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.

Endometrioid carcinoma is a common malignant epithelial tumor of the uterus and ovary, exhibiting variable histomorphology and immunophenotype. Sex cord-like endometrioid carcinoma (SCLEC) is a rare histologic subtype with significant morphologic and immunohistochemical variability. Extra-ovarian, extra-uterine SCLEC arising from the broad ligament has been rarely reported. We report 2 cases of SCLEC arising from the broad ligament. The first patient, a 62-yr-old woman, presented with vague abdominal pain, and diagnostic imaging suggested a broad ligament fibroid. The second patient, a 47-yr-old woman, presented with a clinical history of abdominal pain and abnormal uterine bleeding. Diagnostic imaging suggested a subserosal fibroid. Histologic evaluation revealed a sex cord-like pattern with only rare foci of conventional endometrioid carcinoma. Immunohistochemical evaluation of both cases showed positivity for CK-7, EMA, ER, PR, CDX-2, CD-10, and nuclear β-catenin, while CK-20, PAX-8, GATA3, TTF-1, WT-1, napsin-A, p16, p53, inhibin, calretinin, chromogranin, and CEA were negative. The diagnosis of primary broad ligament SCLEC is extremely challenging. A thorough histologic and immunohistochemical evaluation is essential before excluding differential diagnoses.

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.

Lymphovascular space invasion (LVSI) is defined as tumor cells within blood vessels or lymphatic endothelial-lined spaces and, until recently, its prognostic significance in cervical cancer was somewhat controversial and less well studied than for some other tumor types in the female genital tract. Based on the available literature, there is now strong evidence that LVSI is not only a significant prognostic factor, especially in early-stage cervical cancers (squamous cell carcinomas and adenocarcinomas), but is also a predictive factor for lymph node metastases. Consequently, while LVSI does not impact FIGO or TNM staging, its presence should be recorded in the pathology report and considered in management decisions regarding adjuvant treatment, as suggested by various international guidelines. More recently, the extent of LVSI (substantial vs. focal vs. negative) has been demonstrated to predict survival in cervical cancer, although this is an area where more study is required both to determine whether substantial LVSI is of prognostic significance and to ascertain the optimal definition of substantial LVSI. LVSI can be diagnosed on routine microscopic examination without ancillary tests in most cases and thus can be reported even in low-resource settings. There are, however, various pathologic issues both in diagnosing and quantifying LVSI, with no universal recommendations. In this review, we examine the significance of LVSI in cervical cancer in terms of prognostication and in dictating the need for adjuvant treatment. We also discuss practical issues related to the pathologic reporting of LVSI.

Previous studies have evaluated the utility of estrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry (IHC) in differentiating uterine versus extrauterine leiomyosarcomas (LMS). At best, these studies have shown only modest sensitivity and specificity for these markers in this context. In our own practice, we have noticed that retroperitoneal LMS, such as those arising in the wall of the inferior vena cava, frequently exhibit a remarkable resemblance not to uterine LMS, but rather to uterine leiomyomas (LM) with bizarre nuclei, formerly known as symplastic LM. This includes areas with bland nuclear cytology, punctuated by the presence of cells with large bizarre nuclei but a paradoxically low mitotic index. We refer to these areas in retroperitoneal LMS as "symplastic-like." It has been our experience that these "symplastic-like" areas are frequently the predominant or exclusive component in small core biopsies of retroperitoneal LMS, even when the resection of these tumors reveals the presence of more conventional high-grade LMS morphology. In female patients, symplastic-like morphology in a smooth muscle tumor at an intra-abdominal site raises the possibility of iatrogenic dissemination of a uterine LM with bizarre nuclei from a prior myomectomy or morcellation procedure. We hypothesized that negative staining for ER and PR by IHC could effectively exclude a uterine origin, given the high sensitivity of these markers for all variants of uterine LM. After successfully using ER and PR IHC in our clinical practice on a few index cases, we decided to study a larger cohort of carefully selected cases to systematically determine the sensitivity and specificity of these markers in this very specific context. Confining our search to include only female patients, we identified 8 cases of retroperitoneal LMS that had been confirmed radiologically, intraoperatively and/or histologically to originate from a retroperitoneal source and 6 cases of uterine-based LM with bizarre nuclei, all diagnosed at our institution over an 8-year period. We tested only whole slides for ER and PR IHC. ER and PR were both completely negative in all 8 cases of retroperitoneal LMS and were both strongly expressed in all 6 cases of LM with bizarre nuclei. In conclusion, despite conflicting data in the literature regarding the utility of ER and PR in distinguishing uterine versus extrauterine smooth muscle tumors, we endorse the use of these markers for the specific distinction of retroperitoneal LMS with symplastic-like features from disseminated uterine LM with bizarre nuclei in female patients.