This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.

Extrauterine mesonephric-like carcinoma (ExUMLC) is a rare female genital tract tumor associated with advanced stage disease and distant recurrences. Although there is a histologic and mutational overlap with extrauterine low grade endometrioid carcinoma (ExULGEC), the distribution of the main components of the tumor microenvironment (TME) in these two neoplasms is not known. In this study we evaluated the clinicopathologic characteristics and the main lymphocyte populations in different compartments of the TME in cases of ExUMLC (18) and ExULGEC (17) - diagnosed at a single institution. A multiplex immunofluorescence panel including CD3, CD4, CD8, CD20, CD56, pancytokeratin, Foxp3, and Ki-67 was applied in all cases. The median age of ExUMLC was 60.5 years (range: 37–69 years), while in ExULGEC was 53 years (range: 22–83 years). The tumor compartment and total area analyzed of ExUMLC were significantly enriched in CK + Ki-67 + cells [(tumor: median 478 vs. 37.4 cells/mm2, p = 0.029) and (total: median 304.5 vs. 33.2 cells/mm2, p = 0.044)], CD3 + CD4+ T-cells [(tumor: median 0.6 vs. 0 cells/mm2, p = 0.01) and (total: median 2.6 vs. 0.3 cells/mm2, p = 0.022)], and CD3 + CD4+Foxp3 + T-cells [(tumor: median 0 vs. 0 cells/ mm2, p = 0.035) and (total: median 0.8 vs. 0 cells/mm2, p = 0.007)]. Importantly, distances from CK + to CD3 + CD4+ cells were also significantly lower in the ExUMLC group compared to ExULGEC. ExUMLC has a unique lymphoid microenvironment characterized by an overall low concentration of lymphocytes with a higher concentration of CD4 + T-cells and classic Tregs when compared to ExULGEC. This “cold” and immunosuppressive TME may be implicated in the more aggressive biology, and potentially pose a challenge for targeted treatment options in patients with ExUMLC.

Mirvetuximab soravtansine is an antibody-drug conjugate targeting FRα, which has not only shown antitumor activity and tolerability in ovarian carcinoma with FRα high expression, but has also been incorporated into NCCN guidelines to treat patients with platinum-resistant disease. Sequential cases were retrieved from a previously published cohort of gynecologic pathology cases in which FOLR1 immunohistochemistry had been performed at our institution. Clinical and pathologic data collected included patients' age, tumor histotype, tumor grade (if reported or relevant to histotype), primary tumor site, FIGO stage, and type of specimen. FOLR1 immunohistochemical results were collected from the report, including the overall tumor percentage and intensity reported, and subsequently determined if this was an overall positive or negative result (positivity defined as per current recommendations for therapy eligibility, 75%, 2-3+ intensity). The FOLR1 immunohistochemical slide was reviewed by 2 gynecologic pathologists and jointly recorded the following parameters: percent of cells staining at each level of intensity (0-3), range of staining intensity (0-3), percent of cells with membranous, cytoplasmic, or mixed staining, apical-only versus any membranous staining, percent of cells with complete membranous staining, and presence of abrupt transition (0 - no staining at all, juxtaposed to 2-3+ staining). One hundred twenty cases were reviewed and scored, 119 of which had original reported scores available for comparison. The staining intensity record was 0 in 9 (7.5%) of the cases, 0-1 in 3 (2.5%), 0-2 in 11 (9.2%), 0-3 in 88 (73.3%), 1-3 in 3 (2.5%), 2-3 in 4 (3.3%), and 3 in 2 (1.7%). The percent of positive cells at 2-3+ intensity as per quartile of cases was 12 (10.0%) cases with 0%, 14 (11.7%) cases with 1%-24%, 15 (12.5%) with 25%-49%, 28 (23.3%) with 50%-74%, and 51 (42.5%) with ≥75%. Using the original clinical reports, 67 (56.3%) of 119 cases were positive; 55 (67.9%) of 81 resection cases were positive, while 12 (31.6%) of 38 biopsy cases were positive. On re-review, 51 (42.5%) of all 120 cases were positive, with 41 (50%) of 82 resection cases being positive and 10 (26.3%) of 38 biopsy cases being positive. Overall, 18 (15.1%) of 119 cases had a clinically significant change (i.e. positive to negative or negative to positive). When broken down by type of specimen, 16 (19.8%) of 81 resection cases had a significant change, while only 2 (5.3%) of 38 biopsy cases had a significant change. Of the original scores taken from the report, the score was clearly stated in 117 reports, of which 47 cases were reported within 65% to 85% 2-3+ intensity. Seventeen of these 47 on rescoring were changed significantly as to a clinical action outcome; all 17 of these were changed from "positive" to "negative." The 18th case, which was changed on rescoring, was the singular case that was changed from "negative" to "positive," which was originally reported at 60% and on review was scored 75%. On rescoring of all 120 cases, 32 cases were 65% to 85% 2-3+ intensity. The heterogeneous staining pattern of FRα expression may lead to difficulties in scoring and interpretation, which can have an impact on clinical management.

Objectives:To present a rare case of mixed vaginal tumor with atypical features and to discuss clinical management in the context of uncertainty regarding biological behavior. Methods:We present the clinical course of a 50-year-old woman with a history of endometriosis and a recurrent vaginal mass who was diagnosed with a mixed tumor with atypical features and uncertain behavior. Following wide local excision, the multidisciplinary team reached a consensus to proceed with close surveillance without initiating adjuvant therapy. Results:The patient underwent excision of a 1 × 2 cm pedunculated vaginal mass with 1-2 cm margins. Pathology confirmed a mixed tumor with atypical features, 13 mitoses per 10 high-power fields, and irregular borders. Postoperatively, the patient had episodes of severe vaginal pain and swelling, including foul-smelling discharge and dysuria at day 9, and recurrent pain at 1 and 2 months. Imaging demonstrated only mild postsurgical changes without abscess, and symptoms resolved with antibiotics and supportive care. Given the absence of high-risk pathological features and no evidence supporting adjuvant therapy, the multidisciplinary team recommended surveillance. Three months after resection, the patient remained without evidence of disease. Conclusions:This case underscores the need for greater awareness and research to guide management and recurrence prevention for rare vaginal tumors. Complete resection is critical, and the potential benefits of adjuvant therapy must be weighed against risks such as sexual dysfunction, psychological impact, and treatment-related morbidity.

Several gonadal neoplasms harbor recurrent CTNNB1 mutations, including sex cord-stromal tumors, such as Sertoli cell tumor, NOS and gonadal signet ring stromal tumor, ovarian and testicular microcystic stromal tumor (MCST), in addition to gonadal solid pseudopapillary neoplasms (SPN). Despite being classified as separate entities, they have notable morphologic and immunophenotypic similarities. Of note, gonadal SPNs have been regarded as the counterparts of pancreatic SPN, but their relationship remains poorly understood. We analyzed 28 gonadal sex cord-stromal tumors, including testicular Sertoli cell tumors NOS (n=8), MCSTs (n=2), and signet ring stromal tumor (n=6), ovarian MCSTs (n=11), signet ring stromal tumor (n=1), together with ovarian SPNs (n=4) and pancreatic SPNs (n=9). Histologic features were reviewed, and immunohistochemistry for SF-1, SOX9, WT1, β-catenin, inhibin, and calretinin was performed. CTNNB1 mutation status was assessed by NGS in selected cases. DNA methylation profiling was performed successfully in 25 tumors (61%). All gonadal tumors showed overlapping morphologic features, comprising variable combinations of tubular, solid, signet ring and microcystic patterns, although the abundance of individual patterns varied between entities. Pancreatic SPNs showed similar cytologic features to gonadal tumors and commonly exhibited solid and pseudopapillary architecture with frequent cystic structures but lacked true tubular differentiation. Immunohistochemically, SF-1 expression was present in 27/31 (87%) tested gonadal tumors whereas all pancreatic SPNs were negative (4/4). Diffuse nuclear β-catenin expression was identified in all evaluable gonadal and pancreatic tumors (35/35, 100%). SOX9 and WT1 were expressed in 19/21 (90%) and 24/25 (96%) of gonadal tumors, respectively. In contrast, pancreatic SPNs were negative for SF-1 and WT1 in all evaluable cases (4/4 each), with only a single case showing focal SOX9 positivity. Inhibin and calretinin expression was largely absent in gonadal tumors, with only rare focal or weak positivity (3 cases) and a single ovarian MCST showing diffuse calretinin expression. Methylation analysis demonstrated closely related epigenetic profiles among gonadal CTNNB1-driven tumors, regardless of their histologic classification, whereas pancreatic SPNs formed a separate cluster. These findings indicate that several CTNNB1-driven tumors of the gonads currently classified as different entities share morphologic, immunophenotypic, and epigenetic features, supporting the concept that they represent variations within the same spectrum. Despite some morphologic overlap, these gonadal tumors are different from pancreatic SPN based on DNA methylation signatures.

Background: The role and optimal sequencing of systemic therapy in patients with high-volume peritoneal mesothelioma (PeM) undergoing curative-intent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains unclear. We compared perioperative outcomes in patients undergoing upfront CRS/HIPEC (U-CRS) versus those receiving neoadjuvant therapy (NAT). Methods: This single-institution retrospective study included patients with PeM (2009-2023) who underwent CRS/HIPEC with a peritoneal carcinomatosis index (PCI) > 20. Primary outcomes were prolonged operative time (OT), defined as > 75th percentile for the study cohort, and 90-day postoperative complications. Secondary outcomes included complete cytoreduction with CC-0 score, recurrence-free survival (RFS), and overall survival (OS). Results: Of 45 patients, 14 (31 %) underwent U-CRS and 31 (69 %) received NAT. Most NAT patients (94 %) were treated with a platinum agent and pemetrexed, with or without bevacizumab, for a median of 6 cycles. Median PCI was similar between groups (U-CRS: 28; NAT: 27; p = 0.73). Median OT was 572 min (U-CRS) vs. 645 min (NAT; p = 0.17). Grade III-V complications occurred in 50 % of U-CRS vs. 32 % of NAT patients (p = 0.42). NAT was not independently associated with prolonged OT or severe complications on multivariable analyses. Rates of CC-0 resection, RFS, and OS were similar between groups. Conclusions: NAT is feasible and safe in patients with high-volume PeM undergoing CRS/HIPEC, without negatively affecting perioperative outcomes. The neoadjuvant setting offers a valuable platform for investigating novel therapies aimed at improving long-term outcomes in PeM. Synopsis: Neoadjuvant systemic therapy before CRS/HIPEC for high-volume peritoneal mesothelioma is feasible and safe with similar operative times and complication rates as upfront surgery, supporting its use as a platform to evaluate novel therapies to improve long-term outcomes in peritoneal mesothelioma.

Urothelial carcinoma arising in a mature cystic teratoma of the ovary is a rare event with only 13 cases reported thus far. In this article, we present the clinicopathologic features of one such case and a review of the literature. The patient was a 76-yr-old African American postmenopausal woman who presented with a painful abdominal mass and weight loss. The left ovarian tumor was 36 cm in greatest dimension and contained several papillary areas, the largest being 10 cm. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and pelvic washings. Microscopically, the papillary excrescences represented an invasive, high-grade papillary urothelial carcinoma, while the cyst in the background was a mature cystic teratoma. Immunohistochemically, the urothelial carcinoma was positive for CK7, CK20, GATA-3, uroplakin II, p40, p63, and ER (20%, weak intensity), while negative for WT1 and PR; p53 expression was aberrant (nuclear overexpression). Next-generation sequencing (NGS) showed a microsatellite-stable tumor with low tumor mutational burden, and molecular alterations typically seen in urothelial carcinomas, including KRAS gain of function, ARID1A loss of function, RB1 loss of function, and two TP53 loss of function mutations. In addition, PDL1 positivity was present, representing a clinically actionable target. The tumor was FIGO stage 1A. No adjuvant therapy was given, and the patient is alive with no evidence of disease after a follow-up of 7 mo.

The DESTINY-PanTumor02 phase II trial, showing a remarkable response to fam-trastuzumab deruxtecan-nxki (Enhertu), has triggered an increase in HER2 testing for drug eligibility. We evaluated HER2 immunohistochemical (IHC) and FISH testing results and the extent of Enhertu use in gynecologic tract clear cell carcinomas (GT-CCC) at a tertiary care center. Sixty-five GT-CCC with HER2 IHC testing performed at our institution (2018 to 2024) were identified: 49 ovarian (OCCC), 14 endometrial (ECCC), and 2 peritoneal. The 2018 ASCO/CAP criteria were used for HER2 scoring (the standard during the time frame of this study). Overall HER2 IHC scores were: 0 [n=12 (18.5%)], 1+ [n=9 (13.8%)], 2+ [n=40 (61.5%)], 3+ [n=4 (6.2%)]. FISH confirmed amplification in 22.9% OCCCs and 25% ECCCs (18.8% of IHC 2+ and all IHC 3+). Cases with unusual staining patterns (USP; strong nuclear and cytoplasmic) did not show FISH amplification. HER2 0/1+ and cases with USP were more frequent in biopsies (41.7%) and metastatic tumors (45.5%) compared with resections (30.2%) and primary sites (29.6%). Intratumoral heterogeneity was seen in 7.7% of cases. Among HER2 3+ cases, only 1 patient received anti-HER2 therapy (Herceptin followed by Enhertu) and had a mixed response. Of the HER2 2+ with positive FISH, 4 received anti-HER2 therapy, and only 1 patient had a good response. Based on current HER2 eligibility guidelines, our study shows that more than half of GT-CCC cases, that is, IHC HER2+, would be eligible for anti-HER2 therapy. However, few patients in our cohort received this therapy. Further studies are needed to evaluate the efficacy of anti-HER2 therapy for advanced/recurrent GT-CCC.

Folate receptor alpha has been shown to have possible mechanisms of tumorigenesis in malignancies, becoming a potential target for therapy. Mirvetuximab soravtansine is an antifolate receptor alpha monoclonal antibody, with an approved FOLR1-2.1 immunohistochemical biomarker. After IRB approval, a retrospective review of gynecologic pathology cases was performed to identify cases in which FOLR1 immunohistochemistry (IHC) was performed at our institution over a period of 9 months as part of clinical care for therapy eligibility. Clinical data collected included patients’ age, tumor histotype, tumor grade, primary tumor site, FIGO stage, dates of recurrence/progression, and use of mirvetuximab therapy. FOLR1 IHC data were recorded, including the date specimen obtained, date IHC was performed, site tested, case type, percentage tumor staining, and intensity. Cases were deemed positive or negative according to current recommendations (75%, 2−3+intensity). Two hundred sixteen cases were identified. Patient ages ranged from 25 to 83 years old (median: 59 yr). Staining intensity was reported as 0 in 15 (6.9%) cases, weak (1+) in 8 (3.7%), moderate (2+) in 27 (12.5%), strong (3+) in 27 (12.5%), weak-to-moderate (1−2+) in 15 (6.9%), and moderate-to-strong (2−3+) in 99 (45.8%); intensity was not provided in 25 (11.6%). Percentage of tumor staining ranged from 0 to 100, with a median of 60. The IHC was overall deemed positive in 98 (45.4%) cases and negative in 118 (54.6%). By histotype, 5 of 17 (29.4%) low-grade serous carcinomas, 88 of 162 (54.3%) high-grade serous carcinomas, 3 of 5 (60%) of carcinosarcomas, and 2 of 6 (33.3%) of mixed carcinomas were positive. No case of clear cell CA, endometrioid CA, Mullerian CA NOS, serous borderline, mucinous CA, or granulosa cell tumor was positive. The primary site of disease was tubo-ovarian in 192 (88.9%) cases, peritoneal in 8 (3.7%) cases, uterine in 3 (1.4%) cases, and unknown in 13 (6%) cases. By site on which immunohistochemical stain was performed: primary site positive in 53 of 96 (55.2%) cases, metastatic site at time of diagnosis/debulking positive in 23 of 41 (52.1%) cases, and metastatic/recurrent cases positive in 22 of 79 (27.8%) cases. There was a statistically significant correlation when comparing the positivity rates between these sites (P = 0.0004). Survival data were examined with high-grade serous carcinoma, with no statistically significant difference between positive and negative cases in overall survival (P = 0.622) or progression-free survival (P = 0.711). Biopsy specimens were positive in 17 (25%) cases, while negative in 51 (75%), whereas resection specimens were positive in 81 (54.7%) and negative in 67 (45.3%), a statistically significant difference (P < 0.0001). Cases that were <19 months old had 38 (36.2%) positive and 67 (63.8%) negative, compared with cases ≥19 months old that had 60 (54.1%) positive and 51 (45.9%) negative, a statistically significant difference (P = 0.0084). Significant differences in FOLR1 staining were noted between histotypes, age of the specimen, type of case tested, and site of disease tested. Further testing is needed to help determine the best tissue to be utilized for this new biomarker.

The purpose of this study is to evaluate the effectiveness of opportunistic salpingectomy (OS), a procedure that aims to remove only the fallopian tubes of general population risk women, for the prevention of epithelial ovarian cancer. Currently, the method of prevention for individuals at high risk of ovarian cancer involves a bilateral salpingo-oophorectomy (BSO), a procedure that removes both the fallopian tubes and ovaries. However, this procedure is not recommended for individuals of the general population, who make up about 80% of ovarian cancers, due to negative health implications to the cardiovascular and skeletal systems because of surgically induced menopause. The effectiveness of the OS in preventing ovarian cancers and how the procedure impacts the histotype distribution of ovarian cancers remains unknown. This study uses a population-based approach and a case-based approach to determine the effectiveness of OS and its impact on histotype distribution, respectively. For the population-based analysis, we will search through clinical databases to acquire cases of individuals who have had an OS and a tumor. A control population who have their fallopian tubes in-tact will also be acquired. A cox-proportional hazard analysis will be performed to determine the effectiveness of the procedure. Using pathological records, the case-based ascertainment of tumors from individuals who have had an OS will be selected and reviewed for histotype confirmation. Fallopian tubes of these patients will also be reviewed for precursor lesions. This cohort will be compared to a historical histotype distribution of ovarian cancers. For the population-based approach, we have to date, identified less than five serous ovarian cancers in individuals who have had an OS (n=40, 477). A comparator surgery was used as a control and showed 21 cancers. For the case-based approach, we have partnered with 23 collaborating institutions from around the world to identify tumors in individuals who have had an OS. We have identified 26 epithelial ovarian cancers, with the most lethal gynecological histotype, high grade serous carcinoma (HGSC), accounting for 23.1% of the total proportion of epithelial ovarian cancer cases (n=6/26). This is significantly less than the historical histotype distribution of HGSC, which is 69.3% (Fisher’s exact test, p<0.0001). One HGSC case had a precursor lesion called a serous tubal intraepithelial carcinoma (STIC) while reviewing fallopian tubes of this individual. TP53 mutation analysis on one HGSC tumor sample showed a frameshift mutation in TP53 (c229fs) with the tumor and the corresponding STIC staining negative for p53 protein expression by immunohistochemistry. This evidence demonstrates the effectiveness of opportunistic salpingectomy for the prevention of ovarian cancer and shows a histotype distribution shift, with the most lethal gynecological malignancy having a significant reduction in cases following the procedure. Ramlogan Sowamber, Alice J. Mei, Paramdeep Kaur, Julianne McLeod, Emily McKay, Alex Lukey, Jamie Bakkum-Gamez, Natalia Buza, Paul Cohen, Kyle Devins, Rhonda Farrell, Christine Garcia, Blake Gilks, Ellen Goode, Anjelica Hodgson, Brooke Howitt, Pei Hui, Jutta Huvila, Anthony Karnezis, Kianoosh Keyhanian, Mary Kinloch, Martin Köbel, Felix KF. Kommoss, Lawrence Kushi, Janice S. Kwon, Kara Long-Roche, Anais Malpica, Jessica N. McAlpine, Dianne Miller, Esther Oliva, Andrea Palicelli, Aleksandra Paliga, Carlos Parra-Herran, Celeste Leigh Pearce, Sharnel Perera, Jurgen M. Piek, Haiyan Qiu, Joseph Rabban, Robert Rome, Miranda Steenbeek, Rebecca Stone, Aline Talhouk, Kristin M. Tischer, Britton Trabert, Penelope M. Webb, John R. Zalcberg, Gillian E. Hanley, David G. Huntsman. Evaluating the effectiveness of opportunistic salpingectomy (OS) for the prevention of epithelial ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr B045.

Fibrin-associated large B-cell lymphoma (FA-LBCL) is a rare type of lymphoma usually associated with EpsteinBarr virus (EBV) infection. We report a case incidentally detected in a right ovarian mass of a 53-year-old woman. The patient presented with bloating and weight gain over 8 months. Imaging studies showed a 20.7 cm, complex right adnexal mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Macroscopic examination revealed a 25 x 18.5 x 9.5 cm predominantly cystic right ovarian mass with focal solid areas. Microscopically, most of the mass was a leiomyoma with hyaline necrosis and extensive cystic degeneration. In areas, the cyst showed focally necrotic, fibrinous material associated with small aggregates of round and atypical lymphoid cells with prominent karyorrhexis and mitotic activity These large cells were confined within the cystic spaces. Immunohistochemical analysis showed that the atypical cells were positive for CD20, CD30, CD79a and MUM1/IRF4, and were negative for CD3, CD10 and BCL6, supporting B-cell lineage. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER ISH) was also positive in the atypical cells supporting the diagnosis of EBV-positive fibrin-associated large B-cell lymphoma. The patient subsequently received four cycles of chemotherapy using rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP). Computed tomography (CT) scan of the neck, chest, abdomen and pelvis 5 months after the last chemotherapy cycle showed no evidence of disease. After a follow-up of 17 months, the patient is alive with no evidence of disease. This report is being used to discuss the salient features of this rare entity and its differential diagnosis.

Objective Low-grade serous ovarian carcinoma (LGSOC) and high-grade serous ovarian carcinoma (HGSOC) are distinct entities. Although typically occurring in pure forms, some present as synchronous or metachronous mixed histotypes. Methods This retrospective study examined patients with mixed LGSOC and HGSOC treated between 1994 and 2024 at MD Anderson Cancer Center (MDACC). Diagnoses were confirmed by MDACC gynecologic pathologists. Demographics, clinical characteristics, diagnosis rendered by referral institution, treatment, immunohistochemistry, somatic tumor testing, and survival outcomes were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, with log-rank tests to compare cohorts, p < 0.05 significant. Results Among 39 cases, 85 % were synchronous, and 15 % were metachronous. Seven (25 %) of patients tested for germline mutations (n = 28) had germline BRCA mutations. Of the 35 cases diagnosed at referral institutions, only eight (23 %) were correctly identified as mixed. Sixteen (41 %) patients underwent somatic tumor testing, revealing three KRAS, one NRAS, and eight TP53 mutations. All patients underwent cytoreductive surgery, with 97 % receiving adjuvant therapy and 26 % maintenance therapy. Recurrence occurred in 90 % of cases. Median PFS was 17 months, and median OS was 56.7 months, with a 5-year survival rate of 48.5 %. There was no statistically significant difference when comparing PFS or OS by BRCA status, primary vs interval cytoreduction, residual disease, tumor presentation, or maintenance therapy. Conclusion Diagnosing mixed LGSOC and HGSOC remains challenging. Despite low TP53 mutation rates, survival outcomes resembled those of HGSOC. These findings advocate for further investigations to identify risk factors and biomarkers for low-grade to high-grade transformation and to improve treatment strategies.

GLI1 -altered tumors of the gynecologic tract are extremely rare. We report 3 cases of ovarian PTCH1::GLI1 fusion tumor in patients ranging from 54 to 58 yrs of age, who presented with unilateral FIGO stage I tumors. The tumors ranged from 12 to 20 cm and consisted of uniform epithelioid cells with eosinophilic/clear cytoplasm, arranged in nests and trabeculae surrounded by delicate vessels. Variable features included short spindle cells within a myxoid stroma, follicles, small glands/Call-Exner body-like structures, dilated vessels/blood lakes, focal pleomorphism, nuclear grooves, and necrosis. Mitoses ranged from 1 to 10/10 HPFs. Immunohistochemical marker results/number of tumors tested (including primary tumors and recurrences) were as follows: positive for SF-1 (6/6), CD56 (4/4), EMA (3/5), keratins (3/5), SMA (2/5), CD10 (3/4), S100 (3/4), caldesmon (2/3), D2-40 (2/2), Ber-EP4 (2/2), and MOC-31 (1/1), and negative for WT-1 (5/5), calretinin (5/5), inhibin (4/5), ER (4/5), and PR (5/5). Diagnoses initially rendered included adult granulosa cell tumor, unclassified sex cord-stromal tumor, low-grade Müllerian adenocarcinoma, and low-grade endometrioid stromal sarcoma. Surgery was the primary treatment for all. One patient had multiple recurrences at 7, 9, and 13 yrs, had additional surgery, received chemotherapy and radiotherapy, and was alive with no evidence of disease at 13.6 yrs. Another patient had omental recurrence at 5 yrs, received chemotherapy, immunotherapy, and tyrosine kinase inhibitor-targeted therapy, and was alive with disease at 7.9 yrs. The third patient was alive with no evidence of disease at 2 mos. Ovarian PTCH1::GLI1 fusion tumors represent a diagnostic challenge and may recur after several years. Their proper recognition may prompt the use of targeted therapy.