cancer patients. Notably, leukemia and brain tumor patients were more likely to present with this anomaly [7, 8].
Additionally, rib hypoplasia (underdeveloped ribs) and aplasia (missing ribs) have been reported in association with various malignancies. Loder et al. (2007) found that children with malignancies were more likely to have fewer ribs, with 44 cases of 22 ribs and 10 cases of 23 ribs, compared to just 16 cases in the control group (p = 0.003) [11]. Schumacher et al. (1992) also reported that 1.2% of cancer patients had rib aplasia or hypoplasia, compared to 0.5% in controls (Table 1) [7].
Study |
Year |
Sample Size |
Key Findings |
Cancer Types |
Types of Rib Anomalies |
Conclusion |
Schumacher et al. [7] |
1992 |
1000 cancer, 200 controls |
Rib anomalies more common in cancer patients (21.8% vs. 5.5% in controls). Neuroblastoma had the highest rate (33%). |
Neuroblastoma, Brain tumors, Leukemia, Soft tissue sarcoma, Wilms' tumor, Ewing sarcoma |
CRs, Bifurcations, Synostoses, Aplasia/Hypoplasia |
Rib anomalies may be linked to tumor development. Further research needed. |
Merks et al. [8] |
2005 |
906 cancer, 881 controls |
CRs were more common in cancer patients (8.6% vs. 6.1% in controls), particularly in leukemia and astrocytoma. |
ALL, Astrocytoma, Germ Cell Tumors |
CRs, Bifid ribs, Rib synostosis |
Rib anomalies could indicate genetic mutations linked to cancer. |
Loder et al. [11] |
2007 |
218 cancer, 200 controls |
Rib anomalies were more frequent in cancer patients (18% vs. 8%). Neural tumors had the highest incidence (35%). |
Neural tumors, Lymphoproliferative malignancies, Solid tumors |
Fewer than 24 ribs, Rib fusions, Bifurcations |
Possible link between rib anomalies and homeobox gene mutations. |
Zierhut et al. [12] |
2011 |
625 cancer, 1499 controls |
Significant association found between rib anomalies and leukemia, renal tumors, and hepatoblastoma. |
AML, Renal tumors, Hepatoblastoma |
Fewer or more than 24 ribs, CRs, Bifurcations |
Rib anomalies could be a marker for cancer predisposition. More research needed. |
ALL: Acute Lymphoblastic Leukemia, AML: Acute Myelogenous Leukemia, CR: Cervical rib |
Future Perspectives
Future research should focus on large-scale, multicenter studies to validate these findings and establish whether RAs, particularly numerical variations, bifurcations, synostoses, and hypoplasia, can be predictive markers for specific cancers. Advances in imaging technologies, such as high-resolution computed tomography and magnetic resonance imaging, may enhance the accuracy of rib anomaly detection and contribute to more precise correlations with cancer risk.
Genetic and molecular studies are also needed to explore the role of Hox genes and other developmental pathways in skeletal formation and oncogenesis. Identifying genetic mutations contributing to RAs and tumor development could lead to novel insights into cancer predisposition syndromes. Additionally, investigating the role of environmental and epigenetic factors in the occurrence of RAs and malignancies may provide a more comprehensive understanding of their shared etiology.
From a clinical perspective, integrating rib anomaly screening into routine pediatric check-ups for high-risk populations could help in early cancer detection. However, before implementing such screening, further studies must determine the predictive value of RAs and whether they can be used as independent risk markers.
Ultimately, interdisciplinary collaboration between geneticists, radiologists, oncologists, and developmental biologists will be crucial in advancing understanding of the link between RAs and childhood cancer. As research continues, these efforts may pave the way for novel diagnostic strategies and targeted therapies for pediatric malignancies.
Conclusion
CRs may serve as valuable indicators of underlying genetic and developmental abnormalities linked to pediatric cancers. Understanding these connections could ultimately contribute to improved cancer screening, early diagnosis, and personalized treatment strategies for children at risk.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: FHK and BAA were significant contributors to the conception of the study and the literature search for related studies. HAN and MNH involved in the literature review, study design, and manuscript writing. SKA, AKG, WNS, HSN, LJM, ASH, OMH, SOA, AHA, LAS and ADS were involved in the literature review, data collection, the study's design, and the critical revision of the manuscript. FHK and BAA confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: Perplexity (Deep Research) and ChatGPT (GPT-4.5) were used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.

Management of Lower Limb Varicose Veins Using Endovenous Laser Ablation, Micro-Phlebectomy, and Sclerotherapy Using Multimodal Analgesia
Fahmi H. Kakamad, Fuad E. Fuad, Soran H. Tahir, Ayoob A. Mohammed, Rezheen J. Rashid, Hiwa O....
Abstract
Introduction
Previously, the conventional surgical procedure of high-ligation and saphenous stripping was commonly used to treat varicose veins (VVs). However, contemporary advancements have led to the rapid evolution of VV management. This study shares a single center's experience in treating patients with lower limb VVs through endovenous laser ablation in combination with phlebectomy and sclerotherapy using multimodal analgesia.
Methods
This case series study included consecutive patients diagnosed with lower limb VVs. The inclusion criteria encompassed VVs categorized from score C1 to C6 (clinical, etiologic, anatomic, and pathophysiological), saphenofemoral incompetence, and patients aged between 18 and 75.
Results
A total of 153 patients were enrolled. The majority were female (73.0%), resulting in a female-to-male ratio of 2.73:1. The age of patients ranged from 18 to 73 years, with a mean age of 40.8 ± 11.7 years. Regarding post-procedural complications, wounds developed in 25 patients (16.3%), making it the most common complication, while thrombophlebitis occurred in 15 cases (9.8%), skin discoloration in nine cases (5.9%), and recanalization and DVT each in a case (0.7%). Due to extensive varicose veins, 31 patients (20.0%) required a sclerotherapy session six weeks after the operation. Patients could return to routine daily activities within 4 to 10 hours. Overall, the patient satisfaction rate (complete and partial) was 85%. Only a case of recurrence (0.7%) was reported after a one-year follow-up.
Conclusion
Endovenous laser ablation, in combination with phlebectomy and sclerotherapy using multimodal analgesia, may yield a satisfactory outcome in patients with moderate to severe VVs.
Introduction
Varicose veins (VVs) are abnormally twisted and dilated blood vessels, typically located in the lower limbs. They originate from damaged or faulty venous valves, which may subsequently give rise to painful swelling and the potential formation of blood clots [1]. It is the most commonly encountered among vascular diseases, affecting up to one-third of the population and profoundly impacting the quality of life [2]. Increased age, female gender, multiparity, obesity, a history of deep venous thrombosis (DVT), and engagement in occupations involving extended periods of standing are all recognized as significant risk factors associated with the onset of VVs [3]. Historically, VVs were often viewed as a cosmetic problem, and patient preferences largely influenced treatment decisions. However, advancements in medical imaging, particularly duplex ultrasonography, revolutionized the understanding of VVs by providing a more precise assessment of venous reflux and allowing healthcare professionals to accurately diagnose the underlying venous insufficiency contributing to VVs [4]. Previously, the conventional surgical procedure of high-ligation and saphenous stripping was commonly used for the treatment of VVs. However, contemporary advancements have led to the rapid evolution of VV management, offering minimally invasive interventions such as radiofrequency (RFA), laser ablations, foam, liquid sclerotherapy, and microphlebectomy [5]. Endovenous laser ablation (EVLA) uses laser energy to occlude impaired veins, rerouting blood circulation toward healthier venous pathways. Microphlebectomy presents another alternative therapeutic modality involving the surgical removal of superficial veins via small puncture incisions. Sclerotherapy entails the injection of a sclerosing agent into afflicted veins, resulting in their closure and redirection of blood flow [6]. This study aims to share the experience of a single center in treating patients with lower limb VVs through EVLA in combination with phlebectomy and sclerotherapy under multimodal analgesia. The study avoided citing suspicious data by checking for predatory behavior among the referenced studies [7].
Methods
Study design
The study was a single-center case series encompassing consecutive patients diagnosed with lower limb VVs and treated at the Thoracic and Vascular Surgery Department of Smart Health Tower from January 2020 to September 2023. Patients provided consent to participate in the study and to authorize the publication of any related data.
Data collection
Following data de-identification, the necessary information was retrospectively gathered from patients' profiles within the department's database. This included patient demographics, chief complaint, clinical score, affected side, severity of the condition, ultrasound examination results, and treatment outcomes.
Eligibility criteria
The inclusion criteria encompassed VVs categorized from score C1 to C6 (clinical, etiologic, anatomic, and pathophysiological) (CEAP), presence of saphenofemoral incompetence, and patients aged between 18 and 75 years. The exclusion criteria comprised any prior treatment of VVs, suspicion or confirmation of DVT or occlusion, contraindications to anesthesia, and refusal to undergo the treatment procedure.
Intervention
In the pre-operative phase, approximately 30 minutes before the operation, patients received a combination of medications, including pethidine (50 mg subcutaneously), ketorolac (30 mg intramuscularly), and ondansetron (8 mg), if there were no contraindications. In the operating theater, intravenous pethidine was administered after properly marking the varicose vein sites by injecting normal saline, patient positioning, and monitoring. This was followed by a slow tramadol infusion (100 mg) and paracetamol (1000 mg). Continuous administration of dexmedetomidine (100 –150 µg in 100 ml of normal saline) was initiated, with oxygen supplementation adjusted as necessary. Antiemetic drugs, aside from ondansetron, were administered during the procedure unless contraindicated. In rare cases of anxiety or the requirement for minimal sedation, fentanyl (50 µg), midazolam (1mg), or a combination of both were included.
The EVLA procedure started with a Doppler ultrasound by a radiologist to guide a needle to access the great saphenous vein (GSV). Then, a guide wire was carefully inserted into the vein, followed by the placement of an introducer sheath, which might include a dilator. Just below knee level was the preferred entry point for the insufficient GSV due to its larger size, straight course, and lower risk of nerve injury. The laser (1470 nm) was inserted into the varicose vein after verifying the laser's tip position by observing the red standby light through the skin with a diameter between 200 and 600 mm (dependent on the varicose vein and the laser parameters). The laser's settings were customized as necessary, and it was carefully withdrawn through the vein using a technique suited to the specific situation. The laser power was calibrated according to the vein size, with a minimum setting of 42 watts. The power was determined by multiplying the vein diameter by a factor of 7. After major vein ablation, micro-avulsion was done for the visible varicose veins using a particular instrument (Drawsh) (Figure 1). The reticular and telangiectasia were injected with a foamy solution consisting of two ml of polidocanol and eight ml of atmospheric air (1:4) as the sclerosing agent.
Statistical analysis
The data organization was conducted using Microsoft Excel 2019. Descriptive analysis was performed using the Statistical Package for the Social Sciences (SPSS) Version 25 for qualitative data synthesis. The data were presented as medians, means, standard deviations, frequencies, percentages, and ranges.
Results
A total of 153 patients were enrolled in this study. The majority were female (73.0%), resulting in a female-to-male ratio of 2.73:1. The age of patients ranged from 18 to 73 years, with a mean age of 40.8 ± 11.7 years. Over half of the cases were overweight (54.9%), and the mean BMI was 26.3 ± 4.2. The major chief complaint was pain (17.7%), followed by swelling (15.0%) and lower limb discoloration (5.2%). The disease was asymptomatic in 59.5% of the cases. The disease presented as VVs (C2) in most cases (73.9%), although 21 (13.7%) presented with reticular veins (C1) and 10 (6.5%) with telangiectasia (C1). Disease severity was moderate in over half of the cases (53.6%), followed by severe in 51 cases (33.3%). The majority of patients (61.4%) had bilateral lower limb involvement, while the remaining patients had unilateral involvement, with 22.2% affected in the left lower limb and 16.3% in the right lower limb. The mean diameters of the GSV undergoing treatment were 9 mm.
The mean reflux duration of the affected veins was 1.1 seconds, ranging from 0.6 to 2.5 seconds, with the procedure duration ranging from 45 to 220 minutes. Regarding post-procedural complications, wounds developed at the site of sclerosant injection in 25 patients (16.3%), making it the most common complication, while thrombophlebitis occurred in 15 cases (9.8%), skin discoloration in nine cases (5.9%), and recanalization and DVT each in a case (0.7%). The thrombophlebitis cases were treated with an anti-inflammatory agent. Wounds healed with proper dressing within two to three weeks. Due to extensive VVs, 31 patients (20.0%) required sclerotherapy six weeks after the operation. Additionally, all instances of skin discoloration resolved spontaneously. Patients could return to routine daily activities within 4 to 10 hours. Overall, 54.3% of the patients were completely satisfied with the outcome. Meanwhile, 30.7% were partially satisfied, and 15.0% were not satisfied with the procedure. Only a case of recurrence was reported during the one-year follow-up (Table 1).
Variables |
Frequency / Percentage |
Demographics |
|
Age range (median, mean ± SD), years |
18 – 73 (40, 40.8 ± 11.7) |
BMI (mean± SD), kg/m2 Underweight Normal Overweight Obesity |
26.3 ± 4.2 3 (2.0%) 52 (34.0%) 84 (54.9%) 14 (9.1%) |
Gender Male Female |
41 (27.0%) 112 (73.0%) |
Chief complaint Pain Swelling Lower limb discoloration Itching Extensive varicose vein impending rupture |
27 (17.7%) 23 (15.0%) 8 (5.2%) 4 (2.6%) 91 (59.5%) |
CEAP classification C1 C2 C3 C4 C5 C6 |
21 (13.7%) 113 (73.9%) 8 (5.2%) 6 (3.9%) 5 (3.3%) 0 (0.0%) |
Severity status Mild Moderate Severe |
20 (13.1%) 82 (53.6%) 51 (33.3%) |
Affected site Right lower limb Left lower limb Both lower limbs |
25 (16.3%) 34 (22.2%) 94 (61.4%) |
Reflux duration (seconds), mean (range) |
1.1 (0.6-2.5) |
Diameter of GSV (mm), mean (range) |
9 (6-22) |
Operation time (minutes), mean (range) |
70 (45-220) |
Returning to routine daily activity (hours), mean (range) |
6 (4-10) |
Satisfaction level Completely satisfied Partially satisfied Not satisfied |
47 (30.7%) 23 (15.0%) |
Post-procedure complications Wounds at the site of injections Thrombophlebitis Skin discoloration Recanalization Deep vein thrombosis |
25 (16.3%) 15 (9.8%) 9 (5.9%) 1 (0.7%) 1 (0.7%) |
Post laser injection (sclerotherapy) Yes No |
122 (80.0%) |
Recurrence |
1 (0.7%) |
Discussion
The VVs represent a prevalent condition, with occurrence rates typically ranging from 29.5% to 39.0% in women and 10.4% to 23.0% in men [1]. Annually, the condition manifests in approximately 2.6% of women and 1.9% of men. Its prevalence consistently rises with age, a trend often associated with increased height, weight, and body mass [1,8]. Chronic venous disease exacerbates the severity of symptoms, progressing from telangiectasia, characterized by the formation of threadlike patterns on the skin (referred to as spider veins), to VVs. This progression often imposes a substantial negative impact on the patient's quality of life [9]. In the current study, consistent with the genuine literature, females were predominantly affected, with a female-to-male ratio of 2.73:1. The mean age of patients, 40.8 years, aligns with previous findings [1,8]. The primary manifestation of the disease was VVs in the majority of cases (73.9%), indicating significant disease progression. Among the cases, the severity was moderate in 53.6% and severe in 33.3%.
Aligned with technological advancements, continual investigation has been undertaken to explore therapeutic approaches for treating VVs through endovenous methodologies [10]. A pivotal milestone occurred in 2001 when Navarro et al. reported the inaugural utilization of thermal endovenous ablation employing an 810 nm diode laser [11]. Subsequently, a consistent evolution in laser technology has ensued, accompanied by many studies employing diverse wavelengths and laser modalities [10,12,13]. At present, the Food and Drug Administration (FDA) has approved lasers of various wavelengths, including 810, 940, 980, and 1470 nm diode lasers, alongside 1319 and 1320 nm neodymium-doped yttrium aluminum garnet (Nd: YAG) lasers. Simultaneously, the progression of laser technology has stimulated research into thermal ablation techniques for the GSV using radiofrequency energy. The FDA endorsement for the application of radiofrequency energy in endovenous ablation procedures was granted in 1999 [10]. In 2002, Weiss et al. published the initial cases wherein patients underwent thermal ablation employing radiofrequency energy [14]. The current clinical practice guidelines advocate for ablation (EVLA and RFA) as the primary treatment for superficial venous insufficiency while recommending phlebectomy or sclerotherapy for addressing varicosities [15]. In the present study, EVLA (1470 nm) was employed in combination with phlebectomy and sclerotherapy to manage VVs in 153 patients.
A meta-analysis of 119 studies found success rates of 94% for EVLA and 84% for RFA from data on 12,320 legs [16]. Puggioni et al. reported one-month follow-up success rates of 100% for EVLA and 96% for RFA [17]. Bozoglan et al. reported no significant complications such as DVT, pulmonary embolism, or skin burns in either EVLA or RFA. Minor complications included induration (20.7% in EVLA and 31% in RFA), ecchymosis (31% in EVLA and 27.6% in RFA), and edema (27.6% in EVLA and 65.5% in RFA). They claimed that most minor complications, such as hematoma and ecchymosis, were attributed to the use of tumescent anesthesia rather than the procedures themselves. They reported a recanalization rate of 6.8% in the RFA group, while no instances of recanalization were noted in the EVLA group. Patient satisfaction levels were significantly higher with EVLA at 51.7% compared to the 31.0% satisfaction rate observed for RFA. Only 17.2% of patients reported satisfaction with both procedures. Individuals in the EVLA group typically returned to daily activities within 0.9 days, while those in the RFA group took an average of 1.3 days to resume regular activities. The mean duration of procedures was 31.2 minutes for EVLA and 32.7 minutes for RFA [10]. Another study involving 148 patients undergoing EVLA reported pain in over 50% of patients, hematoma in 40.5%, superficial vein thrombosis in 6.8%, induration in 6.8%, hyperpigmentation in 3.4%, infection and dysesthesia in less than 2%, and nerve damage occurring in less than 1% of cases [18]. Additionally, a meta-analysis reported the incidence of thrombophlebitis and hematoma at 4.9% and 4.4%, respectively [19]. Kawai et al. performed EVLA with and without phlebectomy and found hematoma in 26.6% of cases with phlebectomy and 23.2% of cases without phlebectomy. They reported no instances of DVT [15]. Because sclerotherapy plays a significant role in managing and diminishing the appearance of VVs, which have reached a severe stage [1], they needed additional sclerotherapy in 8 cases (3.2%) in the phlebectomy group and 26 cases (3.7%) in the non-phlebectomy group. The operation time ranged from 27 to 40 minutes in the EVLA with the phlebectomy group and 19 to 31 minutes in the counterpart group. Recanalization was observed in four cases (1.6%) in the EVLA with the phlebectomy group and in 25 cases (3.6%) in the latter group [15]. In this study, developing wounds was the most prevalent complication (16.3%), followed by thrombophlebitis (9.8%) and skin discoloration (5.9%). Thrombophlebitis was treated with an anti-inflammatory agent, skin discoloration resolved spontaneously, and wounds healed within a few weeks with dressing. The duration of the operation in the present study ranged from 45 to 220 minutes, with a mean of 70 minutes. The recanalization rate (0.7%) was lower than the rate reported by Kawai et al. [15] but higher than that reported by Bozoglan et al [10]. Patients returned to daily activities within 4 to 10 hours, and the overall treatment satisfaction (partial and complete) reached 85%, surpassing Bozoglan et al.'s [10]. There was a case of DVT, and sclerotherapy was required in 20% of cases due to the severity of the disease.
Regarding the working principle, EVLA enables veins to absorb energy for heat generation, leading to vein obliteration. The energy utilized during the procedure significantly impacts the outcome. It has been discovered that energy delivery directly influences recurrence, with lower energy levels yielding poorer outcomes than higher energy levels [20]. The recurrence rate for up to 10 years was found to be 66% in EVLA, and 36% of the patients needed reintervention [21]. To mitigate the risk of recurrence, a laser wavelength of 1470 nm was employed in the procedures of the current study. After one year of follow-up, only a case of recurrence was reported. This study has some drawbacks, including a retrospective design that means crucial data may be overlooked for discussion and a short follow-up period to properly indicate the recurrence rate.
Conclusion
Endovenous laser ablation, in combination with phlebectomy and sclerotherapy using multimodal analgesia, may yield a satisfactory outcome in patients with moderate to severe VVs.
Declarations
Conflicts of interest: The authors have no conflicts of interest to disclose.
Ethical approval: Not applicable.
Patient consent (participation and publication): Patients provided consent to participate in the study and to authorize the publication of any related data.
Source of Funding: Smart Health Tower.
Role of Funder: The funder remained independent, refraining from involvement in data collection, analysis, or result formulation, ensuring unbiased research free from external influence.
Acknowledgements: None to be declared.
Authors' contributions: FHK was a major contributor to the study's conception and to the literature search for related studies. SHT, AAM, and RJR were the radiologists who provided access to the cases. HOA, BAA, and MNH were involved in the literature review, study design, and writing of the manuscript. FEF, KAS, and BYA were the anesthesiologists who anaesthetized the cases. DHMS, FJA, NSS, PMK, BAA, AMM and SJJ were involved in the literature review, the study's design, the critical revision of the manuscript, and the table processing. All authors have read and approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.
Annotations on Indeterminate Cytology of Thyroid Nodules in Thyroidology: Novi Sub Sole?
Ilker Sengul, Demet Sengul
Letter to the Editor
Dear Editor,
Indeterminate cytology (IC) remains the most challenging issue for health professionals working in thyroidology, thyroidologists [1-4]. We read a great deal of the article by Ali et al [5]. entitled "Clinicopathological Features of Indeterminate Thyroid Nodules: A Single-center Cross-sectional Study," published in 3rd volume, Barw Medical Journal. This study addresses a challenging and crucial issue by examining the characteristics and malignancy rates of thyroid nodules with IC, the most controversial category for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The authors evaluated the clinicopathological features of the thyroid nodules with Category III, TBSRTC, in a single-center cross-sectional study [5].
One of the strengths of the article is its focus on the challenges in managing IC. Ali and colleagues [5] thoroughly examine comprehensive data, including demographic details, medical history, laboratory tests, preoperative imaging, cytologic evaluation, and histopathological diagnosis. The results indicate a notable malignancy rate in Category III, TBSRTC. Furthermore, the study points out that malignancy tended to be younger, while benign nodules were significantly larger than malignant ones. The study also found a significant association between malignant nodules and Thyroid Imaging Reporting and Data System (TI-RADS) categories 4 and 5 and benign with TI-RADS 2 and 3, which findings align with some existing literature, providing valuable insights into the clinical assessment of IC.
However, several limitations of the study warrant consideration. Firstly, its single-center and retrospective design may limit the generalizability of the findings to diverse populations and settings. As the authors acknowledge, the retrospective data collection might have resulted in missing crucial information. While TI-RADS scoring was provided, more specific ultrasound features of thyroid nodules could have been beneficial. Of note, does including or excluding noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), which has been considered a low-risk entity by the current understanding, affect and/or alter the overall results and the assessment of diagnostic performance and study outcome(s)? [2-4] Furthermore, which caliber of the needle had been utilized throughout the study with or without local and/or topical anesthetic agent(s), and would the utilization of thicker or finer needles in order to obtain cytologic samples with or without any local and/or topical anesthesia alter the outcome(s) of this study? [2] Moreover, which edition of TBSRTC has been used for the work and would stress the up-to-date 3rd edition of TBSRTC [3], considering both the novel and crucial subdivisions of category III might affect the study’s relevant outcome(s)? [3,4] Another point of attention is the relatively short data collection period compared to the publication. Finally, while the discussion section compares the findings with various studies in the literature, a more in-depth exploration of the methodological differences and potential discrepancies in results could have been provided. For instance, the conflicting views in the literature regarding the relationship between nodule size and malignancy risk could have been further contrasted with the study's findings. The authors also acknowledge the small sample size as a limitation. For future research, multi-center and prospective studies with detailed imaging, such as elastography and contrast-enhanced sonography, and investigations into the role of molecular markers in thyroid nodules with Category III could improve diagnostic accuracy and potentially reduce unnecessary surgical interventions.
In conclusion, this study significantly contributes to the evaluation of IC in thyroidology despite its limitations. However, considering the noted limitations, further research with more comprehensive and methodologically robust studies in this area is warranted. This issue merits further investigation.
Sincerely,

Exploring Large Language Models Integration in the Histopathologic Diagnosis of Skin Diseases: A Comparative Study
Talar Sabir Ahmed, Rawa M. Ali, Ari M. Abdullah, Hadeel A. Yasseen, Ronak S. Ahmed, Ameer M....
Abstract
Introduction
The exact manner in which large language models (LLMs) will be integrated into pathology is not yet fully comprehended. This study examines the accuracy, benefits, biases, and limitations of LLMs in diagnosing dermatologic conditions within pathology.
Methods
A pathologist compiled 60 real histopathology case scenarios of skin conditions from a hospital database. Two other pathologists reviewed each patient’s demographics, clinical details, histopathology findings, and original diagnosis. These cases were presented to ChatGPT-3.5, Gemini, and an external pathologist. Each response was classified as complete agreement, partial agreement, or no agreement with the original pathologist’s diagnosis.
Results
ChatGPT-3.5 had 29 (48.4%) complete agreements, 14 (23.3%) partial agreements, and 17 (28.3%) none agreements. Gemini showed 20 (33%), 9 (15%), and 31 (52%) complete agreement, partial agreement, and no agreement responses, respectively. Additionally, the external pathologist had 36(60%), 17(28%), and 7(12%) complete agreements, partial agreements, and no agreements responses, respectively, in relation to the pathologists’ diagnosis. Significant differences in diagnostic agreement were found between the LLMs and the pathologist (P < 0.001).
Conclusion
In certain instances, ChatGPT-3.5 and Gemini may provide an accurate diagnosis of skin pathologies when presented with relevant patient history and descriptions of histopathological reports. However, their overall performance is insufficient for reliable use in real-life clinical settings.
Introduction
The healthcare sector is undergoing significant transformation with the emergence of large language models (LLMs), which have the potential to revolutionize patient care and outcomes. In November 2022, OpenAI introduced a natural language model called Chat Generative Pre-Trained Transformer (ChatGPT). It is renowned for its ability to generate responses that approximate human interaction in various tasks. Gemini, developed by Google, is a text-based AI conversational tool that utilizes machine learning and natural language understanding to address complex inquiries. These models generate new data by identifying structures and patterns from existing data, demonstrating their versatility in producing content across different domains. Generative LLMs rely on sophisticated deep learning methodologies and neural network architectures to scrutinize, comprehend, and produce content that closely resembles human-created outputs. Both ChatGPT and Gemini have gained global recognition for their unprecedented ability to emulate human conversation and cognitive abilities [1-3].
ChatGPT offers a notable advantage in medical decision-making due to its proficiency in analyzing complex medical data. It is a valuable resource for healthcare professionals, providing quick insights derived from patient records, medical research, and clinical guidelines [1,4]. Moreover, ChatGPT can play a crucial role in the differential diagnostic process by synthesizing information from symptoms, medical history, and risk factors, and comprehensively processing this data to present a range of potential medical diagnoses, thereby assisting medical practitioners in their assessments. This has the potential to improve diagnostic accuracy and reduce instances of misdiagnosis or delays [4].
The integration of ChatGPT and Gemini into the medical decision-making landscape has generated interest from various medical specialties. Multiple disciplines have published articles highlighting the significance and potential applications of ChatGPT and Gemini in their respective fields [2,5]. Despite the growing number of these models used in diagnostics, patient management, preventive medicine, and genomic analysis across medicine, the integration of LLMs in dermatology remains limited. This study emphasizes the exploration of large language models, highlighting their less common yet promising role in advancing dermatologic diagnostics and patient care [6]
This study aims to explore the role of LLMs and its decision-making capabilities in the field of pathology, specifically in dermatologic conditions. It focuses on ChatGPT 3.5 and Gemini and compares their accuracy and concordance with the diagnoses of human pathologists. The study also investigates the potential advantages, biases, and constraints of integrating LLM tools into pathology decision-making processes.
Methods
Case Selection
A pathologist selected 60 real case scenarios, with half being neoplastic conditions and the other half non-neoplastic, from a hospital’s medical database. The cases involved patients who had undergone biopsy and histopathological examination for skin conditions. The records included information on age, sex, and the chief complaint of the patients, in addition to a detailed description of the histopathology reports (clinical and microscopic description without the diagnosis).
Consensus Diagnosis
Two additional board-certified pathologists reviewed each case, reaching a collaborative consensus diagnosis through a meticulous review of clinical and microscopic descriptions. This process ensured diagnostic accuracy and reliability while minimizing individual biases.
Eligibility Criteria
The study included cases that had complete and relevant histopathological reports and comprehensive patient demographic information. Specifically, cases were included if they provided a definitive diagnosis in the histopathological report and contained detailed patient data such as age, gender, and clinical history. Cases were excluded if the histopathological report was incomplete, lacked critical patient information, or if the diagnosis could not be definitively made based solely on the textual description.
Sampling Method
The selection process involved a systematic review of available cases from the hospital's medical database to ensure a representative sample of different dermatologic diagnoses. A random sampling method was employed to minimize selection bias and to ensure the sample was representative of the broader population of dermatologic conditions within the database. The selected cases span a range of common and less common dermatologic conditions, enhancing the generalizability of the study’s findings.
Evaluation by AI Systems and External Pathologist
In March 2023, these cases were evaluated using two LLM systems, namely ChatGPT-3.5 and Gemini. In addition, an external board-certified pathologist was tested similarly to the AI systems, receiving only the necessary histopathology report descriptions (without histopathological images) to ensure a fair comparison between the LLM systems and the external pathologist.
Pathologists’ Experience
The Pathologists involved in the study had a minimum of eight years of experience in their respective specialties, handling an average of 30 cases per month. This level of experience ensured a deep familiarity with a wide range of case scenarios. Crucially, the pathologists conducted their assessments were fully informed of the study design, including the comparative analysis with AI systems. Their expertise and understanding were vital in upholding the integrity and reliability of the diagnostic evaluations throughout the study
AI Prompting Strategy
The LLM systems were initially greeted with a prompt saying “Hello,” followed by standardized inquiries presented as: “Please provide the most accurate diagnoses from the texts that will be given below.” Each case was individually presented by copy-pasting it from a Word document and requesting each system to provide a diagnosis of the case scenario based on the information presented. The first response of each system to the inquiry was documented. If no diagnosis was given, the prompt was repeated as such: “Please, based on the histopathological report information given above, provide the most likely disease that causes it.” Until a diagnosis was obtained. In some cases, after a diagnosis was provided, an additional question was asked to specify the histologic subtype of the condition (e.g., if the diagnosis was “seborrheic keratosis”, the system was asked to specify the histologic subtype). Furthermore, the board-certified external pathologist was tested with the same questions, and the correct diagnosis was inquired.
Response Categorization
The responses from both systems and the external pathologist were categorized into three subtypes: complete agreement with the original diagnosis by the human pathologists, partial agreement, or none agreement. The criteria for categorizing agreement levels into "complete," "partial," and "none agreement" are based on the distinction between general and specific diagnostic classifications. For instance, when the original diagnosis provides a detailed type and subtype (e.g., "Seborrheic keratosis, irritated type"), an AI tool's or external pathologist's response was classified as demonstrating "complete agreement" if it accurately identifies both the general diagnosis ("Seborrheic keratosis") and the specific subtype ("irritated type"). This classification acknowledges that accurate identification of both components reflects a thorough understanding and alignment with the original diagnosis. Conversely, an assessment was categorized as "partial agreement" if the response correctly identifies the general diagnosis but inaccurately specifies the subtype. Furthermore, a diagnosis was classified as demonstrating "no agreement" when both the general diagnosis and subtype provided by the AI tool or external pathologist are incorrect. These classification criteria draw upon established methodologies in diagnostic agreement studies, emphasizing the importance of distinguishing between different levels of agreement based on the precision and correctness of diagnostic outputs [7].
Data Processing and Statistical Analysis
The initial processing of the acquired data involved several steps before statistical analysis. First, the data were inputted into Microsoft Excel 2019. Subsequently, they were transferred to Statistical Package for the Social Sciences software (SPSS) 27.0 and the DATA tab for further analysis. Fleiss kappa was utilized to measure agreement among Chat GPT, the external pathologist, and Gemini. Additionally, Chi-square tests were applied to investigate associations between the two LLMs and the external pathologist. In this study, significance was defined as a p-value of < 0.05. A literature review was performed for the study, selectively considering papers from reputable journals while excluding those from predatory sources based on established criteria [8].
Results
ChatGPT-3.5 provided 29 (48.4%) complete agreement, 14 (23.3%) partial agreement, and 17 (28.3%) none agreement responses for the scenarios presented. In contrast, Gemini offered 20 (33%), 9(15%), and 31 (52%) complete agreement, partial agreement, and none agreement responses, respectively, for the same scenarios. Moreover, the external pathologist provided 36 (60%) complete agreement, 17 (28%) partial agreement, and 7 (12%) none agreement responses (Table 1). The complete details of the scenarios, including the diagnosis from the pathologists, ChatGPT’s, Gemini’s, and the external pathologist diagnoses are available in (Supplement 1).
Variables |
Frequency/percentage |
Pathological classification Neoplastic Non-neoplastic |
30 (50%) 30 (50%) |
Neoplastic Benign Malignant |
19 (31.7%) 11 (18.3%) |
Non-neoplastic Dermatosis Infectious, pilosebaceous Connective tissue disease Infectious Granulomatous Vascular Epidermal maturation/keratinization disorder Dermatosis, pilosebaceous Pilosebaceous Panniculitis, Dermatosis, infectious Dermatosis, pigmentation disorder Granulomatous, panniculitis Bullous |
9 (15%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 2 (3.3%) 1 (3.3%) 1 (1.7%) 1 (1.7%) 1 (1.7%) 1 (1.7%) |
External Pathologist Complete agreement Partial agreement None agreement |
36 (60%) 17 (28%) 7 (12%) |
ChatGPT Complete agreement Partial agreement None agreement |
29 (48.4%) 14 (23.3%) 17 (28.3%) |
Gemini Complete agreement Partial agreement None agreement |
20 (33%) 9 (15%) 31 (52%) |
The agreement between Chat GPT, the external pathologist, and Gemini was assessed using Fleiss' kappa, which indicated a statistically significant at a level of <0.001, demonstrating slight to moderate agreement with respect to the original diagnosis made by the pathologists. Out of the 29 questions where Chat GPT agreed with the original diagnosis, only 12 (41.4%) instances also received complete agreement from both Gemini and the external pathologist (Table 2).
Variables | External pathologist |
Measurement of Agreement (Fleiss) |
Significance level |
|||
Complete agreement |
Partial agreement |
None agreement |
||||
Gemini |
Complete agreement |
12 (41.4%) |
1(7.1%) |
2 (11.8%) |
0.25 | <0.001 |
Partial agreement |
3 (10.4%) |
1(7.1%) |
0 (0.0%) |
|||
None agreement |
1(3.4%) |
0(0.0%) |
0 (0.0%) |
|||
Complete agreement |
2 (7%) |
3(21.4%) |
0 (0.0%) |
|||
Partial agreement |
1(3.4%) |
3(21.4%) |
0 (0.0%) |
|||
None agreement |
5(17.2%) |
2(14.4%) |
9 (53%) |
|||
Total |
29 |
14 |
17 |
When assessing the agreement between Chat GPT, the external pathologist, and Gemini, using the external pathologist as the reference, the external pathologist showed complete agreement with the original diagnosis in 36 cases. Among these, Chat GPT achieved complete agreement in 19 cases (52.7%), while Gemini achieved complete agreement in 15 cases (41.7%). Additionally, the external pathologist showed none agreement with the original diagnosis in only 7 cases. Among these, Chat GPT achieved none agreement in 5 cases (71.4%), while Gemini achieved none agreement in 6 cases (85.7%). Statistical analysis indicated significant differences in agreement levels between AI tools (ChatGPT and Gemini) and the external pathologist, with a P-value of <0.001 (Table 3).
AI tools | ChatGPT |
P-value |
|||
Complete agreement |
Partial agreement |
None agreement |
|||
ChatGPT |
Complete agreement |
19(52.7%) |
8(47.1%) |
2(28.6%) |
<0.001 |
Partial agreement |
6(16.7%) |
8(47.1%) |
0(0%) |
||
None agreement |
11(30.6%) |
1(5.8%) |
5(71.4%) |
||
Gemini |
Complete agreement |
15(41.7%) |
4(23.5%) |
1(14.3%) |
<0.001 |
Partial agreement |
5(13.9%) |
4(23.5%) |
0(0%) |
||
None agreement |
16(44.4%) |
9(53%) |
6(85.7%) |
||
Total |
36(100%) |
17(100%) |
7(100%) |
In addition, the agreement between the external pathologist, ChatGPT, and Gemini was assessed for both neoplastic and non-neoplastic cases. Statistical analysis revealed significant differences in the agreement levels between the LLMs and the external pathologist, with a P-value of <0.001, highlighting the statistically significant disparity in agreement rates between the AI tools and the external pathologist (Table 4 and 5).
AI tools | External pathologist | P-value | |||
Complete agreement |
Partial agreement |
None agreement |
|||
ChatGPT |
Complete agreement |
11(61.1%) |
2(40%) |
4(57.1%) |
<0.001 |
Partial agreement |
3(16.7%) |
3(60%) |
1(14.3%) |
||
None agreement |
4(22.2%) |
0(0%) |
2(28.6%) |
||
Gemini |
Complete agreement |
9(50%) |
1(20%) |
1(14.3%) |
<0.001 |
Partial agreement |
7(38.9%) |
4(80%) |
4(57.1%) |
||
None agreement |
2(11.1%) |
0(0%) |
2(28.6%) |
||
Total non-neoplastic cases |
18(100%) |
5(100%) |
7(100%) |
AI tools | External pathologist | P-value | |||
Complete agreement |
Partial agreement |
None agreement |
|||
ChatGPT |
Complete agreement |
8(44.4%) |
0(40%) |
4(40%) |
<0.001 |
Partial agreement |
8(44.4%) |
2(1000%) |
0(0%) |
||
None agreement |
2(11.1%) |
0(0%) |
6(60%) |
||
Gemini |
Complete agreement |
6(33.3%) |
0(20%) |
3(30%) |
<0.001 |
Partial agreement |
9(50%) |
2(100%) |
5(50%) |
||
None agreement |
3(16.7%) |
0(0%) |
2(20%) |
||
Total neoplastic cases |
18(100%) |
2(100%) |
10(100%) |
Discussion
Despite being in existence for over five decades, LLM has recently garnered substantial attention in the public sphere. The increased focus on LLMs in the medical field has led to speculation about the potential replacement of doctors by these systems. However, LLMs are more likely to serve as a complementary tool, aiding clinicians in efficiently processing data and making clinical decisions. This is substantiated by the fact that LLMs can "learn" from extensive collections of medical data. Modern systems are also noted for their self-correcting capabilities. As electronic medical records become more prevalent, there is a growing reservoir of stored patient data. While having access to more data is undoubtedly advantageous, scanning through patient charts can be challenging. Algorithms have been developed to sift through patient notes and detect individuals with specific risk factors, diagnoses, or outcomes. This capability is particularly valuable because, in theory, a LLM system could be developed to review and extract data from medical charts, including pathology reports, and promptly identify patients at highest risk for conditions that could cause significant morbidity or mortality if missed by the physician [6,9].
The field of pathology is no exception to the adaptation of LLMs and the utilization of these technological advancements. Various in recent years have assessed LLM’s accuracy, potential use, and associated limitations. For instance, a study by Vaidyanathaiyer et al., evaluated ChatGPT's proficiency in pathology through thirty clinical case scenarios. These cases were evenly distributed across three primary subcategories: hematology, histopathology, and clinical pathology, with ten cases from each category. The researchers reported that ChatGPT received high grade of “A” on nearly three-quarters of the questions; in the remaining questions, and “B” grades on remaining questions. They found that ChatGPT demonstrated moderate proficiency in these subcategories, excelling in rapid data analysis and providing fundamental insights, though it had limitations in generating thorough and elaborate information [10]. Furthermore, Passby et al. demonstrated capacity of ChatGPT to address multiple-choice inquiries in the Specialty Certificate Examination of dermatology, with ChatGPT-4 outperforming ChatGPT-3.5, scoring 90% versus 63%, respectively, compared to an approximate passing score of 70% [11]. In an investigation by Delsoz et al., twenty corneal pathologies with their respective case descriptions were provided to ChatGPT-3.5 and ChatGPT-4. ChatGPT-4 performed better, correctly answering 85% of the questions, whereas ChatGPT-3.5 answered only 60% correctly [12]. The current study found that ChatGPT-3.5 performed similarly in the percentage of correct responses. However, this study further evaluated the LLM responses and found that nearly 23.3% and 15% of ChatGPT and Gemini answers, respectively, were fair but still had inaccuracies. This highlight areas where these systems can improve, as they sometimes almost answer correctly but not fully. For instance, when a histopathology report of squamous cell carcinoma in situ was given to ChatGPT-3.5, it answered with squamous cell carcinoma. On further prompting, the system favored an invasive squamous cell carcinoma over an in-situ one, even when the suggestion was made to it whether an in-situ lesion was more appropriate for that scenario. similarly, in the case of guttate psoriasis, Gemini answered with only “psoriasis” did not specify the type, while ChatGPT-3.5 responded with “psoriasis vulgaris”. In a study by Rahsepar et al. on pulmonary malignancies, Google Bard (the former name of Gemini) provided 9.2% partially correct answers, similar to Gemini's 15% partially correct responses in this study. However, ChatGPT-3.5 answered 17.5% of lung cancer questions incorrectly, whereas in the present study, ChatGPT-3.5’s incorrect answers were nearly twice as frequent. This may be due to ChatGPT broader access to data and medical information on lung cancer compared to the dermatological conditions tested in this study, highlighting the limitations and risks of relying on these systems for rarer diseases [13].
Although existing language models have access to extensive medical data, they often lack a nuanced understanding of individual diseases or specific patient cases. They have not undergone specialized training for medical tasks, relying solely on the provided data and information. The unclear methodology behind the LLM's diagnostic process leads to skepticism regarding the reliability of LLM-generated diagnoses. Consequently, their ability to accurately diagnose complex or unique cases may be limited, as demonstrated in the current study on skin histopathology cases. Notably, in a few cases, LLMs declined to provide a diagnosis on the initial prompt, citing concerns about giving medical advice, and only issued a diagnosis after repeated prompting with the same scenario. Despite their ability to offer insights based on existing knowledge, LLMs may lack a complete understanding of the intricate details and visual indicators crucial for pathologists' diagnosis. In the current study, the pathologist initially examined the histopathology slides and then provided the report to the AI systems. Another issue is that preserving the integrity of LLMs and safeguarding the confidentiality of associated data from unauthorized access is critical, particularly in scenarios involving sensitive patient information [14,15]. The case scenarios in this study did not include specific patient identifiers. Additionally, failure to evolve the LLM tools utilized in the pathological assessment alongside advancements in clinical practice and treatment poses the risk of stagnation and adherence to outdated methodologies. Although it is possible to manually update LLM algorithms to align with new protocols, their efficacy depends heavily on the availability of pertinent data, which might not be readily accessible during transitional periods. Such adaptations could introduce errors, particularly in pathology, through misclassifications of entities as classification and staging systems undergo revisions. Another concern is automation bias, which refers to the tendency of clinicians to regard LLM-based predictions as flawless or to adhere to them without questioning their validity. This bias often emerges soon after exposure to new technology and may stem from concerns about the legal consequences of disregarding an algorithm's output. Research across various fields has shown that automation bias can reduce clinician accuracy, affecting areas such as electrocardiogram interpretation and dermatologic diagnoses. Clinicians at all proficiency levels, including experts, are susceptible to this phenomenon [3,14-16].
The LLM has numerous applications in the medical field, with various technologies being developed at an unprecedented pace. For example, in the field of epilepsy, Empatica has created a wearable monitor called Embrace, which detects the onset of seizures in patients with epilepsy and notifies designated family members or trusted physicians. This innovation enhances safety and facilitates early management of such cases and received FDA approval six years ago [17]. Additionally, one of the earliest uses of LLM was for the detection of atrial fibrillation. AliveCor mobile application, which facilitates ECG monitoring and atrial fibrillation detection using a mobile phone, was FDA-approved. Recent findings from the REHEARSE-AF study indicated that traditional care methods are less effective at detecting atrial fibrillation in ambulatory individuals compared to remote ECG monitoring using Kardia [17,18]. Another example is the artificial immune recognition system, which has demonstrated remarkable accuracy in diagnosing tuberculosis by using support vector machine classifiers. These advanced systems significantly outperform traditional methods, making them a robust tool in identifying tuberculosis cases with high reliability. This underscores the potential of these models to enhance diagnostic processes in infectious diseases [19]. The advancements across various medical disciplines render the application of LLMs in histopathological diagnostics increasingly viable and anticipated for future clinical implementation. This progress motivates further research by scientists and numerous companies, as the focus has shifted from questioning whether LLM will be used in pathology or not to when and how these models will be utilized precisely.
One limitation of this study is that the aforementioned LLM systems were not evaluated for their ability and accuracy in directly reaching a diagnosis from histopathological images. Instead, the study relied on providing necessary information from the histopathological reports in text form, which imposes practical constraints and still requires an expert pathologist. Future studies focusing on both histopathological images and texts are necessary to further evaluate the comprehensive capabilities of LLM tools in this domain.
Conclusion
In certain instances, ChatGPT-3.5 and Gemini may provide an accurate diagnosis of skin conditions when provided with pertinent patient history and descriptions of histopathological reports. Specifically, Gemini showed higher accuracy in diagnosing non-neoplastic cases, while ChatGPT-3.5 demonstrated better performance in neoplastic cases. However, despite these strengths, the overall performance of both models is insufficient for reliable use in real-life clinical settings.
Declarations
Conflicts of interest: The author(s) have no conflicts of interest to disclose.
Ethical approval: Not applicable.
Patient consent (participation and publication): Not applicable.
Funding: The present study received no financial support.
Acknowledgements: None to be declared.
Authors' contributions: RMA and AMA were significant contributors to the conception of the study and the literature search for related studies. DSH and SHM involved in the literature review, study design, and manuscript writing. TSA, HAY, RSA, and AMS were involved in the literature review, the study's design, the critical revision of the manuscript, and data collection. RMA and DSH confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.
Use of AI: ChatGPT-3.5 was used to assist in language editing and improving the clarity of the introduction section. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.
Data availability statement: Not applicable.