International Journal of Gynecological Pathology最新文献

Glomus tumors of the female genital tract are rare, and to our knowledge, malignant glomus tumors (MGTs) of the female genital tract have not been previously reported. The diagnosis of MGTs is challenging, given their morphologic and immunophenotypic overlap with other common uterine mesenchymal tumors, especially in the absence of classic benign glomus tumor components. Here, we report a case involving a 34-year-old woman with uterine MGT that was positive for smooth muscle actin, h-caldesmon, cyclin D1, and synaptophysin, and negative for desmin. CARMN::NOTCH2 fusion was identified using hybrid capture-based next-generation sequencing. The presence of CARMN::NOTCH2 fusion combined with supportive immunohistochemical and morphologic features validated the diagnosis of MGT. The patient underwent 4 courses of chemotherapy with ifosfamide and pirarubicin. She had no evidence of tumor recurrence or metastasis at 20 months, as confirmed at the latest follow-up visit. The findings from this case highlight the morphologic and immunohistochemical features that are diagnostic of this rare uterine tumor. Furthermore, this report summarizes the morphologic criteria for malignancy and the key points for its differential diagnosis.

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the uterus is an infrequent entity. Moreover, the coexistence of EBV-positive DLBCL and endometrioid carcinoma in the form of a collision tumor has not been reported in the literature to date. This report details the clinical, histologic, immunohistochemical, and molecular characteristics of a collision tumor consisting of EBV-positive DLBCL and endometrioid carcinoma of the uterine corpus. The patient was a 63-yr-old postmenopausal woman who presented with vaginal bleeding. Ultrasonography detected a 2.3×1.0 cm mildly hyperechoic mass within the uterine corpus. Histologically, the tumor consisted of sheets of medium- to large-sized lymphoid cells intermixed with low-grade endometrioid carcinoma. Immunohistochemically, the neoplastic lymphoid cells exhibited strong CD20 expression, and EBV-encoded small RNA in situ hybridization signals were detected in most of these cells. The endometrioid carcinoma cells strongly expressed estrogen receptor and cytokeratin 18. Molecular analysis revealed clonal rearrangement of the B-cell receptor gene. To the best of our knowledge, no prior cases of collision tumors comprising EBV-positive DLBCL and endometrioid carcinoma have been reported. It is essential to differentiate such collision tumors from endometrioid carcinoma with florid-reactive lymphocytic infiltration and dedifferentiated carcinoma of the uterine corpus. A meticulous analysis of patient's clinical features and of the lesion's histologic, immunophenotypic, and genetic characteristics is necessary for an accurate diagnosis.

To evaluate whether deeper histologic sections and tissue-blocking practices improve the diagnosis of endometriosis in peritoneal biopsies. We retrospectively reviewed 148 peritoneal biopsy cases with clinical suspicion of endometriosis from June 1, 2024 to April 1, 2025. Cases with incidental findings, unrelated surgeries, or mass-forming lesions without peritoneal sampling were excluded. We analyzed the influence of block number per biopsy site and the use of additional histologic level sections on diagnostic yield. Associations with surgical approach and reporting pathologist were also assessed. Across all biopsies, detection of endometriosis increased with submission of more tissue blocks per biopsy site: 60% (1 block), 74% (2 blocks), and 86% (≥3 blocks) (P=0.00048). However, this effect did not persist in within-patient comparisons, suggesting confounding by extent of disease. Additional histologic levels were ordered in 32.5% of cases and were associated with increased detection in otherwise negative cases (P=0.039). No significant association was found between the level of use and the number of biopsies per patient or blocks per site. Surgeons with endometriosis subspecialty training had significantly higher diagnostic yields (P=0.0008), as did patients with more biopsy sites sampled (P=0.0009). Among pathologists, diagnostic yield ranged from 59% to 91% (P=0.014), and yield was not explained by usage of level sections. More biopsy sites (extent of disease), submission of more tissue blocks per site, and additional levels improve pathology diagnosis in surgery for peritoneal endometriosis. Variation among surgeons and pathologists underscores the need for standardized protocols and collaborative approaches to optimize histologic confirmation.

NTRK-rearranged spindle cell neoplasm is a recently described mesenchymal neoplasm that usually occurs in the uterine cervix of premenopausal women with variable clinical behavior. Typical immunohistochemical profile includes CD34 and S100 positivity with negative staining for desmin, estrogen receptor (ER), and progesterone receptor (PR). We report a case of NTRK-rearranged spindle cell neoplasm with a previously unreported fusion partner (NTRK1::TIMP3) located within the uterine corpus and with an unusual staining pattern, diffusely positive for desmin and PR, while negative for CD34 and S100. We also provide a literature review of NTRK-rearranged spindle cell neoplasms of the uterine corpus.

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.

Low-grade and high-grade serous neoplasms are generally considered to be separate entities with distinct morphologic features, pathogenesis and clinical behavior. However, rare tumors defy this dualistic classification. Herein, we describe an incidental serous neoplasm confined to the fallopian tube with both low-grade and high-grade features, including ciliated cells and low proliferative rate, along with variable nuclear pleomorphism and an aberrant p53 cytoplasmic expression pattern by immunohistochemistry. Whole exome sequencing revealed a subclonal TP53 splice mutation, supporting this to be an unusual high-grade serous neoplasm of the fallopian tube, which likely evolved from a low-grade serous precursor. This case highlights issues concerning the definition and diagnostic criteria for serous tubal intraepithelial carcinoma and further demonstrates high-grade transformation of low-grade serous neoplasia to be an early pathogenic event.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an autosomal dominant disorder caused by germline fumarate hydratase (FH) pathogenic variants (PVs), characterized by cutaneous leiomyomas, early-onset uterine leiomyomas, and aggressive papillary renal cell carcinoma. While FH-deficient (FH-d) uterine leiomyomas have been proposed as a screening tool for identifying patients, prospective studies remain limited. Over a 6-yr study period, 1838 uterine smooth muscle tumors (uSMTs) were evaluated at our institution and prospectively screened for FH-d morphologic features. Seventy-one tumors (3.9%) showed features suggestive of FH-deficiency, prompting FH immunohistochemistry (IHC), which confirmed FH loss in 41 cases (58%). Among 41 patients with FH-d tumors, the median patient age was 43 yr, and most underwent hysterectomy for symptomatic leiomyomas, abnormal vaginal bleeding, or pelvic pain. Thirty-six patients (88%) had 2 or more leiomyomas, while 5 had a single tumor. The cohort included 39 FH-d leiomyomas, 1 uterine smooth muscle tumor of uncertain malignant potential (STUMP), and 1 FH-d adenomyoma, a previously unreported entity. Genetic counseling was offered to 36 of 41 (88%) patients. Fifteen patients declined testing or did not follow up with the genetic counseling appointment. Among 19 patients tested for FH and other hereditary cancer-related genes, 5 (26%) had FH germline pathogenic mutations, and 1 patient had a variant of unknown significance. Pelvic MRI in mutation carriers showed no abnormalities. In conclusion, FH-d uSMTs represented 2.2% of all uSMTs in our series. A combined morphologic and IHC screening approach can effectively identify patients at risk for HLRCC, facilitating genetic counseling and family screening.

Transitional cell metaplasia (TCM) resembling benign urothelium is commonly seen around the distal fallopian tube and/or neighboring mesothelial surface; however, its histogenesis remains largely unknown. We observed the emergence of a cytokeratin (CK) 17-positive reserve cell layer in early TCM foci beneath the tubal epithelium, leading us to hypothesize that TCM could be derived from reserve cells. To elucidate the histogenetic process of TCM, we analyzed the histomorphologic features and immunoprofiles for CK17, CK5/6, p63, GATA-3, estrogen receptor (ER), and androgen receptor (AR) in TCM foci arising in the tubal epithelium (31 foci) and pelvic mesothelium (35 foci). Overall, the histologic features and immunoprofiles of TCM in the tubal epithelium and pelvic mesothelium were similar, but distinct differences appeared during TCM development. A single-layered CK17-expressing reserve cells became apparent beneath the tubal epithelium, and the CK17 expression disappeared as these cells multiplied. In contrast, a short segment of normal mesothelium next to the tubo-peritoneal junction expressed CK17 even before the emergence of a single-layered reserve cells beneath the mesothelium, suggesting a potential reserve/stem cell function within the mesothelium itself. Then, the single-layered cells in both areas multiplied and differentiated to display urothelial characteristics, including nuclear grooves and clear cytoplasm. Strong CK5/6, p63, and GATA-3 expression appeared in the single-layered reserve cell stage and was maintained thereafter to the fully differentiated TCM. AR was expressed in both normal tubal epithelium and pelvic mesothelium, and the intensity of AR and ER were reciprocal during the entire histogenetic process of TCM in most reserve cell-derived populations (98.5%), AR expression being significantly stronger than ER. The histogenesis of TCM was initiated from the emergence of reserve cells beneath the tubal epithelium and pelvic mesothelium, which then multiplied and differentiated into urothelium. AR might have an important role during the histogenesis of TCM.

We aimed to assess fibrin deposition in placentas of patients with preeclampsia (PE) with fetal growth restriction (FGR) and the relationship with fibrinogen-like protein 2 (FGL2). In this case-control study, pregnant women with PE (n=48), PE with FGR (n=44), FGR (n=43), and healthy pregnant women (n=43) at term gestation were recruited. We compared the baseline characteristics, blood coagulation parameters, and placenta characteristics. Masson's trichrome staining was used to categorize 2 types of fibrinoid. FGL2 expression was examined by immunohistochemical staining. The PE+FGR placentas showed more obvious fetal and maternal vascular malperfusion and maternal-fetal interface fibrin deposition when compared with the others. Increased fibrin-type and matrix-type fibrinoids were found in the placenta of the PE+FGR group when compared with the controls. FGL2 was localized in the junction of these 2 types of fibrinoid, as well as extravillous trophoblastic layers and decidual stromal cells. The PE+FGR group had significantly lower FGL2 expression levels. Placental vascular malperfusion with massive maternal-fetal interface fibrin deposition was found in PE with FGR. We report the characteristic colocalization of 2 types of placental fibrinoid deposition and FGL2 immunoreactivity and, therefore, help in elucidating the mechanisms in the pathology of PE with FGR.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare neoplasms that typically follow a benign course. However, metastasis occurs in rare cases and features associated with poor outcomes are only recently being described. These include: size >5 cm, at least moderate cytologic atypia, >3 mitosis per 10 high-powered fields, infiltrative borders, necrosis, GREB1 rearrangements, ESR1 rearrangements, and NCOA2/3 fusions. To our knowledge, prominent sclerosis has not been described in UTROSCT, nor has it been associated with an increased risk of metastasis. We present the case of a 51-yr-old woman with UTROSCT with corded/trabecular growth and sclerosis. The presence of sclerosis resulted in the misdiagnosis of her uterine tumor as leiomyoma and her lung metastasis as sclerosing epithelioid fibrosarcoma. The correct diagnosis of UTROSCT with lung metastasis was reached upon a morphologic comparison of the primary and metastatic tumors and the performance of a broad panel of immunohistochemical stains revealing the tumor to be CD99, CD56, ER, and inhibin positive and negative for rearrangements in 138 targeted genes, including genes commonly described as rearranged in endometrial stromal sarcomas, Ewing sarcoma and sclerosing epithelioid fibrosarcoma. The panel did not include GREB1 or ESR or NCOA3 , but NCOA1/2 rearrangements were not detected. Our case highlights the diagnostic dilemma introduced by the presence of sclerosis in UTROSCT. We suspect prominent sclerosis may be another feature predictive of malignant potential in UTROSCT.