International Journal of Gynecological Pathology最新文献

Antibody-drug conjugates (ADC) are emerging therapies with promising results in the treatment of solid tumors. In this study, we aimed to evaluate biomarker expression of ADCs, including folate receptor alpha (FOLR1), Nectin-4, trophoblast cell surface antigen 2 (Trop-2), and tissue factor (TF) in a diverse cohort of gestational trophoblastic disease. Immunohistochemistry for FOLR1, Nectin-4, Trop-2, and TF was evaluated in tissue microarray of 18 complete hydatidiform moles (CHM) and whole tissue sections of 62 gestational trophoblastic neoplasia (GTN) by 2 gynecologic pathologists. Western blotting for FOLR1, Nectin-4, and Trop-2 was performed in JEG-3 and JAR choriocarcinoma cell lines, 2 CHM and 3 GTN clinical samples. Results: The overall immunohistochemical positive rate in GTN was 11% for FOLR1, 59% for Nectin-4, 38% for Trop-2, and 26% for TF. Choriocarcinomas showed 27% positivity for FOLR1, 75% for Nectin-4, 40% for Trop-2, and 25% for TF. Epithelioid trophoblastic tumors (ETT) were positive for Nectin-4 in 58%, for Trop-2 in 79%, and for TF in 67% of cases. Placental site trophoblastic tumors were positive only for Nectin-4 (23% of cases). In CHM, only Nectin-4 revealed a higher degree of expression and limited staining for the other markers. Western blotting showed FOLR1 expression in CHM, JEG-3, and JAR; Nectin-4 in CHM and PSTT; and Trop-2 in CHM, JEG-3, and choriocarcinoma. Conclusion: A subset of GTN shows expression for FOLR1, Nectin-4, Trop-2, and TF, particularly choriocarcinoma and ETT. These results suggest that patients with GTN could potentially benefit from ADC treatment.

Chronic salpingitis presents with various inflammatory patterns due to different causes. Eosinophil-rich salpingitis is rare and primarily associated with parasitic infestations. We aim to report our findings of eosinophil-rich salpingitis in a series of women who presented with ruptured hemorrhagic ovarian corpus luteum cysts and tubal schistosomiasis accompanied by ectopic tubal pregnancies. Eight women (age range: 31-40 yr, average age: 34 yr) met the inclusion criteria for eosinophil-rich salpingitis. The tubes showed a dense eosinophilic infiltrate throughout the tubal wall with edema and hemosiderin pigment deposition. The mucosal plicae were broadened due to vascular congestion, edema, and conspicuous eosinophilic infiltrates with siderophages. Luminal hemorrhage was present. Six patients had ipsilateral ruptured hemorrhagic ovarian corpus luteum cysts with ruptured tubal ectopic pregnancies, whereas 2 patients had Schistosoma ova in the tube. The close proximity of the tubal fimbriae to the ovary suggests that the tubal cavity is a potential reservoir of the extruded contents from ruptured hemorrhagic luteal cysts. Theoretically, the engulfed contents could move down the tubal lumen, adhere to the epithelium, and elicit an allergic inflammatory reaction in the tubal mucosa and mural wall. This phenomenon may play a role in postinflammatory fibrous adhesion and ectopic pregnancies. Eosinophilic salpingitis is a rare, unilateral, localized, secondary inflammatory reaction of the fallopian tubes. Apart from parasitic infestations, an inflammatory response to ruptured hemorrhagic corpus luteum cysts should be considered as a potential association when other causes are excluded. Certain histopathologic features may provide clues to this association. Further validation is warranted to determine whether these findings are associations or mere coincidences.

Intraoperative frozen section provides surgeons with information that guides them to perform the most reasonable procedure. The aim of the study was to determine the accuracy of FS and share the experience of establishing FS services for implementation in similar low- and middle-income countries. This pilot study was conducted between January 2022 and December 2022, including women who underwent gynecologic surgeries, using a structured questionnaire. Data was analyzed with SPSS 23.1, and tables were employed for data presentation. The overall accuracy, sensitivity, and specificity of frozen section analysis were calculated, and the experiences of establishing frozen section services are shared. Seventy-six frozen section samples were sent for histopathology analysis. Seventy (92%) cases comprised adnexal lesions, 3 (4%) cases represented uterine lesions, and 3 (4%) cases were lymph nodes. Most (70%) of the ovarian samples were reported as benign, and 18 (26%) as malignant. One of the 3 uterine samples was reported as sarcoma, and 2 of the lymph nodes as secondary malignancy. The overall accuracy of frozen section for the detection of any benign, borderline, and malignant ovarian neoplasms was 90%. The average turnaround time was 25 min and was more than 30 min in 39% of cases. Although FS pathology helped avoid unnecessary extensive surgeries in some patients, it was inappropriately utilized in 30% of the cases, and mechanisms to address discrepant results and assuring quality were not robust. The overall accuracy of the frozen section was comparable to most international data, demonstrating its feasibility and practicality in low-resource settings. However, quality improvement mechanisms should be thoroughly considered.

TRPS1 is a novel immunohistochemical marker that is known to stain normal mammary epithelium and breast carcinomas (especially triple negative carcinomas). TRPS1 staining has also been reported in normal skin appendages, benign and malignant cutaneous neoplasms, and anogenital mammary-like glands (AGMLG). However, research regarding TRPS1 staining in various neoplasms derived from AGMLG is limited. Past studies have focused on two neoplasms of AGMLG-hidradenoma papilliferum (HP) and extramammary Paget disease (EMPD). We confirm the finding that TRPS1 is positive in the epithelium of HP and we report its expression in a variety of other benign and malignant lesions derived from vulvar AGMLG, including fibroepithelial lesion (FEL), lactating adenoma (LA), fibroepithelial polyp with AGMLG, and mammary-type adenocarcinoma (MAc). The majority of TRPS1 staining was diffuse and displayed strong (3+) intensity. We show that TRPS1 is significantly more sensitive than GCDFP-15 in lesions of AGMLG and is comparable to GATA3. TRPS1 was also more sensitive than mammaglobin, but the finding did not reach statistical significance. TRPS1 demonstrated diffuse staining in these lesions significantly more often than either GCDFP-15 or mammaglobin. This study was limited by its small sample size, due to the rarity of some entities such as the malignant MAc (n=3).

We report an unusual uterine polypoid mesenchymal tumor in a 52-year-old resembling the soft tissue neoplasm ossifying fibromyxoid tumor (OFMT). The neoplasm was morphologically low-grade with hypocellular areas containing bland spindle cells in a fibromyxoid stroma, cellular areas resembling typical low-grade endometrial stromal sarcoma (LGESS), and abundant mature bone. The cellular areas were ER and CD10 positive and cyclin D1 negative, and the hypocellular areas were ER and CD10 negative, with approximately 50% of the nuclei being cyclin D1 positive. The tumor harbored a BRD8::PHF1 fusion. This fusion has been reported rarely in uterine mesenchymal neoplasms, which have been designated as LGESS or high-grade endometrial stromal sarcoma. In reporting this case, we review previously reported uterine mesenchymal neoplasms with a BRD8::PHF1 fusion. Since OFMT commonly contains PHF1 fusions, we discuss the most appropriate terminology for the neoplasm we report and suggest that it is best classified as an LGESS with OFMT-like morphology.

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate approved for the treatment of adult patients with folate receptor 1 (FRα; FOLR1) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Per the FDA approval, FOLR1 positivity is defined as ≥75% of viable tumor cells showing moderate (2+) or strong (3+) membranous immunostaining ("PS2+"). Given this disease's high recurrence rate and relatively limited therapeutic options, there is utility in exploring consistency in FOLR1 reporting. Tubo-ovarian high-grade serous carcinoma (HGSC) samples from our institution's archives were included in tissue microarrays (n=806), whole tissue sections (n=51), or cell blocks (n=30) and evaluated using the Ventana FOLR1 (FOLR1-2.1) RxDx Assay. FOLR1 staining was heterogeneous across different anatomic sites (average FOLR1 PS2+ was 50.2 from adnexal sites compared with 47.4 from omental sites, P =0.015). Similarly, heterogeneity was noted in pre- versus post- neoadjuvant chemotherapy specimens (on average, FOLR1 PS2+ score increased by 17.7 from pre- to post- therapy, P =0.0089). Lastly, specimen type may also influence FOLR1 staining (average abdominal fluid FOLR1 PS2+ score was 25.5 and average surgical FOLR1 PS2+ score was 56.9, P =0.000034). Agreement among 9 readers was initially substantial, with a Fleiss kappa of 0.661 (95% CI: 0.636-0.685). For the subset of cases with the worst agreement initially, a training session with reference cases improved interobserver agreement. Our study highlights several factors contributing to heterogeneity in FOLR1 reporting. Future studies are needed to better understand the impact of FOLR1 heterogeneity on patient response to therapy.

Microcystic adnexal carcinoma (MAC) and eccrine cutaneous mixed tumor (ECMT) are both cutaneous adnexal tumors that may occur in the vulvar region, but are very rare at this site. Consequently, they may not enter the differential diagnosis of vulvar lesions for gynecologic pathologists in a subspecialized practice setting. Here we report a case of MAC and a case of ECMT recently diagnosed at our institution and underscore key histologic and immunophenotypic features of each lesion that can assist in their correct identification. Both MAC and ECMT have a tubular to corded pattern of lesional cells within a desmoplastic to chondromyxoid stroma. However, MAC shows true eccrine sweat duct differentiation, characterized by 2 SOX10 negative cell layers, including an outer p63+/p40+/EMA- basal cell layer and an inner p63-/p40-/EMA+ ductal layer. The main differential diagnostic considerations for vulvar MAC include other cutaneous adnexal tumors with true eccrine sweat duct differentiation, namely syringoma and squamoid eccrine ductal carcinoma (SEDC). Conversely, ECMT is characterized by a single SOX10+ cell population without immunoreactivity for p63 or p40. The main differential diagnostic considerations for ECMT include the apocrine variant of cutaneous mixed tumor (ACMT)-the cutaneous analog of salivary gland pleomorphic adenoma-and other SOX10+ salivary gland-type neoplasms. Unlike the recently described vulvar analog of HPV-associated multiphenotypic sinonasal carcinoma, neither MAC nor ECMT are HPV-associated and both are therefore p16 negative. In summary, we report one case each of vulvar MAC and ECMT and discuss the key histologic features and ancillary testing results that can help to differentiate these lesions from their morphologic mimics.

Mesonephric-like adenocarcinoma (MLA) is a rare and aggressive gynecologic malignancy that has only been recognized in the last decade. It arises in the endometrium, ovaries, and other extrauterine sites (often in association with endometriosis) and closely mimics a variety of other tumor types that occur in these locations. While it shows significant morphologic, immunohistochemical, and molecular homology with cervical mesonephric adenocarcinoma, there are many clinicopathologic features that suggest müllerian derivation, and this is now well established. As research on MLA has accumulated, questions have emerged about optimal practices for the diagnosis of these challenging tumors. In 2022, faculty at M.D. Anderson Cancer Center convened the Mesonephric-like Adenocarcinoma (MLA) Consortium, comprised of international pathologists, gynecologic oncologists, medical oncologists, radiation oncologists, and basic science investigators with expertise in MLA, with the goals to enhance understanding of these tumors, refine diagnostic criteria, improve treatment options, and facilitate research collaborations. An initial review from the consortium was published in 2025, and included diagnostic recommendations from the group's pathologists. Controversies remain, however, about the morphologic, immunohistochemical, and molecular criteria that should be used to establish a diagnosis of MLA. Herein, the pathologists from the MLA Consortium provide a comprehensive evaluation of the literature on MLA diagnostic criteria, address ongoing controversies in this area, and provide practical guidance for pathologists considering this entity.

Mesonephric-like adenocarcinoma (MLA) is a rare gynecologic malignancy primarily arising in the uterine corpus and ovaries. It shares remarkable similarities in its histomorphology, immunophenotype, and molecular features with mesonephric adenocarcinoma of the cervix. Controversy remains regarding whether the MLA originates from the mesonephric or Müllerian ducts. In this study, we retrospectively analyzed the clinicopathologic, immunohistochemical, and molecular characteristics of 9 MLA cases. Among these, we observed 2 unique cases for the first time: 1 case of ovarian MLA coexisting with a benign mucinous cystadenoma and 1 case of MLA located on the cervical mucosal surface. In addition, 1 case presented with a mesenteric MLA component intermixed with clear cell carcinoma, and endometriosis was detected around the cancerous tissue and in the adjacent ovary. Of the remaining 6 cases, 3 were associated with endometriosis or adenomyosis. Next-generation sequencing of 7 cases revealed KRAS mutations in 5 cases and mutations in PTEN/BRAF and ERBB3 in 1 case each. The identification of MLA in atypical locations such as the mesentery and cervical mucosa expands the histologic spectrum of this tumor and provides further support for the hypothesis of a Müllerian epithelial origin. The findings of this study broaden the known morphologic and anatomic distribution of MLA and contribute to a better understanding of its pathogenesis.