International Journal of Gynecological Pathology最新文献

{"title":"Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations.","authors":"Padmini A Manrai, Austin McHenry, Tong Sun, Alessandro D Santin, Elena Ratner, Douglas I Lin, Julia A Elvin, Pei Hui, Natalia Buza","doi":"10.1097/PGP.0000000000001050","DOIUrl":"10.1097/PGP.0000000000001050","url":null,"abstract":"<p><p>Targeted anti-HER2 therapy has been recently added to the standard treatment recommendations in endometrial serous carcinoma. Current eligibility requires testing for HER2 overexpression and/or gene amplification by immunohistochemistry and by fluorescence in situ hybridization. However, clinical trials have also demonstrated the efficacy of anti-HER2 drugs against activating ERBB2/HER2 mutations in a variety of solid tumor types, and fam-trastuzumab deruxtecan is now approved by the US Food and Drug Administration for HER2 -mutant non-small cell lung cancer. This study aimed at evaluating the detailed clinical, histomorphological, immunohistochemical, and molecular characteristics of gynecologic malignancies with ERBB2/HER2 mutations. We identified 16 tumors with 19 ERBB2/HER2 mutations in our departmental archives: 11 endometrial primaries, 2 endocervical adenocarcinomas, 1 ovarian mucinous adenocarcinoma, 1 tubo-ovarian undifferentiated carcinoma, and 1 high-grade endometrioid adenocarcinoma of Mullerian origin. ERBB2/HER2 mutations most often involved the tyrosine kinase domain (52.6%), and the most frequent specific mutation was R678Q (31.6%), involving the juxtamembrane domain. More than half (54.5%) of endometrial carcinomas and half of all tumors were MMR-deficient, resulting from MSH6 loss in all but 2 tumors. None of the tumors (0%) were POLE- mutated, while 18.8% were TP53 -mutated. HER2 IHC was negative (score 0 or 1+) in 12 tumors (67%) and equivocal (score 2+) in 4 tumors (33%), whereas none of the tumors were scored as HER2 3+. Score 2+ was associated with R678Q, L755S, I767M mutations, and ERBB2/HER2 rearrangement with a breakpoint in exon 23. Concurrent ERBB2/HER2 amplification was identified in 2 endometrial carcinomas, with HER2/CEP17 ratios of 3.1 and 3.5. We also queried the cBioportal database, which revealed 70 ERBB2/HER2 -mutant gynecologic tumors with a total of 77 ERBB2/HER2 mutations, most often involving the active site of the tyrosine kinase domain (n=36; 46.8%), and the most common specific mutation was S310F (n=20; 26%), located in the extracellular domain. Our results provide important details regarding the clinicopathological and molecular associations of potentially actionable ERBB2/HER2 mutations in endometrial carcinoma and other gynecological cancer types and contribute to addressing clinical treatment needs and improving pathology testing recommendations in the future.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"144-154"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446137","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":"Comparison of PD-L1, VISTA, LAG-3, and GAL-3 Expressions and Their Relationships to Mismatch Repair Protein and p53 Expression in 529 Cases of Endometrial Carcinoma.","authors":"Dilara Irem Arslan-Kahraman, Betul Ogut, Mehmet Arda Inan, Ferah Kazanci, Mehmet Anil Onan, Mehmet Erdem, Ozlem Erdem","doi":"10.1097/PGP.0000000000001049","DOIUrl":"10.1097/PGP.0000000000001049","url":null,"abstract":"<p><p>The aim of this study is to evaluate the expressions of programmed death-ligand 1 (PD-L1), V-domain Ig suppressor of T-cell activation (VISTA), lymphocyte activation gene-3 (LAG-3), and galectin-3 (GAL-3), in mismatch repair-deficient (MMRd)/MMR-proficient and abnormal p53 expressing endometrial carcinomas and their relationship with clinical-histopathological features. Patients who underwent surgery for endometrial carcinoma between January 2008 and December 2018 were included in the study. Immunohistochemical analysis of MLH1, PMS2, MSH2, MSH6, p53, PD-L1, VISTA, LAG-3, and GAL-3 was performed on the tissue samples of microarray. A total of 529 patients were included. MMRd and p53-mutant tumors accounted for 31.5% and 11.5% of cases, respectively. PD-L1 and LAG-3 expressions in the MMRd and p53-mutant groups were higher than in the MMR-proficient group ( P < 0.001). GAL-3 expression in the MMR-proficient group was statistically higher than in the MMRd and p53-mutant groups ( P < 0.001). Mean age, grade, International Federation of Gynecology and Obstetrics stage, lymphovascular invasion, and lymph node metastasis were significantly higher in the p53-mutant group ( P < 0.001). In the group with PD-L1 expression, nonendometrioid histologic type, tumor grade, and lymphovascular invasion were significantly higher ( P < 0.001). Tumor grade, lymphovascular invasion, lymph node metastasis, and microcystic, elongated and fragmented pattern of invasion were significantly higher in the group with high VISTA expression ( P < 0.05). Tumor grade was significantly higher in the group with LAG-3 expression ( P < 0.001). Immunohistochemically determined subgroups and PD-L1, VISTA, LAG-3, and GAL-3 expression levels may be useful indicators of molecular features, and clinical outcomes also may have important implications for the development of targeted therapies in endometrial carcinoma.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"130-143"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446115","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":"Whole-exome Sequence Analysis of Gastric-type Adenocarcinoma of the Uterine Cervix and Adjacent Lobular Endocervical Glandular Hyperplasia in the Same Case.","authors":"Tsutomu Miyamoto, Koichi Ida, Yasuhiro Tanaka, Shiho Asaka, Tanri Shiozawa","doi":"10.1097/PGP.0000000000001052","DOIUrl":"10.1097/PGP.0000000000001052","url":null,"abstract":"<p><p>Lobular endocervical glandular hyperplasia (LEGH) may be a precursor lesion of gastric-type adenocarcinoma of the uterine cervix (GAS). However, the genetic mechanisms underlying its carcinogenesis remain unclear. To elucidate the oncogenic process from LEGH to GAS, we compared gene mutations in early-stage GAS and adjacent LEGH in the same case. Fresh-frozen tissue sections were obtained from a patient with Stage IB3 GAS and adjacent LEGH who had undergone hysterectomy. Using laser microdissection, we harvested the LEGH and GAS portions separately from these sections and extracted the genomic DNA. Somatic variant analysis using whole-exome sequencing used DNA from the normal myometrium as a reference sequence. Somatic variants involving amino acid substitutions were detected in 61 and 125 locations in LEGH and GAS, respectively. Seven variants were common in both lesions, of which the pathogenic variant was GNAS only (c.2531G>A, p.R844H), a mutation frequently reported in pancreatic and colorectal cancers. LEGH had no other pathogenic variants; another pathogenic variant in GAS was found only at the same amino acid site as GNAS (c.2530C>T, p.R844C). In the present case, LEGH and GAS shared the same pathogenic variant of GNAS , indicating that both lesions had a common origin. Furthermore, the current results showed that the second GNAS variant is associated with the progression of LEGH to GAS. Further studies are required to elucidate GAS's pathogenesis and biological characteristics.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":"125-129"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125674","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":"Sclerosis in Metastatic Uterine Tumor Resembling Ovarian Sex Cord Tumor: Diagnostic Dilemma Presented by Unusual Morphology.","authors":"Li Lei, Omonigho Aisagbonhi","doi":"10.1097/PGP.0000000000001098","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001098","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468171","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":"A Trichoadenoma/Trichoepithelioma/Trichoblastoma-like Lesion in the Uterine Cervix Focally Mimics an Adenoid Basal Tumor.","authors":"Sanika Satoskar, Timothy J Vanderkwaak, Jaroslaw Jedrych, Russell Vang, Deyin Xing","doi":"10.1097/PGP.0000000000001106","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001106","url":null,"abstract":"<p><p>The presence of ectodermal adnexal structures in the uterine cervix, including sebaceous glands, hair follicles, and sweat glands, has been well documented in the literature. In theory, there exists the possibility of developing cutaneous-type lesions from the ectopic ectodermal structures in this location. Here we report the first case of cervical hair follicle-derived proliferations reminiscent of trichoadenoma, trichoepithelioma, and trichoblastoma (TA/TE/TB) in a 52-year-old woman who underwent a prophylactic hysterectomy due to a germline microphthalmia-associated transcription factor (MITF) gene mutation. The lesion was an incidental finding in the cervix, exhibiting a spectrum of morphologic features ranging from germinative TB with basaloid cells, to TE with some degree of infundibulocystic differentiation, to well-differentiated TA. In some areas, hair follicle-like structures were associated with sebaceous glands, forming pilosebaceous units. The proliferations in the TB-like area resembled adenoid basal epithelioma/carcinoma; however, ancillary studies, particularly patchy p16 expression and non-detection of HPV, argued against this diagnosis. Similar to adenoid basal tumors, the TB-like lesion focally expressed NKX3.1, suggesting that it might be related to ectopic prostatic tissue or exhibit prostatic-lineage differentiation. While the theory of misplaced embryonal tissue, or an acquired metaplastic process, has been discussed, the histopathologic origin of these lesions remains largely unknown.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585723","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":"Molecular Classification of Endometrial Carcinoma: Insights From a Teaching Hospital.","authors":"Samah Saharti, Fadwa Altaf","doi":"10.1097/PGP.0000000000001096","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001096","url":null,"abstract":"<p><strong>Abstract: </strong>Endometrial carcinoma is a heterogeneous disease with distinct molecular subtypes that have varied prognosis and therapeutic implications. Since the development of molecular signatures of malignancy is prominent, we are trying to implement this development in our cases of previously diagnosed endometrial cancer. The aim was to determine the prevalence of specific molecular alterations and correlate the genetic profile with the pathologic features and clinical characteristics. We identified 100 cases of endometrial carcinoma, which were eventually classified using immunostains for mismatch repair (MMR) and p53 proteins, in addition to Sanger analysis for POLE gene (Ex, 9, 13, 14). Our findings showed a high prevalence of nonspecific molecular profile (NSMP) in 46 cases (46%), and MMR deficiency in 30 cases (30%). The worst prognosis was observed in the p53 mutant pattern expressed tumors. No statistical difference in pathologic characteristics was observed when the molecular classification was applied. Of note, mutual molecular grouping assignment appears to be present in 5 (5%) of cases of endometrial carcinoma. This is the first study conducted in Saudi Arabia that investigated the prevalence and implications of these molecular subtypes in endometrial carcinoma. The percentage of cases in our result is similar to what had been published globally.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468169","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":"Eosinophilic Salpingitis.","authors":"Badr AbdullGaffar, Amal Almulla","doi":"10.1097/PGP.0000000000001104","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001104","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468166","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":"Female Adnexal Tumor of Probable Wolffian Origin (FATWO): An Unusual Case With Development of Peritoneal Lesions After 3 Decades.","authors":"Manisha Goel, Elin Rønne, Ellen Veronika Vesterfjell, Guro Aune, Jennifer A Bennett","doi":"10.1097/PGP.0000000000001103","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001103","url":null,"abstract":"<p><p>Female adnexal tumor of presumed Wolffian origin (FATWO) is a rare gynecologic neoplasm favored to arise from mesonephric (Wolffian) remnants. Although most tumors are benign, rare recurrences have been reported. Herein, we present a case of a 65-year-old female with incidental peritoneal lesions detected on routine ultrasound that morphologically and immunohistochemically were diagnostic of FATWO. Review of her medical history uncovered a remote history (>30 years) of a para-ovarian cystectomy, which was punctured intraoperatively. Slide review confirmed the diagnosis of FATWO, thereby suggesting iatrogenic dissemination from the original procedure. This report highlights the importance of a thorough review of the medical record when encountering a nonprototypical location for a distinctive tumor. In addition, the slow-growing nature of these lesions, as well as the absence of atypical histologic features, further contributes to the hypothesis that the majority of FATWOs are benign.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585724","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":"The Role of hCG Expression in Endometrial Cancer Prognosis.","authors":"Varol Gülseren, Mehmet Dolanbay, Fulya Çağli, Mine Dağgez, Nahit Topaloğlu, Figen Öztürk, Bülent Özçelik, İbrahim Serdar Serin, Kemal Güngördük","doi":"10.1097/PGP.0000000000001102","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001102","url":null,"abstract":"<p><p>This study aims to investigate the expression pattern of human chorionic gonadotropin (hCG) in the tissue of endometrioid type endometrial cancer (EEC) using immunohistochemistry, and also to investigate the effect of hCG expression pattern on prognosis and survival in EEC. We evaluated patients who were operated between 2010 and 2020 in the obstetrics and gynecology clinic of our center due to EEC. In total, 194 women were determined to be in either the hCG-negative group (n=137) or the hCG-positive group (n=57). The detection rate of deep myometrial invasion (16.8% vs. 36.8%; P=0.002), lymphovascular space invasion (10.9% vs. 24.6%; P=0.015), and metastatic lymph node (6.7% vs. 21.8%; P= 0.003) in patients with hCG-positive staining were analyzed to be significantly higher. Five-year disease-free survival (DFS) (P= 0.015) and overall survival (OS) (P= 0.024) rates were found to be higher in the hCG-negative group. hCG expression was found to be an independent risk factor for recurrence, and DFS in grade I-II EEC was limited to the uterus and with superficial myometrial invasion (low risk). No independent risk factors for OS were analyzed. hCG positivity is a risk factor with poor prognostic factors in endometrial cancer. It was concluded that hCG expression in low-risk EEC is a valuable negative prognostic factor for recurrence and DFS.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046514","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":"The Morphologic and Molecular Heterogeneity of Fumarate Hydratase-deficient Leiomyomas: Integrative Molecular Profiling of Uterine Smooth Muscle Tumors With Histologic Feature Correlation.","authors":"Julianne M Szczepanski, David B Chapel, Tao Huang, Trinh Pham, Rahul Mannan, Rohit Mehra, Andrew P Sciallis, Scott Tomlins, Stephanie L Skala, Aaron M Udager","doi":"10.1097/PGP.0000000000001101","DOIUrl":"https://doi.org/10.1097/PGP.0000000000001101","url":null,"abstract":"<p><p>The morphologic features of uterine smooth muscle tumors (USMTs) are subject to interobserver variability and are complicated by consideration of features of fumarate hydratase deficiency (FHd) and other morphologic subtypes, with difficult cases occasionally diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP). We compare immunohistochemical findings and detailed morphologic analysis of 45 USMTs by 4 fellowship-trained gynecologic pathologists with comprehensive molecular analysis, focusing on FHd leiomyomas (n=15), compared to a variety of other USMTs with overlapping morphologic features, including 9 STUMPs, 8 usual-type leiomyomas (ULM), 11 apoplectic leiomyomas, and 2 leiomyomas with bizarre nuclei (LMBN). FHd leiomyomas, defined by immunohistochemical (IHC) loss of FH and/or 2SC accumulation, showed FH mutations and/or FH copy loss in all cases, with concurrent TP53 mutations in 2 tumors. Severe and/or symplastic-type cytologic atypia was seen more often in FHd leiomyomas with only FH copy loss (6/8, and 2/2 with concurrent TP53 mutations) compared to those with FH mutations (2/7) and typically showed increased genomic instability. This subset of FHd tumors often showed morphologic overlap with STUMPs and LMBN, but all cases of FHd tumors showed 2SC accumulation and/or FH loss by IHC. In conclusion, we highlight the importance of investigating USMTs with severe and/or symplastic-type cytologic atypia with FH and 2SC IHC, as many of these tumors are FH-deficient via focal deep deletion (2-copy loss) of the FH locus. In addition, we report the presence of concurrent TP53 mutations in FHd tumors with more severe cytologic atypia; further data about clinical outcomes for these tumors are needed.</p>","PeriodicalId":14001,"journal":{"name":"International Journal of Gynecological Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046506","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}