{"paper_id":"a6eb7b2f-756d-4b49-97cc-c12ceceb19ff","body_text":"Ori gi nal Article | Özgün Araştırma\nTurk J Reprod Med Surg \n©Copyright 2026 The Author(s). Published by Galenos Publishing House on behalf of Society of Reproductive Medicine and Surgery. \nLicensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 (CC BY-NC-ND) International License.\nABSTRACT\nObjective: Endometriosis affects about 10% of reproductive-aged \nwomen and has been linked to increased malignancy risk, particularly \novarian cancer. However, data on the broader range of cancers and \ntheir clinical features in endometriosis patients remain limited. To \nevaluate clinical features, treatment characteristics, and malignancy \nhistory of endometriosis patients managed at a tertiary gynecology \ncenter and to compare the characteristics of patients with and \nwithout malignancy.\nMaterial and Methods: This retrospective study included 191 \npatients with histopathologically or ultrasonographically confirmed \nadvanced endometriosis (revised American Society for Reproductive \nMedicine stage III-IV) treated between 2012 and 2021. Clinical data \nwere obtained from medical records and telephone interviews, while \nmalignancy diagnoses were verified via national health records and \npathology reports.\nResults: Median age was 39 years (range: 21-62), and median CA-\n125 level was 43 U/mL (range: 5-548). Malignancy was detected \nin 6 patients (3.1%) at a median age of 41 years (range: 32-50). \nMost malignancies were non-gynecological (4/6, 66.7%), including \npapillary thyroid carcinoma (n=2), breast cancer (n=1), and malignant \nmeningioma (n=1). Gynecological cancers (2/6, 33.3%) included \novarian clear cell carcinoma and synchronous endometrial and breast \ncancer. No significant differences were found between patients with \nand without malignancy regarding age (p=0.327), CA-125 levels \n(p=0.706), pain symptoms, hormonal therapy, or prior surgery (all \np>0.05).\nÖZ\nAmaç: Endometriozis, üreme çağındaki kadınların yaklaşık %10’unu \netkileyen ve özellikle over kanseri olmak üzere artmış malignite \nriskiyle ilişkilendirilen bir hastalıktır. Ancak endometriozisli hastalarda \njinekolojik olmayan kanserler dahil geniş malignite spektrumuna ilişkin \nveriler sınırlıdır. Bu çalışmanın amacı, üçüncü basamak bir jinekoloji \nmerkezinde izlenen endometriozisli hastaların klinik özellikleri, tedavi \nyaklaşımları ve malignite öykülerini değerlendirmek ve malignite \nöyküsü olan ve olmayan hastalar arasındaki farkları karşılaştırmaktır.\nGereç ve Yöntemler: Bu retrospektif çalışma, 2012-2021 yılları \narasında ileri evre (revize Amerikan Üreme Tıbbı Derneği evre III-\nIV) endometriozis tanısı histopatolojik veya ultrasonografik olarak \ndoğrulanmış 191 hastayı içermektedir. Klinik veriler hasta dosyaları ve \ntelefon görüşmeleriyle toplanmış, malignite tanıları ulusal sağlık kayıt \nsistemi (e-Nabız) ve patoloji raporları aracılığıyla doğrulanmıştır.\nBulgular: Hastaların medyan yaşı 39 (aralık: 21-62), medyan CA-\n125 düzeyi 43 U/mL (aralık: 5-548) idi. Altı hastada (%3,1) malignite \nsaptandı; medyan tanı yaşı 41 (aralık: 32-50) idi. Malignitelerin çoğu \njinekolojik olmayan tipteydi (4/6, %66,7): iki papiller tiroid karsinomu, \nbir meme kanseri ve bir malignant meningioma. Jinekolojik \nmaligniteler (2/6, %33,3) bir over berrak hücreli karsinomu ve eş \nzamanlı endometrial-meme kanseri idi. Malignite varlığı ile yaş, CA-\n125 düzeyi, ağrı semptomları, hormonal tedavi öyküsü veya cerrahi \ngirişim açısından anlamlı fark saptanmadı (tümü p>0,05).\nSonuç: Endometriozisli hastalarda malignite nadir (%3,1) olmakla \nbirlikte, çoğunlukla jinekolojik olmayan kanserlerden oluşmuştur. \n Berivan GÜZELBAĞ1,2,  Nehir PİŞKİN3,  Ayşegül BESTEL3,  Engin ÇELİK4, \n Hale GÖKSEVER ÇELİK5,6\nMalignancy History in Patients with Endometriosis: \nA Retrospective Observational Study\nEndometriozisli Hastalarda Malignite Spektrumu: Retrospektif Gözlemsel Bir Çalışma\n1University of Health Sciences Türkiye, İstanbul Haseki Training and Research Hospital, Department of Obstetrics and Gynecology, İstanbul, \nTürkiye\n2Biruni University, Institute of Graduate Studies, Department of Molecular and Medical Genetics, İstanbul, Türkiye\n3University of Health Sciences Türkiye, Kanuni Sultan Süleyman Training and Research Hospital, Department of Obstetrics and Gynecology, \nİstanbul, Türkiye\n4Acıbadem Ataşehir Hospital, Clinic of Obstetrics and Gynecology, İstanbul, Türkiye\n5Acıbadem Mehmet Ali Aydinlar University Faculty of Medicine, Acıbadem Fulya Hospital, Department of Obstetrics and Gynecology, \nİstanbul, Türkiye\n6Acıbadem Fulya Hospital IVF and Endometriosis Center, Clinic of Obstetrics and Gynecology, İstanbul, Türkiye\nAddress for Correspondence/Yazışma Adresi: Berivan GÜZELBAĞ, MD, University of Health Sciences Türkiye, İstanbul Haseki Training and Research \nHospital, Department of Obstetrics and Gynecology; Biruni University, Institute of Graduate Studies, Department of Molecular and Medical Genetics, \nİstanbul, Türkiye\nE-mail: drguzelbag@gmail.com ORCID: orcid.org/0000-0002-1141-6381\nReceived/Geliş Tarihi: December 23, 2025 Ac cep ted/Kabul Tarihi: April 8, 2026\nEpub: April 15, 2026\nCite this article as: Güzelbağ B, Pişkin N, Bestel A, Çelik E, Göksever Çelik H. Malignancy history in patients with endometriosis: a retrospective \nobservational study. Turk J Reprod Med Surg. [Epub Ahead of Print]  \nDOI: 10.24074/tjrms.2026-116989 \n\n \nGüzelbağ et al. Malignancy Spectrum in Endometriosis Patients\nINTRODUCTION\nEndometriosis is a common chronic gynecological disorder \ncharacterized by the presence of endometrial-like tissue \noutside the uterine cavity, affecting approximately 10% \nof women of reproductive age worldwide. 1 The disease \nis frequently associated with debilitating pelvic pain \nsymptoms, including dysmenorrhea, dyspareunia, chronic \npelvic pain, dysuria, and painful defecation, and may \nsignificantly impair fertility and quality of life.2\nBeyond its benign nature, endometriosis has attracted \nincreasing attention due to its potential association with \nmalignancy. Epidemiological studies have consistently \nreported an increased risk of certain ovarian cancer \nsubtypes, particularly clear cell (3.4-fold) and endometrioid \n(2.3-fold) carcinomas, in women with endometriosis. 3-5 \nRecent large-scale meta-analyses have confirmed an \noverall 1.9-fold increased risk of endometriosis-associated \novarian cancer.4 In addition to ovarian cancer, associations \nbetween endometriosis and other malignancies, including \nthyroid cancer (1.4-fold increased risk), breast cancer, \nand endometrial cancer, have been reported; however, \nthe magnitude of these associations varies across studies \nand the underlying mechanisms remain incompletely \nunderstood.4,6,7\nSeveral hypotheses have been proposed to explain the \nrelationship between endometriosis and malignancy, \nincluding chronic inflammation, hormonal dysregulation, \noxidative stress, immune dysfunction, and shared genetic \nand epigenetic alterations. 1,8-10 Despite these proposed \nmechanisms, identifying clinical features that may distinguish \npatients with endometriosis who develop malignancy from \nthose who do not remains challenging. Biomarkers such \nas serum CA-125 are widely used in the clinical evaluation \nof endometriosis; however, their specificity for malignancy \ndetection in this population is limited due to elevation in \nbenign endometriosis and other inflammatory conditions.2\nGiven the heterogeneity of endometriosis and the relatively \nlow incidence of malignancy, real-world data describing \nthe clinical characteristics of patients with endometriosis \nwith and without a history of malignancy remain limited. \nTherefore, the aim of this study was to evaluate the \nclinical features, treatment characteristics, and malignancy \nhistory of patients with endometriosis managed at a \ntertiary gynecology center and to compare clinical and \ndemographic characteristics between patients with and \nwithout a confirmed history of malignancy.\nMATERIAL AND METHODS\nThis retrospective observational study was conducted \nat University of Health Sciences Türkiye, Kanuni Sultan \nSüleyman Training and Research Hospital, a tertiary referral \ncenter in İstanbul, Türkiye. The study included women \nwho presented to the gynecology outpatient clinics and \nwere diagnosed with endometriosis at the Department \nof Obstetrics and Gynecology between January 2012 \nand March 2021. This study was approved by the Clinical \nResearch Ethics Committee of University of Health Sciences \nTürkiye, Kanuni Sultan Süleyman Training and Research \nHospital, İstanbul, Türkiye (approval no: KAEK/2021.02.79, \ndate: 25.02.2021). The study was conducted in accordance \nwith the principles of the Declaration of Helsinki. Given the \nretrospective nature of the study and use of anonymized \ndata, the requirement for individual informed consent was \nwaived by the ethics committee.\nWomen aged 18 to 65 years with a confirmed diagnosis \nof endometriosis were eligible for inclusion. The diagnosis \nof endometriosis was established based on one of the \nfollowing criteria: (1) histopathological confirmation \nfollowing laparoscopic or laparotomic surgery, or (2) typical \nultrasonographic findings consistent with advanced-\nstage disease [revised American Society for Reproductive \nMedicine (rASRM) stage III-IV], as assessed by experienced \ngynecologists with expertise in endometriosis imaging. \nPatients were excluded if they had no confirmed diagnosis \nof endometriosis, were outside the specified age range, \nor could not be contacted by telephone for the structured \ninterview. For patients reporting a history of malignancy, \nonly those with available pathology records confirming \nthe malignancy diagnosis were included in the malignancy \ngroup. A total of 191 women met the inclusion criteria and \nhad complete data for the key study variables, constituting \nthe final study cohort.\nData collection was performed in two phases. First, \ndemographic, clinical, and laboratory data were \nABSTRACT ÖZ\nConclusion: Malignancy was rare (3.1%) but predominantly non-\ngynecological, contrasting with literature emphasizing ovarian cancer. \nThe lack of distinct predictors highlights the complexity of cancer \nrisk in endometriosis and the need for careful clinical follow-up in \nthis population, though prospective studies with control groups are \nneeded to establish definitive surveillance recommendations.\nKeywords: Endometriosis, malignancy, ovarian cancer, thyroid \ncancer, breast cancer\nBu bulgu, literatürdeki over kanseri vurgusundan farklıdır. Belirgin \nklinik öngördürücülerin olmaması, endometrioziste kanser risk \ndeğerlendirmesinin karmaşıklığını, bu popülasyonda dikkatli klinik \ntakibin önemini ve jinekolojik olmayan maligniteler için de kontrol \ngruplu prospektif çalışmalara ihtiyaç duyulduğunu göstermektedir.\nAnahtar Kelimeler: Endometriozis, malignite, over kanseri, tiroid \nkanseri, meme kanseri\n\n \nGüzelbağ et al. Malignancy Spectrum in Endometriosis Patients\nretrospectively extracted from the hospital electronic \nmedical record system. Variables obtained from medical \nrecords included age at study inclusion, serum CA-125 \nlevels (measured at initial presentation or during follow-\nup), pain-related symptoms (dysmenorrhea, dyspareunia, \nchronic pelvic pain, dysuria, and painful defecation), \nhistory of hormonal treatment (including combined oral \ncontraceptives, progestins, and gonadotropin-releasing \nhormone agonists), use of analgesic medications (non-\nsteroidal anti-inflammatory drugs or other analgesics), and \nprevious surgical interventions related to endometriosis \n(laparoscopy or laparotomy).\nSecond, information regarding a history of malignancy was \nobtained through structured telephone interviews conducted \nbetween March 2021 and September 2021. Patients were \nsystematically questioned about any cancer diagnosis, \nincluding type, date of diagnosis, stage, and treatment \nreceived. For all patients who reported a malignancy \ndiagnosis, hospital pathology records were reviewed in detail \nto verify the diagnosis. Only histopathologically confirmed \nmalignancies were included in the malignancy group for \nanalysis. Self-reported malignancies without pathological \ndocumentation, benign tumors, and premalignant lesions \n(such as cervical intraepithelial neoplasia or atypical \nhyperplasia) were not classified as malignancies.\nStatistical Analysis\nStatistical analyses were performed using SPSS software \n(version 21.0; SPSS Inc., Chicago, IL, USA). Descriptive \nstatistics were used to summarize the characteristics of the \nstudy population. The normality of continuous variables was \nassessed using the Shapiro-Wilk test and visual inspection \nof histograms. Due to non-normal distribution, continuous \nvariables were expressed as median (minimum-maximum) \nand compared between groups using the Mann-Whitney U \ntest. Categorical variables were presented as numbers and \npercentages and compared using Fisher’s exact test, which \nwas chosen over the chi-square test due to the small number \nof patients in the malignancy group (n=6). Multivariable \nregression analyses were not performed due to the limited \nnumber of patients with confirmed malignancy, which \nprecluded adequate statistical power for adjusted analyses. \nAll statistical tests were two-tailed, and a p-value <0.05 was \nconsidered statistically significant.\nRESULTS\nA total of 191 patients with a confirmed diagnosis of \nendometriosis were included in the final analysis. The \nmedian age at study inclusion was 39 years (range: 21-\n62). Serum CA-125 levels were available for all patients, \nwith a median value of 43 U/mL (range: 5-548). Baseline \ndemographic and clinical characteristics of the study \npopulation are summarized in Table 1. Dysmenorrhea \nwas the most frequently reported symptom, affecting 136 \npatients (71.2%), followed by chronic pelvic pain in 110 \npatients (57.6%) and dyspareunia in 98 patients (51.3%). \nLower urinary and gastrointestinal symptoms were also \ncommon, with dysuria reported by 65 patients (34.0%) \nand painful defecation by 62 patients (32.5%). Regarding \ntreatment history, more than half of the patients (n=106, \n55.5%) had received hormonal treatment for endometriosis \nmanagement, and 92 patients (48.2%) reported regular use \nof analgesic medications. Previous endometriosis-related \nsurgical interventions had been performed in 69 patients \n(36.1%), while the remaining patients were managed \nmedically.\nA history of malignancy was identified in 6 patients (3.1% \nof the cohort), and all cases were histopathologically \nconfirmed through review of the national health records \nsystem (e-Nabız) and hospital pathology records. Among \nthese patients, 2 (33.3%) had gynecological malignancies \nand 4 (66.7%) had non-gynecological malignancies. The \ngynecological malignancies included one ovarian clear \ncell carcinoma (diagnosed at age 49) and one case of \nsynchronous endometrial and breast cancer (diagnosed at \nage 42). The non-gynecological malignancies included an \nadditional isolated breast cancer (diagnosed at age 37), \ntwo papillary thyroid carcinomas (diagnosed at ages 32 \nand 50), and one malignant meningioma (World Health \nOrganization grade 3, diagnosed at age 40). The median \nage at malignancy diagnosis was 41 years (range: 32-50).\nComparisons between patients with and without a history of \nmalignancy are presented in Table  2. Patients with malignancy \nhad a median age of 41 years (range: 32-50) compared to 39 \nyears (range: 21-62) in those without malignancy (p=0.327). \nThe median serum CA-125 level was 46 U/mL (range: 17-\n75) in patients with malignancy compared to 44 U/mL  \nTable 1. Baseline clinical characteristics of patients \nwith endometriosis\nVariable Total cohort \n(n=191)\nAge, years, median (min-max) 39 (21-62) \nSerum CA-125 (U/mL), median (min-\nmax) 43 (5-548) \nDysmenorrhea, n (%) 136 (71.2%) \nDyspareunia, n (%) 98 (51.3%) \nChronic pelvic pain, n (%) 110 (57.6%) \nDysuria, n (%) 65 (34.0%) \nPainful defecation, n (%) 62 (32.5%) \nHormonal treatment history, n (%) 106 (55.5%) \nAnalgesic use, n (%) 92 (48.2%) \nPrevious endometriosis-related \nsurgery, n (%) 69 (36.1%) \nmin: Minimum, max: Maximum\n\n \nGüzelbağ et al. Malignancy Spectrum in Endometriosis Patients\n(range: 5-548) in those without malignancy (p=0.706). \nPain-related symptoms showed no significant differences \nbetween the two groups. Dysmenorrhea was present in \n50.0% of patients with malignancy compared to 71.6% \nwithout malignancy (p=0.359). Dyspareunia (33.3% vs. \n51.4%, p=0.439), chronic pelvic pain (83.3% vs. 56.3%, \np=0.240), dysuria (33.3% vs. 34.4%, p=1.000), and painful \ndefecation (16.7% vs. 32.8%, p=0.666) also showed no \nstatistically significant differences. Treatment characteristics \nwere comparable between groups. Hormonal treatment \nhistory was more common in patients with malignancy \n(83.3% vs. 54.6%, p=0.229), while analgesic use (33.3% \nvs. 48.1%, p=0.685) and previous endometriosis-related \nsurgery (16.7% vs. 36.6%, p=0.666) showed no significant \ndifferences.\nDISCUSSION\nIn this retrospective observational study, we evaluated the \nclinical characteristics and malignancy history of patients \nwith endometriosis managed at a tertiary care center. \nMalignancy was identified in a small subset of patients, with \nall cases histopathologically confirmed through the national \nhealth records system (e-Nabız) and hospital pathology \nrecords. Notably, the majority of malignancies were non-\ngynecological, including papillary thyroid carcinomas, \nbreast cancers (one concurrent with endometrial cancer), \nand malignant meningioma. Only a minority of patients \nhad gynecological malignancies, with one case of ovarian \nclear cell carcinoma. Patients with and without malignancy \nshowed no statistically significant differences in age, CA-125 \nlevels, pain-related symptoms, hormonal treatment history, \nor previous surgical interventions. It should be emphasized \nthat the present study was not designed to assess cancer \nrisk relative to the general population; rather, it aimed to \ndescribe the spectrum of malignancies observed within an \nendometriosis cohort. Accordingly, no conclusions regarding \nincreased malignancy risk can be drawn from these data.\nThe association between endometriosis and malignancy \nhas been most extensively studied in relation to ovarian \ncancer. Large-scale epidemiological studies and meta-\nanalyses have consistently demonstrated that women with \nendometriosis have an increased risk of certain ovarian \ncancer subtypes, particularly clear cell carcinoma (3.4-\nfold increased risk) and endometrioid carcinoma (2.3-\nfold increased risk). 4,5,11 The overall risk of endometriosis-\nassociated ovarian cancer is approximately 1.9-fold higher \ncompared to women without endometriosis, with meta-\nanalyses reporting odds ratios ranging from 1.4 to 1.9 across \ndifferent study designs. 4,12 Clear cell and endometrioid \nhistotypes are strongly associated with endometriosis, with \ncoexistence observed in approximately 20-50% of these \ncases.13 Large cohort studies have confirmed this association \nacross diverse populations, 14-16 with particularly elevated \nrisks observed among women with histopathologically \nconfirmed endometriosis. 17 In our cohort, ovarian cancer \naccounted for only a small proportion of malignancies, which \ncontrasts with the literature emphasizing ovarian cancer as \nthe predominant malignancy risk in endometriosis. This \nrelatively low proportion may reflect the young median age \nof our cohort, as endometriosis-associated ovarian cancer \ntypically develops at a median age of 47-52 years,11 and the \nlimited follow-up period in our retrospective study design.\nA striking finding in our study was the predominance of \nnon-gynecological malignancies, which contrasts with the \nexisting literature that primarily emphasizes gynecological \ncancer risk in endometriosis. In our cohort, we identified \npapillary thyroid carcinomas, breast cancers, and malignant \nmeningioma. Recent large-scale studies have reported \nmodest but statistically significant associations between \nendometriosis and thyroid cancer risk. A comprehensive \nmeta-analysis by Kvaskoff et al. 4 demonstrated a 1.39-\nfold increased risk of thyroid cancer among women with \nendometriosis, while a Korean nationwide cohort study \nreported a 1.34-fold increased risk.6 Systematic reviews and \nTable 2. Comparison of patients with and without a history of malignancy\nVariable Malignancy (+) (n=6) Malignancy (-) (n=185) p-value\nAge, years, median (min-max) 41 (32-50) 39 (21-62) 0.327\nSerum CA-125 (U/mL), median (min-max) 46 (17-75) 44 (5-548) 0.706\nDysmenorrhea, n (%) 3 (50.0) 131 (71.6) 0.359\nDyspareunia, n (%) 2 (33.3) 94 (51.4) 0.439\nChronic pelvic pain, n (%) 5 (83.3) 103 (56.3) 0.240\nDysuria, n (%) 2 (33.3) 63 (34.4) 1.000\nPainful defecation, n (%) 1 (16.7) 60 (32.8) 0.666\nHormonal treatment history, n (%) 5 (83.3) 100 (54.6) 0.229\nAnalgesic use, n (%) 2 (33.3) 88 (48.1) 0.685\nPrevious endometriosis-related surgery, n (%) 1 (16.7) 67 (36.6) 0.666\nmin: Minimum, max: Maximum\n\n \nGüzelbağ et al. Malignancy Spectrum in Endometriosis Patients\nmeta-analyses have also confirmed increased risks for extra-\novarian malignancies, including thyroid cancer (summary \nrelative risk 1.38).7 The association with breast cancer remains \nmore controversial, with most meta-analyses showing \nonly minimal association or no significant association. 4,7 \nHowever, some population-based studies have suggested \nslightly higher risks, particularly among younger women \nwith endometriosis. 18,19 Large cohort studies from diverse \npopulations have reported increased risks for multiple cancer \ntypes, including breast, thyroid, and endometrial cancers.18,20 \nHowever, findings remain inconsistent across studies, with \nsome large prospective cohorts reporting no significant \nincrease in overall cancer risk after endometriosis diagnosis \nhighlighting the complexity of these associations. 21 Earlier \nhospital-based studies also reported increased cancer risks \nfollowing endometriosis diagnosis, though effect sizes \nvaried considerably.22 One patient in our cohort presented \nwith synchronous endometrial and breast cancer, which may \nreflect shared hormonal risk factors, as both endometriosis \nand these malignancies are estrogen-dependent conditions. \nThe mechanisms underlying the association between \nendometriosis and non-gynecological malignancies remain \npoorly understood but may involve chronic inflammation, \nimmune dysregulation, shared genetic susceptibility, and \nhormonal factors.4,9 Genetic studies have identified shared \nmolecular pathways between endometriosis and various \ngynecological cancers, including alterations in genes \ninvolved in cell cycle regulation and tumor suppression. 23 \nOur findings underscore the heterogeneous nature of \nmalignancies observed in women with endometriosis, and \nsuggest that future prospective studies with control groups \nare needed to establish evidence-based surveillance \nrecommendations beyond gynecological malignancies.\nSerum CA-125 levels were similar between patients with \nand without malignancy in our cohort, suggesting limited \nutility of this biomarker for distinguishing malignancy in \nthe context of endometriosis. CA-125 is widely used in the \nclinical evaluation of endometriosis and ovarian masses; \nhowever, it is known to be elevated in various benign \ngynecological conditions, including endometriosis, and is \ninfluenced by disease extent, inflammatory activity, and \nmenstrual cycle phase. 2 The lack of specificity of CA-125 \nfor malignancy detection in patients with endometriosis has \nbeen well documented in the literature. Previous studies \nhave shown that elevated CA-125 levels in endometriosis \npatients reflect disease burden and inflammatory processes \nrather than malignant transformation. Our findings are \nconsistent with these reports, reinforcing that CA-125 alone \nis insufficient to reliably distinguish benign endometriosis \nfrom malignant conditions. The development of more \nspecific biomarkers for early detection of endometriosis-\nassociated malignancies remains an important area for \nfuture research.\nPain-related symptoms and treatment characteristics \nshowed no significant differences between patients with \nand without a history of malignancy. These findings are \nconsistent with previous studies suggesting that symptom \nseverity and pain phenotype do not reliably predict \nmalignant transformation in endometriosis.4,24 The absence \nof distinct clinical features that differentiate patients who \ndevelop malignancy from those who do not emphasizes \nthe complexity of disease behavior and underscores the \nchallenge of identifying high-risk patients based on clinical \npresentation alone. This highlights the importance of regular \nsurveillance and individualized risk assessment rather than \nreliance on symptom profiles for cancer screening in women \nwith endometriosis.\nStudy Limitations\nSeveral important limitations should be acknowledged. \nFirst, the small number of malignancy cases severely limited \nstatistical power and precluded multivariable analyses. \nConsequently, all between-group comparisons should be \ninterpreted with caution, as the observed non-significant \nresults (p>0.05) may reflect a type II error rather than \na true absence of association. Second, the biologically \nheterogeneous nature of the malignancies observed —\nencompassing gynecological, thyroid, breast, and central \nnervous system cancers— precludes meaningful grouped \nanalysis and limits the ability to draw conclusions regarding \nany specific cancer type or its relationship to endometriosis. \nThird, the retrospective design, lack of systematic follow-\nup, and inability to contact all eligible patients limit \nour ability to estimate true cancer incidence rates or \nassess the natural history of malignant transformation in \nendometriosis. Fourth, the relatively young median age \nof our cohort may explain the low proportion of ovarian \ncancer, as endometriosis-associated ovarian cancer \ntypically develops at older ages. Fifth, the absence of a \ncontrol group of women without endometriosis precludes \nany comparison of malignancy rates and therefore does \nnot allow conclusions regarding increased malignancy \nrisk. The present study is descriptive in nature and aims to \ncharacterize the spectrum of malignancies observed in this \ncohort, rather than to quantify cancer risk relative to the \ngeneral population. Sixth, the precise temporal relationship \nbetween endometriosis and malignancy diagnoses could \nnot be formally established. Although no malignancy was \nclinically detected at the time of endometriosis diagnosis, \nthe possibility of subclinical or asymptomatic malignancy at \nthat point cannot be excluded. Malignancy diagnoses were \nidentified through telephone interviews conducted in 2021, \nand the interval between endometriosis and malignancy \ndiagnoses was not systematically recorded, which precludes \ncausal inference. Finally, the inclusion of only advanced-\nstage (rASRM III-IV) endometriosis patients from a tertiary \nreferral center introduces a potential referral bias and limits \ngeneralizability to the broader endometriosis population, \nincluding those with early-stage disease in whom the \nmalignancy spectrum may differ. \n\n \nGüzelbağ et al. Malignancy Spectrum in Endometriosis Patients\nThis study provides valuable real-world data on the \nspectrum of malignancies observed in women with \nendometriosis, with several notable strengths, including \nhistopathological verification of all malignancy diagnoses \nthrough the national health records system (e-Nabız) and \nhospital pathology records, and systematic assessment \nof comprehensive clinical parameters in a real-world \ntertiary gynecology center setting. Our findings have \nimportant clinical implications. The predominance of non-\ngynecological malignancies underscores the heterogeneous \nmalignancy spectrum in women with endometriosis and the \nneed for future prospective studies to establish evidence-\nbased surveillance recommendations. 25 Clinicians should \nbe aware that non-gynecological malignancies, including \nthyroid and breast cancers, were observed in this cohort, \nthough the absence of a control group precludes definitive \nconclusions regarding increased risk. The absence of \ndistinct clinical features differentiating patients who develop \nmalignancy underscores the importance of individualized \nrisk assessment and regular surveillance according to age-\nspecific cancer screening guidelines. \nCONCLUSION\nIn conclusion, malignancy was uncommon in this cohort \n(3.1%), with the majority being non-gynecological cancers, \nwhich contrasts with literature emphasizing ovarian cancer \nrisk. Malignancy was not associated with distinct clinical \ncharacteristics. These findings highlight the heterogeneous \nnature of cancer risk in endometriosis and suggest that \nfuture prospective studies with control groups are needed \nto better define surveillance recommendations in this \npopulation. \nEthics\nEthics Committee Approval: This study was approved \nby the Clinical Research Ethics Committee of University \nof Health Sciences Türkiye, Kanuni Sultan Süleyman \nTraining and Research Hospital, İstanbul, Türkiye (approval \nno: KAEK/2021.02.79, date: 25.02.2021). The study \nwas conducted in accordance with the principles of the \nDeclaration of Helsinki.\nInformed Consent: Given the retrospective nature of \nthe study and use of anonymized data, the requirement \nfor individual informed consent was waived by the ethics \ncommittee.\nAcknowledgments\nThe authors thank the medical records staff of University of \nHealth Sciences Türkiye, Kanuni Sultan Süleyman Training \nand Research Hospital for their assistance with data \ncollection and the staff of the national health records system \n(e-Nabız) for providing access to pathology records. We are \ngrateful to all patients whose de-identified data contributed \nto this research.\nFootnotes\nAuthorship Contributions\nConcept: B.G., E.Ç., H.G.Ç., Design: B.G., A.B., Data \nCollection or Processing: B.G., N.P ., A.B., Analysis or \nInterpretation: B.G., E.Ç., H.G.Ç., Literature Search: N.P ., \nA.B., Writing: B.G., A.B., E.Ç., H.G.Ç.\nConflict of Interest: No conflict of interest was declared by \nthe authors.\nFinancial Disclosure: The authors declared that this study \nreceived no financial support.\nUse of Artificial Intelligence: Artificial intelligence tools \nprovided assistance during the language editing and \nformatting process of this manuscript. ChatGPT (OpenAI) \nwas employed for grammar checking and enhancing clarity \nof expression. All scientific content, data analysis, result \ninterpretation, and conclusions represent the original \nwork of the authors. 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