Zitong Zhao, Timothy Kwang Yong Tay, Tony Kiat Hon Lim, Liang Seah Tay, Gek San Tan, Wui Seng Khoo, Inny Busmanis, Shing Lih Wong
{"title":"Endometrial Mesonephric-like Carcinosarcoma With Shared KRAS, TP53, and RB1 Mutations: Report of a Rare Case Highlighting Diagnostic Challenges and Novel Molecular Insights, and Review of the Literature.","authors":"Zitong Zhao, Timothy Kwang Yong Tay, Tony Kiat Hon Lim, Liang Seah Tay, Gek San Tan, Wui Seng Khoo, Inny Busmanis, Shing Lih Wong","doi":"10.1097/PGP.0000000000001203","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001203","url":null,"abstract":"<p><p>Mesonephric-like carcinosarcoma (MLCS) is an uncommon gynecologic malignancy comprising mesonephric-like adenocarcinomatous (MLA) and high-grade (HG) sarcomatous elements. We describe an endometrial MLCS in a 63-yr-old woman showing divergent p53 immunohistochemical expression, with abnormal expression in the MLA component and normal expression in the sarcomatous component. Dedifferentiated carcinoma and uterine mesenchymal tumors are primary differential diagnoses when sarcomatous elements predominate or exhibit round-cell morphology. A review of 25 endometrial MLCS cases, including ours, showed advanced-stage presentation in 48% (12/25), recurrence in 60% (15/25) and disease-related death in 28% (7/25) of cases, underscoring its aggressive behavior. Heterologous differentiation occurred in 16% of cases but was not essential for diagnosis when unequivocal HG sarcomatous cells were present. Component-specific next-generation sequencing of our case revealed identical KRAS, TP53, and RB1 mutations in both components, with additional PTPRT mutation and KLF5 amplification restricted to the MLA component, representing a novel molecular signature with potential therapeutic implications.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tumor Grade in Molecularly Defined Endometrial Carcinoma: Prognostic Implications of the ESGO-ESTRO-ESP 2025 Guidelines.","authors":"Mikko Loukovaara, Annukka Pasanen, Ralf Bützow","doi":"10.1097/PGP.0000000000001202","DOIUrl":"10.1097/PGP.0000000000001202","url":null,"abstract":"<p><p>As an update to the 2021 guidelines, the 2025 endometrial carcinoma risk classification by the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) combines grade 3 endometrioid and nonendometrioid carcinomas into a single \"high-grade\" category and indicates that, within the mismatch repair-deficient (MMRd) molecular subgroup, tumor grade has limited relevance. We evaluated the prognostic value of tumor grade within the 2025 ESGO-ESTRO-ESP framework in a retrospective, single-center cohort of 1115 patients (median follow-up: 69 mo). Molecular classification and estrogen receptor status were determined by immunohistochemistry and polymerase-ε (POLE) sequencing. A 3-category histopathologic classification (grade 1-2 endometrioid, grade 3 endometrioid, and nonendometrioid) was associated with survival within MMRd, no-specific-molecular-profile (NSMP), and p53-abnormal subgroups. Analyses were not feasible in POLE ultramutated carcinomas. Within the MMRd and NSMP groups, disease-specific survival did not differ between grade 3 endometrioid and nonendometrioid carcinomas, supporting their combination into a single high-grade category for adjusted analysis. In localized MMRd tumors, deep myometrial invasion, cervical stromal invasion, and focal or substantial lymphovascular space invasion (LVSI) were associated with poor survival. In localized NSMP tumors, the pooled high-grade category and substantial LVSI predicted poor survival, with similar outcomes observed in stage IIB and IIC tumors. We confirm the lack of independent prognostic impact of grade in MMRd, as reflected in the guidelines. In NSMP, substantial LVSI but not estrogen receptor status has prognostic value beyond grade, supporting refinement of risk stratification in clinical practice.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ambrus Mályi, Erika Tóth, Ildikó Vereczkey, Andrea Kohánka, Zsombor Melegh
{"title":"Papillary Thyroid Carcinoma With an STRN::ALK Fusion Arising From a Mature Ovarian Teratoma.","authors":"Ambrus Mályi, Erika Tóth, Ildikó Vereczkey, Andrea Kohánka, Zsombor Melegh","doi":"10.1097/PGP.0000000000001131","DOIUrl":"10.1097/PGP.0000000000001131","url":null,"abstract":"<p><p>Somatic malignancy arising from a mature ovarian teratoma is a rare phenomenon, occurring in 1% to 3.5% of cases. These somatic tumors are most commonly epidermal malignancies, but they can develop from any somatic component, including thyroid tissue. Increasing evidence suggests that in such cases, the pathogenesis is driven by the same mutational profile as seen in their conventional somatic counterparts. Here, we report the first case of an STRN::ALK fusion in a papillary thyroid carcinoma arising from the thyroid component of a mature ovarian teratoma. The patient presented with a 68 mm mass in the right ovary, which was histopathologically confirmed as a mature teratoma. Within the thyroid component, papillary thyroid carcinoma was identified. Next-generation sequencing revealed an STRN::ALK fusion, supported by positive ALK immunohistochemistry in the carcinoma. The identification of these genetic signatures not only aids in diagnosis but also provides potential therapeutic targets in the case of disease progression.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"323-327"},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High-grade Endometrial Stromal Sarcoma With a Novel ING3::BCOR Fusion.","authors":"Istem Kose, Saloni Walia","doi":"10.1097/PGP.0000000000001144","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001144","url":null,"abstract":"<p><p>High-grade endometrial stromal sarcoma (HGESS) is a rare tumor that typically occurs over a wide age range, from 14 to 71 yr, often presenting with nonspecific clinical symptoms. This tumor group displays heterogeneous tumor morphology and a growing number of molecular alterations. The most common alterations are YWHAE::NUTM2 fusion and BCOR gene alterations, including fusions and internal tandem duplications. Here, we report a HGESS with a novel ING3::BCOR fusion. A 74-yr-old female presented with vaginal bleeding and underwent myomectomy. Hematoxylin & eosin (H&E) sections revealed a spindle cell proliferation with both hypocellular and hypercellular areas. Cytologic atypia was mild to moderate, with a mitotic count of 5/10 high-power fields; the background stroma had focal myxoid and collagenous changes. Focal necrosis and pleomorphism were observed. Ancillary studies showed CD10 and diffuse cyclin D1 positivity by immunohistochemistry (IHC). Estrogen receptor (ER), progesterone receptor (PR), ALK1, S100, HMB45, and CD34 were negative and p53 showed a wild-type staining pattern. RNA-based next-generation sequencing showed an ING3::BCOR fusion, confirming the diagnosis of HGESS with ING3::BCOR fusion. HGESS is an evolving entity with an increasing number of genetic alterations, including genetic fusion involving the BCOR gene. HGESS with BCOR fusion should be considered in tumors with a combination of spindle cell growth, myxoid background, foci of coagulative necrosis, diffuse cyclin D1 positivity, and a negative hormone receptor status. Accurate diagnosis requires an integrated approach that combines histopathologic evaluation, IHC, and molecular testing.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":"45 4","pages":"328-331"},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnostic Proficiency of Large Language Models in the Interpretation of Cervical Cytopathology.","authors":"Iason Psilopatis, Kleio Vrettou","doi":"10.1097/PGP.0000000000001168","DOIUrl":"10.1097/PGP.0000000000001168","url":null,"abstract":"<p><p>To evaluate the diagnostic proficiency of well-established multimodal Large Language Models (LLMs)-specifically Gemini, Claude, and Copilot-in interpreting cervical cytopathology (PAP smears). This diagnostic accuracy study used 30 representative cases from the \"Cytopathology of the Uterine Cervix-Digital Atlas,\" which represented the gold standard. The models were tested using a standardized, zero-shot prompt to distinguish between normal cells, benign modifications (infections), and cervical cell abnormalities. The models demonstrated significant variability. While Gemini and Copilot showed high proficiency (90%) in identifying normal physiological morphology, performance declined sharply for infectious pathogens and dysplastic/neoplastic lesions. Notably, all models misclassified several invasive carcinomas as benign or low-grade lesions. Claude exhibited a high rate of \"diagnostic escalation,\" frequently misidentifying normal cells as having abnormalities. Current LLMs are inadequate for the definitive diagnosis of cervical dysplasia and malignancy due to significant rates of overdiagnosis and failure to detect invasive carcinomas. They should be viewed as emerging educational aids rather than autonomous diagnostic tools, requiring rigorous human oversight.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"297-303"},"PeriodicalIF":2.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ovarian Epithelioid Tumor With FUS::CREM Fusion in a 63-Year-Old Woman: A Case Report of an Emerging Entity Associated With Systemic Inflammation.","authors":"Hiroshi Kajiyama, Yoko Kashima, Tomoyuki Otani, Kazuko Sakai, Naoki Shiraishi, Kazuto Nishio, Yukiko Shishido-Hara, Akihiko Ito, Sachiko Minamiguchi, Noriomi Matsumura","doi":"10.1097/PGP.0000000000001142","DOIUrl":"10.1097/PGP.0000000000001142","url":null,"abstract":"<p><p>Intra-abdominal epithelioid neoplasm with EWSR1/FUS::CREB fusions is an emerging entity characterized by a broad age distribution, epithelioid morphology, variable epithelial marker expression, prominent lymphoplasmacytic infiltration, and systemic inflammation. A few ovarian cases have been reported. We describe a 63-yr-old woman who presented with anemia and elevated C-reactive protein. She underwent surgery for a 14-cm right ovarian mass. Grossly, the tumor was solid with cystic change and hemorrhage, and had a light tan cut surface. Histologically, it consisted of uniform sheets of epithelioid cells with ample pale eosinophilic cytoplasm, divided by fibrotic septa with dense lymphoplasmacytic infiltration. Immunohistochemically, the tumor was positive for EMA, WT1, and vimentin; focally positive for CAM5.2; and negative for AE1/AE3, estrogen and progesterone receptors, PAX8, sex cord markers, desmin, HMB45, and Melan A. The Ki-67 labeling index was 20%. The differential diagnoses, including poorly differentiated carcinoma, sex cord-stromal tumors, perivascular epithelioid cell tumor, and inflammatory myofibroblastic tumor, were considered. Whole-genome sequencing revealed a FUS::CREM gene fusion. Based on clinicopathologic and genomic features, the tumor was classified as an ovarian example of EWSR1/FUS::CREB fusion-associated epithelioid neoplasm. Inflammation-related laboratory abnormalities resolved postoperatively. No adjuvant therapy was administered, and the patient remained disease-free at 12 mo. This represents the third reported ovarian tumor with FUS::CREM fusion and the seventh adnexal tumor with EWSR1/FUS::CREB family fusion. Prognostic information on these adnexal tumors is limited, but given the aggressive nature of analogous extra-adnexal and testicular tumors, cautious management and further studies are warranted.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"311-317"},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glandular Crowding of the Endometrium: Clinical Outcomes of a Diagnostic Gray Zone.","authors":"Anat Zeidel, Lisa Cole","doi":"10.1097/PGP.0000000000001165","DOIUrl":"10.1097/PGP.0000000000001165","url":null,"abstract":"<p><p>Endometrioid intraepithelial neoplasia (EIN) is a well-defined premalignant lesion of the endometrium, characterized by crowded glands exceeding the amount of stroma, cytologic atypia distinct from background endometrium, and a sufficiently sized lesion (often designated as 1 mm). However, some endometrial samples contain foci of crowded glands that fall short of these criteria. These diagnostically indeterminate areas, often described as \"atypical glandular crowding,\" present challenges in both interpretation and clinical management. To assess their significance, we conducted a retrospective review of endometrial specimens diagnosed with atypical glandular crowding over an 8-yr period (2016-2024) at Baystate Medical Center. Cases were identified through a free-text database search and included when at least one follow-up specimen was available within 1 yr of the index biopsy. Demographic, clinical, and histopathologic data were recorded, and outcomes were classified as benign, EIN, or carcinoma. Among 79,998 gynecologic specimens, 167 cases (0.2%) met the inclusion criteria, with 127 unique patients analyzed. Within 1 yr, 36 patients (28.3%) were diagnosed with EIN (n=31) or endometrioid carcinoma (n=5), most within 4 mo of the initial biopsy. Notably, roughly one-quarter of these cases arose within endometrial polyps, and their risk of EIN or carcinoma (~25%) was similar to that of nonpolypoid lesions. Thus, atypical glandular crowding carries a substantial short-term risk of a premalignant or malignant diagnosis on follow-up, with ~1 in 4 patients being diagnosed with EIN or carcinoma within a year. Recognition of this subdiagnostic but clinically significant pattern should prompt timely re-sampling, as early follow-up often reveals occult neoplastic lesions not captured in the initial biopsy.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"291-296"},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren J Ray, Erdembileg Chuluunerdene, Mirna B Podoll, Yin P Hung, Jaclyn C Watkins
{"title":"Uterine Arteriovenous Malformations: An Underrecognized Putative Cause of Postpartum Hemorrhage, Abnormal Uterine Bleeding, and Pelvic Pain.","authors":"Lauren J Ray, Erdembileg Chuluunerdene, Mirna B Podoll, Yin P Hung, Jaclyn C Watkins","doi":"10.1097/PGP.0000000000001160","DOIUrl":"10.1097/PGP.0000000000001160","url":null,"abstract":"<p><p>Arteriovenous malformations (AVMs) are vascular anomalies defined by direct communications between arteries and veins with bypassing of the capillary network. Such lesions may be congenital or acquired. In the uterus, AVMs are considered uncommon, with rare case reports-predominantly in the clinical and radiology literature-citing them as a possible source of abnormal uterine bleeding (AUB) or postpartum hemorrhage (PPH). Uterine AVMs (UAVMs) are largely favored to be acquired, arising secondary to trauma (eg, prior c-section, myomectomy, curettage) or, theoretically, due to an obstructive process distorting vasculature (eg, large leiomyomata). The rarity of reported cases to date has yielded an estimated incidence of 0.10% among premenopausal women. However, the personal experience of 2 academic gynecologic pathologists suggests a higher incidence of incidentally discovered uterine UAVMs. The aim of this study is to highlight the clinicopathologic features and putative etiologies of a series of UAVMs. Clinical presentations, gross findings, and histologic features of 12 UAVMs diagnosed from 2018 to 2023 from 2 institutions were reviewed. Cases arose in both premenopausal and postmenopausal women (range 24-55 yr) and were diagnosed as part of routine, nonconsultative practice. All patients were status post hysterectomy for benign pathologies (eg, leiomyomata, adenomyosis, endometriosis, postpartum hemorrhage), with the most common clinical presentations being chronic pelvic pain (n=6) and AUB (n=5). Histologically, all cases demonstrated incidentally discovered AVMs, hallmarked by the presence of an admixture of small to medium-sized arteries and veins without an intervening capillary network, arising in both the uterine cervix and corpus. Immunohistochemistry was pursued in select cases, which demonstrated an admixture of ERG and CD31-positive vasculature in the lesional foci. Most putative etiologies for AVM formation were obstructive (n=6), followed by a combination of obstructive and prior uterine intervention (n=4), prior uterine intervention only (n=1) and syndromic association (n=1). We demonstrate that UAVMs are likely an underrecognized cause of AUB, PPH, and chronic pelvic pain and often arise in the setting of obstructive benign pathology (eg, leiomyomata). Recognition of UAVMs, both clinically and pathologically, is important in determining the etiology of otherwise unexplained AUB and chronic pelvic pain.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"285-290"},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahlam Ali, Pelin Onur, Anas Mohamed, Shamsu Bello, Abul Kalam Azad, Doctor Goldstein, Tiffany Hebert
{"title":"Comparative Molecular Profiling of Basal Cell Carcinomas in Sun-Exposed and Anogenital Regions.","authors":"Ahlam Ali, Pelin Onur, Anas Mohamed, Shamsu Bello, Abul Kalam Azad, Doctor Goldstein, Tiffany Hebert","doi":"10.1097/PGP.0000000000001201","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001201","url":null,"abstract":"<p><p>Basal cell carcinoma (BCC) is the most common skin malignancy and is strongly associated with ultraviolet (UV) radiation. However, BCC arising in sun-protected areas such as the anogenital region remains poorly characterized. To compare the molecular profiles of anogenital BCC with those of BCC arising in sun-exposed skin, a retrospective analysis was performed on BCC cases identified between 2017 and 2025. Formalin-fixed, paraffin-embedded tissue samples were analyzed using a targeted next-generation sequencing panel (Oncomine Precision Assay GX). Clinicopathologic features and mutational profiles were compared. Nine anogenital BCC cases and 23 sun-exposed BCC cases were included. Mutations were identified in 14 of 23 (60.8%) sun-exposed cases, most commonly involving TP53, with additional alterations in SMO, FGFR3, ERBB2, RET, ERBB4, and PDGFRA. In contrast, no mutations were detected in the anogenital BCC group. Despite histologic similarity, anogenital BCC demonstrates a distinct molecular profile, suggesting an alternative pathogenesis. Further genomic studies are warranted.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuang Niu, Kyle Molberg, Kelley Carrick, Glorimar Rivera Colon, Katja Gwin, Wenxin Zheng, Jeffrey A SoRelle, Diego H Castrillon, Elena Lucas, Hao Chen
{"title":"Endometrioid Versus Seromucinous Borderline Ovarian Tumors: Divergent Molecular Signatures and a Shared Role as Precursors to Endometrioid Carcinoma.","authors":"Shuang Niu, Kyle Molberg, Kelley Carrick, Glorimar Rivera Colon, Katja Gwin, Wenxin Zheng, Jeffrey A SoRelle, Diego H Castrillon, Elena Lucas, Hao Chen","doi":"10.1097/PGP.0000000000001174","DOIUrl":"10.1097/PGP.0000000000001174","url":null,"abstract":"<p><p>Endometrioid borderline tumors (EBTs) and seromucinous borderline tumors (SMBTs) are rare ovarian neoplasms with distinct histologic features. However, the molecular profiles of EBTs and SMBTs remain incompletely characterized. We performed histologic evaluation and DNA/RNA next-generation sequencing (NGS) using a 1425-gene pan-cancer panel on 11 EBTs and 10 SMBTs to define their mutational landscapes, conduct cross-comparisons between EBTs and SMBTs, and evaluate both against established profiles of endometrioid carcinoma and low-grade serous carcinoma. Histologically, EBTs showed adenofibromatous (64%) or intracystic (36%) growth patterns, with morule formation in 36% of cases. Aberrant nuclear β-catenin expression was observed in 73% of EBTs, significantly higher than in SMBTs (0%, P =0.001). β-catenin abnormalities and morules were absent in SMBTs. 73% EBT and 60% SMBT were associated with endometriosis. Genetically, most EBTs harbored CTNNB1 mutations (73%) with additional alterations in KRAS (36%), ARID1A (27%), ATR (27%), KMT2D (27%), PIK3CA (18%), PIK3R1 (18%), PTEN (18%), AKT1 (18%), TP53 (18%), and several others (≤18%). In contrast, SMBTs lacked CTNNB1 mutations but frequently had KRAS (60%), BRAF (30%), PIK3CA (20%), PIK3R1 (20%), PTEN (20%), ATM (20%), ZFHX3 (20%), AUTS2 (20%), CIC (20%), FAT1 (20%), and PLAT (20%) mutations, with 20% showing concurrent KRAS/PIK3CA mutations. Pathway analysis revealed predominant WNT/β-catenin signaling in EBTs versus RAS-MEK-ERK pathway alterations in SMBTs resembling the seromucinous variant of ovarian endometrioid carcinoma, with additional involvement of PI3K-PTEN-AKT-mTOR and SWI/SNF chromatin remodeling pathways in both. These findings demonstrate that EBTs and SMBTs possess distinct morphologic and molecular profiles, expanding the molecular characterization of early ovarian endometrioid-type neoplasms.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"253-261"},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}