International Journal of Gynecological Pathology最新文献

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.

We report 2 unusual cervical carcinomas, in patients aged 29 and 55, comprising a combination of HPV-independent mesonephric adenocarcinoma and high-grade undifferentiated carcinoma. Immunohistochemistry showed negative staining or marked reduction in staining with epithelial markers (cytokeratins and EMA), PAX8, and GATA3 in the undifferentiated carcinoma component compared with the mesonephric adenocarcinoma component. Molecular testing revealed pathogenic variants (PVs) or likely PVs in KRAS and in the SWI/SNF genes SMARCA4, ARID1A, and ARID1B in 1 case and PVs or likely PVs in KRAS, ARID1A, ARID1B, and PIK3CA in the other. We propose that these neoplasms represent dedifferentiated mesonephric adenocarcinomas. As far as we are aware, this phenomenon of dedifferentiation within a mesonephric adenocarcinoma has not been reported previously. Both tumors exhibited aggressive behavior with rapid local recurrence or metastasis of the undifferentiated carcinoma component. PVs in SWI/SNF genes may be associated with the process of dedifferentiation.

High-grade serous carcinoma (HGSC) and its precursor, serous tubal intraepithelial carcinoma (STIC), usually exhibit cytologic features reminiscent of fallopian tube secretory cells, their presumed cell-of-origin. While it is not uncommon to encounter focal areas of cytoplasmic clearing in HGSC, we have occasionally observed extensive foamy change in STIC and tubal HGSC, which morphologically mimics mucinous differentiation, and to a lesser extent, clear cell carcinoma. In this report, we describe the histologic, immunophenotypic, and ultrastructural features of STIC/tubal HGSC with extensive foamy cell change. From 5 tubo-ovarian HGSC resections (chemotherapy-naive, n=4; post-neoadjuvant chemotherapy, n=1), STIC (n = 2), or tubal HGSC (n = 3) with extensive foamy cytoplasm were identified. Mucicarmine and Periodic acid Schiff/Alcian blue pH 2.5 stains were negative in the foamy cells, excluding mucin and glycogen accumulation. By immunohistochemistry, the tubal lesions retained Müllerian (tubal) differentiation (PAX8+, n=5; ER+, n=5; WT1+, n=4; PR+, n=3), along with aberrant p53 expression (n=5; concordant with somatic TP53 mutations detected by targeted next-generation sequencing). CDX2 and Napsin-A were absent, while HNF-1β and racemase showed variable staining. Adipophilin showed patchy expression in 2 cases, suggestive of lipid content. Ultrastructurally, foamy STIC/HGSCs contained numerous empty micro-vacuoles and macro-vacuoles, with occasional dilated rough endoplasmic reticulum. In contrast, fallopian tubes with true mucinous metaplasia (n=3) were highlighted by mucin stains and showed reduced or absent Müllerian marker expression. Foamy cell change is a distinctive cytoplasmic alteration in STIC and HGSC. The presence of this histologic feature should prompt immunohistochemical studies to confirm serous differentiation.

Chronic histiocytic intervillositis (CHI) is a rare placental inflammatory condition characterized by the infiltration of monocytes into the intervillous space. CHI is associated with serious neonatal complications. In the present systematic review and meta-analysis, we assessed the relationship between CHI and maternal and neonatal outcomes. The meta-analysis involved searching databases such as EMBASE, PubMed, Web of Science, and SCOPUS for studies on idiopathic CHI up to May 1, 2024. Included studies assessed pregnancy outcomes, including gestational age and live birth status, while excluding nonidiopathic cases. The quality of the studies and risk of bias were evaluated using the Newcastle-Ottawa Quality Scale (NOS). Meta-analyses were then conducted to estimate the frequencies of various pregnancy outcomes. Initially, 402 articles were identified, leading to the inclusion of 12 studies that met the criteria for final analysis. The studies encompassed a total of 568 pregnancies, with sample sizes ranging from 16 to 111 participants and mean ages between 29.8 and 34 yr. The meta-analysis revealed pooled frequencies of 40% for intrauterine growth retardation (IUGR), 55% for live births, and 20% for intrauterine fetal death (IUFD). Sensitivity analyses demonstrated no significant differences when the analysis was restricted to low-risk studies. In conclusion, this meta-analysis highlights the significant associations between CHI and adverse pregnancy outcomes, including high rates of intrauterine growth retardation and intrauterine fetal death. These findings underscore the importance of early detection and management of CHI.

Ovarian clear cell carcinoma (OCCC) is an endometriosis-related neoplasm, in which traditional histologic grading does not show prognostic significance. Tumor budding was associated with poorer outcomes in OCCC in previous studies. We aimed to evaluate the prognostic significance of tumor budding in OCCC in an independent cohort. Seventy patients diagnosed with OCCC were retrospectively identified. Slides from primary ovarian resections were reviewed by 2 pathologists blinded to outcomes. Tumor budding was defined as single or clusters of <5 tumor cells in peritumoral and/or intratumoral nonhyalinized stroma. Most patients were diagnosed at an early stage (stage I: 69%; II: 20%; III: 10%; IV: 1%). Twenty-one patients experienced recurrences (30%) and 2 progressive disease (3%). At the last follow-up, 52 patients had no evidence of disease, 6 were alive with disease, and 12 died of disease. The median follow-up time was 66.7 mo. Tumor budding was identified in 41 cases (59%) with a kappa coefficient of 0.60. On univariate analysis, tumor budding ( P =0.022) and stage ( P =0.0005) were associated with shorter progression-free survival (PFS), but only stage was independently associated with shorter PFS on multivariate analysis ( P =0.003). Higher stage was the only variable associated with shorter overall survival ( P =0.037). Tumor budding was associated with higher stage ( P =0.039), absence of endometriosis ( P =0.042) and adenofibroma ( P =0.046), tumor-associated inflammation ( P =0.002), and higher mitotic activity ( P =0.022). There was no association between tumor budding and molecular characteristics in 32 cases with somatic tumor sequencing. Tumor budding was not independently associated with worse outcomes in this cohort of OCCC, although it was significantly associated with specific clinicopathologic features, including higher stage. Stage was the only independent variable predictive of poorer survival, which appears to drive the prognostic significance of tumor budding.

Numerous emerging molecularly defined subtypes of uterine leiomyosarcoma (LMS) have been described in recent years. Here we report our experience with a challenging case of the recently described CDKN2C/CIC null subtype of LMS - a LMS subtype that is frequently epithelioid in appearance, is wild-type for both TP53 and RB1 and may exhibit low-grade histology that falls short of LMS. The 48-year-old patient was initially diagnosed with an epithelioid leiomyoma with a component of intravenous leiomyomatosis. Recurrence occurred 5 years later with an extensive disease burden in the abdomen and pelvis. Upon review, the lesion in the hysterectomy specimen and the recurrent tumor had similar morphology. This included (1) focal epithelioid morphology meeting current diagnostic criteria for epithelioid LMS and (2) other areas with morphology indistinguishable from leiomyoma (LM), including conventional spindle cell LM, cellular LM, and LM with bizarre nuclei. Targeted next-generation molecular analysis performed on both the original tumor in the hysterectomy specimen and the tumor from the recurrence showed the same CDKN2C/CIC null profile. This case highlights the striking intratumoral heterogeneity that is possible in CDKN2C/CIC null LMS, including areas morphologically indistinguishable from LM. Clinicopathological findings in this case, including features that may assist in recognizing this challenging LMS subtype, are discussed. We underscore the importance of early diagnosis, which can facilitate appropriate adjuvant and/or maintenance therapy that may decrease the morbidity associated with extensive debulking surgery.

We sought to present and describe all cases of mesonephric adenocarcinoma (MNAC) and mesonephric-like adenocarcinomas (MLAs) at our institution. These cancers are rare, morphologically similar tumors of the female reproductive tract. In this case series, we present 13 new cases of MNAC/MLA that were identified at St. Luke's University Health Network from 2016 to 2024. Demographics, clinical characteristics, and pathologic findings were collected from chart review. There were 6 uterine, 5 ovarian, and 2 cervical MNAC/MLAs. At presentation, more than half of the patients presented at early stages with 7, 2, 3, and 1 diagnosed at stages I, II, III, and IV, respectively. All patients underwent upfront surgical resection and were recommended adjuvant therapy. One patient declined adjuvant treatment. At the time of writing, 9 of 13 patients have completed treatment and have no evidence of disease, 1 is alive with disease, 1 is currently undergoing treatment, and 2 died of disease. Median overall survival (OS) was 15 mo (95% CI: 2.2-27.8 mo). Current literature regarding MNACs/MLAs suggests an overall poor prognosis, with the majority presenting at advanced stages. This case series describes patients diagnosed with early-stage disease and reports on their histopathology, treatment regimens, and clinical outcomes. The majority of these patients are without recurrence after upfront treatment. Continued surveillance of these patients to determine long-term outcomes is necessary to further elucidate overall prognosis.