American Journal of Surgical Pathology最新文献

{"title":"Reporting Prostatic Atypical Intraductal Proliferations: Call for a Different Approach.","authors":"Murali Varma, Glen Kristiansen, Gladell P Paner, Ming Zhou","doi":"10.1097/PAS.0000000000002437","DOIUrl":"10.1097/PAS.0000000000002437","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"854"},"PeriodicalIF":4.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing the Diagnosis of Germ Cell Tumors in Patients Presenting With Metastatic Disease: A Series of 55 Cases Emphasizing Challenges Commonly Encountered in Core Biopsies.","authors":"Swati Bhardwaj, Mohammad Salimian, Andres Matoso, John Gross, Pedram Argani, Ezra Baraban","doi":"10.1097/PAS.0000000000002438","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002438","url":null,"abstract":"<p><p>Germ cell tumors (GCTs) are the most common nonhematopoietic malignancies in young men and typically present as primary testicular masses. However, in ∼12% of cases, GCTs manifest as metastatic disease without a known testicular primary, leading to significant diagnostic challenges. We retrospectively reviewed 55 cases of GCTs presenting as metastases, focusing on the morphologic and immunohistochemical pitfalls encountered in core biopsy specimens. Among a total of 55 cases, seminoma was the most common histologic subtype (61%), followed by embryonal carcinoma (14%) and mixed GCTs (13%), with a median age of 44 years (range: 21 to 87 y). The most frequently biopsied metastatic sites were the retroperitoneum (55%) and left neck (22%). Notably, only 7% of cases had an identified testicular mass at diagnosis. Only a third (32%) of cases were submitted with an initial diagnosis of GCT, while 10% were misclassified as non-GCT malignancies. Histologic features such as crush artifact (83%) and necrosis (54%) frequently obscured morphology, leading to extensive IHC panels. Cytokeratin expression (particularly CAM 5.2 and AE1/3) was identified in 51% of cases, often confounding the diagnosis. A greater number of IHC stains were performed at outside institutions compared with intramurally (9 vs. 4, P=0.0001). The use of OCT3/4 and CD30 proved crucial in diagnosing seminomas and embryonal carcinomas, respectively. In rare cases (n=4) with atypical histology, fluorescence in situ hybridization (FISH) for isochromosome 12p provided additional diagnostic support. Diagnosing metastatic germ cell tumors in needle biopsies remains a significant challenge, often compounded by lack of a known testicular mass, cytokeratin expression, and confounding histologic features such as crush artifact and necrosis that could be used as clues rather than impediments to diagnosis. Awareness of these findings, along with careful integration of clinical context, histology, and immunohistochemistry, is critical to avoid misdiagnosis, particularly in light of the exquisite chemosensitivity of GCTs. The use of reliable markers like OCT3/4 and CD30, coupled with a high index of suspicion in men with retroperitoneal or left neck masses, can aid in improving diagnostic accuracy.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Reply to \"Reporting Prostatic Atypical Intraductal Proliferations: Call for a Different Approach\".","authors":"Jane K Nguyen, Reza Alaghehbandan, Christopher J Weight, Zeyad Schwen, Christopher G Przybycin, Jonathan L Myles, Sean R Williamson, Jesse K McKenney","doi":"10.1097/PAS.0000000000002434","DOIUrl":"10.1097/PAS.0000000000002434","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"854-858"},"PeriodicalIF":4.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPNMB Expression Identifies FLCN-Associated Eosinophilic Renal Tumors With Heterogeneous Clinicopathologic Spectrum and Gene Expression Profiles.","authors":"Qiu-Yuan Xia, Xiao-Tong Wang, Hui-Zhi Zhang, Yao Fu, Ming Zhao, Sheng-Bing Ye, Rui Li, Xuan Wang, Ru-Song Zhang, Ru Fang, Qiu Rao","doi":"10.1097/PAS.0000000000002435","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002435","url":null,"abstract":"<p><p>FLCN-associated eosinophilic renal tumors mainly refer to hybrid oncocytic/chromophobe tumors (HOCT) and other oncocytic tumors related to Birt-Hogg-Dubé (BHD) syndrome, which can sometimes occur sporadically. Accurate diagnosis of FLCN-associated tumors is challenging due to their morphologic heterogeneity and the lack of reliable biomarkers. We evaluated the clinicopathologic and IHC profiles of 18 eosinophilic renal tumors with targeted DNA sequencing-confirmed FLCN mutations, including 10 typical HOCT and 8 unclassified tumors. Fourteen of these, plus 45 cases from the control group, were profiled transcriptionally by RNA-seq. Ten typical HOCT displayed consistent mosaic morphology and immunohistochemical patterns. Eight unclassified FLCN-mutated tumors exhibited diverse morphologies, including chromophobe renal cell carcinoma (ChRCC)-like, succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC)-like, and histiocyte-rich patterns, lacking obvious hybrid cellular components and typical immunohistochemical features. Despite this heterogeneity, glycoprotein non-metastatic melanoma protein B (GPNMB) was identified as a highly sensitive biomarker for FLCN-mutated tumors, showing strong and diffuse positivity in both typical HOCT, unclassified FLCN-mutated tumors, and in the oncocytosis surrounding the tumors. RNA sequencing revealed that typical HOCT formed a unique gene expression cluster, distinct from recognized renal tumor types. Some unclassified FLCN-mutated tumors were grouped with HOCT, while others remained unclassified among known kidney tumors, existing independently. This study expanded the morphologic spectrum of FLCN-mutated renal tumors and highlighted GPNMB as a valuable diagnostic marker for both typical and unclassified FLCN-mutated tumors. GPNMB should be utilized to screen eosinophilic renal tumors that cannot be classified, aiding in the precise diagnosis and management of BHD or sporadic FLCN mutation-related patients.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dublin International Society of Urological Pathology (ISUP) Consensus Conference on Best Practice Recommendations on the Pathology of Urachal Neoplasms.","authors":"Henning Reis, Hikmat Al-Ahmadie, Nadine T Gaisa, Antonio Lopez-Beltran, Fiona Maclean, Toyonori Tsuzuki, Isabela Werneck da Cunha, Mahul B Amin, Jonathan Aning, Manju Aron, Daniel Athanazio, Richard M Bambury, Liang Cheng, Anuradha Gopalan, Christian Gulmann, Charles C Guo, Carole Harris, Gopa Iyer, Rafael E Jimenez, Masahiro Jinzaki, Eiji Kikuchi, Priti Lal, Kosuke Miyai, George J Netto, Chin-Chen Pan, Valeria Panebianco, Bas Wg van Rhijn, Arlene Siefker-Radtke, Steven C Smith, Tibor Szarvas, Sara E Wobker, Glen Kristiansen, Gladell P Paner","doi":"10.1097/PAS.0000000000002416","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002416","url":null,"abstract":"<p><p>This manuscript summarizes the first part of the proceedings of the 2023 Dublin ISUP Consensus Conference encompassing the best practice recommendations on the pathology of neoplasms of urachal origin. The rationale for convening this consensus conference was the lack of structured and consented histopathologic recommendations in these rare tumors. Consensus among the meeting participants (n=80) was reached on the following statements: (1) combination of gross, histologic, clinical and imaging findings with exclusion of secondary tumor metastasis are to be used in the diagnosis of urachal carcinoma; (2) the 2022 World Health Organization (WHO) separate criteria for the diagnosis of urachal adenocarcinoma and for nonglandular carcinoma should be applied; (3) specific elements are to be evaluated and recorded in the gross examination of resection specimens containing urachal tumors; (4) sampling considerations for resection specimens containing urachal tumors are advised; (5) participants are against using 5% or 10% cutoff for the extent of intraepithelial carcinoma in urachal mucinous cystic tumor of low malignant potential; (6) use of immunohistochemical markers for the differential diagnosis of urachal adenocarcinomas in transurethral resection (TUR) specimen is considered optional; (7) similar tumor classificatory (nosology) rules for carcinomas arising from bladder mucosa (eg, urothelial carcinoma, squamous cell carcinoma, and neuroendocrine carcinoma) should be applied for nonglandular urachal carcinomas; (8) a new staging approach other than the previously proposed systems should be designed for urachal carcinoma; (9) a system modifying the current Tumor-Node-Metastasis (TNM)/American Joint Committee on Cancer (AJCC) staging system for urinary bladder cancer is considered appropriate for a study in urachal carcinoma; and (10) several histologic elements are to be reported when diagnosing urachal carcinoma in TUR and resection specimens. This report from the Dublin ISUP consensus conference will serve as a practice recommendation for pathologists and as a guide for future standardized reporting protocols and research regarding urachal tumors. In addition, an international database for urachal cancers under the guidance of ISUP is being planned to be established to address pertinent issues in the pathology of urachal cancers.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144232920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathologic Grading of Residual Tumor Predicts Survival of Intrahepatic Cholangiocarcinoma Patients Treated With Neoadjuvant Therapy: Major Pathologic Response and Its Clinical Significance.","authors":"Gaohua Wu, Xiufen Chen, Rongkui Luo, Ye Xin Koh, Tony Kiat Hon Lim, Valerie Chew, Jian Zhou, Jia Fan, Qiang Gao, Kai Zhu, Ruoyu Shi","doi":"10.1097/PAS.0000000000002359","DOIUrl":"10.1097/PAS.0000000000002359","url":null,"abstract":"<p><p>Neoadjuvant therapy (NAT) is increasingly used to treat patients with initially unresectable intrahepatic cholangiocarcinoma (iCCA). A histopathologic grading system for residual tumors that can predict patient survival is lacking in the literature. This retrospective study enrolled 151 iCCA patients who received NAT. The percentage of residual viable tumor (%RVT) extent was calculated by RVT surface area/total tumor bed area ×100 and scored in 5% increments. Kaplan-Meier and Cox regression analyses were used to investigate its correlations with recurrence-free survival (RFS) and overall survival (OS). Tumor regression grading by the College of American Pathologists (CAP) and MD Anderson (MDA) methodologies were also validated. A 10% RVT-based tumor regression score (TRS) showed a significant correlation with both OS and RFS. TRS and major pathologic response (mPR) were therefore defined as follows: TRS 1/mPR, tumor with 0 to 10% RVT; TRS 2, more than 10% RVT. Patients graded as TRS 1/mPR had superior OS ( P =0.006) and RFS ( P <0.001) compared with those with TRS 2 in univariate analysis. In a multivariate analysis including ypTNM stages, lymphovascular invasion, and perineural invasion, TRS 1/mPR was also found to be an independent prognostic factor for both OS (hazard ratio [HR]: 0.226; 95% CI: 0.053-0.966, P =0.045) and RFS (HR: 0.474; 95% CI: 0.231-0.974, P =0.042). As for the CAP and MDA grading methodologies, they were found to correlate with RFS (CAP: P =0.002; MDA: P =0.001), but not with OS (CAP: P =0.181; MDA: P =0.09). Our study revealed that a TRS of ≤10% RVT significantly correlates with longer OS and RFS and can be suggested as an mPR in iCCA. This indicator is easily applicable, prognostically relevant, and could be further validated in future prospective clinical trials.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"578-587"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding Insights Into PRAME Expression in Merkel Cell Carcinoma.","authors":"Jesús Machuca-Aguado, Rosa Rendón-García, Juan José Ríos-Martín","doi":"10.1097/PAS.0000000000002346","DOIUrl":"10.1097/PAS.0000000000002346","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"635-637"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant Giant Cell Tumor of Bone: A Clinicopathologic Series of 28 Cases Highlighting Genetic Differences Compared With Conventional, Atypical, and Metastasizing Conventional Tumors.","authors":"David J Papke, S Krisztian Kovacs, Igor Odintsov, Jason L Hornick, Kevin A Raskin, Erik T Newman, Santiago Lozano-Calderón, Ivan Chebib, Yin P Hung, G Petur Nielsen","doi":"10.1097/PAS.0000000000002387","DOIUrl":"10.1097/PAS.0000000000002387","url":null,"abstract":"<p><p>Giant cell tumors of bone are locally aggressive, frequently harbor H3F3A p.G34W mutations, and rarely undergo malignant transformation. The pathogenesis of malignant transformation remains incompletely characterized. Herein, we present 28 malignant giant cell tumors of bone from 14 males and 14 females, aged 16 to 65 (median 39) years. Primary sites included long bones (n=20), pelvis (n=3), vertebrae (n=2), and rarely rib, phalanx, and cuneiform (n=1 each). Sixteen (62%) of 26 tumors with available history represented malignant transformation or recurrence of conventional giant cell tumors of bone, at intervals of 1.3 to 35 (median 7.3) years before malignant transformation. Eight of 15 patients with available treatment history received denosumab before a diagnosis of malignancy. Ten (38%) of 26 tumors with available history likely arose de novo, including 7 with conventional areas and 3 H3F3A -mutant sarcomas lacking conventional giant cell tumor of bone. Of 28 malignant giant cell tumors of bone, 18 (64%) and 10 (36%) harbored osteoblastic and chondroblastic elements, respectively. Among 23 tumors with available genetic testing or surrogate immunohistochemistry, 17 (74%) were p.G34W-mutant, whereas other tumors carried H3F3A p.G34L (n=2), p.G34V (n=2), and p.G34R (n=1) alterations; 1 tumor harbored H3F3B p.K116E and p.R117S in cis. Seven (70%) of 10 malignant giant cell tumors of bone showed complex copy number alterations by single nucleotide polymorphism (SNP) array, DNA next-generation sequencing (NGS), and/or karyotype analysis. In contrast, complex chromosomal alterations were lacking in 32 conventional giant cell tumors of bone tested (24 by karyotype, 7 by SNP array, 1 by DNA NGS), 3 atypical giant cell tumors of bone with isolated marked nuclear atypia (2 by karyotype, 1 by SNP array) and 3 metastasizing conventional giant cell tumors of bone (2 by DNA NGS, 1 by karyotype). Clinical follow-up was available for 20 patients (71%), and one additional patient had metastases at presentation. Overall, 14 of 21 patients (67%) developed metastases, and 10 of 20 patients with follow-up (50%) died of disease at 2 months to 9.6 years (median 7 mo). Most patients were treated with chemotherapy; 1 patient (PD-L1 TPS >95%) was treated with pembrolizumab, with complete clinical response of metastatic disease at 2.5 years. In conclusion, malignant giant cell tumors of bone typically arise from long bones, harbor osteosarcomatous and/or chondrosarcomatous differentiation, and show significant risk for distant metastasis and demise. Our data suggest that copy number analysis may be useful in distinguishing malignant giant cell tumors of bone from their conventional, atypical, and metastasizing conventional counterparts.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"539-553"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Endometrial Gastric (Gastrointestinal)-type Mucinous Adenocarcinoma: A Detailed Clinicopathologic and Molecular Analysis of 27 Cases.","authors":"Harsimar Kaur, Lawrence Hsu Lin, David L Kolin, Andre Pinto, Carlos Parra-Herran, Mark Catherwood, Koen Van de Vijver, Natalia Buza, W Glenn McCluggage, Marisa R Nucci","doi":"10.1097/PAS.0000000000002382","DOIUrl":"10.1097/PAS.0000000000002382","url":null,"abstract":"<p><p>Endometrial gastric (gastrointestinal)-type mucinous adenocarcinoma (EmGA) is rare and was introduced as a new entity in the latest World Health Organization (WHO) classification of female genital tumors. Herein, we report a detailed clinicopathologic, immunohistochemical, and molecular study of 27 EmGA, the largest published series to date. The cohort consisted of 27 patients (median age 69 y; range 42 to 87 years). Histologically all cases showed gastric/gastrointestinal differentiation with foamy apical cytoplasm with distinct cell borders (n=21), goblet cells (n=9), signet ring cells (n=4), and Paneth cells (n=1). Using FIGO grading, 5 were grade 1, 14 grade 2, and 8 grade 3. Tumors were positive for MUC6 (10/21), CK7 (22/24), CK20 (16/24), CDX2 (24/26), and Claudin 18 (9/12). In all, 12/27 exhibited aberrant p53 expression and 3/26 showed MLH1 and PMS2 loss, including 2 with confirmed MLH1 gene promoter methylation. Next-generation sequencing showed pathogenic variants in TP53 (13/20), KRAS (7/20), PIK3CA (5/20), BRCA2 (4/20), SMAD4 (3/20), and POLE (1/20). Using TCGA classification (based on cases with available molecular results), 1/20 was POLE mutated, 2/20 were mismatch repair deficient (MMRd), 4/20 were no specific molecular profile (NSMP), and 13/20 were TP53 abnormal. FIGO stage (2009 staging system) ranged from IA to IVB. Outcome data (21 patients; follow-up of 2 to 77 mo) showed that 2 patients died of disease at 14 and 46 months after diagnosis, 1 patient died from other causes at 28 months, 8 were alive with disease, and 10 were alive with no evidence of disease. Like the cervical counterpart, primary EmGA has a distinctive morphologic appearance, harbors frequent TP53 mutations, and can be associated with adverse outcomes despite low-grade morphology and/or low-stage at presentation. They may be represented in all 4 TCGA molecular groups.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"564-577"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Molecular-genetic Spectrum of Canalicular Adenoma-like Subtype of Pleomorphic Adenoma of Salivary Glands.","authors":"Natálie Klubíčková, Frederica Loghides, Mari F C M van den Hout, Valérie Costes-Martineau, Gerardo Ferrara, Miguel Rito, Veronika Hájková, Petr Grossmann, Petr Šteiner, Inka Kovářová, Michal Michal, Ilmo Leivo, Alena Skálová","doi":"10.1097/PAS.0000000000002377","DOIUrl":"10.1097/PAS.0000000000002377","url":null,"abstract":"<p><p>Canalicular tumors of the salivary glands have recently emerged as an entity characterized by distinct morphology and recurrent HMGA2 gene rearrangement. In this study, we analyzed 40 cases intending to elucidate their features further. The monophasic or biphasic tumors exhibited a growth pattern of interconnected anastomosing trabeculae and canaliculi, accompanied by a classical pleomorphic adenoma in one-third of the cases. Invasive growth into surrounding adipose tissue was revealed in one case which was, therefore, diagnosed as epithelial-myoepithelial carcinoma. Although the tumor cells uniformly expressed HMGA2 protein in all cases, cytokeratin 7, S100 protein, and SOX10 displayed either diffuse positivity or highlighted the luminal and abluminal cell populations, respectively. Areas with morphological oncocytoid change and AR-immunopositivity of luminal cells were seen in 13/14 (93%) of tested biphasic cases. HMGA2 rearrangement was detected by RNA-sequencing in 30 cases. The most common alteration was an HMGA1::WIF1 fusion, but several novel or rare fusion partners were identified, including ARID2 , FHIT , MSRB3 and its antisense variant MSRB3-AS1 , IFNG-AS1 , and the long intergenic region LINC02389 . In addition, FISH revealed HGMA2 break-apart in the remaining 10 cases where targeted sequencing failed to detect any alteration or where RNA sequencing could not be performed. Notably, the loss of the 3'-untranslated region of HMGA2 emerges as the common denominator for the described rearrangements, possibly disrupting its negative regulation by small regulatory RNAs. Awareness of this lesion ensures appropriate diagnosis and clinical management, especially with regard to the possibility of malignant transformation described in this and previous studies.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"554-563"},"PeriodicalIF":4.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}