International Journal of Gynecological Pathology最新文献

Cellular angiofibroma is a benign mesenchymal neoplasm which usually occurs in the vulvovaginal or inguinoscrotal areas. Although benign, cellular angiofibroma may rarely undergo sarcomatous transformation. We report a case of vulvar cellular angiofibroma with sarcomatous transformation in a 62-yr-old woman and a literature review of previously reported cases. By immunohistochemistry, our case was positive for vimentin and ER, mostly negative for smooth muscle markers, and showed patchy reactivity for CD10, Pan-TRK, and Rb1. The bland component was negative for p16 with wild-type p53 expression, while the sarcomatous area showed strong, diffuse p16 staining with p53 overexpression. Targeted DNA and RNA next-generation sequencing of the bland area showed chromosome 9p/9q copy number loss, while the sarcomatous area showed TP53 (p.G154V) mutation (90% allele frequency) and copy number loss of chromosome 17p (including TP53 ). Whole transcriptome sequencing was negative for tumor-associated gene fusions. As the lesion was completely encapsulated and excised, and with limited published data indicating an uneventful clinical course, the decision was made to follow the patient with no further therapeutic intervention. Four months following excision, the patient has no signs or symptoms of local recurrence.

Klippel-Trenaunay syndrome (KTS) is a rare overgrowth disorder characterized by capillary malformations, vascular anomalies, and limb length discrepancies. It is a congenital, mostly sporadic disorder with unknown pathogenesis, though recent studies have shown an association with somatic mosaic-activating mutations in the PIK3CA gene. The prognosis is variable, depending on the clinical presentation. Visceral involvement in KTS is rare, usually in the form of hemangiomas or venous malformations. Varied neoplastic pathologies have been reported in KTS; however, unlike other overgrowth syndromes, no clear association between KTS and malignancy has so far been elucidated. We report herein an account of a 2-yr-old female child with KTS who presented with abdominal distention and was diagnosed to have a serous borderline tumor (SBT) of bilateral fallopian tubes. Fallopian tube SBT is exceptionally rare and, to the best of our knowledge, has only been reported once previously in a premenarchal patient, who, incidentally, also had KTS. Bilateral fallopian tube involvement in a pediatric SBT has not been described hitherto.

This study represents a omprehensive characterization of high-grade endometrial carcinoma (EC) of no specific molecular profile (NSMP) to improve our understanding of their poor clinical outcome. A previously molecularly classified cohort of 412 high-grade EC from the Danish Cancer Registry was extensively reviewed by 2 expert pathologists blinded for associated clinical and molecular data. Immunohistochemistry (IHC) was performed to determine ER, PR, and L1CAM status and a 10% cut-off value was applied for positivity. Shallow whole-genomic sequencing (sWGS) and next-generation sequencing (NGS) was performed to describe the molecular landscape. Survival analysis was performed using the Kaplan-Meier method, and survival difference was tested using the log-rank test. Of the 57 high-grade NSMP tumors, ER negativity was found in 30 (53%). All clear cell NSMP EC (n=12, 21%) were ER negative. L1CAM overexpression was found in 29 high-grade NSMP EC (53%) and showed overlap (n=20, 69%) with ER negativity. A high frequency of copy number (CN) events and fraction genome altered (FGA) was observed, with the median number of CN events clustering by ER status (28 vs. 43, P <0.05). Overall, the cohort showed a 52% (CI: 31.6%, 72.4%) 5-yr overall survival (OS) and 61% (CI: 42.6%, 79.4%) 5-yr disease-specific survival (DSS). No significant additional prognostic refinement was found when stratifying for ER status (5-yr OS: 46% vs. 65%, P =0.068). High-grade NSMP ECs are a heterogenous group of tumors with high prevalence of loss of ER, L1CAM overexpression, and substantial copy number alterations. Within this group, no prognostic effect of ER was identified, providing support for grouping these tumors into one risk group. This work adds to the growing body of evidence that both high-grade and/or loss of ER expression can be used to identify NSMP EC patients with a poor clinical outcome.

Mature and immature teratomas can coexist with other tumor types and they may undergo malignant change in any one of their elements. In the present study, we present our institutional experience of these rare associations with teratomas. This was a retrospective study over a period of 10 years (January 2014 to December 2023) on histopathologically diagnosed cases of ovarian teratomas. The clinicopathologic features of malignant transformation (MT), other associations, as well as co-existing tumors with ovarian teratomas were analyzed. There was a total of 602 (21%) ovarian teratomas out of all ovarian tumors (n=2858) reported during the study period. In all, 41/602(6.8%) cases were immature teratomas with the presence of gliomatosis peritonei in 7 cases. Mature cystic teratoma (MCT) cases also had gliomatosis peritonei (n=9) along with nodal gliomatosis in 3 cases. Neoplasms arising in teratomas (n=6) included carcinoid tumor (n=2), small cell neuroendocrine carcinoma (n=1), mucinous adenocarcinoma (n=2), and low-grade mucinous neoplasm of the appendix present within the teratoma (n=1). Of a total of 18 cases of struma ovarii, one case each of papillary thyroid carcinoma and follicular thyroid carcinoma was seen. Squamous cell carcinoma (n=4) was the commonest malignant transformation noted. Growing teratoma syndrome (n=4) and NMDA-associated encephalitis (n=3) associated with teratoma were also seen. Neoplasms/conditions co-existing with teratomas in the same ovary (n=9) included mucinous cystadenoma (n=1), serous cystadenofibroma (n=1), high-grade serous carcinoma (n=1), fibrothecoma (n=2), hydatid cyst (n=1), sclerosing stromal tumor (n=1), adult granulosa cell tumor (n=1), and metastatic signet ring cell carcinoma (n=1). Although the clinical course of MCT is typically indolent, pathologists should be aware of malignant transformation and other rare co-existing entities, highlighting the importance of adequate sampling of the tumors.

Accurate diagnosis and prognostic stratification of uterine leiomyosarcoma (LMS) is becoming more important with more nuanced clinical management. Two recent studies by Momeni-Boroujeni and Chapel reported a 7-marker surrogate immunohistochemistry (IHC) diagnostic panel and a morphologic risk stratification schema, respectively. Our objective was to test these approaches in a local cohort. Thirty-four consecutive LMS cases diagnosed at Foothills Medical Center, Calgary, Alberta, Canada (2016-2022) underwent detailed histopathologic review and surrogate IHC panel (TP53, RB1, ATRX, PTEN, DAXX, MTAP, and MDM2). Associations of molecular alterations, morphologic features and survival were studied. Abnormal staining was detected for RB1 (65%), TP53 (62%), ATRX (44%), PTEN (32%), MTAP (15%), DAXX (9%), and MDM2 (6%). Seventy-nine percent of cases showed abnormality in ≥2 molecular markers, confirming a LMS diagnosis. However, 21% of cases showed only one or no abnormality and these cases were associated with a lower nuclear grade and mitotic count, which may cause diagnostic difficulties. While molecular alterations did not predict survival, morphologic risk stratification distinguished low-risk, intermediate-risk, and high-risk groups with significant differences in disease-specific survival (log-rank P = 0.030). While these findings validate the sensitivity of an IHC-based diagnostic panel in confirming the vast majority of LMS diagnoses, a subset, which more likely shows ambiguous diagnostic features, probably requires genomic testing. The previously proposed morphologic criteria seem to provide a robust prognostic stratification.

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).