Nooshin K Dashti, Amy A Swanson, Vatsal Patel, Deyin Xing, Michael Feely, Gary L Keeney, Sounak Gupta, J Kenneth Schoolmeester
{"title":"Leiomyosarcomas of the Visceral Adnexal and Uterine Ligaments and Adnexal Connective Tissue: Immunohistochemical, Molecular Genetic, and MDM2 Fluorescence In Situ Hybridization Analysis.","authors":"Nooshin K Dashti, Amy A Swanson, Vatsal Patel, Deyin Xing, Michael Feely, Gary L Keeney, Sounak Gupta, J Kenneth Schoolmeester","doi":"10.1097/PGP.0000000000001064","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001064","url":null,"abstract":"","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Ben-Mussa, Rajeev Shah, Simon Rajendran, W Glenn McCluggage
{"title":"A Population-based Study Investigating the Incidence of Human Papillomavirus-Associated and Human Papillomavirus-Independent Cervical Adenocarcinomas.","authors":"Ali Ben-Mussa, Rajeev Shah, Simon Rajendran, W Glenn McCluggage","doi":"10.1097/PGP.0000000000001063","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001063","url":null,"abstract":"<p><p>Cervical adenocarcinomas are now classified as human papillomavirus (HPV)-associated and HPV-independent types with the former being more common. However, population-based studies regarding the relative incidences of the 2 types are few. This study investigates the incidence of cervical adenocarcinomas in Northern Ireland (a country with a relatively stable population of ~1.8 million) over a recent 9-year period (2015-2023). Overall, there were 146 primary cervical adenocarcinomas, 130 HPV-associated (89%) and 16 HPV-independent (11%). The median age was 43 years (range: 24-82) for HPV-associated and 62.5 years (range: 31-84) for HPV-independent neoplasms; this was statistically significant (P < 0.001). The calculated age-adjusted incidence of the patients with HPV-associated and HPV-independent neoplasms was 1.68 and 0.20 per 100,000 person-years, respectively. The HPV-independent neoplasms were more often advanced stage at diagnosis; 97 of 130 (75.4%) of the HPV-associated cases were diagnosed at Stage I compared with 5 of 16 (31.3%) of the HPV-independent cases. The HPV-independent neoplasms were mostly gastric-type (56.3%) with smaller numbers of clear cells and mesonephric. Despite the relatively short follow-up, the mortality of patients with HPV-independent adenocarcinomas was significantly higher than patients with HPV-associated neoplasms (56.3% vs 5.4%) with a median survival of just over a year (13.2 mo) in the former for those who died.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan T Nguyen, Dale Waring, King M Wan, Christine Loo
{"title":"Superficial and Invasive Spread of High-grade Squamous Intraepithelial Lesion and Squamous Cell Carcinoma: A Case Report.","authors":"Dan T Nguyen, Dale Waring, King M Wan, Christine Loo","doi":"10.1097/PGP.0000000000001062","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001062","url":null,"abstract":"<p><p>We present a case of extensive spread of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia grade 3 (CIN3) with foci of invasive squamous cell carcinoma (SCC) in a premenopausal woman. Superficial spread of CIN3 and cervical SCC to the endometrium and/or fallopian tubes is rare, especially in countries with cervical cancer screening programs. Our case occurred during the COVID-19 pandemic, which may have been a major contributing factor to delayed detection and, consequently extensive spread.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brittany Gilmore, Linda Logan, Wendy McKinnon, Elise Everett, Bronwyn H Bryant
{"title":"Endometrial Cancer in a Family With RAD51D Gene Mutation.","authors":"Brittany Gilmore, Linda Logan, Wendy McKinnon, Elise Everett, Bronwyn H Bryant","doi":"10.1097/PGP.0000000000000981","DOIUrl":"10.1097/PGP.0000000000000981","url":null,"abstract":"<p><p>RAD51 complex plays an important role in homologous recombination deficiency and germline mutations have a well-documented association with breast and tubo-ovarian carcinoma, as well as serous-type endometrial carcinoma. We report a family of French Canadian ancestry with a germline mutation in RAD51D and two sisters presenting with endometrial carcinoma, endometrioid-type. The risk factors for endometrial adenocarcinoma, endometrioid-type are discussed in the context of the RAD51-associated carcinomas described to date.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"349-353"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zitong Zhao, Ravichandran Nadarajah, Inny Busmanis
{"title":"Synchronous Bilateral Ovarian Mesonephric-like Adenocarcinomas with Separate Origins from High-Grade Mullerian Adenosarcoma and Endometriosis: Report of a Rare Case.","authors":"Zitong Zhao, Ravichandran Nadarajah, Inny Busmanis","doi":"10.1097/PGP.0000000000000997","DOIUrl":"10.1097/PGP.0000000000000997","url":null,"abstract":"<p><p>Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from Mullerian epithelium with mesonephric transdifferentiation. Emerging evidence suggests that MLA may be classified as an endometriosis-associated neoplasm. The presence of a sarcomatous component within MLA is extremely rare, with common differential diagnoses including the spindle cell component of MLA, carcinosarcoma, as well as mixed Mullerian adenocarcinoma and adenosarcoma. Herein, we report a 58-year-old Chinese woman with bilateral ovarian solid-cystic masses. The left ovarian mass comprised a biphasic tumor with a predominantly high-grade sarcomatous component displaying heterologous mesenchymal differentiation, including liposarcoma, rhabdomyosarcoma and chondrosarcoma-like areas, with a null-type p53 expression. The epithelial component ranged from a bland appearance in areas diagnostic of adenosarcoma to a clearly invasive carcinoma, both with mesonephric-like phenotype, being negative for estrogen receptor, progesterone receptor, and Wilms' tumor 1, variably positive for paired box gene 8, GATA binding protein 3, and thyroid transcription factor 1, with a wild-type p53 expression. The differing p53 expression between the epithelial and sarcomatous elements mitigated against a diagnosis of carcinosarcoma. The right ovarian mass showed endometriosis with focal direct evidence of the development of malignancy within a benign endometriotic cyst, exhibiting the identical immunoprofile of MLA but originating as another malignancy. To the best of our knowledge, this case represents the first reported case of synchronous bilateral ovarian MLAs with separate origins, from high-grade Mullerian adenosarcoma and endometriosis respectively, which broadens the morphologic spectrum of MLA and provides further evidence supporting the Mullerian origin theory.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"382-388"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spencer D Martin, Karina C Martin, C Blake Gilks, Richard I Crawford, Lien N Hoang
{"title":"PRAME Immunohistochemistry for Distinguishing Vulvar and Vaginal Melanoma From Benign Melanocytic Nevi.","authors":"Spencer D Martin, Karina C Martin, C Blake Gilks, Richard I Crawford, Lien N Hoang","doi":"10.1097/PGP.0000000000001004","DOIUrl":"10.1097/PGP.0000000000001004","url":null,"abstract":"<p><p>Vulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities. PReferentially expressed Antigen in MElanoma (PRAME) is a melanoma-associated protein, and immunohistochemistry (IHC) for PRAME distinguishes cutaneous, oral mucosal, and retinal melanoma from atypical nevi. Given the biological differences between VVM and cutaneous melanoma, the utility of PRAME IHC for the diagnosis of VVM is unknown. We accrued a cohort of 20 VVM and 21 benign vulvar melanocytic nevi. We found that nuclear PRAME IHC staining with 4+ intensity was present in 85% of the VVM and 0% of the nevi. With the assistance of PRAME IHC, we found evidence of close or positive margin involvement in 3 of 10 cases where margins were originally diagnosed as negative for melanoma in situ. Our study is the first to assess PRAME IHC in a cohort of VVM cases and provides confidence for using PRAME IHC to assist with diagnosis and margin assessment in this rare disease.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"389-396"},"PeriodicalIF":2.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina H Wei, Evita Sadimin, Mark Agulnik, Susan E Yost, Teri A Longacre, Oluwole Fadare
{"title":"SMARCA4 / BRG1 -deficient Uterine Neoplasm With Hybrid Adenosarcoma and Carcinoma Features: Expanding the Molecular-morphologic Spectrum of SMARCA4 -driven Gynecologic Malignancies.","authors":"Christina H Wei, Evita Sadimin, Mark Agulnik, Susan E Yost, Teri A Longacre, Oluwole Fadare","doi":"10.1097/PGP.0000000000000996","DOIUrl":"10.1097/PGP.0000000000000996","url":null,"abstract":"<p><p>SMARCA4 gene encodes BRG1 , a member of the SWItch/sucrose non-fermentable protein family involved in epigenetic transcriptional regulation of important cellular processes. In the uterine corpus, SMARCA4 / BRG1 deficiency is associated with a novel class of undifferentiated uterine sarcomas, characterized by younger age onset, rhabdoid histology, focal phyllodiform architecture, high-risk pathologic findings, and dismal prognosis. Herein, we report a case of a 34-year-old Asian woman with a SMARCA4 / BRG1 -deficient uterine tumor fulfilling the clinicopathologic features of an undifferentiated uterine sarcoma. However, the tumor exhibited several unique features that have not been previously emphasized, including (1) conspicuous phyllodiform architecture recapitulating conventional adenosarcoma, (2) rhabdoid tumor cells forming cords and keratin-positive cohesive epithelial islands, and (3) cooccurrence with a spatially distinct and discrete endometrial complex atypical hyperplasia from the rest of the proliferation. By immunohistochemistry, the tumor cells were diffusely positive for synaptophysin, whereas BRG1 was lost. Pertinent molecular findings included frameshift mutations in the SMARCA4 gene, mutations in histone modification and chromatin remodeling genes, including KMT2C , ARID1B , KAT6A , and NCOR1 , and mutations in Wnt signaling involving APC and CTNNB1 . Copy number gain in MDM2 and CDK4 were also identified. The tumor mutation burden was intermediate (6.8/MB) and it was microsatellite stable. On balance, our case exhibited morphologic and molecular features that overlap with (1) an undifferentiated uterine sarcoma, (2) an adenosarcoma with sarcomatous overgrowth, and (3) a mixed adenosarcoma and undifferentiated endometrial carcinoma. These hybrid features further expand the molecular-morphologic spectrum of SMARCA4 / BRG1 -deficient uterine neoplasms.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"354-361"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11166733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Estrogen/Progesterone Receptor Expression and Cancer Antigen 125 Level as Preoperative Predictors to Estimate Lymph Node Metastasis in Endometrioid Endometrial Cancer.","authors":"Shao-Chi Wang, Chen-Hsuan Wu, Hung-Chun Fu, Yu-Che Ou, Ching-Chou Tsai, Ying-Yi Chen, Ying-Wen Wang, Szu-Wei Hunag, Szu-Yu Huang, Jui Lan, Hao Lin","doi":"10.1097/PGP.0000000000000984","DOIUrl":"10.1097/PGP.0000000000000984","url":null,"abstract":"<p><p>Loss of estrogen receptor/progesterone receptor (ER/PR) in endometrial cancer (EC) is associated with tumor progression and poor outcomes. Elevated pretreatment cancer antigen 125 (CA 125) level is a risk factor for lymph node metastasis (LNM). We evaluated whether the combination of ER/PR expression and CA 125 level could be used as a biomarker to predict LNM. We retrospectively investigated patients with endometrioid EC who underwent complete staging surgery during January 2015 to December 2020. We analyzed ER/PR status using immunohistochemical staining, and quantified its expression using the sum of both ER/PR H -scores. Receiver operating characteristic curves were used to identify optimal cutoff values of H -score and CA 125 levels for predicting LNM. A nomogram for predicting LNM was constructed and validated by bootstrap resampling. In 396 patients, the optimal cutoff values of the ER/PR H -score and CA 125 were 407 (area under the receiver operating characteristic curve: 0.645, P =0.001) and 40 U/mL (area under the receiver operating characteristic curve: 0.762, P <0.001), respectively. Multivariate analysis showed that CA 125 ≥40 UmL (odds ratio: 10.02; 95% CI: 4.74-21.18) and ER/PR H -score <407 (odds ratio: 4.20; 95% CI: 1.55-11.32) were independent predictors. An LNM predictive nomogram was constructed using these 2 variables and our model yielded a negative predictive value and negative likelihood ratio of 98.3% and 0.14, respectively. ER/PR expression with pretreatment CA 125 levels can help estimate LNM risk and aid in decision-making regarding the need for lymphadenectomy in patients with endometrioid EC.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"316-325"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41114097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metastatic Hepatocellular Carcinoma Represents an Important but Rare Pitfall in the Diagnostic Evaluation of ER Negative Ovarian Malignancy: A Case Report.","authors":"Mthulisi Viki, Rebecca Morrow","doi":"10.1097/PGP.0000000000000995","DOIUrl":"10.1097/PGP.0000000000000995","url":null,"abstract":"<p><p>Metastatic hepatocellular carcinoma (HCC) to the ovary is a rare and challenging histopathological diagnosis in the absence of the relevant clinical history. The differential diagnoses of a hepatoid tumor in the ovary are extensive, and correct diagnosis requires well-considered clinical-pathologic correlation. Familiarity with the diverse architectural patterns and immunophenotype of HCC is essential; however, even in the setting of known hepatic disease, a well-developed pseudoglandular pattern may be a convincing morphologic mimic of a primary surface epithelial ovarian malignancy. We describe a diagnostically challenging case of a 50-year-old woman with metastatic HCC exhibiting a prominent pseudoglandular pattern mimicking primary endometrioid adenocarcinoma, and an approach to overcome this important pitfall.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"378-381"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna K Dietl, Matthias W Beckmann, Frederik A Stuebs, Paul Gass, Julius Emons, Arndt Hartmann, Ramona Erber
{"title":"PD-L1 Expression and Silva Invasion Pattern in Villoglandular Adenocarcinoma of the Uterine Cervix.","authors":"Anna K Dietl, Matthias W Beckmann, Frederik A Stuebs, Paul Gass, Julius Emons, Arndt Hartmann, Ramona Erber","doi":"10.1097/PGP.0000000000001006","DOIUrl":"10.1097/PGP.0000000000001006","url":null,"abstract":"<p><p>Villoglandular adenocarcinoma (VGA) of the uterine cervix is a rare subtype of endocervical adenocarcinoma in young women. Between 2007 and 2020, all women with endocervical adenocarcinoma were retrospectively reviewed to find patients with VGA. Eight patients in whom pure VGA had been diagnosed were included. The mean age at initial diagnosis was 36.3 years (range 24-46). After surgical treatment, patients were followed up for 59 months (range 16-150). To date, all patients are alive with no evidence of disease. Neither lymph node involvement nor lymphovascular invasion was found. Furthermore, we examined the samples with a focus on morphological invasion pattern (Silva), stromal tumor-infiltrating lymphocytes (sTILs), and immunohistochemical programmed death ligand-1 (PD-L1) expression. PD-L1 expression was observed in 7/8 using the combined positive score (cutoff≥1%), 1/8 of VGAs using the tumor proportion score (cutoff≥1%), and 7/8 using the immune cell (cutoff≥1%). Using combined positive score and immune cell, PD-L1 expression was seen in 7/8 of pattern B and C tumors, with significantly higher expression in tumors with destructive-type patterns ( P <0.05, A vs. B+C). Using tumor proportion score, no significant difference in PD-L1 expression was seen between VGAs with different invasion patterns. VGAs demonstrated twice higher sTILs in tumors with destructive-type invasion patterns. Our observations suggest that PD-L1 expression, tumor invasion patterns, and sTILs do not correlate with the excellent prognosis of pure VGA.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"397-404"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}