Head and neck pathology最新文献

{"title":"FGFR3::TACC3 Fusion and NOTCH1 Loss-of-Function in a Case of HPV-Associated Sinonasal Squamous Cell Carcinoma: Diagnostic Challenge and Implications for Targeted Therapy.","authors":"Xu Cao, Hong Yu, Reham Hamdy Abdulazim Soliman, Pei Ying, Songlin Zhang, Li Liang","doi":"10.1007/s12105-026-01947-7","DOIUrl":"10.1007/s12105-026-01947-7","url":null,"abstract":"<p><p>Sinonasal squamous cell carcinoma (SNSCC) comprises a heterogeneous group of tumors with emerging molecular subtypes. Human papillomavirus (HPV)-associated SNSCC is a distinct entity, although actionable genomic alterations beyond HPV-driven pathways remain underexplored. Distinguishing HPV-associated SNSCC from carcinoma ex inverted papilloma can be particularly challenging in limited biopsy specimens, as these lesions may appear morphologically similar. We report a case of HPV-associated SNSCC with concurrent FGFR3::TACC3 fusion and NOTCH1 p.C1416 stop-gain mutation.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncocytic Intraductal Carcinoma of the Parotid Gland with STRN::ALK Fusion.","authors":"Reham H Soliman, Chris Shi, Kevin E Fisher, Hong Yu, Fouad El-Dana, Xu Cao, Li Liang, Pei Ying, Songlin Zhang","doi":"10.1007/s12105-026-01948-6","DOIUrl":"10.1007/s12105-026-01948-6","url":null,"abstract":"<p><p>Intraductal carcinoma (IDC) of the salivary gland is an uncommon epithelial neoplasm characterized by a predominantly intraductal or intracystic proliferation rimmed by a myoepithelial cell layer. Advances in molecular profiling have revealed recurrent gene fusions in IDC, most frequently involving RET, although fusions implicating other kinase genes have also been described. Among these, ALK rearrangements are rare and remain poorly characterized. Herein, we report a case of oncocytic IDC of the parotid gland harboring a STRN::ALK fusion, further expanding the molecular landscape of this tumor. Although this fusion has been previously reported in intercalated duct IDC, to our knowledge, this is the first report of this specific fusion in oncocytic IDC.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NUT Carcinoma Arising in Stensen's Duct: First Reported Case and Literature Review.","authors":"Mariel Bedell, Seungwon Kim, Mana Mohebnasab, Diana Bell","doi":"10.1007/s12105-026-01943-x","DOIUrl":"10.1007/s12105-026-01943-x","url":null,"abstract":"<p><strong>Background: </strong>NUT carcinoma is a rare and aggressive malignancy defined by rearrangements of NUTM1, most commonly with partner BRD4 or BRD3, and carries a dismal prognosis. Carcinoma arising from Stensen's (parotid excretory) duct is itself an exceedingly rare entity, with only 30 previously reported cases spanning diverse morphologies.</p><p><strong>Case presentation: </strong>We report the first case of NUT carcinoma arising from Stensen's duct in a 37-year-old female who presented with an enlarging right buccal submucosal mass, initially favored on imaging to represent a chronic inflammatory process. Punch biopsy was originally interpreted as invasive squamous cell carcinoma. Surgical resection revealed a high-grade basaloid carcinoma with abrupt keratinization centered at the parotid papilla with retrograde ductal spread. Immunohistochemistry demonstrated NUT positivity, and fluorescence in situ hybridization confirmed NUTM1 translocation. RNA sequencing identified a BRD4::NUTM1 fusion, establishing the diagnosis of NUT carcinoma. Incidentally, next-generation sequencing identified a BRCA1 mutation, confirmed to be germline on subsequent germline testing. The patient was treated with surgical resection, adjuvant cisplatin chemotherapy, and external beam radiation, with no evidence of disease on PET-CT two months after diagnosis.</p><p><strong>Conclusion: </strong>This case expands the morphologic spectrum of Stensen's duct carcinoma, underscores the challenges in clinical, radiologic, and pathologic interpretation of masses at this site, and suggests a potential association between homologous recombination deficiency and this translocation-associated malignancy.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pitfalls in Bone and Soft Tissue Pathology of the Head and Neck: Primary Intraosseous Rhabdomyosarcoma/FUS::TFCP2-Rearranged Spindle Cell Rhabdomyosarcoma and Transdifferentiated/Dedifferentiated/Undifferentiated Melanoma.","authors":"Omar Habeeb","doi":"10.1007/s12105-026-01942-y","DOIUrl":"10.1007/s12105-026-01942-y","url":null,"abstract":"<p><strong>Purpose: </strong>Because of their relative rarity, bone and soft tissue lesions of the head and neck region can present a diagnostic challenge to anatomic pathologists who practice in a general surgical pathology model-while novel lesions may be unfamiliar to subspecialty head and neck pathologists.</p><p><strong>Methods: </strong>This review focuses on a diagnostically confounding neoplasm that arises in the bone (primary intraosseous rhabdomyosarcoma / FUS::TFCP2-rearranged spindle cell rhabdomyosarcoma) and soft tissue (trans-/de-/undifferentiated melanoma) of the head and neck region-each of which can easily be mistaken for more common entities.</p><p><strong>Results: </strong>The clinical, radiological, and histopathologic findings (including the molecular pathogenesis) of each neoplasm is discussed-along with selected differential diagnoses.</p><p><strong>Conclusion: </strong>The accurate recognition of these neoplasms ensures that patients are reviewed, treated, and followed at the appropriate multidisciplinary meeting.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13315038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence-Assisted Histopathologic Diagnosis and Grading of Oral Epithelial Dysplasia: A Systematic Review and Functional Meta-synthesis.","authors":"Carlos M Ardila, Eliana Pineda-Vélez, Alejandro I Díaz-Laclaustra","doi":"10.1007/s12105-026-01937-9","DOIUrl":"10.1007/s12105-026-01937-9","url":null,"abstract":"<p><strong>Purpose: </strong>Artificial intelligence (AI) has emerged as a promising tool for digital pathology, with potential applications in the histopathologic evaluation of oral epithelial dysplasia (OED). This systematic review synthesized current evidence on AI-assisted histopathologic diagnosis and grading of OED, focusing on diagnostic performance, methodological quality, certainty of evidence, and functional roles of AI systems in the diagnostic workflow.</p><p><strong>Methods: </strong>A systematic search of PubMed/MEDLINE, Scopus, and Embase was conducted. Eligible studies evaluated AI, machine learning, deep learning, convolutional neural network (CNN), Transformer-based, or computational pathology methods applied to microscopic or digital histopathologic images of OED or oral potentially malignant disorders with dysplasia. Data on study characteristics, image format, analytical level, model architecture, reference standard, validation strategy, and diagnostic performance were extracted.</p><p><strong>Results: </strong>Thirteen studies published between 2017 and 2026 met the inclusion criteria. AI applications were grouped into three functional domains: detection of dysplastic epithelium, grading of dysplasia severity, and diagnostic assistance through enhanced image interpretation. Included studies used heterogeneous analytical approaches, ranging from handcrafted-feature machine-learning pipelines and CNN-based cellular or tissue-level classifiers to whole-slide image segmentation, DenseNet, Vision Transformer, and hybrid computational pathology pipelines. Several studies reported high experimental performance, including accuracy above 90% in selected detection or grading tasks. However, performance estimates were frequently derived from curated image-, patch-, region-, or slide-level datasets rather than patient-level diagnostic workflows. Substantial heterogeneity in datasets, grading frameworks, image formats, model architectures, validation strategies, and performance metrics precluded quantitative meta-analysis. Risk-of-bias concerns mainly involved patient selection, index-test evaluation, and flow/timing. The overall certainty of evidence was very low.</p><p><strong>Conclusions: </strong>AI shows potential to support histopathologic detection and grading of OED, but current evidence remains insufficient for clinical implementation. Future studies require standardized reference standards, transparent reporting, patient-level validation, external multicenter testing, and prospective evaluation in real diagnostic workflows.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathology-informed Generative Adversarial Network Augmentation Improves Classification of Peripheral Nerve Sheath Tumors by Modeling Morphological Variability: A Pilot Investigation.","authors":"Giovanna Calabrese Dos Santos, Hyago Vieira Lemes Barbosa Silva, Anna Luíza Damaceno Araújo, Thaís Cerqueira Reis Nakamura, Micael Gil Scholl Santos, Anderson Faria Claret, Felipe Augusto Pereira de Figueiredo, Sebastião Silvério de Sousa-Neto, Daniela Giraldo-Roldán, Leonardo Marcello Rener de Freitas, Luiz Paulo Kowalski, Alan Roger Santos-Silva, Marcio Ajudarte Lopes, Pablo Agustin Vargas, Matheus Cardoso Moraes","doi":"10.1007/s12105-026-01939-7","DOIUrl":"10.1007/s12105-026-01939-7","url":null,"abstract":"<p><strong>Background: </strong>Peripheral nerve sheath tumors (PNSTs) of the head and neck (H&N) show histopathological overlap. Although convolutional neural networks (CNNs) have demonstrated feasibility in soft tissue tumor classification, limited intra-class variability related to perineurioma remains a critical constraint for rare tumor subtypes.</p><p><strong>Methods: </strong>This retrospective diagnostic accuracy study with internal validation included 30 patients diagnosed with PNSTs. Whole-slide images were digitized at 20× magnification and partitioned using a strict patient-wise split. Synthetic perineurioma patches were generated using a modified Pix2Pix-based Generative Adversarial Network (GAN) incorporating a bottleneck architecture and self-attention modules. Two morphology-driven augmentation strategies were evaluated: (1) intra-phenotypic expansion by cross-patient patch pairing within the sclerosing subtype and (2) inter-phenotypic interpolation by cross-phenotype patch pairing between sclerosing and intraneural variants. EfficientNetV2-B0 pre-trained on ImageNet was trained under three configurations: original dataset only, original + Experiment A synthetic patches, and original + Experiment B synthetic patches. All performance metrics were computed exclusively on an independent yet internal test set composed of original images.</p><p><strong>Results: </strong>GAN-based augmentation improved global classification performance compared with the baseline model trained on original images only (accuracy 0.733). Intra-phenotypic expansion increased accuracy to 0.767 and achieved the highest balanced accuracy (0.750) and macro-F1 (0.740). Inter-phenotypic interpolation yielded the highest overall accuracy and competitive multiclass agreement metrics. Perineurioma recall improved from 0.34 (baseline) to 0.51 with intra-phenotypic augmentation and 0.47 with inter-phenotypic interpolation, while specificity remained ≥ 0.999 across all strategies.</p><p><strong>Conclusions: </strong>Structured, pathology-informed GAN augmentation improved CNN classification of PNSTs, particularly for the morphologically heterogeneous perineurioma class. Intra-phenotypic expansion primarily improved rare-class sensitivity, whereas inter-phenotypic interpolation improved multiclass agreement and global robustness. These findings support morphology-driven synthetic enrichment as a clinically meaningful strategy to improve AI performance in underrepresented tumor entities and potentially support diagnostic decision-making in digital pathology environments.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical Expression of CK13 and Molecular Analysis of KRT13 and APC in Odontogenic Ghost Cell Lesions, Adenoid Ameloblastoma, and Conventional Ameloblastoma.","authors":"Lucas Fabian Polti, Juan Manuel Arteaga Legarrea, Estefanía Sicco, Felipe Martins Silveira, Lauren Frenzel Schuch, Vanesa Pereira Prado, Ronell Bologna Molina, María Luisa Paparella, Fernanda Faria Rocha, Marina Gonçalves Diniz, Ricardo Santiago Gomez, Silvia Ferreira de Sousa, Felipe Paiva Fonseca","doi":"10.1007/s12105-026-01938-8","DOIUrl":"10.1007/s12105-026-01938-8","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to evaluate the immunohistochemical expression of CK13 and specific mutations in KRT13 and APC genes in cases of calcifying odontogenic cyst (COC), dentinogenic ghost cell tumor (DGCT), adenoid ameloblastoma (AA), and conventional ameloblastoma (CA).</p><p><strong>Materials and methods: </strong>Twenty-nine cases (22 COC, 2 DGCT, 1 AA, and 4 CA) were collected from two diagnostic centers. Immunohistochemical analysis of CK13 expression and polymerase chain reaction (PCR)-based molecular investigation of specific mutations (APC E1080* and KRT13 M239V and Y281H) were performed.</p><p><strong>Results: </strong>CK13 expression in COC was observed in the suprabasal/superficial layers of the cystic epithelium in 14 cases-64%; ghost cells showed positivity in 12 cases-54%. DGCT cases were negative in the epithelial proliferation but positive in ghost cells. The AA case was negative. Three CA cases demonstrated positivity in suprabasal/central cells. None of the cases harbored the investigated mutations. However, the intronic polymorphism KRT13 c.735 + 10A > G (dbSNP rs7211235) was identified in 16 COC cases, one DGCT case, one AA case, and one CA case, whereas KRT13 c.735 + 6C > T (dbSNP rs181122697) was detected in one COC case. Additionally, one case harbored a previously unreported silent/synonymous mutation, KRT13 c.690G > A (p.E230E), of unknown significance.</p><p><strong>Conclusions: </strong>CK13 expression in COC and CA suggests squamous differentiation of odontogenic epithelium. The detected KRT13 genetic variations are probably not associated with tumorigenic mechanisms in COC, DGCT, AA, and CA. The APC E1080* mutation was not identified in any of the entities included in the present study. Further studies are therefore required to more precisely define the genetic profile of these entities and, particularly, to clarify the potential biological relationship between dentinogenic ghost cell tumor and adenoid ameloblastoma.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMARCB1-Deficient Malignant Orbital Neoplasm with Features Overlapping Myxoid Epithelioid Sarcoma: A Diagnostic Challenge.","authors":"Michiko Hosaka, Terufumi Kubo, Ken Yamashita, Taro Sugawara, Yohei Arihara, Hayato Watabe, Takatoshi Yotsuyanagi, Kohichi Takada, Shintaro Sugita, Reiko Watanabe","doi":"10.1007/s12105-026-01946-8","DOIUrl":"10.1007/s12105-026-01946-8","url":null,"abstract":"<p><p>Myxoid epithelioid sarcoma is a rare morphologic variant of epithelioid sarcoma characterized by abundant myxoid stroma and frequent loss of SMARCB1/INI1 expression. Orbital involvement is exceptionally uncommon. We report a case of a SMARCB1-deficient malignant orbital neoplasm with features overlapping myxoid epithelioid sarcoma in a 61-year-old man presenting with visual disturbance. Imaging studies revealed a 2.5-cm medial orbital mass without evidence of another primary lesion. The tumor was excised without prior biopsy. Histologically, the lesion was predominantly composed of abundant myxoid stroma containing scattered atypical epithelioid, signet ring-like, and spindle cells, with focal fascicular proliferation infiltrating skeletal muscle. Immunohistochemically, tumor cells were positive for pan-cytokeratin, EMA, vimentin, and CD34, while negative for S100, ΔNp63 (p40), p63, SS18-SSX, and TLE1. Complete loss of SMARCB1/INI1 expression was observed in tumor cells. The overall findings suggested a SMARCB1-deficient malignant neoplasm showing substantial morphologic and immunophenotypic overlap with myxoid epithelioid sarcoma. This case highlights the diagnostic challenges posed by SMARCB1-deficient tumors arising in unusual anatomical sites and expands the clinicopathological spectrum of myxoid epithelioid sarcoma-like neoplasms involving the orbit.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proliferative Periostitis: Often Overlooked Onion-Skinning.","authors":"Reed A McKinney, Caitlyn A Menicucci, Logan C Helquist, Connor K Guttmann, Patrick J Murphy, Brian D Rethman","doi":"10.1007/s12105-026-01941-z","DOIUrl":"10.1007/s12105-026-01941-z","url":null,"abstract":"<p><strong>Background: </strong>Proliferative periostitis, also known as Garré osteomyelitis, is an uncommon periosteal reaction characterized by reactive bone formation secondary to chronic low-grade inflammation or infection, most often in pediatric patients.</p><p><strong>Case presentation: </strong>This image report describes a 6-year-old female who presented with a two-week history of right cheek swelling along the buccal aspect of tooth #30 and the lateral border of the mandible.</p><p><strong>Diagnosis: </strong>Correlation of the clinical, radiographic, and histologic findings supported the diagnosis of proliferative periostitis.</p><p><strong>Conclusion: </strong>Familiarity with radiographic and histologic findings help to ensure an accurate diagnosis.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEK::AFF2 Fusion-Associated Nonkeratinizing Squamous Cell Carcinoma with Noncontiguous Middle Ear and Sinonasal Involvement.","authors":"Yan Li, Linxiang Ma, Wenlin Yang, Renya Zhang, Ting Wang","doi":"10.1007/s12105-026-01933-z","DOIUrl":"10.1007/s12105-026-01933-z","url":null,"abstract":"<p><strong>Background: </strong>DEK::AFF2 fusion-associated nonkeratinizing squamous cell carcinoma is a recently recognized HPV-independent entity characterized by deceptively bland morphology and potential mimicry of benign or inflammatory lesions.</p><p><strong>Case presentation: </strong>A 21-year-old woman presented with recurrent left-sided otorrhea and progressive hearing loss. Imaging demonstrated noncontiguous lesions involving the left middle ear/mastoid compartment and the sinonasal region. Histologically, both lesions showed nonkeratinizing squamous proliferation with focal papillary/inverted architecture, mild to moderate cytologic atypia, and focal stromal invasion. Immunohistochemically, the tumor exhibited diffuse nuclear AFF2 expression, positivity for CK5/6 and p40, wild-type p53 expression, and negative p16 and INSM1. Targeted next-generation sequencing confirmed DEK::AFF2 fusion in both lesions.</p><p><strong>Conclusion: </strong>This case expands the anatomic spectrum of DEK::AFF2 fusion-associated nonkeratinizing squamous cell carcinoma by demonstrating noncontiguous middle ear and sinonasal involvement. Recognition of its characteristic morphologic, immunophenotypic, and molecular features is essential to avoid misdiagnosis.</p>","PeriodicalId":520636,"journal":{"name":"Head and neck pathology","volume":"20 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}