International Journal of Gynecological Pathology最新文献

{"title":"p53 Normal and p53 Abnormal Clear Cell Ovarian Carcinomas: Clinical Characteristics and Biomarker Profiles.","authors":"Piret Hellberg, Annukka Pasanen, Jonna Similä-Maarala, Ralf Bützow, Heini Lassus","doi":"10.1097/PGP.0000000000001191","DOIUrl":"10.1097/PGP.0000000000001191","url":null,"abstract":"<p><p>A new concept of molecular classification for clear cell ovarian carcinoma (CCOC) has been proposed: TP53 wild-type and TP53 mutated. Our aim was to evaluate this classification at the immunohistochemical level in p53 normal and abnormal subgroups. Clinicopathologic factors and 12 immunohistochemical biomarkers (p53, PR, ER, β-catenin, vimentin, ARID1A, HNF1-β, E-cadherin, c-erb-B2, MIB-1, p16, and L1CAM) and patient prognosis were analyzed in 132 CCOCs. The p53 abnormal group presented with significantly worse disease-specific overall survival (DSS) and disease-free survival (DFS) than the p53 normal group, which was largely due to higher stage and a more frequent presence of residual tumor in the p53 abnormal group. Furthermore, higher stage and presence of residual tumor were markers of poor outcome within both p53 subgroups. Interestingly, the presence of ascites was related to shorter DSS only in p53 normal cases. The p53 normal group was also characterized by a higher frequency of ARID1A loss and HNF1-β positivity, whereas p16 overexpression and ER positivity were more common in p53 abnormal cases. Interestingly, ARID1A loss correlated with poor DSS in the p53 abnormal group. In the p53 normal tumors, ER positivity was associated with better DSS and p16 positivity with worse DFS. L1CAM positivity was associated with residual tumor only in the p53 normal group. Our findings support the existence of 2 distinct molecular subgroups of CCOC, p53 normal and p53 abnormal, with diverse characteristics and patient outcomes. Clinical and molecular differences were discovered within these subgroups.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"340-348"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042231","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":"NTRK -rearranged Spindle Cell Neoplasm of the Uterus: An Emerging Entity.","authors":"Haley Corbin, Shikha Malhotra, Kanika Goel, John M Skaugen, Rohit Bhargava","doi":"10.1097/PGP.0000000000001143","DOIUrl":"10.1097/PGP.0000000000001143","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"399-404"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488510","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":"Epithelioid Trophoblastic Tumor Presenting as a Large Cystic Mass: Diagnostic Clue From Foreign DNA Sequences Detected by Comprehensive Genomic Profiling.","authors":"Yui Kojima, Akiko Tonooka, Tomohiro Chiba, Sanshiro Okamoto, Shogo Nishino, Akiko Abe, Satomi Kitai, Murasaki Aman, Yuichiro Sato, Naomi Hayashi, Ippei Fukada, Shunji Takahashi, Kengo Takeuchi","doi":"10.1097/PGP.0000000000001156","DOIUrl":"10.1097/PGP.0000000000001156","url":null,"abstract":"<p><p>Epithelioid trophoblastic tumor (ETT) is an extremely rare gestational trophoblastic neoplasm typically presenting as solid nodular lesions. We report an unusual case of ETT in a postmenopausal woman in her 50s that occurred 20 years after her last pregnancy. The tumor presented as a 19-cm multilocular cystic mass protruding from the cervix and was suspected to be infected. Initial histopathological examination revealed a solid proliferation of epithelioid to spindle cells expressing cytokeratins and p40, leading to a provisional diagnosis of sarcomatoid carcinoma. Comprehensive genomic profiling (CGP) was performed because of uncertainty regarding the primary site. Unexpectedly, CGP revealed DNA sequences of foreign origin, which prompted consideration of gestational trophoblastic disease rather than contamination. Additional immunohistochemical staining demonstrated positivity for HSD3B1, a specific marker of trophoblastic differentiation, confirming a diagnosis of ETT. Complete surgical resection was achieved, with no recurrence during 18 months of follow-up. This case has 2 important teaching points. First, ETT can present as a large cystic lesion rather than as a classical solid mass, likely as a result of extensive necrosis and superimposed infection. Second, detection of foreign DNA sequences during genomic profiling of a uterine tumor should alert pathologists to the possibility of gestational trophoblastic disease, given that these tumors are of fetal origin with a distinct genetic profile differing from that of maternal tissue. Recognition of these features is crucial for accurate diagnosis and appropriate management of this rare neoplasm.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"405-411"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289898","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":"Uterine Myxoid Inflammatory Myofibroblastic Sarcoma (MIMS) Harboring Pathogenic KRAS Mutations and Expressing ER, PR, and CD10.","authors":"Jin Xu, David Kushner, Paul S Weisman","doi":"10.1097/PGP.0000000000001192","DOIUrl":"10.1097/PGP.0000000000001192","url":null,"abstract":"<p><p>Myxoid inflammatory myofibroblastic sarcoma (MIMS) is a recently described aggressive sarcoma with deceptively bland spindled cells with a myofibroblastic phenotype and myxoid stroma. These tumors are negative for ALK gene rearrangements, but have been shown to harbor gene fusions involving PDGFRA/B , JAK1 , and PML and/or mutations involving KRAS . Only one uterine case has been previously reported. Here we report the second case of uterine MIMS. This tumor arose in a 40-yr-old woman patient and showed a conspicuously whorled architecture with myxoid stroma and so-called organoid aggregates. By immunohistochemistry, the tumor was positive for CD10, estrogen receptor (ER), and progesterone receptor (PR) with focal smooth muscle actin expression and no staining for ALK, desmin, h-caldesmon, HMB-45, or cathepsin-K. Next-generation sequencing analysis revealed the presence of 2 pathogenic mutations in KRAS , as well as pathogenic mutations in RAD51B and LATS1 . No gene fusions in PDGFRA/B , JAK1 , PML , ALK, ROS1, PLAG1 , or any other gene were identified by whole transcriptomic RNA sequencing. Given its deceptively bland appearance and its propensity, at least in the uterus, to express both CD10 and ER with only focal SMA expression, MIMS can be mistaken for an endometrial stromal tumor, an ALK and ROS1 -negative uterine inflammatory myofibroblastic tumor, or other cytologically bland fusion-driven uterine mesenchymal neoplasms.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"395-398"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042242","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":"\"Dark Paget\" Cells in Extramammary Paget Disease of the Vulva-Diagnostic Features and Interpretative Pitfalls.","authors":"Susanne K Jeffus, Jacob T Wooldridge, Katharina Janda, Charles M Quick, Mugahed Hamza","doi":"10.1097/PGP.0000000000001179","DOIUrl":"10.1097/PGP.0000000000001179","url":null,"abstract":"<p><p>Extramammary Paget disease (EMPD) is characterized by intraepithelial neoplastic glandular cells with hyperchromatic nuclei and abundant pale, mucin-rich cytoplasm. One of our authors previously reported 3 cases of primary EMPD exhibiting an unusual morphology characterized by darker pagetoid cells (\"Dark Paget\"). Our study aims to identify additional cases to further describe this unique presentation. Our database was queried for vulvar EMPD (2018-2025). We defined \"Dark Paget\" cells as smaller in size with an increased nuclear to cytoplasmic ratio, a striking absence of abundant pale cytoplasm, and hyperchromatic nuclei with irregular contours. Support was provided by staining with CK7 (and additional stains as applicable) for all patients. Patient age, clinical presentation and treatment were recorded. A total of 96 vulvar EMPD specimens were identified, of which 10 cases from 3 patients (age range: 34-84 yr, mean: 72) fit the morphologic criteria for \"Dark Paget.\" EMPD was clinically suspected in all (10/10, 100%) cases; all 10 (100%) represented a recurrence and shared similar prior treatment modalities. On low-power magnification, \"Dark Paget\" mimicked an HPV-associated squamous intraepithelial lesion in 6 (60%) and differentiated vulvar intraepithelial neoplasia in 4 (40%) cases. This unusual presentation of vulvar EMPD, termed \"Dark Paget,\" represents a diagnostic pitfall, potentially leading to delay in proper diagnosis and management. Awareness of this subtle presentation and careful histopathologic evaluation, combined with a low threshold for ancillary staining, is essential to avoid misdiagnosis. A potential association between patients with recurrent disease, \"Dark Paget\" morphology and prior treatment modalities requires further investigation.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"358-365"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716657","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":"Identification of Placental Mesenchymal Dysplasia and Twin Pregnancy With Complete Hydatidiform Mole: A Clinicopathological Analysis.","authors":"Yan Qin, Hongyi Gao, Jiali Zhang, Jiexia Yang","doi":"10.1097/PGP.0000000000001184","DOIUrl":"10.1097/PGP.0000000000001184","url":null,"abstract":"<p><p>To investigate the clinicopathologic characteristics for differentiating placental mesenchymal dysplasia (PMD) from twin pregnancy with complete hydatidiform mole and coexisting fetus (CHMCF), a retrospective analysis was conducted on the clinical and pathologic data of 5 cases of CHMCF and 2 cases of PMD diagnosed in our department between April 2016 and December 2024, supplemented by a literature review. The microscopic features of PMD included stem villous hyperplasia with thick-walled stromal vessels, abundant villous stroma exhibiting edema and mucoid degeneration, an admixture of grape-like edematous villi and normal-appearing villi, and mild trophoblastic hyperplasia with pseudoinclusions. Immunohistochemically, PMD showed p57 positivity in villous trophoblasts but was negative in villous stromal cells. The microscopic characteristics of CHM are: hydropic swelling predominantly involving intermediate and terminal villi, often with central cistern formation, avascularity, and marked trophoblastic proliferation. Immunohistochemically, CHM demonstrated p57 negativity in both trophoblasts and villous stromal cells, along with high Ki-67 expression in trophoblasts. Placental mesenchymal dysplasia is a rare and often underdiagnosed placental abnormality associated with an increased risk of preterm birth and intrauterine fetal death. Its imaging appearance can resemble a hydatidiform mole, but its implications for maternal and fetal management and prognosis are vastly different. Therefore, accurate differentiation is crucial for appropriate patient counseling and clinical management. Clinicians and pathologists should be aware of this possibility.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"366-376"},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770964","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":"Novel Gene Fusions and Pathogenic CTNNB1 Mutation in Pilomatrix-like High-grade Endometrioid Carcinoma: Expanding the Molecular Spectrum.","authors":"Dorukhan Gül, Ahmet Erbağci, Furkan Aknar, İlker Nihat Ökten, Abdullah Aydın","doi":"10.1097/PGP.0000000000001212","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001212","url":null,"abstract":"","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864814","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":"Uterine Tumor With Myogenic Differentiation and SRF::RELA Fusion Manifesting as Endometrial Polyp.","authors":"Monika Manethová, Jan Hojný, Pavel Dundr","doi":"10.1097/PGP.0000000000001209","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001209","url":null,"abstract":"<p><p>We report a case of a uterine mesenchymal tumor with myogenic differentiation and SRF::RELA fusion occurring in a 23-year-old woman manifesting as an endometrial polyp. The tumor consisted of bland spindle cells with a predominantly fascicular growth pattern and entrapment of the endometrial glands and vessels. The tumor was positive for smooth muscle markers and CD10. NGS RNA analysis revealed SRF::RELA fusion. NGS DNA analysis revealed no pathogenic variants or copy-number alterations. On follow-up 12 months after curettage, the patient showed no signs of the disease. To the best of our knowledge, only 3 cases of uterine tumors with SRF::RELA fusion arising in the gynecologic tract have been described previously, and all show benign behavior so far. Differential diagnosis includes both benign and potentially aggressive entities, such as leiomyoma, inflammatory myofibroblastic tumor, perivascular epithelioid cell tumor, uterine adenosarcoma, low-grade endometrial stromal sarcoma, and uterine sarcoma with KAT6B/A::KANSL1 fusion.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678599","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":"Folate Receptor Immunohistochemical Staining Heterogeneity in Gynecologic Cancers.","authors":"Barrett C Lawson, Anais Malpica","doi":"10.1097/PGP.0000000000001210","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001210","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Mirvetuximab soravtansine is an antibody-drug conjugate targeting FRα, which has not only shown antitumor activity and tolerability in ovarian carcinoma with FRα high expression, but has also been incorporated into NCCN guidelines to treat patients with platinum-resistant disease. Sequential cases were retrieved from a previously published cohort of gynecologic pathology cases in which FOLR1 immunohistochemistry had been performed at our institution. Clinical and pathologic data collected included patients' age, tumor histotype, tumor grade (if reported or relevant to histotype), primary tumor site, FIGO stage, and type of specimen. FOLR1 immunohistochemical results were collected from the report, including the overall tumor percentage and intensity reported, and subsequently determined if this was an overall positive or negative result (positivity defined as per current recommendations for therapy eligibility, 75%, 2-3+ intensity). The FOLR1 immunohistochemical slide was reviewed by 2 gynecologic pathologists and jointly recorded the following parameters: percent of cells staining at each level of intensity (0-3), range of staining intensity (0-3), percent of cells with membranous, cytoplasmic, or mixed staining, apical-only versus any membranous staining, percent of cells with complete membranous staining, and presence of abrupt transition (0 - no staining at all, juxtaposed to 2-3+ staining). One hundred twenty cases were reviewed and scored, 119 of which had original reported scores available for comparison. The staining intensity record was 0 in 9 (7.5%) of the cases, 0-1 in 3 (2.5%), 0-2 in 11 (9.2%), 0-3 in 88 (73.3%), 1-3 in 3 (2.5%), 2-3 in 4 (3.3%), and 3 in 2 (1.7%). The percent of positive cells at 2-3+ intensity as per quartile of cases was 12 (10.0%) cases with 0%, 14 (11.7%) cases with 1%-24%, 15 (12.5%) with 25%-49%, 28 (23.3%) with 50%-74%, and 51 (42.5%) with ≥75%. Using the original clinical reports, 67 (56.3%) of 119 cases were positive; 55 (67.9%) of 81 resection cases were positive, while 12 (31.6%) of 38 biopsy cases were positive. On re-review, 51 (42.5%) of all 120 cases were positive, with 41 (50%) of 82 resection cases being positive and 10 (26.3%) of 38 biopsy cases being positive. Overall, 18 (15.1%) of 119 cases had a clinically significant change (i.e. positive to negative or negative to positive). When broken down by type of specimen, 16 (19.8%) of 81 resection cases had a significant change, while only 2 (5.3%) of 38 biopsy cases had a significant change. Of the original scores taken from the report, the score was clearly stated in 117 reports, of which 47 cases were reported within 65% to 85% 2-3+ intensity. Seventeen of these 47 on rescoring were changed significantly as to a clinical action outcome; all 17 of these were changed from \"positive\" to \"negative.\" The 18th case, which was changed on rescoring, was the singular case that was changed from \"negative\" to \"positive,\" which was originally reported at","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669397","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":"An Endometrioid Carcinoma With an Adenoma Malignum-like Pattern of Invasion: New Insight into Molecular Features.","authors":"Meng Jia, Shi-Li Yu, Ping-Li Sun","doi":"10.1097/PGP.0000000000001205","DOIUrl":"10.1097/PGP.0000000000001205","url":null,"abstract":"<p><p>Adenoma malignum-like (AM-L) pattern is the least common invasion type in endometrioid carcinoma of the uterus and is characterized by a bland morphologic appearance in accordance with International Federation of Gynecology and Obstetrics Grade 1 endometrioid carcinoma. However, the biological behavior of the AM-L pattern is not always indolent, and it may present at an advanced tumor stage. Although several studies have described the clinicopathological features of this pattern, the molecular alterations have not yet been explored. Here, we report a case of endometrioid carcinoma with AM-L invasion pattern and analyzed its genetic alterations using a next-generation sequencing panel that included 571 genes. Six single nucleotide variations or insertion/deletion alterations were detected, including ARID1A exon 4 c.1848dup p.(S617Lfs*6), CTNNB1 exon 3 c.101G>A p.(G34E), PTEN exon 5 c.332G>A p.(W111*), PTEN exon 6 c.548dup p.(N184Efs*6), BCOR exon 10 c.4376A>G p.(N1459S), and MAPK4 exon 6 c.1594G>A p.(G532S). Neither POLE nor TP53 alteration was detected. No copy number variations or gene fusions were observed. The microsatellite status was stable, and the tumor mutational burden was low. The molecular features demonstrate the endometrioid nature of the AM-L pattern. Further studies are needed to explore the significance of these genetic alterations in this particular pattern and to clarify their oncogenic mechanism.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455895","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}