American Journal of Surgical Pathology最新文献

{"title":"Musculoskeletal Histopathology of Klippel-Trénaunay Syndrome: A Clinicopathologic Study of 21 Cases With Long-Term Orthopedic Follow-Up.","authors":"Aarti E Sharma, Igor Odintsov, Yin P Hung, Andrew L Folpe, Jason L Hornick, Edward F DiCarlo, Yaxia Zhang","doi":"10.1097/PAS.0000000000002627","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002627","url":null,"abstract":"<p><p>Klippel-Trénaunay syndrome (KTS) is a rare congenital vascular-overgrowth disorder within the broader spectrum of PIK3CA-related overgrowth syndromes. Although clinical, radiologic, and orthopedic manifestations are well described, the histologic spectrum of KTS-associated pathology remains under-characterized. Clinicopathologic findings from 21 patients with clinically established KTS were reviewed, including 18 with longitudinal clinical follow-up and 3 consultation cases of rare malignant mesenchymal neoplasms. Cases were identified from institutional pathology and clinical databases, and available hematoxylin and eosin-stained sections and ancillary studies were reviewed. The cohort included 11 males and 10 females. Among the 18 clinically followed patients, 12 had limb length discrepancy or asymmetric limb overgrowth, 9 had documented deep vascular malformations, 4 had intra-articular/synovial malformations, and 10 underwent initial orthopedic evaluation or intervention before age 18. Orthopedic morbidity clustered into mechanical overgrowth-related, vascular malformation-related, and soft tissue/wound-related complications. Histologic findings included superficial and/or deep slow-flow vascular malformations, ulceration and granulation tissue, hemosiderin-laden reactive synovium, and destructive hemorrhagic arthropathy. Intra-articular disease recapitulated a hemophilic arthropathy-like pattern, with hemosiderotic synovitis, papillary synovial hyperplasia, and progressive joint destruction with loss of articular cartilage, exposed subchondral bone destruction and remodeling, all attributable to long-standing intra-articular hemorrhage. Three consultation cases showed malignant mesenchymal neoplasia, including 2 angiosarcomas. Recognition of these patterns is important for pathologists evaluating specimens from patients with known or suspected KTS, particularly when findings mimic hemophilic arthropathy, diffuse-type tenosynovial giant cell tumor, nonsyndromic vascular malformation, and/or end-stage destructive arthropathy.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164078","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":"Recurrent PDGFRB-Mutations in the Epithelioid Variant of Fibrous Papules.","authors":"Thibault Kervarrec, Ziyad Alsugair, Nicolas Macagno, Brice Thamphya, Franck Tirode, Aurélie Houlier, Sandrine Paindavoine, Alexandra Meurgey, Arnaud De la Fouchardière, Eric Frouin, Eduardo Calonje, Sylvie Fraitag, John Hanna, Anne Champagnac, Aline Baltres, Daniel Pissaloux, Marie Karanian","doi":"10.1097/PAS.0000000000002635","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002635","url":null,"abstract":"<p><p>Fibrous papule (FP) is a common benign dermal mesenchymal lesion presenting as a solitary, dome-shaped papule mostly located on the nose. The morphologic spectrum is broad, and a number of variants have been described, including hypercellular, clear cell, pigmented, pleomorphic, granular, inflammatory, and epithelioid. The latter is very rare. In the current study, we present a comprehensive morphologic, immunohistochemical, and molecular characterization of 16 additional cases of epithelioid fibrous papule (EFP). The cohort included 7 females and 9 males, with a median age at diagnosis of 42 years (range: 7 to 83 y). Anatomic distribution showed predilection for the head and neck region (n=14). Microscopically, all lesions presented as a dome-shaped, well-circumscribed dermal proliferation composed of epithelioid and spindle-shaped cells arranged in nests or individual units and embedded in an abundant eosinophilic stroma. Neoplastic cells displayed uniform morphology with abundant pale cytoplasm and medium-sized nuclei. Focal immunoreactivity for CD68 and CD163 was detected in 7 and 5 cases, respectively. Molecular analysis revealed pathogenic alterations in the PDGFRB gene in all 16 cases, including missense mutations p.Y562C (n=5), p.N666K (n=5), p.N666H (n=1), p.P584L (n=1), p.R562C (n=1), and p.V568A (n=1). One case each exhibited an in-frame deletion, p.R561_R565del and p.W566_S574delinsC, respectively. In summary, epithelioid fibrous papule is characterised by distinct morphologic features and harbours recurrent, activating PDGFRB mutations.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163685","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":"Vulvovaginal Epithelioid Mesenchymal Neoplasm With \"Deciduoid\" Morphology: Report of a Novel Entity Frequently Associated With Inactivating Germline BAP1 Variants.","authors":"András Rókusz, Ayoma D Attygalle, Zsombor Melegh, Bálint Scheich, Bálint András Deák, Annett Hölsken, Ildikó Vereczkey, Katalin Dezső, Abbas Agaimy, W Glenn McCluggage","doi":"10.1097/PAS.0000000000002633","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002633","url":null,"abstract":"<p><p>A wide variety of mesenchymal lesions arise in the vulvovaginal region, some relatively site-specific. We report 4 cases of a novel vulvovaginal mesenchymal lesion, which we term vulvovaginal epithelioid mesenchymal neoplasm with \"deciduoid\" morphology, reflecting the predominant morphologic feature of epithelioid cells with a granular glassy \"deciduoid\" appearance. The tumors arose in women aged 34 to 48 years and involved the vagina (2 cases) or the vulval Bartholin's gland region (2 cases). The size ranged from 25 to 55 mm and they were solid and well-circumscribed. The tumors were composed of epithelioid and lesser numbers of spindle-shaped cells with abundant granular glassy eosinophilic cytoplasm, imparting a \"deciduoid\" morphology; there was prominent vascularity and a mild lymphoid infiltrate. Immunohistochemistry showed consistent diffuse estrogen receptor, progesterone receptor, CD63, and vimentin positivity with no other consistent immunophenotype. Two of the tumors showed immunohistochemical BAP1 loss and exhibited inactivating germline BAP1 variants (BAP1 tumor predisposition syndrome). On molecular testing, all tumors showed copy number loss of genes in 14q and/or 17q regions. Alterations of genes involved in the MAPK pathway were also present in all cases (including NF1 loss, a likely pathogenic variant in FLT3, and variants of unknown significance in FLT3, BMPR1A, and RUNX1). One of the cases harbored a novel FBXL20::MSI2 fusion. On follow-up (8 mo to 15 y), none of the tumors recurred. In reporting this novel neoplasm, we describe in detail the morphologic, immunohistochemical, and molecular features, discuss the differential diagnosis and histogenesis, and establish this novel entity as part of the BAP1 tumor predisposition syndrome.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172058","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":"Further Molecular Evidence Supporting the Neoplastic Nature of the Leydig Cells in Ovarian Sertoli-Leydig Cell Tumors.","authors":"Clemence Scard, Alexis Trecourt, Francoise Descotes, Marc Barritault, Mojgan Devouassoux-Shisheboran","doi":"10.1097/PAS.0000000000002634","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002634","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163693","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":"Clinicopathological Characteristics of Merkel Cell Carcinoma in Younger Patients: A Retrospective Study.","authors":"Jawad Aqeel, Joseph S Durgin, Jasmine S Saleh, Paul W Harms, Elisabeth A Pedersen, Rajiv M Patel, Scott C Bresler","doi":"10.1097/PAS.0000000000002628","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002628","url":null,"abstract":"<p><p>Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine carcinoma that predominantly affects older adults. MCC arising in younger patients is exceedingly rare, and its clinicopathologic features remain poorly described. We retrospectively reviewed clinical records, histopathology, and outcomes of patients aged 18 to 50 years diagnosed with MCC at a single tertiary care center between 2009 and 2025. A total of 13 patients were identified with a median age of 40 years (range: 18 to 50 y); 61.5% were female. Of 11 patients with available data, 36.4% had pre-existing immune suppression. Tumors arose most commonly on the extremities (46.2%), followed by the head and neck (23.1%), trunk (15.4%), and unknown primary (15.4%). The most common growth pattern was nodular (63.6%), followed by infiltrative (27.3%). Median Breslow depth was 10.5 mm and median mitotic rate was 46/mm². Immunohistochemical staining was consistent with MCC in all cases. Merkel cell polyomavirus was detected by large T antigen chromogenic in situ hybridization and/or immunohistochemistry in 62.5% of assessable cases (5/8). Lymph node metastases were present at presentation in 60.0% of patients, and distant metastases developed in 54.5%. Kaplan-Meier estimated overall survival was 74.1% at 2 years and 59.3% at 5 years. In this single-institution cohort, early-onset MCC was associated with elevated rates of immune suppression and a substantial burden of regional and distant metastatic disease, highlighting clinicopathologic distinctions from predominantly older historical MCC populations.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134919","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":"Diagnostic Utility of USP6 RNA Chromogenic In Situ Hybridization in the Differential Diagnosis of Nodular Fasciitis and Aneurysmal Bone Cyst.","authors":"Margarita Muñoz de Toro, Jennifer Tan, Phoebe L Li, Xiaohua Qian, Gregory R Bean, David I Suster, Gregory W Charville","doi":"10.1097/PAS.0000000000002626","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002626","url":null,"abstract":"<p><p>Recurrent USP6 gene rearrangements underlie a subset of mesenchymal neoplasms, including nodular fasciitis and aneurysmal bone cyst. These rearrangements place USP6 under the regulatory control of another gene's constitutively active promoter, resulting in USP6 overexpression. Recently, it has been demonstrated in a limited number of cases that detection of USP6 overexpression by RNA chromogenic in situ hybridization (CISH) can serve as a surrogate marker for USP6-rearranged tumors. To further assess the diagnostic utility of USP6 RNA CISH, we evaluated its application in 1210 bone and soft tissue tumors, using a combination of whole tissue sections and tissue microarrays. USP6 overexpression, defined as RNA CISH staining in >1% of lesional cells, was observed in 92% (36/39) of nodular fasciitis cases and in 85% (17/20) of primary aneurysmal bone cysts. All examples of nodular fasciitis (15/15) and primary aneurysmal bone cyst (8/8) with USP6 fusion confirmed by molecular genetic testing were positive for overexpression. Other tumors staining positive for USP6 included cellular fibroma of tendon sheath (3/3, 100%) and myositis ossificans (3/3, 100%). Although USP6 RNA CISH proved to be highly specific for USP6-rearranged lesions when assessed in 1145 negative control cases reflecting 53 other tumor types, positivity was rarely seen in isolated cases of angiosarcoma (1/16, 6%), malignant peripheral nerve sheath tumor (1/80, 1%), and carcinosarcoma (1/7, 14%). Taken together, these findings indicate that USP6 RNA CISH represents a useful diagnostic tool; careful interpretation remains critical to its successful implementation, given that isolated examples of non-USP6-rearranged tumors rarely stain positive.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134903","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":"Clinicopathological Characterization of Digital Papillary Adenocarcinoma With Emphasis on Low-risk Human Papillomavirus In Situ Hybridization and BRAF-VE1 Immunohistochemistry.","authors":"Daniel S Alt, Steven M Hrycaj, Simon J Warren, Jaclyn Plotzke, May P Chan, Klaus J Busam, Thomas Brenn, Katharina Wiedemeyer","doi":"10.1097/PAS.0000000000002588","DOIUrl":"10.1097/PAS.0000000000002588","url":null,"abstract":"<p><p>Digital papillary adenocarcinoma (DPA) is a rare malignant sweat gland tumor affecting fingers and toes most commonly. Human papillomavirus type 42 (HPV42), a low-risk HPV type, is an important diagnostic criterion. No uniform mutational signature has been detected in DPA except for BRAF mutations encoding p.V600E in small case series and in single case reports. The aim of this study was to add to the data on the prevalence of low-risk HPV/HPV42 detection and BRAF-VE1 immunohistochemistry in digital papillary adenocarcinoma. H and E-stained sections and immunohistochemistry for S100, SOX10, SMA, p63/p40, CK7, CK5/6, YAP1, and BRAF-VE1 were reviewed, and in situ hybridization (ISH) for low-risk HPV (including HPV42) or specifically HPV42 was performed. Clinical follow-up was obtained from patient records. Twenty-eight tumors were included and presented on the fingers (23), feet (4), and vulva (1) with a median size of 1.5 cm. The patient age ranged from 11 to 88 years (median: 49.5; M:F=6:1). Histopathologically, digital papillary adenocarcinomas presented as multinodular, poorly- or well-circumscribed tumors in the dermis and subcutaneous tissue, with solid, cystic, and papillary growth patterns. Cytologic atypia was mild to moderate. All tumors were positive for low-risk HPV and/or HPV42. BRAF-VE1 immunohistochemistry was negative in all tumors. Two patients developed distant metastases; all other patients were alive without recurrence (median follow-up: 46.5 mo, range: 5 to 192 mo). In conclusion, this study does not support the pathogenic role of BRAF p.V600E in digital papillary adenocarcinoma but confirms low-risk HPV/HPV42 infection as the only driver in all tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1166-1173"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434745","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":"Giant Cell Urothelial Carcinoma: Morphometric Insights and Associations With Aggressive Clinical Features.","authors":"Huili Li, Amir Akbari, Matthew Schuler, Rodrigo Salgado Esteves, Kenneth J Pienta, Burles A Johnson Iii, Ezra Baraban, Andres Matoso","doi":"10.1097/PAS.0000000000002576","DOIUrl":"10.1097/PAS.0000000000002576","url":null,"abstract":"<p><p>Giant cell urothelial carcinoma (GCUC) is an exceedingly rare histologic subtype with 50+ reported cases. To date, 3 case series have been reported. Scant chemotherapy and immunotherapy responses were reported with variable results. We report the largest GCUC series, including 27 GCUC and 27 matched control urothelial carcinoma (CoUC) patients, most (>90%) of whom had more than 5 years of follow-up, including neoadjuvant and adjuvant therapy status. We further characterized the nuclear size ratio of giant tumor cells to background tumor cells and analyzed urothelial differentiation markers (GATA3, CK5/6), p53, tumor-infiltrating lymphocytes (CD19 and CD3), and therapeutic targets (TROP2, Nectin4, PDL1, and HER2). Morphometric analysis of giant tumor cells demonstrated that they were, on average, 12 times larger than surrounding nongiant tumor cells. GCUC showed many histologic and immunophenotypic features similar to CoUC. GCUC was enriched for higher stages (T3/4 and metastatic disease) than CoUC and showed a trend toward worse OS than conventional urothelial carcinoma, but was similar to urothelial carcinoma with variant histology. GCUC included 3 low-stage (T1/2) patients, who had significantly worse OS than low-stage CoUC, suggesting early extensive workup and oncologic intervention. Chemotherapy slightly improved OS in both GCUC and CoUC patients without statistical significance. Compared with CoUC, GCUC appeared to have more tumor-infiltrating T cells, but without statistical significance. There were no expression differences in TROP2, Nectin4, PDL1, and HER2. However, a subset of GCUC patients might benefit from target therapies (PDL1, Nectin4), warranting more cohort studies.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1184-1194"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196978","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":"Next-Generation Sequencing of Multivergent Morphologies in Colorectal Carcinomas Identifies Unique Targetable Alterations.","authors":"Brent K Larson, Elias Makhoul, Alexandra Gangi, Jun Gong, Maha Guindi, Andrew Hendifar, Danielle Hutchings, Michael Kozak, Keith Lai, Arsen Osipov, Eric Vail, Kevin M Waters","doi":"10.1097/PAS.0000000000002582","DOIUrl":"10.1097/PAS.0000000000002582","url":null,"abstract":"<p><p>Typically, colorectal carcinoma (CRC) is morphologically relatively homogeneous. Uncommon morphologic patterns may be enriched for rare molecular drivers. This study examined the clinicopathologic characteristics of CRC with multivergent morphology (defined as 2 discrete nonconventional morphologic cytoarchitectural patterns) and whether potentially targetable molecular alterations could be identified by interrogating 2 distinct morphologic areas. Evaluation of representative sections from 213 consecutive CRC resections identified 11 with multivergent morphology. Next-generation sequencing (NGS) was performed on 2 morphologically discrete areas from multivergent cases. Compared with the remaining 202 CRCs, multivergent CRCs were larger (mean: 6.4 vs. 4.4 cm; P =0.038), had a higher T stage (100% vs. 78.2% ≥T3; P =5.0×10 -4 ), a higher N stage (90.9% vs. 42.1% ≥N1, P =7.0×10 -4 ), and more frequently had distant metastasis (36.4% vs. 10.9%; P =0.041). Multivergent CRCs were more likely to be mismatch repair (MMR)-deficient (45.5% vs. 15.8%; P =0.034) and to have an atypical MMR pattern (27.3% vs. 0.5%; P =1.7×10 -7 ). Both areas of multivergent CRC often harbored molecular alterations associated with eligibility for Food and Drug Administration (FDA)-approved therapies (63.6%; 7/11) and clinical trials (72.7%; 8/11). Not uncommonly, a molecular alteration associated with eligibility for FDA-approved therapy (45.5%; 5/11) and clinical trials (72.7%; 8/11) was isolated to only one of the sequenced areas. Multivergent CRC is rare but associated with targetable molecular alterations. NGS of multiple areas with different morphologies may help identify potential therapeutic targets. While most cases have recognizable driver alterations, the less common, targetable alterations identified in these cases could open additional trial options for salvage therapy.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1195-1204"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576892","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":"DEK::AFF2 Fusion Sinonasal Tract and Skull Base Nonkeratinizing Squamous Cell Carcinoma : An Expanded Single‑Center Series of 50 Cases Extending the Clinicopathologic Spectrum.","authors":"Changwen Zhai, Hongqin Liu, Jiahao Zhang, Shuyi Wang, Lan Lin","doi":"10.1097/PAS.0000000000002590","DOIUrl":"10.1097/PAS.0000000000002590","url":null,"abstract":"<p><p>DEK::AFF2 fusion‑positive sinonasal tract and skull base nonkeratinizing squamous cell carcinoma ( DEK::AFF2 SCC) is a rare and recently recognized entity; however, its clinicopathologic and demographic features remain incompletely defined. We aimed to further refine and supplement the characterization of this entity. We retrieved institutional pathology records and identified 50 DEK::AFF2 SCCs at a single institution (2009-2025). The cohort included 20 males and 30 females aged 18-74 years (median, 50.5 y). The most common presenting symptoms were nasal obstruction and epistaxis. The predominant primary site was the paranasal sinus, followed by the nasal cavity and nasopharynx. Histologically, most tumors exhibit mixed exophytic and endophytic growth patterns, complex anastomosing trabeculae, monotonous cytomorphology, acantholytic changes, and tumor-infiltrating neutrophils. High-grade histologic features and infiltration were observed in 24% of the cases; 6% presented features resembling mucoepidermoid carcinoma, and 4% presented an ameloblastoma-like appearance. Immunohistochemically, more than 70% of the cases coexpressed squamous and glandular markers. The recurrence rate was 59.2%, the lymph node metastasis rate was 24.5%, the distant metastasis rate was 20.4%, and the disease‑related mortality rate was 24.5%, with a median follow-up period of 71 months (range, 5-235 mo). This study expanded the histologic spectrum of DEK::AFF2 SCC and demonstrated its aggressive behavior, highlighting the need for accurate differentiation from mimics and long‑term surveillance.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1174-1183"},"PeriodicalIF":4.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629112","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}