Abstract

Introduction

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor that can lead to severe complications and carries a risk of distant metastasis. This study aims to provide a comprehensive overview of CXPA through a case series and a review of the literature.

Methods

This was a single-center retrospective case series. The patients were included from November 2018 to December 2024. All confirmed cases of CXPA that were diagnosed and managed with complete clinical data were included in this study. Cases with incomplete data were excluded.

Results

Six patients were included, with ages ranging from 45 to 88 years (mean ± SD: 64 ± 15.36; median: 62). Most were male (66.7%), with an even distribution of occupations. All presented with preauricular swelling lasting 2 to 10 years, and three had left-sided tumors. Fine needle aspiration identified 33.3% as benign and 16.7% as malignant. Ultrasound examination showed solid tumors in four cases, three of which were well-defined. Three (50%) underwent total parotidectomy, and three (50%) underwent superficial parotidectomy. Histopathological examination revealed adenocarcinoma ex pleomorphic adenoma in 50% and squamous cell carcinoma ex pleomorphic adenoma in 16.7%. Tumor sizes ranged from 3.5 to 6 cm (mean: 4.73 ± 1.24 cm). Capsular invasion was present in all cases, with lymph node involvement in 33.3%, lympho-vascular invasion in 16.7%, and perineural invasion in 50%. Adjuvant therapy included radiotherapy or chemoradiotherapy.

Conclusion

Although CXPA is very rare, it is a serious condition; surgical approach with or without adjuvant therapy may result in preferable outcomes.

Introduction

Salivary gland tumors are uncommon neoplasms of the head and neck region. Among them, pleomorphic adenoma is the most prevalent benign type, accounting for approximately 70% of all salivary gland tumors [1]. The parotid gland is the most frequent site of occurrence for salivary gland tumors, followed by the submandibular gland and the minor salivary glands [2]. If left untreated, pleomorphic adenoma carries a risk of malignant transformation, with the risk reaching up to 9.5% after 15 years and continuing to increase over time [3].

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor that develops from a pre-existing benign pleomorphic adenoma, accounting for approximately 5% of all head and neck malignancies [4]. CXPA constitutes approximately 3.6% of all salivary gland neoplasms, 6.2% of all mixed tumors, and 11.6% of all malignant salivary gland neoplasms. This malignancy predominantly occurs between the sixth and eighth decades of life and shows a slight female predominance [5]. Historical data reveal geographical variation in the incidence of this tumor relative to primary parotid malignancies, with reported rates of 12–13% in the United States, 14% in Switzerland, and up to 25% in the United Kingdom [1]. CXPA has also been referred to by other names, including carcinoma ex mixed tumor, carcinoma ex adenoma, and carcinoma ex benign pleomorphic adenoma [5].

The risk of malignant transformation is heightened by patient-related factors such as advanced age and a history of smoking, as well as disease-related factors, including larger tumor size and higher histological grade [1]. As a rare and complex disease, the clinical and pathological understanding of CXPA continues to evolve with ongoing research and advancements in diagnostic techniques [1]. This study aims to provide a comprehensive overview of CXPA by analyzing six cases, with a focus on clinical presentation, diagnostic approaches, treatment outcomes, and a review of the literature. The references have been evaluated for credibility using the most up-to-date criteria [6].

Methods

Study design

This single-center case series included consecutive patients diagnosed with CXPA who were treated between November 2018 and December 2024.

Data collection

After de-identification, the necessary data were retrospectively obtained from patient records in the Head and Neck clinic database. Extracted variables included patient demographics, occupation, clinical presentation, ultrasound (U/S) findings, treatment approach, outcomes, histopathological findings, and follow-up information. The follow-up period ranged from 1 to 5 years.

Eligibility criteria

All confirmed cases of CXPA that were diagnosed and managed with complete clinical data were included in this study. Cases with incomplete data were excluded.

Intervention

All patients underwent a thorough preoperative assessment, including a detailed clinical examination with an emphasis on facial nerve function, as well as imaging to assess lesion size, location, extent, and potential local invasion. Surgical procedures were performed under general anesthesia with the patient positioned supine and the head turned contralaterally to the lesion side. A standard Blair (lazy-S) incision was utilized, beginning anterior to the tragus, extending around the earlobe, and continuing into a natural skin crease in the upper neck to ensure optimal surgical access and cosmetic appearance.

Following subplatysmal flap elevation, dissection was carried out to identify the main trunk of the facial nerve, typically located at the stylomastoid foramen, just inferior and medial to the tympanomastoid suture. In cases of partial parotidectomy, only the superficial lobe of the gland was excised, preserving the facial nerve and its branches. In total parotidectomy, both superficial and deep lobes were removed, with caution to maintain all major branches of the facial nerve. Dissection proceeded using fine instruments and bipolar cautery under loupe magnification to enhance visualization and minimize nerve trauma.

Hemostasis was achieved using bipolar coagulation and ligation of feeding vessels. Redivac drains were placed in the surgical bed and secured with sutures to facilitate postoperative drainage and reduce the risk of hematoma or seroma formation. Skin closure was performed in layers using absorbable sutures for the deep plane and non-absorbable or subcuticular sutures for the skin to optimize healing and reduce scar formation.

Post-intervention considerations

Postoperatively, patients received protocol-based analgesia and prophylactic antibiotics. The diagnosis was confirmed through histopathological examination of the surgical specimens.

Statistical analysis

Data entry and coding were performed using Microsoft Excel 2019. Descriptive statistical analysis of qualitative data was conducted using the Statistical Package for the Social Sciences (SPSS) Version 25. Results were presented as means, frequencies, and percentages.

Results

This study included 6 patients, whose raw data are presented in Tables 1 & 2. Ages ranged from 45 to 88 years, with a median age of 62 and a mean age of 64 ± 15.36 years. Most of the patients were males (66.67%), with occupations evenly distributed (33.33% housewives, 33.33% unemployed, and 33.33% workers). Family history was unremarkable in all patients. Smoking was reported in only 1 patient. All the patients presented with preauricular swelling, with duration of symptoms ranging from 2 to 10 years. The left parotid gland was affected in 3 (50%) patients. Upon fine needle aspiration (FNA), 2 (33.33%) of the tumors were benign, while only 1 (16.67%) tumor was malignant with certainty. On U/S, 4 of the tumors were solid, 3 of which were well-defined. Lymph nodes were suspicious for involvement in 2 (33.33%) patients. three patients (50%) underwent total parotidectomy, while the other 3 (50%) underwent superficial parotidectomy. Histopathology revealed adenocarcinoma ex pleomorphic adenoma in 3 (50%) patients, and squamous cell carcinoma ex pleomorphic adenoma in 1 (16.67%) patient. Tumor sizes ranged from 3.5 to 6 cm (mean: 4.73 ± 1.24). Lymph node involvement was seen in 2 (33.33%) patients. Capsular invasion was observed in all patients, lympho-vascular invasion in 1 (16.67%) patient, and perineural invasion in 3 (50%) patients. Adjuvant therapy included radiotherapy and chemoradiotherapy (Table 3). No cases of recurrence were reported, and one patient passed away from old age.

Discussion

The median age of this study was 62 years, which is close to a study by Suzuki et al., which had a median age of 60 years [7]. The mean age of 64 in the current study was also comparable to other studies. For example, a retrospective study of 73 patients with CXPA had a mean age of 61 years [8]. However, a lower mean of 55.1 was reported by Seok et al. [9]. Kato et al. reported four cases, one of which involved a 48-year-old individual [3]. Recently, another case of CXPA in a 45-year-old male was also reported [10]. When compared to pleomorphic adenoma, the mean age of diagnosis is shown to be higher by 13 years [9].

The current series demonstrated a male predominance, consistent with findings from a systematic review by Key et al., in which males accounted for 58.9% of cases [1]. In this series, the parotid gland was involved in 100% of cases, higher than the typical range reported in the literature, which may reflect referral bias. Nevertheless, the parotid remains the most commonly affected salivary gland subsite [1].

Patients presented with symptom durations ranging from 2 to 10 years, which is notably shorter than what is commonly reported in earlier literature. A comprehensive review, for example, documented a mean symptom duration of 23.3 years [5]. Longer durations reaching 50 years have also been reported [3]. However, more recent reports indicate shorter intervals; Keerthi et al. reported a case with only six months of symptoms [11]. The short symptom durations in the current study may reflect earlier detection and referral patterns or more aggressive tumor biology, leading to earlier presentation.

One of the diagnostic challenges was the low sensitivity of FNA for malignancy at 16.67%, which is a known limitation of FNA in CXPA diagnosis. In a series of 16 patients, only seven (43%) were identified as malignant [12]. In a cohort of 260 patients, 170 patients (65.4%) had a preoperative FNA. In 156 of those (91.8%), the FNA diagnosed a benign tumor, with the rest having an unsatisfactory or nondiagnostic FNA [13]. Parotid FNA carries two potential sources of false-negative results: sampling a benign area of a pleomorphic adenoma rather than the malignant component, and misclassifying a low-grade CXPA as a benign pleomorphic adenoma [13].

Tumor sizes in reported cases range from 1 to 26 cm [4]. Similarly, the sizes observed in the present study fall within this typical range. A multivariate analysis has identified tumor size ≥4 cm as a factor associated with worse prognosis. Notably, six patients in the current series (66.7%) had tumors larger than 4 cm but demonstrated favorable outcomes, suggesting that effective treatment protocols may mitigate the impact of tumor size on prognosis.

Recent studies have shown that the most frequently encountered histological types in CXPA are highly malignant adenocarcinoma and undifferentiated carcinoma. However, a wide spectrum of other subtypes has also been reported, including squamous cell carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, papillary carcinoma, and terminal duct carcinoma [11]. In the current series, adenocarcinoma accounted for 50% of cases, while squamous cell CXPA was observed in one patient. This aligns with findings from a retrospective study of 24 patients, which reported six cases of adenocarcinoma and a single case of squamous cell carcinoma [12].

Certain pathological features, such as invasiveness, have been studied in the literature. In particular, extracapsular extension and invasion measuring ≥1.5 mm have been linked to an increased risk of recurrence and mortality [1]. Capsular invasion was present in all cases in the current series, with 50% showing focal infiltration. Lympho-vascular invasion was observed in 16.67%, and perineural invasion in 50%. Similar findings have been reported in the literature, such as Kim et al.'s study of 17 CXPA patients, where lympho-vascular invasion was seen in three patients [14]. In a cohort of 215 patients with parotid gland tumors, 14 of whom were diagnosed with CXPA, perineural invasion was documented in 21.4% [15]. In a retrospective study of 51 patients, 45.1% exhibited perineural invasion [16]. Another study involving 37 CXPA patients found 43% with perineural invasion and 40.5% with lympho-vascular invasion [17]. Perineural invasion significantly impacts distant metastasis, tumor-specific survival, and overall survival (P < 0.05), and tends to be associated with locoregional recurrence (P = 0.086). In multivariate analysis, perineural invasion is identified as an independent prognostic factor for overall survival [16].

Lymph node invasion was observed in 33.3% of the patients, which is comparable to findings from previous studies. For instance, a review involving 619 patients reported lymph node involvement, both single and multiple nodes, in 29.6% of cases [18]. Another retrospective analysis of 51 patients revealed that 33.3% of the patients had lymph node involvement [16]. In their study, Zhao et al. identified advanced T stage and lymph node involvement as important factors for an unfavorable clinical outcome [16]. 

Treatment of CXPA involves an ablative surgical procedure, which may or may not be followed by reconstructive surgery [5]. To date, no universally accepted treatment protocol exists for this tumor type [4]. Zhao et al. emphasized that the extent of surgical intervention should be individualized, taking into consideration the tumor’s location, size, and the involvement of adjacent anatomical structures. For parotid gland tumors, a total or radical parotidectomy is generally recommended for frankly invasive CXPA, with facial nerve resection indicated if direct tumor infiltration is evident [16]. In the present series, three patients underwent superficial parotidectomy, one of whom also underwent suprahyoid lymph node dissection and excision of the sublingual gland due to regional extension, and the other three underwent total parotidectomy.

Adjuvant therapies for CXPA may include radiotherapy or chemotherapy, primarily aimed at improving local control and potentially enhancing survival outcomes [10]. However, due to the rarity of the disease, data on the specific efficacy of radiotherapy are limited [16]. In a retrospective analysis of 63 patients, Chen et al. reported that postoperative radiotherapy significantly improved local disease control, although it did not confer a clear survival benefit [19]. Chemotherapy is generally reserved for patients with advanced, recurrent, or metastatic disease and is used primarily for palliative purposes. The role of radiotherapy remains controversial and is typically considered in cases with high-grade histology, positive margins, perineural invasion, or lymph node involvement [20]. Historically, CXPA has been regarded as a high-grade malignancy, often necessitating adjuvant radiotherapy. This classification is reflected in data from a national American cancer database, which demonstrated that a higher proportion of patients with CXPA were selected to receive chemoradiotherapy [1]. Three patients received adjuvant chemoradiotherapy, all of whom had good outcomes.

Patients diagnosed with noninvasive or minimally invasive CXPA generally exhibit favorable outcomes, with low recurrence rates and minimal risk of metastasis. In contrast, those with frankly invasive tumors have a significantly poorer prognosis. Reported recurrence rates for invasive CXPA range from 23% to 50%, and distant metastases may occur in up to 70% of cases, reflecting the aggressive biological behavior of the invasive subtype [4]. No recurrences were observed in this series. While this may indicate effective treatment approaches, it could also be due to the relatively short follow-up periods.

Conclusion

Although CXPAs are very rare, they are serious conditions that may originate from benign conditions.  Surgical approach with or without adjuvant therapy might result in good outcomes.

Declarations

Conflicts of interest: The authors have no conflicts of interest to disclose.

Ethical approval: The study was ethically reviewed and approved by the Scientific Committee of the Kscien organization (Approval No. 2025-38).

Patient consent (participation and publication): Not applicable

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: AMS and SHH were major contributors to the study's conception and to the literature search for related studies. AMA was the pathologist who performed the histopathological diagnosis. AJQ and AHA were the radiologists who performed and assessed the cases. MMA, HAA, and AAQ were involved in the literature review, study design, and writing of the manuscript.  RMA, IJH, STSA, and MLF were involved in the literature review, the study's design, the critical revision of the manuscript, and the table processing. AMS and MMA confirm the authenticity of all the raw data. All authors have read and approved the final version of the manuscript

Use of AI: ChatGPT-4.0 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.

Abstract

Introduction

Echinococcosis, caused by tapeworms of the Echinococcus genus, remains a significant zoonotic disease globally. The disease is particularly prevalent in areas with extensive livestock farming. Humans primarily acquire infection through consumption of contaminated food or water, often from environmental contamination by definitive host feces. This study aimed to detect the presence of E. granulosus DNA (deoxyribonucleic acid) in water and vegetable samples collected from Sulaymaniyah Governorate, Iraq.

Methods

A cross-sectional study was conducted in Sulaymaniyah Governorate, Iraq, in April 2025. Water and vegetable samples were collected from both urban and rural areas. DNA extraction was performed from all samples, and E. granulosus DNA was explored using a qPCR (quantitative polymerase chain reaction) assay. Sample processing included filtering water, washing vegetables, and DNA extraction under optimized conditions.

Results

A total of 245 samples, comprising 98 (40.0%) water samples and 147 (60.0%) vegetable samples, were analyzed, with 111 (45.3%) from urban and 134 (54.7%) from rural areas. Despite the comprehensive sampling, no E. granulosus DNA was detected in any sample. All control reactions yielded positive results, but no amplification was observed in the field samples, indicating the absence of E. granulosus contamination.

Conclusion

This study found no evidence of E. granulosus DNA in water or vegetable samples from Sulaymaniyah, Iraq, suggesting a low likelihood of environmental contamination in this region. but seasonal changes, the restricted sample size, and methodological limitations mean that the presence of contamination cannot be completely excluded.

Introduction

Echinococcosis is a globally prevalent zoonotic disease caused by the larval or adult stages of tapeworms belonging to the genus Echinococcus (family Taeniidae). Recognized as one of the oldest documented human infections, its history dates to Hippocrates. The two primary forms affecting humans are cystic echinococcosis, also known as hydatid disease or hydatidosis, caused by Echinococcus granulosus, and alveolar echinococcosis, caused by Echinococcus multilocularis [1].

Echinococcosis has a worldwide distribution, with higher prevalence reported in areas such as Eastern Europe, South Africa, the Middle East, South America, Australia, and the Mediterranean, where livestock farming is widespread [1]. In some communities, the human incidence exceeds 50 cases per 100,000 person-years, with prevalence rates ranging from 5% to 10%. The World Health Organization (WHO) identifies CE as one of the major foodborne parasitic diseases globally [2].

Domestic dogs are the main definitive hosts for both Echinococcus species and represent the greatest risk for transmitting cystic and alveolar echinococcosis to humans. Dogs acquire infection by consuming livestock offal containing hydatid cysts and subsequently shed parasite eggs in their feces, which contaminate the environment, including soil, water, and grazing areas. Livestock become infected by ingesting these eggs while grazing, and humans are typically infected through the consumption of contaminated food or water [1].

Hydatid cysts can develop in nearly any organ, though the liver is most commonly affected (approximately 75%), followed by the lungs (15%), with rare involvement of the brain (2%) and spine (1%). Early stages of infection are often asymptomatic, with clinical manifestations emerging only when cysts enlarge or become complicated [3].

Environmental contamination with Echinococcus eggs can be substantial in endemic areas with high definitive host prevalence, creating a risk for human infection. However, contamination through food and the environment has long been overlooked, even though ingestion of infective eggs from these sources is the primary route of human infection [4].

This study aimed to detect the presence of E. granulosus DNA (deoxyribonucleic acid) in water and vegetable samples collected from both urban and rural areas of Sulaymaniyah Governorate, Iraq, using a sensitive qPCR (quantitative polymerase chain reaction) assay. All references were assessed using trusted predatory journal lists to verify their scholarly integrity [5].

Methods

Study design

A cross-sectional study design was employed. Water and vegetable samples were collected in April 2025 from multiple sites across Sulaymaniyah Governorate, Iraq. Sampling sites were randomly selected across the area to ensure the representativeness of both urban and rural areas. Sampling was conducted under sterile conditions, and all collected material was immediately transferred to the molecular biology department at Smart Health Tower for laboratory processing.

Sample collection

Water samples were collected directly from rivers, irrigation canals, and storage sources into sterile polypropylene containers. For each randomly selected site, one liter of water was obtained using sterile polypropylene containers. Vegetable samples, including commonly consumed leafy greens and root crops. Approximately 200 g per sample was collected using sterile gloves and placed in clean polyethylene bags. All containers and bags were clearly labeled with the date, site of collection, and sample type. Samples were maintained at 4–8 °C in insulated boxes with ice packs and processed within 6 h of collection.

Sample processing

Upon arrival at the laboratory, water samples were filtered through sterile membrane filters to concentrate parasitic elements. The residues retained on the filters were rinsed with sterile phosphate-buffered saline (PBS) (pH 7.4) and collected for downstream analysis. Vegetable samples were washed by agitation in 500 mL sterile PBS for 10 minutes at 150 rpm. The wash solutions were collected and centrifuged at 3,000 × g for 10 minutes. Resulting pellets were retained for downstream molecular examination.

To enhance DNA extraction efficiency, the pellets were subjected to mechanical disruption using a sterile mortar and pestle under liquid nitrogen, followed by three freeze–thaw cycles between liquid nitrogen (–196 °C) and a 37 °C water bath. This process facilitated rupture of eggshells or larval teguments, releasing nucleic acids for downstream extraction. The homogenate was then processed immediately for DNA extraction.

DNA extraction

Genomic DNA was extracted using the PureLink Genomic DNA Mini Kit (K1820-01, Invitrogen, Thermo Fisher Scientific, USA) according to the manufacturer’s instructions, with modifications adapted for E. granulosus. The procedure included sequential steps of lysis, binding, washing, and elusion. During the lysis step, the processed samples were incubated with Genomic Lysis/Binding Buffer and Proteinase K at 55–60 °C until complete digestion was achieved. RNase A was added during this stage to eliminate RNA contaminants. Following lysis, ethanol was added to the lysates, which were then transferred to silica-based spin columns.  The washing step involved sequential treatment with PureLink Wash Buffer 1 and Wash Buffer 2 to remove salt, proteins, and other contaminants. A final dry spin was performed to eliminate residual ethanol. For elusion, PureLink Genomic Elution Buffer was added to the columns, and DNA was released into sterile collection tubes following centrifugation.

DNA quality assessment

The quality and concentration of the extracted DNA were evaluated using a spectrophotometer (NanoDrop, Thermo Fisher Scientific, USA). Absorbance was measured at 260 nm and 280 nm to determine purity. Purity assessment was performed by calculating the A260/A230 ratio, with acceptable values ranging between 1.9 and 2.2. DNA integrity was further confirmed by electrophoresis on a 1% agarose gel prepared in 1X Tris-borate-EDTA buffer and stained with ethidium bromide. Bands were visualized under ultraviolet illumination, and intact high-molecular-weight bands were taken as indicators of high-quality genomic DNA.

Preparation of primers and probes

Primers and probes were prepared according to the manufacturer’s instructions (Sigma-Aldrich). Stock solutions for each primer and probe were resuspended in nuclease-free water, briefly vortexed, and centrifuged. Working solutions were prepared by diluting the stock solutions 1:10 in nuclease-free water.

qPCR reaction mixture preparation

Luna Universal Probe qPCR Master Mix and other reaction components were thawed at room temperature and then placed on ice. Each component was briefly mixed by inversion and gentle vortexing. Reaction mixtures were prepared for the required number of samples, including 10% overage. For each 20 µL reaction, the following components were combined: 10 µL Luna® Universal Probe qPCR Master Mix (2X), 1 µL Cox3 forward primer (10 µM), 1 µL Cox3 reverse primer (10 µM), 0.5 µL Cox3 probe-FITC (10 µM), 1 µL template DNA (20–100 ng/µL), and 6.5 µL nuclease-free water (Table 1) [6,7]. The mixture was gently mixed and centrifuged briefly to collect the solution at the bottom of the tube. Aliquots were dispensed into qPCR tubes or plates, and DNA templates were added. Tubes or plates were spun briefly at 2,500–3,000 rpm to remove bubbles.

qPCR cycling conditions

Real-time qPCR was performed using the following thermal profile: initial denaturation at 95 °C for 60 seconds, followed by 40–45 cycles of 95 °C for 15 seconds and 60 °C for 30 seconds, with fluorescence readings collected at the extension step in the Fluorescein Isothiocyanate (green) channel.

Data analysis and standard curve

qPCR data were analyzed according to the instrument manufacturer's instructions. Standard curves were generated by plotting the logarithm of input DNA concentrations against Cq values to determine reaction efficiency, which was considered acceptable between 90–110% (slope –3.6 to –3.1). Correlation coefficients (R²) ≥ 0.98 were accepted. Specificity was verified by ensuring a Cq difference of ≥3 between template-containing and non-template controls. Method detection limits were determined using eight serial dilutions of the initial DNA concentration (100 ng/µL) to assess assay sensitivity. Samples were evaluated relative to standard curves and control reactions, with appropriate dilution factors accounted for.

Results

A total of 245 samples were collected and analyzed, comprising 98 (40.0%) water samples and 147 (60.0%) vegetable samples. Of these, 111 (45.3%) were obtained from urban areas and 134 (54.7%) from rural areas. Geographically, 119 (48.6%) samples were collected from the eastern region, 21 (8.6%) from the western region, 56 (22.8%) from the northern region, and 49 (20.0%) from the southern region of Sulaymaniyah Governorate (Table 2).

The qPCR assay demonstrated clear amplification in the positive controls, which produced sharp exponential fluorescence curves crossing the threshold between cycles 28 and 30. In contrast, all field samples, including both water and vegetables, exhibited flat baseline fluorescence with no detectable signal above the threshold, confirming the absence of amplification (Figure 1). Therefore, none of the 245 field samples tested positive for E. granulosus DNA.

Discussion

Fresh vegetables are a vital part of a nutritious diet, but they may also act as carriers of protozoan cysts and helminth eggs or larvae. The moist conditions required for their growth create a favorable environment for the persistence and transmission of enteroparasitic forms. In many developing areas, the use of irrigation water contaminated with human or animal feces has been recognized as a key factor contributing to high levels of vegetable contamination with helminth eggs [8].

In this cross-sectional study of 245 water and vegetable samples collected from urban and rural areas of Sulaymaniyah, Iraq, no E. granulosus DNA was detected by qPCR. This absence of positive findings contrasts with reports from other regions documenting occasional environmental contamination. For example, Barosi and Umhang (2024) reported the presence of E. granulosus and E. multilocularis eggs in several environmental matrices, including water, soil, vegetables, and berries, with prevalence rates varying considerably [4]. Similarly, the international multicenter MEmE project detected E. granulosus sensu lato DNA in 1.3% of lettuce samples across Europe, with much higher levels reported in certain non-European countries, such as 12% of lettuce in Tunisia [9]. In that study, all positive samples were identified as E. granulosus sensu stricto, the genotype commonly associated with sheep, which confirmed that parasite eggs can adhere to food crops. The same project also recorded particularly high contamination rates in berries, with E. granulosus sensu stricto DNA found in 12% of blueberries from Pakistan and in 81.3% of strawberries from Tunisia [9]. In contrast, this study’s samples yielded no positives, suggesting that contamination of water and vegetables with E. granulosus eggs in Sulaymaniyah may be substantially lower than in the regions surveyed elsewhere.

Regional comparisons also demonstrate variability. In Iran, a neighboring country where hydatidosis is endemic, field surveys using microscopic egg detection have identified taeniid eggs (which include E. granulosus) on fresh produce at notable rates. A large Iranian study reported contamination in 7.8% of more than 2,700 vegetable samples, with lettuce showing the highest frequency [10]. In Shiraz, located in southern Iran, taeniid eggs were detected in 2.5% (2/80) of vegetables from markets and in 4.1% (6/144) of those collected directly from farms [11]. In Qazvin Province, contamination was found in 1.8% of 218 vegetable samples, again involving Taenia/Echinococcus eggs [12]. However, all these surveys relied on microscopy and did not specifically confirm E. granulosus by molecular methods; to date, no study has definitively documented E. granulosus DNA in Iranian produce despite the microscopy-based evidence [13]. In Turkey, environmental investigations have focused mainly on definitive hosts. For example, one survey of red fox feces reported 0.5% positivity for E. granulosus [14].

A few studies outside the Middle East provide context for our negative results. Awosanya et al. (2022) detected E. granulosus sensu lato DNA in environmental samples from Nigeria, with 2% of irrigation water and 7% of soil samples testing positive by PCR [15]. In Japan, Mori and colleagues analyzed river water using environmental DNA methods and detected E. multilocularis DNA in only 0.78% of samples [16], showing that such approaches often yield very low detection rates even in endemic regions. Taken together, these studies indicate that although Echinococcus eggs can contaminate water and crops, detection rates are often low unless contamination levels are substantial.

One possible explanation for the absence of positive findings in this study is the ecological and agricultural context. Environmental conditions in Sulaymaniyah, including climate, farming practices, and seasonality, may have reduced the likelihood of contamination. Experimental studies show that E. granulosus eggs can survive for more than 200 days at 7 °C under humid conditions, about 50 days at 21 °C with low humidity, and only a few hours in hot, dry conditions around 40 °C. Temperature and humidity strongly influence egg infectivity, and the eggs are highly sensitive to desiccation [17]. In Iraqi Kurdistan, late April corresponds to spring, with moderate average temperatures (~22 °C) that could support egg survival. However, rainfall or irrigation may wash eggs away, and dry days may accelerate desiccation. Agricultural practices may also play a role. For instance, if vegetables in Sulaymaniyah (such as irrigated greens) are cultivated and washed in ways that limit contact with dog feces, contamination would be less likely. In addition, the use of treated water or protected cultivation methods would further reduce exposure risk. In contrast, the high detection rates reported in countries such as Tunisia and Pakistan may reflect open-field agriculture combined with climatic or hygiene conditions more favorable to egg persistence.

This study has several important limitations. First, the sample size of 245 and the sampling strategy may have been insufficient to detect low-prevalence contamination. Although 245 samples represent a moderate number, environmental egg contamination could be so sparse that even this number yielded no positives. Second, sampling was conducted at a single time point at the end of April, so seasonal variations were not captured. E. granulosus transmission can be seasonal; for example, dog infections may peak after livestock slaughter in winter. Therefore, a late-spring snapshot may have missed periods of higher contamination or, conversely, periods when spring rains already washed eggs away.

Geographically, the study was confined to Sulaymaniyah governorate, encompassing both urban and rural areas. This region may not represent the entire area of Iraqi Kurdistan or Iraq, or neighboring provinces. As a result, the negative findings cannot be generalized to broader regions or other habitat types.

Despite these limitations, the results are reassuring from a public health perspective, suggesting that under current conditions, contaminated water and vegetables may not constitute a significant route of E. granulosus transmission in Sulaymaniyah. However, other transmission routes, particularly direct contact with infected dogs or handling of contaminated soil, remain relevant. Preventive strategies should therefore continue to focus on regular deworming of dogs, safe disposal of livestock offal, public education on hand and food hygiene, and improvements in slaughterhouse sanitation [1].

Future studies should expand sampling to cover different seasons, larger sample sizes, and additional environmental matrices such as soil and dog feces. Incorporating assays for egg viability alongside qPCR would help determine whether detected DNA reflects viable, infectious eggs or degraded material. Integrating environmental monitoring with veterinary and human epidemiological data will provide a more comprehensive understanding of local transmission dynamics, ensuring that cystic echinococcosis control efforts in Sulaymaniyah remain evidence-based and effective.

Conclusion

No E. granulosus DNA was detected in the water and vegetable samples collected from Sulaymaniyah, Iraq. These results indicate a low likelihood of environmental contamination during the study period, but seasonal changes, the restricted sample size, and methodological limitations mean that the presence of contamination cannot be completely excluded.

Declarations

Conflicts of interest: The authors have no conflicts of interest to disclose.

Ethical approval: Not applicable.

Patient consent (participation and publication): Not applicable

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: RQS and MNH were major contributors to the study's conception and to the literature search for related studies. HAN, AMM, and MMA were involved in the literature review, study design, and writing of the manuscript.  SJQ, AKH, SAF, SMA, SSA, YMM and KKM were involved in the literature review, the study's design, and data collection. TOM, SLE, and HSA 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. RQS and HAN confirm the authenticity of all the raw data.

Use of AI: ChatGPT-4.0 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.

Abstract

Introduction

Fine-needle aspiration (FNA) is commonly used to investigate lymphadenopathy of suspected metastatic origin. The current study aims to find the association between nodal characteristics and cancer-related factors with the rate of false-negative preoperative FNA.

Methods

This retrospective, single-center, cross-sectional study included breast cancer patients with negative preoperative axillary FNA results who underwent postoperative histopathological evaluation. Data were collected from electronic medical records, including clinical, imaging, cytological, and pathological findings. Patients with incomplete records, non-axillary or inconclusive FNAs, positive preoperative FNAs, or unsampled axillae postoperatively were excluded. Key variables analyzed included lymph node size, cortical thickness, tumor grade, histological type, immunohistochemical subtype, and metastatic patterns.

Results

A total of 209 negative axillary FNA samples were analyzed, with a mean patient age of 46.13 years. Invasive ductal carcinoma was the most common diagnosis, and ER-positive tumors were the predominant subtype. Ultrasonography identified suspicious axillary nodes in 20.57% of cases. Histopathology revealed a 27.75% false-negative rate, with a negative predictive value of 78.3%. Larger lymph node size and cortical thickness exhibited lower false-negative rates, while histologic type and ER status showed significant associations with false-negative outcomes (P < 0.05).

Conclusion

The 27.75% false-negative rate of preoperative FNA remains concerning and may not be sufficiently low to justify foregoing definitive axillary staging. The current study found significant associations between false-negative FNA rates and histological subtype and ER status, the latter of which is not explicitly mentioned in the literature.

Introduction

Breast cancer represents the most commonly diagnosed malignancy among women globally. In 2020, it surpassed lung cancer to become the leading cancer diagnosis in women worldwide, with an estimated 2.3 million new cases reported [1,2]. Precise clinical staging plays a pivotal role in assessing prognosis, informing treatment strategies, and anticipating clinical outcomes in breast cancer. A critical component of staging is the evaluation of axillary lymph node involvement, as the presence or absence of metastasis in these nodes substantially influences therapeutic approaches and overall survival rates [3].

Conventional techniques, including sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND), have long been the standard approaches for axillary staging in newly diagnosed breast cancer patients. Despite their diagnostic utility, these invasive procedures are associated with inherent risks and potential postoperative complications, notably lymphedema [1].

Axillary lymph node fine-needle aspiration biopsy (FNAB) has gained recognition as an effective method for staging breast cancer. When performed under ultrasound guidance (US-FNA), this technique allows for targeted sampling of suspicious axillary lymph nodes through a minimally invasive approach, providing a less invasive and potentially less morbid alternative to traditional methods such as SLNB and ALND [4]. This technique exhibits high diagnostic accuracy in detecting metastatic disease. Although the overall diagnostic accuracy of ultrasound-guided FNAB is well documented, the understanding of lymph node characteristics that influence the technique's sensitivity for detecting metastatic disease is limited [5]. Ewing et al. demonstrated that true-positive FNAB results were more likely in larger lymph nodes compared to false-negative results. Furthermore, true positive FNABs were associated with a higher percentage of nodal replacement by carcinoma, in contrast to false negative FNABs [6]. Establishing a precise correlation between the diagnostic sensitivity of FNAB for detecting metastatic malignancies and specific nodal characteristics remains challenging. The current study aims to establish the relationship between nodal characteristics and cancer-related factors with the false-negative FNAB rate through a retrospective analysis of data from 209 patients.

Methods

Study design

This was a retrospective, single-center, cross-sectional study. Data were collected over two months, from November to December 2024. All participants provided informed consent, including agreement to the use of their anonymized data for publication purposes. This study was approved by the Ethics Committee of the Kscien organization (Approval No. 2025-34).

Data source

Data were obtained through a review of electronic medical records, which included demographic information, medical history, presenting complaints, preoperative imaging findings (ultrasound, magnetic resonance imaging, and computed tomography), FNA results, diagnosis, treatment approaches, and postoperative histopathological outcomes.

Eligibility criteria

The study included patients diagnosed with breast cancer who had negative axillary FNA results before surgery and underwent histopathological assessment postoperatively. Exclusion criteria included patients with incomplete medical records, FNAs not sourced from the axillary region, positive preoperative axillary FNA results, FNAs conducted outside the study center, inconclusive FNA findings, cases where the axilla was not sampled after surgery, and hemorrhagic FNA samples. The following characteristics were analyzed: lymph node size, histological cancer type, immunohistochemical subtype, cortical thickness of axillary lymph nodes, tumor grade, and metastatic patterns.

Procedure

Ultrasound-guided FNA was systematically performed, adhering to established clinical protocols. Verbal informed consent was obtained before the procedure, with the target axillary lymph nodes initially identified through palpation and subsequently confirmed using high-frequency linear ultrasound imaging (7–15 MHz transducer). Patients were positioned in supine orientation with ipsilateral arm abduction to optimize anatomical access. Following alcohol antisepsis of the procedural field, a sterile 23-gauge Chiba-type needle connected to a 10 mL syringe via a pistol-grip aspiration device was percutaneously introduced into the lymph node cortex under continuous real-time sonographic visualization. Dynamic negative pressure (5-10 mL suction) was maintained during 3-5 controlled, multidirectional needle passes within the target lesion, with vacuum release executed before needle withdrawal to minimize peripheral blood admixture. Aspirates were promptly processed by smearing on glass slides and fixing in 95% alcohol for hematoxylin and eosin staining. Post-procedural hemostasis was achieved through sustained manual compression for 3 minutes, followed by clinical monitoring for immediate complications.

Statistical analysis

The data were initially collected and recorded in a Microsoft Excel (2024) spreadsheet and subsequently imported into version 25 of the Statistical Package for Social Sciences (SPSS). Categorical data were analyzed using the chi-squared test and Fisher's exact test. The results were presented as frequencies, ranges, percentages, means with standard deviations, and medians. A significance level of P < 0.05 was adopted.

Results

A total of 209 negative samples were included in the study. Ages ranged from 25 to 84, with a mean age of 46.13 years. A family history of cancer was reported in 70 patients (33.49%). The right breast was affected in 106 cases (50.72%). Invasive ductal carcinoma (IDC) was the most common diagnosis (156, 74.64%).  Grade II was the most abundant tumor grade (105, 50.24%). Upon immunohistochemical (IHC) examination, it was revealed that ER+ was the most common subtype of cancer (126, 60.29%) (Table 1).

Ultrasonography of the axilla showed 43 (20.57%) suspicious nodes.  The mean size of the lymph nodes was 11.7mm. Among the included samples, 58 (27.75%) were false negatives upon histopathological examination, while the true negatives were 151 (72.25%). Negative Predictive Value (NPV) was 78.3%. The rate of false negative readings decreased as the size of the lymph nodes increased above the mean size (11.7 mm), and a similar trend was also seen in cortical thickness. However, a statistically significant association wasn’t established (Table 2).

Among the analyzed characteristics, histologic cancer type and ER status were associated with false-negative readings (P-value < 0.05) (Table 3).

Discussion

Recent studies have provided insights into the factors contributing to false-negative FNA results in axillary lymph node evaluation for breast cancer. Earlier research by Ewing et al. identified smaller lymph node size (<1.2 cm) as a significant factor associated with false-negative FNA findings [6]. However, in the present study, lymph node size did not show a statistically significant association with false-negative results. This may be attributed to the fact that lymph node measurements were reported in only 20% of the cases, limiting the power of the analysis. Notably, consistent with previous literature, there was a trend of decreased rate of false-negative results as lymph node size increased beyond the mean threshold of 1.17 cm. It is plausible that a significant association might have emerged had a larger proportion of cases included lymph node size data.

Few recent studies have directly compared false-negative FNA rates among IDC, ILC, and other histological subtypes, representing a notable gap in the literature. Prior work, such as Chung et al., suggested that ILC’s diffuse, discohesive growth and smaller metastatic foci may contribute to higher false-negative rates [7]. Supporting this, Sauer and Kåresen reported false-negative rates of 16% for ILC versus 6% for IDC, indicating that histological subtype may impact FNA sensitivity [8]. In the present study, a statistically significant association was found between histological subtype and false-negative FNA rates: IDC accounted for 75.86% of false negatives, ILC for 18.97%, and other types for 5.17%. It is worth mentioning that this association may be attributed to the higher prevalence of IDC compared to other cancer subtypes. Further research comparing subtype-specific FNA accuracy, particularly between IDC and ILC, is warranted to optimize preoperative axillary staging.

Regarding receptor and HER2 status, current evidence does not support a consistent association with false-negative rates of axillary FNA in breast cancer. Some studies suggest that axillary FNA sensitivity may not significantly differ by breast cancer subtype (including ER/PR/HER2 status), though negative predictive values can vary [9]. The current study found a significant association between ER-positive tumors and false-negative FNA readings. However, PR and HER2 status had no significant association with false FNA readings.

Cortical thickness is a key factor influencing the accuracy of axillary FNA. Thinner cortices (<3.5 mm) are linked to a higher risk of false-negative results, likely due to lower tumor burden and sampling difficulties [6]. Although a statistically significant association was not demonstrated, likely because only ~17% of cases reported cortical thickness, the data suggest an inverse relationship between cortical thickness and false-negative rates, consistent with existing literature. Raising the cortical thickness threshold when selecting nodes for FNA may reduce false negatives and enhance diagnostic accuracy, though this must be balanced against the need for sensitivity in specific clinical contexts.

Tumor grade, which reflects the degree of cellular differentiation and is often associated with tumor aggressiveness and metastatic potential, was not found to be significantly associated with false-negative FNA rates. This aligns with existing literature, where tumor grade has not been identified as a major predictive factor for FNA accuracy. Notably, a higher rate of false negatives was observed among lower-grade tumors. This finding is consistent with the biological behavior of such tumors, which are typically less aggressive and may present with smaller or fewer nodal metastases, making detection more challenging.

Although this study did not demonstrate a statistically significant association between false-negative FNA rates and the differentiation and is often associated with tumor aggressiveness and metastatic potential, was not found to be significantly associated with false-negative FNA rates. This aligns with existing literature, where tumor grade has not been identified as a major predictive factor for FNA accuracy. Notably, a higher rate of false negatives was observed among lower-grade tumors. This finding is consistent with the biological behavior of such tumors, which are typically less aggressive and may present with smaller or fewer nodal metastases, making detection more challenging.

Although this study did not demonstrate a statistically significant association between false-negative FNA rates and the pattern of metastasis (micrometastasis vs. macrometastasis), prior literature has identified a notable link. Iwamoto et al. reported that 25% of patients with negative FNA results were subsequently found to have micrometastases on sentinel lymph node biopsy, contributing to a false-negative rate of approximately 31.5 [10]. Similarly, Fung et al. found micrometastases in 5 out of 16 patients with false-negative FNAs, underscoring the cytological challenge in detecting smaller metastatic foci [11].

In addition to nodal and patient-related factors, human error remains a significant contributor to false-negative FNA results and may compromise the validity of data analysis. These errors include sampling issues, operator dependency, interpretive variability, and subjective clinical decision-making. Alkuwari and Auger reported that nearly all false-negative cases in their study were due to sampling errors rather than misinterpretation [12]. Although less frequent, diagnostic challenges in cytology, particularly with scant cellularity or atypical morphology, can lead to interpretive errors. Moreover, the decision to perform FNA is often based on the clinician’s subjective assessment of nodal suspiciousness, which may result in missed metastases if abnormal nodes are not sampled [13].

A key limitation of this study was the incompleteness of the collected data, with several variables lacking sufficient information. Although the results were mostly in line with the literature, with some unusual findings, it likely affected the pattern of metastasis (micrometastasis vs. macrometastasis), prior literature has identified a notable link. Iwamoto et al. reported that 25% of patients with negative FNA results were subsequently found to have micrometastases on sentinel lymph node biopsy, contributing to a false-negative rate of approximately 31.5 [10]. Similarly, Fung et al. found micrometastases in 5 out of 16 patients with false-negative FNAs, underscoring the cytological challenge in detecting smaller metastatic foci [11].

In addition to nodal and patient-related factors, human error remains a significant contributor to false-negative FNA results and may compromise the validity of data analysis. These errors include sampling issues, operator dependency, interpretive variability, and subjective clinical decision-making. Alkuwari and Auger reported that nearly all false-negative cases in their study were due to sampling errors rather than misinterpretation [12]. Although less frequent, diagnostic challenges in cytology, particularly with scant cellularity or atypical morphology, can lead to interpretive errors. Moreover, the decision to perform FNA is often based on the clinician’s subjective assessment of nodal suspiciousness, which may result in missed metastases if abnormal nodes are not sampled [13].

A key limitation of this study was the incompleteness of the collected data, with several variables lacking sufficient information. Although the results were mostly in line with the literature, with some unusual findings, it likely affected the data analysis and impacted the overall findings.

Conclusion

The 27.75% false-negative rate of preoperative FNA remains concerning and may not be sufficiently low to justify foregoing definitive axillary staging. The current study found significant associations between false-negative FNA rates and histological subtype and ER status, the latter of which is not explicitly mentioned in the literature.

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: LRAP and AMA were major contributors to the study's conception and to the literature search for related studies. MMA, MKA, and HHF were involved in the literature review, study design, and writing of the manuscript. RMA, HAY, SL, SOA, and BOH 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. BOH and MMA confirm the authenticity of all the raw data.

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

For more than a decade, the academic publishing community has been locked in a battle against “predatory journals.” These are commonly understood as outlets that exploit the open access model by charging fees to authors without providing genuine peer review or editorial services [1]. While this campaign has been well-intentioned, its implementation has been riddled with inconsistencies and collateral damage. It is time to re-evaluate our approach—and a promising alternative has recently been proposed.

At the 18th Meeting of the European Association of Science Editors (EASE), Kakamad et al. introduced the concept of the Non-Recommended Journal (NRJ), offering a more nuanced and constructive way to classify questionable journals. Their proposal, outlined in a poster presented at the event, acknowledges a critical truth that the current binary model overlooks: not all low-quality or problematic journals are predatory, and not all accused journals are guilty [2].

One of the core issues with the term “predatory” is its lack of a universally accepted definition. Attempts to label journals as predatory can often be subjective and based on flawed or incomplete criteria. This ambiguity has led to wrongful accusations and the potential defamation of emerging or under-resourced journals that are making genuine efforts to improve. Worse still, some well-established journals exhibit questionable practices yet avoid scrutiny simply because they don’t fit the “predatory” mold [3].

The NRJ framework reframes the discussion by focusing not on intention, but on recommendation. Rather than asking whether a journal is maliciously exploitative, the NRJ model asks whether a journal meets acceptable standards of transparency, editorial rigor, and academic integrity. Journals that do not meet these standards—whether due to deliberate misconduct or lack of infrastructure can be flagged as “non-recommended” without implying criminality or predation [2].

This shift in terminology allows for a more flexible and inclusive way to monitor journal quality. It accounts for the so-called “borderline journals,” which may not be outright deceptive but still fail to uphold scholarly standards. By avoiding the inflammatory label of “predatory,” the NRJ system reduces the risk of reputational harm while still guiding authors, reviewers, and institutions toward better publishing decisions.

Moreover, the NRJ approach invites continuous re-evaluation. Journals can move in and out of this category based on demonstrated improvements, providing a growth mindset rather than cementing stigmas. This dynamic classification also encourages more transparent criteria, ideally informed by independent watchdogs or academic associations rather than commercial blacklists.

It is time we recognize the complexity of the academic publishing ecosystem and evolve beyond the simplistic predator-prey narrative. The NRJ concept represents a practical, fair, and forward-thinking step in that direction. As the academic world continues to grapple with questions of quality, ethics, and accessibility, such innovations are not just welcome, they are essential.

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.

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).

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.

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].

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.

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).

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.

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).

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.

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.