Malignancy History in Patients with Endometriosis: A Retrospective Observational Study

Objective: Endometriosis affects about 10% of reproductive-aged women and has been linked to increased malignancy risk, particularly ovarian cancer. However, data on the broader range of cancers and their clinical features in endometriosis patients remain limited. To evaluate clinical features, treatment characteristics, and malignancy history of endometriosis patients managed at a tertiary gynecology center and to compare the characteristics of patients with and without malignancy.

This retrospective study included 191 patients with histopathologically or ultrasonographically confirmed advanced endometriosis (revised American Society for Reproductive Medicine stage III-IV) treated between 2012 and 2021. Clinical data were obtained from medical records and telephone interviews, while malignancy diagnoses were verified via national health records and pathology reports.

Median age was 39 years (range: 21-62), and median CA- 125 level was 43 U/mL (range: 5-548). Malignancy was detected in 6 patients (3.1%) at a median age of 41 years (range: 32-50). Most malignancies were non-gynecological (4/6, 66.7%), including papillary thyroid carcinoma (n=2), breast cancer (n=1), and malignant meningioma (n=1). Gynecological cancers (2/6, 33.3%) included ovarian clear cell carcinoma and synchronous endometrial and breast cancer. No significant differences were found between patients with and without malignancy regarding age (p=0.327), CA-125 levels (p=0.706), pain symptoms, hormonal therapy, or prior surgery (all p>0.05). ÖZ Amaç: Endometriozis, üreme çağındaki kadınların yaklaşık %10’unu etkileyen ve özellikle over kanseri olmak üzere artmış malignite riskiyle ilişkilendirilen bir hastalıktır. Ancak endometriozisli hastalarda jinekolojik olmayan kanserler dahil geniş malignite spektrumuna ilişkin veriler sınırlıdır. Bu çalışmanın amacı, üçüncü basamak bir jinekoloji merkezinde izlenen endometriozisli hastaların klinik özellikleri, tedavi yaklaşımları ve malignite öykülerini değerlendirmek ve malignite öyküsü olan ve olmayan hastalar arasındaki farkları karşılaştırmaktır. Gereç ve Yöntemler: Bu retrospektif çalışma, 2012-2021 yılları arasında ileri evre (revize Amerikan Üreme Tıbbı Derneği evre III- IV) endometriozis tanısı histopatolojik veya ultrasonografik olarak doğrulanmış 191 hastayı içermektedir. Klinik veriler hasta dosyaları ve telefon görüşmeleriyle toplanmış, malignite tanıları ulusal sağlık kayıt sistemi (e-Nabız) ve patoloji raporları aracılığıyla doğrulanmıştır. Bulgular: Hastaların medyan yaşı 39 (aralık: 21-62), medyan CA- 125 düzeyi 43 U/mL (aralık: 5-548) idi. Altı hastada (%3,1) malignite saptandı; medyan tanı yaşı 41 (aralık: 32-50) idi. Malignitelerin çoğu jinekolojik olmayan tipteydi (4/6, %66,7): iki papiller tiroid karsinomu, bir meme kanseri ve bir malignant meningioma. Jinekolojik maligniteler (2/6, %33,3) bir over berrak hücreli karsinomu ve eş zamanlı endometrial-meme kanseri idi. Malignite varlığı ile yaş, CA- 125 düzeyi, ağrı semptomları, hormonal tedavi öyküsü veya cerrahi girişim açısından anlamlı fark saptanmadı (tümü p>0,05). Sonuç: Endometriozisli hastalarda malignite nadir (%3,1) olmakla birlikte, çoğunlukla jinekolojik olmayan kanserlerden oluşmuştur. Berivan GÜZELBAĞ1,2, Nehir PİŞKİN3, Ayşegül BESTEL3, Engin ÇELİK4, Hale GÖKSEVER ÇELİK5,6 Malignancy History in Patients with Endometriosis: A Retrospective Observational Study Endometriozisli Hastalarda Malignite Spektrumu: Retrospektif Gözlemsel Bir Çalışma 1University of Health Sciences Türkiye, İstanbul Haseki Training and Research Hospital, Department of Obstetrics and Gynecology, İstanbul, Türkiye 2Biruni University, Institute of Graduate Studies, Department of Molecular and Medical Genetics, İstanbul, Türkiye 3University of Health Sciences Türkiye, Kanuni Sultan Süleyman Training and Research Hospital, Department of Obstetrics and Gynecology, İstanbul, Türkiye 4Acıbadem Ataşehir Hospital, Clinic of Obstetrics and Gynecology, İstanbul, Türkiye 5Acıbadem Mehmet Ali Aydinlar University Faculty of Medicine, Acıbadem Fulya Hospital, Department of Obstetrics and Gynecology, İstanbul, Türkiye 6Acıbadem Fulya Hospital IVF and Endometriosis Center, Clinic of Obstetrics and Gynecology, İstanbul, Türkiye Address for Correspondence/Yazışma Adresi: Berivan GÜZELBAĞ, MD, University of Health Sciences Türkiye, İstanbul Haseki Training and Research Hospital, Department of Obstetrics and Gynecology; Biruni University, Institute of Graduate Studies, Department of Molecular and Medical Genetics, İstanbul, Türkiye E-mail: [email protected] ORCID: orcid.org/0000-0002-1141-6381 Received/Geliş Tarihi: December 23, 2025 Ac cep ted/Kabul Tarihi: April 8, 2026 Epub: April 15, 2026 Cite this article as: Güzelbağ B, Pişkin N, Bestel A, Çelik E, Göksever Çelik H. Malignancy history in patients with endometriosis: a retrospective observational study. Turk J Reprod Med Surg. [Epub Ahead of Print] DOI: 10.24074/tjrms.2026-116989 Güzelbağ et al. Malignancy Spectrum in Endometriosis Patients

Endometriosis is a common chronic gynecological disorder characterized by the presence of endometrial-like tissue outside the uterine cavity, affecting approximately 10% of women of reproductive age worldwide. 1 The disease is frequently associated with debilitating pelvic pain symptoms, including dysmenorrhea, dyspareunia, chronic pelvic pain, dysuria, and painful defecation, and may significantly impair fertility and quality of life.2 Beyond its benign nature, endometriosis has attracted increasing attention due to its potential association with malignancy. Epidemiological studies have consistently reported an increased risk of certain ovarian cancer subtypes, particularly clear cell (3.4-fold) and endometrioid (2.3-fold) carcinomas, in women with endometriosis. 3-5 Recent large-scale meta-analyses have confirmed an overall 1.9-fold increased risk of endometriosis-associated ovarian cancer.4 In addition to ovarian cancer, associations between endometriosis and other malignancies, including thyroid cancer (1.4-fold increased risk), breast cancer, and endometrial cancer, have been reported; however, the magnitude of these associations varies across studies and the underlying mechanisms remain incompletely understood.4,6,7 Several hypotheses have been proposed to explain the relationship between endometriosis and malignancy, including chronic inflammation, hormonal dysregulation, oxidative stress, immune dysfunction, and shared genetic and epigenetic alterations. 1,8-10 Despite these proposed mechanisms, identifying clinical features that may distinguish patients with endometriosis who develop malignancy from those who do not remains challenging. Biomarkers such as serum CA-125 are widely used in the clinical evaluation of endometriosis; however, their specificity for malignancy detection in this population is limited due to elevation in benign endometriosis and other inflammatory conditions.2 Given the heterogeneity of endometriosis and the relatively low incidence of malignancy, real-world data describing the clinical characteristics of patients with endometriosis with and without a history of malignancy remain limited. Therefore, the aim of this study was to evaluate the clinical features, treatment characteristics, and malignancy history of patients with endometriosis managed at a tertiary gynecology center and to compare clinical and demographic characteristics between patients with and without a confirmed history of malignancy.

This retrospective observational study was conducted at University of Health Sciences Türkiye, Kanuni Sultan Süleyman Training and Research Hospital, a tertiary referral center in İstanbul, Türkiye. The study included women who presented to the gynecology outpatient clinics and were diagnosed with endometriosis at the Department of Obstetrics and Gynecology between January 2012 and March 2021. This study was approved by the Clinical Research Ethics Committee of University of Health Sciences Türkiye, Kanuni Sultan Süleyman Training and Research Hospital, İstanbul, Türkiye (approval no: KAEK/2021.02.79, date: 25.02.2021). The study was conducted in accordance with the principles of the Declaration of Helsinki. Given the retrospective nature of the study and use of anonymized data, the requirement for individual informed consent was waived by the ethics committee. Women aged 18 to 65 years with a confirmed diagnosis of endometriosis were eligible for inclusion. The diagnosis of endometriosis was established based on one of the following criteria: (1) histopathological confirmation following laparoscopic or laparotomic surgery, or (2) typical ultrasonographic findings consistent with advanced- stage disease [revised American Society for Reproductive Medicine (rASRM) stage III-IV], as assessed by experienced gynecologists with expertise in endometriosis imaging. Patients were excluded if they had no confirmed diagnosis of endometriosis, were outside the specified age range, or could not be contacted by telephone for the structured interview. For patients reporting a history of malignancy, only those with available pathology records confirming the malignancy diagnosis were included in the malignancy group. A total of 191 women met the inclusion criteria and had complete data for the key study variables, constituting the final study cohort. Data collection was performed in two phases. First, demographic, clinical, and laboratory data were

ÖZ

Malignancy was rare (3.1%) but predominantly non- gynecological, contrasting with literature emphasizing ovarian cancer. The lack of distinct predictors highlights the complexity of cancer risk in endometriosis and the need for careful clinical follow-up in this population, though prospective studies with control groups are needed to establish definitive surveillance recommendations.

Endometriosis, malignancy, ovarian cancer, thyroid cancer, breast cancer Bu bulgu, literatürdeki over kanseri vurgusundan farklıdır. Belirgin klinik öngördürücülerin olmaması, endometrioziste kanser risk değerlendirmesinin karmaşıklığını, bu popülasyonda dikkatli klinik takibin önemini ve jinekolojik olmayan maligniteler için de kontrol gruplu prospektif çalışmalara ihtiyaç duyulduğunu göstermektedir. Anahtar Kelimeler: Endometriozis, malignite, over kanseri, tiroid kanseri, meme kanseri Güzelbağ et al. Malignancy Spectrum in Endometriosis Patients retrospectively extracted from the hospital electronic medical record system. Variables obtained from medical records included age at study inclusion, serum CA-125 levels (measured at initial presentation or during follow- up), pain-related symptoms (dysmenorrhea, dyspareunia, chronic pelvic pain, dysuria, and painful defecation), history of hormonal treatment (including combined oral contraceptives, progestins, and gonadotropin-releasing hormone agonists), use of analgesic medications (non- steroidal anti-inflammatory drugs or other analgesics), and previous surgical interventions related to endometriosis (laparoscopy or laparotomy). Second, information regarding a history of malignancy was obtained through structured telephone interviews conducted between March 2021 and September 2021. Patients were systematically questioned about any cancer diagnosis, including type, date of diagnosis, stage, and treatment received. For all patients who reported a malignancy diagnosis, hospital pathology records were reviewed in detail to verify the diagnosis. Only histopathologically confirmed malignancies were included in the malignancy group for analysis. Self-reported malignancies without pathological documentation, benign tumors, and premalignant lesions (such as cervical intraepithelial neoplasia or atypical hyperplasia) were not classified as malignancies. Statistical Analysis Statistical analyses were performed using SPSS software (version 21.0; SPSS Inc., Chicago, IL, USA). Descriptive statistics were used to summarize the characteristics of the study population. The normality of continuous variables was assessed using the Shapiro-Wilk test and visual inspection of histograms. Due to non-normal distribution, continuous variables were expressed as median (minimum-maximum) and compared between groups using the Mann-Whitney U test. Categorical variables were presented as numbers and percentages and compared using Fisher’s exact test, which was chosen over the chi-square test due to the small number of patients in the malignancy group (n=6). Multivariable regression analyses were not performed due to the limited number of patients with confirmed malignancy, which precluded adequate statistical power for adjusted analyses. All statistical tests were two-tailed, and a p-value <0.05 was considered statistically significant.

A total of 191 patients with a confirmed diagnosis of endometriosis were included in the final analysis. The median age at study inclusion was 39 years (range: 21- 62). Serum CA-125 levels were available for all patients, with a median value of 43 U/mL (range: 5-548). Baseline demographic and clinical characteristics of the study population are summarized in Table 1. Dysmenorrhea was the most frequently reported symptom, affecting 136 patients (71.2%), followed by chronic pelvic pain in 110 patients (57.6%) and dyspareunia in 98 patients (51.3%). Lower urinary and gastrointestinal symptoms were also common, with dysuria reported by 65 patients (34.0%) and painful defecation by 62 patients (32.5%). Regarding treatment history, more than half of the patients (n=106, 55.5%) had received hormonal treatment for endometriosis management, and 92 patients (48.2%) reported regular use of analgesic medications. Previous endometriosis-related surgical interventions had been performed in 69 patients (36.1%), while the remaining patients were managed medically. A history of malignancy was identified in 6 patients (3.1% of the cohort), and all cases were histopathologically confirmed through review of the national health records system (e-Nabız) and hospital pathology records. Among these patients, 2 (33.3%) had gynecological malignancies and 4 (66.7%) had non-gynecological malignancies. The gynecological malignancies included one ovarian clear cell carcinoma (diagnosed at age 49) and one case of synchronous endometrial and breast cancer (diagnosed at age 42). The non-gynecological malignancies included an additional isolated breast cancer (diagnosed at age 37), two papillary thyroid carcinomas (diagnosed at ages 32 and 50), and one malignant meningioma (World Health Organization grade 3, diagnosed at age 40). The median age at malignancy diagnosis was 41 years (range: 32-50). Comparisons between patients with and without a history of malignancy are presented in Table 2. Patients with malignancy had a median age of 41 years (range: 32-50) compared to 39 years (range: 21-62) in those without malignancy (p=0.327). The median serum CA-125 level was 46 U/mL (range: 17- 75) in patients with malignancy compared to 44 U/mL Table 1. Baseline clinical characteristics of patients with endometriosis Variable Total cohort (n=191) Age, years, median (min-max) 39 (21-62) Serum CA-125 (U/mL), median (min- max) 43 (5-548) Dysmenorrhea, n (%) 136 (71.2%) Dyspareunia, n (%) 98 (51.3%) Chronic pelvic pain, n (%) 110 (57.6%) Dysuria, n (%) 65 (34.0%) Painful defecation, n (%) 62 (32.5%) Hormonal treatment history, n (%) 106 (55.5%) Analgesic use, n (%) 92 (48.2%) Previous endometriosis-related surgery, n (%) 69 (36.1%) min: Minimum, max: Maximum Güzelbağ et al. Malignancy Spectrum in Endometriosis Patients (range: 5-548) in those without malignancy (p=0.706). Pain-related symptoms showed no significant differences between the two groups. Dysmenorrhea was present in 50.0% of patients with malignancy compared to 71.6% without malignancy (p=0.359). Dyspareunia (33.3% vs. 51.4%, p=0.439), chronic pelvic pain (83.3% vs. 56.3%, p=0.240), dysuria (33.3% vs. 34.4%, p=1.000), and painful defecation (16.7% vs. 32.8%, p=0.666) also showed no statistically significant differences. Treatment characteristics were comparable between groups. Hormonal treatment history was more common in patients with malignancy (83.3% vs. 54.6%, p=0.229), while analgesic use (33.3% vs. 48.1%, p=0.685) and previous endometriosis-related surgery (16.7% vs. 36.6%, p=0.666) showed no significant differences.

In this retrospective observational study, we evaluated the clinical characteristics and malignancy history of patients with endometriosis managed at a tertiary care center. Malignancy was identified in a small subset of patients, with all cases histopathologically confirmed through the national health records system (e-Nabız) and hospital pathology records. Notably, the majority of malignancies were non- gynecological, including papillary thyroid carcinomas, breast cancers (one concurrent with endometrial cancer), and malignant meningioma. Only a minority of patients had gynecological malignancies, with one case of ovarian clear cell carcinoma. Patients with and without malignancy showed no statistically significant differences in age, CA-125 levels, pain-related symptoms, hormonal treatment history, or previous surgical interventions. It should be emphasized that the present study was not designed to assess cancer risk relative to the general population; rather, it aimed to describe the spectrum of malignancies observed within an endometriosis cohort. Accordingly, no conclusions regarding increased malignancy risk can be drawn from these data. The association between endometriosis and malignancy has been most extensively studied in relation to ovarian cancer. Large-scale epidemiological studies and meta- analyses have consistently demonstrated that women with endometriosis have an increased risk of certain ovarian cancer subtypes, particularly clear cell carcinoma (3.4- fold increased risk) and endometrioid carcinoma (2.3- fold increased risk). 4,5,11 The overall risk of endometriosis- associated ovarian cancer is approximately 1.9-fold higher compared to women without endometriosis, with meta- analyses reporting odds ratios ranging from 1.4 to 1.9 across different study designs. 4,12 Clear cell and endometrioid histotypes are strongly associated with endometriosis, with coexistence observed in approximately 20-50% of these cases.13 Large cohort studies have confirmed this association across diverse populations, 14-16 with particularly elevated risks observed among women with histopathologically confirmed endometriosis. 17 In our cohort, ovarian cancer accounted for only a small proportion of malignancies, which contrasts with the literature emphasizing ovarian cancer as the predominant malignancy risk in endometriosis. This relatively low proportion may reflect the young median age of our cohort, as endometriosis-associated ovarian cancer typically develops at a median age of 47-52 years,11 and the limited follow-up period in our retrospective study design. A striking finding in our study was the predominance of non-gynecological malignancies, which contrasts with the existing literature that primarily emphasizes gynecological cancer risk in endometriosis. In our cohort, we identified papillary thyroid carcinomas, breast cancers, and malignant meningioma. Recent large-scale studies have reported modest but statistically significant associations between endometriosis and thyroid cancer risk. A comprehensive meta-analysis by Kvaskoff et al. 4 demonstrated a 1.39- fold increased risk of thyroid cancer among women with endometriosis, while a Korean nationwide cohort study reported a 1.34-fold increased risk.6 Systematic reviews and Table 2. Comparison of patients with and without a history of malignancy Variable Malignancy (+) (n=6) Malignancy (-) (n=185) p-value Age, years, median (min-max) 41 (32-50) 39 (21-62) 0.327 Serum CA-125 (U/mL), median (min-max) 46 (17-75) 44 (5-548) 0.706 Dysmenorrhea, n (%) 3 (50.0) 131 (71.6) 0.359 Dyspareunia, n (%) 2 (33.3) 94 (51.4) 0.439 Chronic pelvic pain, n (%) 5 (83.3) 103 (56.3) 0.240 Dysuria, n (%) 2 (33.3) 63 (34.4) 1.000 Painful defecation, n (%) 1 (16.7) 60 (32.8) 0.666 Hormonal treatment history, n (%) 5 (83.3) 100 (54.6) 0.229 Analgesic use, n (%) 2 (33.3) 88 (48.1) 0.685 Previous endometriosis-related surgery, n (%) 1 (16.7) 67 (36.6) 0.666 min: Minimum, max: Maximum Güzelbağ et al. Malignancy Spectrum in Endometriosis Patients meta-analyses have also confirmed increased risks for extra- ovarian malignancies, including thyroid cancer (summary relative risk 1.38).7 The association with breast cancer remains more controversial, with most meta-analyses showing only minimal association or no significant association. 4,7 However, some population-based studies have suggested slightly higher risks, particularly among younger women with endometriosis. 18,19 Large cohort studies from diverse populations have reported increased risks for multiple cancer types, including breast, thyroid, and endometrial cancers.18,20 However, findings remain inconsistent across studies, with some large prospective cohorts reporting no significant increase in overall cancer risk after endometriosis diagnosis highlighting the complexity of these associations. 21 Earlier hospital-based studies also reported increased cancer risks following endometriosis diagnosis, though effect sizes varied considerably.22 One patient in our cohort presented with synchronous endometrial and breast cancer, which may reflect shared hormonal risk factors, as both endometriosis and these malignancies are estrogen-dependent conditions. The mechanisms underlying the association between endometriosis and non-gynecological malignancies remain poorly understood but may involve chronic inflammation, immune dysregulation, shared genetic susceptibility, and hormonal factors.4,9 Genetic studies have identified shared molecular pathways between endometriosis and various gynecological cancers, including alterations in genes involved in cell cycle regulation and tumor suppression. 23 Our findings underscore the heterogeneous nature of malignancies observed in women with endometriosis, and suggest that future prospective studies with control groups are needed to establish evidence-based surveillance recommendations beyond gynecological malignancies. Serum CA-125 levels were similar between patients with and without malignancy in our cohort, suggesting limited utility of this biomarker for distinguishing malignancy in the context of endometriosis. CA-125 is widely used in the clinical evaluation of endometriosis and ovarian masses; however, it is known to be elevated in various benign gynecological conditions, including endometriosis, and is influenced by disease extent, inflammatory activity, and menstrual cycle phase. 2 The lack of specificity of CA-125 for malignancy detection in patients with endometriosis has been well documented in the literature. Previous studies have shown that elevated CA-125 levels in endometriosis patients reflect disease burden and inflammatory processes rather than malignant transformation. Our findings are consistent with these reports, reinforcing that CA-125 alone is insufficient to reliably distinguish benign endometriosis from malignant conditions. The development of more specific biomarkers for early detection of endometriosis- associated malignancies remains an important area for future research. Pain-related symptoms and treatment characteristics showed no significant differences between patients with and without a history of malignancy. These findings are consistent with previous studies suggesting that symptom severity and pain phenotype do not reliably predict malignant transformation in endometriosis.4,24 The absence of distinct clinical features that differentiate patients who develop malignancy from those who do not emphasizes the complexity of disease behavior and underscores the challenge of identifying high-risk patients based on clinical presentation alone. This highlights the importance of regular surveillance and individualized risk assessment rather than reliance on symptom profiles for cancer screening in women with endometriosis. Study Limitations Several important limitations should be acknowledged. First, the small number of malignancy cases severely limited statistical power and precluded multivariable analyses. Consequently, all between-group comparisons should be interpreted with caution, as the observed non-significant

(p>0.05) may reflect a type II error rather than a true absence of association. Second, the biologically heterogeneous nature of the malignancies observed — encompassing gynecological, thyroid, breast, and central nervous system cancers— precludes meaningful grouped analysis and limits the ability to draw conclusions regarding any specific cancer type or its relationship to endometriosis. Third, the retrospective design, lack of systematic follow- up, and inability to contact all eligible patients limit our ability to estimate true cancer incidence rates or assess the natural history of malignant transformation in endometriosis. Fourth, the relatively young median age of our cohort may explain the low proportion of ovarian cancer, as endometriosis-associated ovarian cancer typically develops at older ages. Fifth, the absence of a control group of women without endometriosis precludes any comparison of malignancy rates and therefore does not allow conclusions regarding increased malignancy risk. The present study is descriptive in nature and aims to characterize the spectrum of malignancies observed in this cohort, rather than to quantify cancer risk relative to the general population. Sixth, the precise temporal relationship between endometriosis and malignancy diagnoses could not be formally established. Although no malignancy was clinically detected at the time of endometriosis diagnosis, the possibility of subclinical or asymptomatic malignancy at that point cannot be excluded. Malignancy diagnoses were identified through telephone interviews conducted in 2021, and the interval between endometriosis and malignancy diagnoses was not systematically recorded, which precludes causal inference. Finally, the inclusion of only advanced- stage (rASRM III-IV) endometriosis patients from a tertiary referral center introduces a potential referral bias and limits generalizability to the broader endometriosis population, including those with early-stage disease in whom the malignancy spectrum may differ. Güzelbağ et al. Malignancy Spectrum in Endometriosis Patients This study provides valuable real-world data on the spectrum of malignancies observed in women with endometriosis, with several notable strengths, including histopathological verification of all malignancy diagnoses through the national health records system (e-Nabız) and hospital pathology records, and systematic assessment of comprehensive clinical parameters in a real-world tertiary gynecology center setting. Our findings have important clinical implications. The predominance of non- gynecological malignancies underscores the heterogeneous malignancy spectrum in women with endometriosis and the need for future prospective studies to establish evidence- based surveillance recommendations. 25 Clinicians should be aware that non-gynecological malignancies, including thyroid and breast cancers, were observed in this cohort, though the absence of a control group precludes definitive

regarding increased risk. The absence of distinct clinical features differentiating patients who develop malignancy underscores the importance of individualized risk assessment and regular surveillance according to age- specific cancer screening guidelines.

In conclusion, malignancy was uncommon in this cohort (3.1%), with the majority being non-gynecological cancers, which contrasts with literature emphasizing ovarian cancer risk. Malignancy was not associated with distinct clinical characteristics. These findings highlight the heterogeneous nature of cancer risk in endometriosis and suggest that future prospective studies with control groups are needed to better define surveillance recommendations in this population. Ethics Ethics Committee Approval: This study was approved by the Clinical Research Ethics Committee of University of Health Sciences Türkiye, Kanuni Sultan Süleyman Training and Research Hospital, İstanbul, Türkiye (approval no: KAEK/2021.02.79, date: 25.02.2021). The study was conducted in accordance with the principles of the Declaration of Helsinki. Informed Consent: Given the retrospective nature of the study and use of anonymized data, the requirement for individual informed consent was waived by the ethics committee. Acknowledgments The authors thank the medical records staff of University of Health Sciences Türkiye, Kanuni Sultan Süleyman Training and Research Hospital for their assistance with data collection and the staff of the national health records system (e-Nabız) for providing access to pathology records. We are grateful to all patients whose de-identified data contributed to this research. Footnotes Authorship Contributions Concept: B.G., E.Ç., H.G.Ç., Design: B.G., A.B., Data Collection or Processing: B.G., N.P ., A.B., Analysis or Interpretation: B.G., E.Ç., H.G.Ç., Literature Search: N.P ., A.B., Writing: B.G., A.B., E.Ç., H.G.Ç. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study received no financial support. Use of Artificial Intelligence: Artificial intelligence tools provided assistance during the language editing and formatting process of this manuscript. ChatGPT (OpenAI) was employed for grammar checking and enhancing clarity of expression. All scientific content, data analysis, result interpretation, and conclusions represent the original work of the authors. Artificial intelligence was not utilized in data collection, statistical analysis, or scientific content generation processes.

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