Diagnosis of Intestinal Endometriosis: A Multicenter Retrospective Study

Background: Intestinal endometriosis occurs when endometrial-like tissue infiltrates the intestinal wall, most often affecting the sig- moid colon and rectum. Methods: Between January 2012 and February 2025, patients with intestinal endometriosis who underwent surgery were examined in five tertiary referral centers: Istanbul Sultan Abdülhamid Han Research and Training Hospital, Izmir Katip Çelebi University, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Başakşehir Çam and Sakura City Hospital, and Izmir City Hospital. Preoperative symptoms, demographic characteristics, menstrual status, operative times, intraoperative blood loss, surgical and pathological findings, antibiotic use, and postoperative complications were retrospectively reviewed. Results: Emergency surgery was required in a significant number of patients (n = 35, 71.4%), primarily due to intestinal obstruction or acute abdomen presentations. Re- section procedures included anterior or low anterior resections for rectosigmoid involvement and colectomies for colonic disease (n = 21, 42.9%), appendectomies performed for acute appendicitis (n = 26, 53.1%), and small bowel resections for small intestinal diseases (n = 2, 4.1%). Postoperative complications were observed in 8 patients, including ileus (n = 2), infections requiring antibiotics (n = 2, Grade II), intra-abdominal abscess requiring percutaneous drainage (n = 1, Grade IIIa), bleeding requiring reoperation (n = 1, Grade IIIb), incisional hernia (n = 1, Grade IIIa), and fat necrosis (n = 1, Grade I). Histopathological examination revealed transmural (full-thickness) bowel wall involvement in three patients and muscularis propria-limited involvement in two patients. One case involved a 67-year-old post- menopausal woman who presented with bowel obstruction and required emergency surgery. Intraoperatively, a rectosigmoid stricture without a visible tumor was identified. Conclusion: Surgeons and clinicians should maintain a high index of suspicion for endometriosis in postmenopausal patients presenting with nonspecific gastrointestinal symptoms or when unexpected findings are encountered during abdominal surgery. Considering intestinal endometriosis in the differential diagnosis, even in the absence of typical risk factors such as hormone replacement therapy or a prior history of endometriosis, is essential for improving diagnostic accuracy and patient outcomes.

colon; differential diagnosis; intestinal endometriosis; small bowel 1. Introduction Endometriosis is a chronic condition characterized by the presence of endometrial-like tissue outside the uterus, affecting up to 15% of women of reproductive age [1]. Clin- ically, it often presents with pelvic pain, dysmenorrhea, dyspareunia, and infertility, with symptoms that typically fluctuate in response to hormonal changes [ 1]. When ectopic endometrial tissue involves the gas- trointestinal tract, most commonly the sigmoid colon and rectum, it is classified as intestinal endometriosis. This sub- type may present with nonspecific gastrointestinal symp- toms such as abdominal pain, constipation, rectal bleeding, and tenesmus [2]. However, due to the considerable overlap of these symptoms with other gastrointestinal disorders, in- cluding irritable bowel syndrome, inflammatory bowel dis- ease, and colorectal malignancies, establishing an accurate diagnosis remains challenging [ 3]. Histopathological evaluation typically reveals en- dometriotic lesions composed of endometrial glands and stroma, often accompanied by hemorrhage and fibrosis. In cases of deeply infiltrative disease, dense adhesions and ex- tensive fibrosis may develop, potentially leading to bowel obstruction or stricture formation. The extent of intestinal wall involvement can vary and may include: • Serosal involvement, which typically leads to adhesions between the bowel and adjacent structures, contributing to anatomical distortion. • Muscularis propria and submucosal involvement, more commonly observed in deep infiltrating endometriosis, often leads to fibrosis and luminal narrowing, potentially necessitating surgical intervention. • Mucosal involvement, although rare, may clinically and endoscopically mimic inflammatory bowel disease or colorectal cancer (Fig. 1). Histologically, it is charac- terized by the presence of endometrial glands and stroma within the mucosa, sometimes accompanied by ulcera- tion or bleeding [ 4]. Fig. 1. Intraoperative image of a strictured rectosigmoid colon segment in a patient with postmenopausal intramural endometriosis. The reported prevalence of intestinal endometriosis varies widely, ranging from 3% to 37% [5]. Symptoms such as dysmenorrhea, dyspareunia, and dyschezia are often sig- nificantly alleviated after surgical treatment [6]. Among the surgical approaches, segmental resection is generally pre- ferred in cases of deep rectal involvement. Although this technique is associated with higher postoperative complica- tion rates, it provides a lower risk of recurrence compared to shaving or disc excision procedures [ 7]. Available surgical options for colorectal endometrio- sis include shaving, disc resection, and segmental resection. Segmental resection is generally indicated for extensive or deep wall infiltration but is associated with an increased risk of complications, including postoperative fever, trans- fusion requirements, and rectovaginal fistula formation [8]. Nevertheless, the recurrence rate after segmental resection is lower than that of more conservative techniques [ 9]. Long-term follow-up studies have demonstrated that sur- gical treatment significantly improves both symptoms and quality of life in patients with rectal endometriosis [ 10]. In this study, we retrospectively analyzed cases of in- testinal endometriosis treated surgically across five tertiary referral centers, with a focus on clinical presentation, sur- gical approaches, and histopathological findings. 2. Materials and Methods Between January 2012 and February 2025, patients with intestinal endometriosis who underwent surgery were retrospectively evaluated across five tertiary referral cen- ters: Istanbul Sultan Abdülhamid Han Training and Re- search Hospital, Izmir Katip Çelebi University, Atatürk Training and Research Hospital, Bakırköy Dr. Sadi Konuk Training and Research Hospital, Başakşehir Çam and Sakura City Hospital, and Izmir City Hospital. All pathology reports diagnosed as “endometriosis” between January 2012 and February 2025 were reviewed. From these, only patients with histopathologically con- firmed intestinal involvement, defined by the presence of endometriotic glands and stroma within the bowel wall, were included. Patients with endometriosis confined to genital or other extragenital sites without intestinal involve- ment were excluded. No additional clinical or radiologi- cal criteria were applied for inclusion; patient selection was based solely on pathological confirmation. Histopathological Diagnosis Intestinal involvement was confirmed on hematoxylin and eosin (H&E)-stained sections by the presence of en- dometrial glands and stroma within the intestinal wall lay- ers, including the serosa, muscularis propria, or submucosa. Cases with involvement limited to the peritoneal surface, without deeper infiltration into the bowel wall, were ex- cluded. Immunohistochemical staining supported the di- agnosis, demonstrating estrogen receptor (ER) positivity in glandular structures and CD10 (cluster of differentia- tion 10) positivity in the surrounding spindle cell stroma. Pathological evaluations were performed independently at each participating center by experienced gastrointestinal pathologists. Although no central pathology review was conducted, all centers adhered to uniform diagnostic crite- ria and applied immunohistochemistry (ER, CD10, PAX8 [Paired Box Gene 8]) when necessary, ensuring diagnostic consistency across the study population. 2 To ensure methodological consistency across the five participating tertiary centers, a standardized data collection form was developed prior to data extraction. This form included predefined variables such as age, menopausal status, presenting symptoms, surgical indications, proce- dures performed, and complications. Investigators at each center independently extracted data using the same form, and all completed datasets were centrally compiled into a unified Excel spreadsheet. Any discrepancies were re- solved through cross-checking among investigators and, when necessary, direct review of surgical or pathology re- ports. This standardized approach minimized reporting het- erogeneity and ensured methodological consistency across centers. A comprehensive set of patient data was systemati- cally recorded and analyzed, including demographic char- acteristics, menopausal status, preoperative symptoms, op- erative time (minutes), estimated intraoperative blood loss (milliliters), surgical and pathological findings, antibiotic regimens, and postoperative complications graded accord- ing to the Clavien-Dindo classification system. Although the study was conducted across five tertiary centers, stan- dardized data collection protocols were applied. Surgical indications and procedures followed current clinical guide- lines. Pathological assessments were performed by ex- perienced gastrointestinal pathologists using routine H&E staining and, when necessary, immunohistochemistry. A uniform data collection form was employed across all cen- ters to ensure consistency in the recorded variables. In our study, to evaluate the effect of surgical site and emergency versus elective status on complications, pa- tients were categorized into four localization groups: (1) appendix, (2) small intestine, (3) colon, and (4) rectum. Complication severity was graded using the Clavien-Dindo classification system. Nonparametric tests (Kruskal-Wallis H test and Mann-Whitney U test) were applied to as- sess differences in complication severity between groups. The relationship between emergency versus elective status and complication severity was analyzed using the Mann- Whitney U test. For comparisons among localization groups, statistical significance was set at p < 0.05. If the Kruskal-Wallis test yielded significance, post hoc Dunn’s test was performed for multiple comparisons to identify the source of the difference. In addition, the Chi-square test was used to examine differences in complication rates be- tween groups. All statistical analyses were conducted us- ing SPSS Statistics version 29.0 (IBM Corp., Armonk, NY , USA). This study was conducted in accordance with the Dec- laration of Helsinki and was approved by the Ethics Com- mittee of Izmir Katip Çelebi University (Approval Number: 0060; dated July 18, 2024). Because this was a retrospec- tive analysis using anonymized patient data, the committee waived the requirement for individual informed consent. Continuous variables were expressed as mean ± standard deviation (SD) or as median with interquartile range (IQR), while categorical variables were presented as frequencies and percentages (%). American Society of Anesthesiol- ogists (ASA) scores were recorded to assess preoperative health status but were not used in subgroup comparisons or clinical decision-making. 3. Results A total of 49 patients with histologically confirmed intestinal endometriosis were identified, and their medical records were retrospectively reviewed. All patients pre- sented with nonspecific symptoms, including abdominal pain, rectal bleeding, and constipation. The mean body mass index among postmenopausal patients was 24.5 kg/m 2. Patient characteristics, includ- ing age, menopausal status, surgical setting (emergency vs. elective), ASA scores, preoperative diagnosis, type of surgical procedure (open, laparoscopic, robotic), operative time, intraoperative blood loss, antibiotic use, length of hos- pital stay, postoperative complications (graded using the Clavien-Dindo classification), follow-up duration, and 30- and 90-day readmission rates, are summarized in Table 1. The mean intraoperative blood loss was 30 mL. All patients were evaluated preoperatively by the De- partment of Gynecology and Obstetrics. Transvaginal ul- trasonography (TVUS) was performed in all but five cases; however, none demonstrated findings suggestive of intesti- nal endometriosis, highlighting the diagnostic challenges and frequent under-recognition of bowel involvement in routine gynecological evaluations. In emergency cases, abdominal contrast-enhanced computed tomography (CE- CT) was routinely performed. In elective cases, rectal le- sions were evaluated with pelvic magnetic resonance imag- ing (MRI), while sigmoid colon pathologies were typically assessed using abdominal CT. Nevertheless, in none of the cases did preoperative imaging indicate endometrio- sis. Consequently, preoperative gynecologic consultation was not obtained for any patient. Neither endoscopic ultra- sound (EUS) nor positron emission tomography-CT (PET- CT) was utilized. All surgeries were performed by gen- eral surgeons without preoperative multidisciplinary team (MDT) involvement. None of the patients had received hor- monal or conservative medical therapy for endometriosis prior to surgery. The mean interval between initial imaging and surgery was 48.6 ± 12.4 days. In all cases, the diag- nosis of intestinal endometriosis was established postoper- atively through histopathological evaluation, and patients were subsequently referred to gynecology for further man- agement. These findings underscore the underdiagnosis of bowel endometriosis despite adequate imaging and clinical evaluation and highlight the need for heightened awareness and multidisciplinary collaboration in suspected cases. Emergency surgery was performed in 35 patients (71.4%). The types of surgical procedures included: 3 Table 1. Demographic characteristics and surgical data. V ariables V alue Menopausal status N (%) Premenopausal 41 (83.7%) Postmenopausal 8 (16.3%) Age (Mean ± SD) 42.4 ± 10.8 years Emergency N (%) Elective surgery 14 (28.6%) Emergency surgery 35 (71.4%) Acute appendicitis 26 Obstruction 8 Perforation 1 Operation time (Median [IQR]) 142.5 (35–240) min Preliminary diagnosis N (%) Rectosigmoid cancer 10 (20.4%) Acute appendicitis 29 (59.2%) Mass in the small intestine 2 (4.1%) Complex polyp 4 (8.2%) Diverticulitis 4 (8.2%) ASA N (%) 1 25 (51%) 2 22 (44.9%) 3 2 (4.1%) Mean hospital stay 4.4 ± 4.5 days Surgical Technique N (%) Open 20 (40.8%) Laparoscopic 26 (53.1%) Robotic 3 (6.1%) Surgery N (%) Resection (colon and rectal diseases) 21 (42.9%) Appendectomy (acute appendicitis) 26 (53.1%) Small bowel resection (small intestinal diseases) 2 (4.1%) Intraoperative blood loss 30 cc Antibiotics used Cefazolin + ornidazole 7 (14.3%) Only cefazolin 42 (85.7%) Postoperative complications (Clavien-Dindo) 0–No complication 41 (83.7%) I–Minor (e.g., wound issues, oral antibiotics) 3 (6.1%) II–Pharmacological treatment 2 (4.1%) IIIa–Radiologic intervention 2 (4.1%) IIIb–Reoperation 1 (2.0%) IV–V 0 (0%) Follow-up Duration (Median) 30 days (11–702 days) Readmission Within 30 days 1 (2.0%) Within 90 days 2 (4.0%) Abbreviations: N, number; SD, standard deviation; IQR, interquartile range; ASA, American Society of Anesthesiologists; min, minutes. • Anterior or low anterior resection, primarily performed for presumed diagnoses such as rectosigmoid carcinoma, rectal polyps, or sigmoid diverticulitis. • Right hemicolectomy, conducted in patients suspected of having right-sided colon cancer. • Appendectomy, performed in cases presumed to be acute appendicitis. 4 Table 2. Comparison of postoperative complication rates and Clavien-Dindo scores across different surgical sites. Group (surgical site) Complication rate Median Clavien-Dindo score Notes Appendix (Group 1) 19% 0.0 Lowest risk; many emergency appendectomies Small Intestine (Group 2) Intermediate Intermediate — Colon (Group 3) Intermediate Intermediate — Rectum (Group 4) 80% 2.0 Highest complication rate p-value 0.033 (Chi-square) 0.020 (Kruskal-Wallis) Statistically significant difference • Small bowel resection, carried out in patients with sus- pected small intestinal masses on radiological imaging. 3.1 Postoperative Complications Postoperative complications occurred in 8 patients (16.3%). These included: • 2 cases of postoperative ileus , all successfully managed with conservative treatment. • 2 cases of postoperative pneumonia accompanied by fever, requiring intravenous antibiotic therapy. • 1 pelvic abscess, drained under interventional radiology guidance on postoperative day 7. • 1 case of postoperative hemorrhage , requiring surgical reoperation on the following day. • 1 wound dehiscence (eventration) , necessitating early surgical repair. • 1 case of subcutaneous fat necrosis with wound dis- charge, managed conservatively. No cases of anastomotic leakage, enteric fistula, or stoma-related complications were observed. 3.2 Notable Cases In one patient, intramural endometriosis was identi- fied. A 67-year-old postmenopausal woman underwent emergency surgery for a suspected rectosigmoid tumor causing obstruction. Intraoperatively, a stricture was ob- served without a visible tumor. The resected segment ex- hibited a 2.5 cm luminal narrowing over a 5 cm length of bowel, with 1 cm wall thickening. Histopathological eval- uation revealed endometrial glands and stroma localized to the muscularis propria. ERs were focally positive, and PAX8 was diffusely positive, confirming the diagnosis of intestinal endometriosis. Another notable case involved a 41-year-old pre- menopausal woman who underwent urgent low anterior resection for suspected rectosigmoid obstruction. A 6 cm stenotic segment with 1.8 cm luminal narrowing and marked bowel wall thickening was identified. Histopathol- ogy revealed deep infiltrating endometriosis with transmu- ral involvement, affecting the mucosa, submucosa, muscu- laris propria, and serosa, closely mimicking a neoplastic le- sion. Immunohistochemistry showed diffuse ER and PAX8 positivity in glandular cells, along with CD10 positivity in stromal tissue. In all cases, intestinal endometriosis was not sus- pected preoperatively and was diagnosed postoperatively solely based on histopathological evaluation. No coexist- ing pathological conditions were identified in the surgical specimens, and the clinical symptoms were attributed ex- clusively to intestinal endometriosis. Statistical analyses revealed statistically significant differences between the surgical localization groups in both complication severity (Clavien-Dindo score) and complica- tion rates. The Kruskal-Wallis H test showed that the dis- tribution of complication severity differed significantly be- tween the groups ( p = 0.020). Post-hoc analyses showed that this difference was primarily driven by the compari- son between the Rectum group (Group 4) and the Appendix group (Group 1) ( p < 0.01). The Rectum group had a significantly higher median Clavien-Dindo score (2.0) and complication rate (80%) compared to the Appendix group, which had a median score of 0.0 and a complication rate of 19%. However, no statistically significant difference in Clavien-Dindo complication scores was observed between the emergency and elective surgery groups (p > 0.05). This finding is likely because the vast majority (71.4%) of the emergency surgery group consisted of appendectomy pro- cedures, which carry a relatively low risk of complications. The Chi-square test also confirmed that complication rates differed significantly between the localization groups ( p = 0.033). The complication profiles of the Small Intestine and Colon groups were intermediate between those of the Rectum and Appendix groups. A comparative summary of complication severity and rates across surgical sites is shown in Table 2. 4. Discussion Intestinal endometriosis, particularly in post- menopausal women, poses a significant diagnostic challenge due to its rarity and nonspecific clinical and radiological features. This condition often mimics other gastrointestinal pathologies, including colorectal carci- noma, inflammatory bowel disease, and diverticulitis, thereby complicating preoperative diagnostic accuracy. Conventional imaging modalities, such as CT, MRI, and colonoscopy, frequently fail to detect the disease, especially in early or atypical cases, since the patholog- ical process typically originates at the serosal surface and progresses inward toward the mucosa [ 11]. A no- table finding of our study is the complete absence of 5 preoperative suspicion of endometriosis in all patients, including one with intramural endometriosis. Intramural localization, confined to the muscularis propria without involvement of the mucosa or serosa, represents one of the most diagnostically challenging forms. Its lack of radiological and endoscopic detectability underscores the

of current noninvasive diagnostic strategies and highlights the necessity of intraoperative assessment and histopathological confirmation. Another remarkable aspect is the occurrence of in- testinal endometriosis in postmenopausal women, a popu- lation traditionally considered hypoestrogenic. Despite the cessation of ovarian estrogen production, several mecha- nisms may sustain ectopic endometrial activity. Periph- eral aromatization of androgens in adipose tissue and skin contributes to extragonadal estrogen production, while lo- cal estrogen biosynthesis within endometriotic lesions— mediated by aromatase expression in stromal cells—plays a pivotal role in lesion maintenance and progression [ 12,13]. In addition, proinflammatory cytokines and growth factors, including interleukins, prostaglandins, and tumor necrosis factor-alpha, contribute to the persistence of endometriotic inflammation and tissue remodeling, even in the absence of systemic hormonal stimulation [ 14]. This complex inter- play of endocrine and paracrine mechanisms may explain the persistence and progression of the disease in this patient subgroup . In our cohort, a substantial proportion of patients, par- ticularly postmenopausal women, underwent emergency surgical intervention due to acute symptoms, such as bowel obstruction or suspected malignancy. These emer- gency procedures served a dual purpose: alleviation poten- tially life-threatening symptoms and providing a definitive histopathological diagnosis. Intraoperative findings fre- quently revealed fibrotic, stenotic bowel segments that had been misinterpreted preoperatively as neoplastic lesions. The absence of typical risk factors, such as hormone re- placement therapy or a prior diagnosis of endometriosis, further contributed to diagnostic delays. Our findings align with the broader surgical litera- ture, which emphasizes that procedural complexity is a key determinant of postoperative outcomes. This is par- ticularly evident in pelvic surgery, where anatomical con- straints markedly increase technical difficulty. Jago et al . [15] observed that bowel surgeries, such as rectal resections for endometriosis, carry a significant risk of both short- and long-term complications, underscoring the importance of meticulous preoperative planning and surgical expertise. Our results support this perspective, showing that the inher- ently higher complexity of rectal procedures was the pri- mary factor influencing complication rates, effectively out- weighing the effect of surgical urgency. This reinforces the principle that risk assessment should be procedure-specific rather than relying solely on broad classifications, such as emergency versus elective status. Although subgroup analyses demonstrated a statisti- cally significant difference in complication rates between rectal and appendiceal endometriosis cases, this disparity likely reflects the inherent complexity and technical chal- lenges of rectal surgery rather than differences in disease biology. The lower complication rates observed in appen- diceal cases, typically managed with less complex proce- dures, may account for this contrast. Given the limited sam- ple size, these findings should be interpreted with caution and considered hypothesis-generating rather than defini- tive. Overall, the rate of postoperative complications in our series was low, and no cases of long-term bowel dysfunc- tion were observed, supporting the feasibility and safety of surgical management even in emergency settings. Never- theless, the requirement for segmental resection in several patients underscores the severity of luminal involvement and the potential for transmural disease progression in long- standing or undiagnosed cases. Given these findings, clinicians should maintain a high index of suspicion for intestinal endometriosis in fe- male patients, regardless of age or menopausal status, who present with unexplained gastrointestinal symptoms, recur- rent subocclusive episodes, or imaging findings sugges- tive of malignancy without confirmatory biopsy. This con- sideration is particularly important during diagnostic la- paroscopy or laparotomy, where direct visualization may provide the first—and sometimes only—opportunity to identify and resect endometriotic lesions. Despite the availability of conventional imaging modalities, including TVUS, abdominal/pelvic CT, and MRI, none of the patients in our cohort exhibit a preoper- ative suspicion of endometriosis. This diagnostic gap un- derscores the limitations of current techniques, particularly in cases lacking classic symptoms or visible pelvic masses. Contributing factors may include submucosal or intramu- ral localization, nonspecific radiologic features, and lim- ited gynecologic assessment in emergency settings. Future clinical practice may benefit from incorporating advanced modalities, such as MRI enterography or EUS, when eval- uating patients with unexplained gastrointestinal symptoms and suspected deep infiltrating endometriosis. This study contributes to the growing body of litera- ture emphasizing the heterogeneous presentation of intesti- nal endometriosis. Previous epidemiological reviews have shown that demographic and reproductive factors—such as early age at menarche, short menstrual cycle length, lean body habitus, and parity—may influence the overall risk of endometriosis [ 16]. Although our dataset did not allow direct comparison with ovarian endometriosis, these char- acteristics may also affect the likelihood of intestinal in- volvement. Unlike prior series that primarily focused on reproductive-age women with classic gynecologic symp- toms, our findings highlight that intestinal endometriosis can also occur in asymptomatic or postmenopausal women, 6 often presenting in contexts unrelated to suspected gyne- cologic disease. By underscoring this overlooked entity in atypical clinical scenarios, we aim to enhance diagnostic awareness and promote earlier surgical referral when appro- priate. Ultimately, a multidisciplinary approach involving surgeons, gynecologists, and pathologists remains essential to improve diagnostic accuracy and optimize outcomes in patients with suspected or incidentally discovered intestinal endometriosis.

This study has several limitations. First, its retro- spective design introduces the potential for selection and reporting bias. Second, although data were collected from five tertiary centers—increasing the generalizability of findings—variations in surgical technique and pathologi- cal evaluation may have introduced heterogeneity. Further- more, due to the retrospective nature of the study and data availability, the median follow-up duration was limited to 30 days, which allowed for the assessment of perioperative outcomes but prevented evaluation of long-term recurrence or functional results. The relatively small sample size over a 13-year period reflects the rarity of pathologically confirmed intestinal en- dometriosis requiring surgical intervention. Although this may limit statistical power and generalizability, the strict inclusion criteria aimed to ensure diagnostic accuracy and cohort homogeneity. 5. Conclusion Intestinal endometriosis can present with a wide range of nonspecific symptoms and may mimic other gastroin- testinal pathologies, such as malignancy or inflammatory diseases. Our multicenter series highlights the diagnostic challenges of bowel endometriosis, particularly in emer- gency surgical settings, where definitive diagnosis is of- ten established postoperatively through histopathological examination. Increasing clinical awareness, especially in reproductive-age women with unexplained gastrointestinal complaints, may facilitate earlier recognition. A multidis- ciplinary approach and individualized treatment plans are essential to improve outcomes and avoid unnecessary ex- tensive surgeries. Availability of Data and Materials The datasets generated and analyzed during the cur- rent study are available from the corresponding author on reasonable request. All data are stored securely in com- pliance with ethical guidelines and patient confidentiality regulations. Author Contributions NK, FM, and FC designed the research study. NK, AUU, SK, HOS, and SB performed the research and col- lected the data. MT provided pathological interpretation and contributed to histopathological evaluation. FC, EK and ÖFO contributed substantially to the conception and design of the study, supervised surgical management, and participated in the interpretation of clinical data. SB con- tributed to data tabulation and figure editing. All authors contributed to editorial changes in the manuscript. All au- thors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. Ethics Approval and Consent to Participate This study was approved by the Ethics Committee of İzmir Katip Çelebi University in July 18, 2024, with the decision number 0060. As this is a retrospective study using anonymized data, individual informed consent for participation was not required. However, one intraopera- tive image is included in the manuscript, for which written informed consent for publication was separately obtained from the patient. The study was carried out in accordance with the guidelines of the Declaration of Helsinki. Acknowledgment We would like to express our sincere gratitude to all the surgical teams, pathologists, and research coordinators at the participating centers for their contributions to data collection and clinical management. We also thank all the peer reviewers for their valuable comments and construc- tive suggestions during the evaluation process. Special thanks to the Department of Pathology at Izmir City Hospi- tal for supporting the histopathological review. Funding This research received no external funding. Conflict of Interest The authors declare no conflict of interest.

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