Abstract
Gene fusions involving the NUTM1 gene (NUT) represent defining genetic markers of a highly aggressive carcinoma type with predilection for the midline structures of children and young adults, hence the original description as NUT midline carcinoma. Recent studies have increasingly documented involvement of the NUTM1 gene in the pathogenesis of other entities as well. We herein describe two cases of auditory canal carcinomas with features of porocarcinoma, both harboring a newly described YAP1-NUTM1 gene fusion. Patients were males aged 28 and 82 years who presented with slowly growing lesions in the external auditory canal. Histologic examination showed monomorphic basaloid and squamoid cells arranged into organoid solid aggregates, nests, ducts, small cysts, and focal pseudocribriform pattern with variable mitotic activity, infiltrative growth, and focal squamous differentiation, particularly in the most superficial part of the tumor. Immunohistochemistry revealed consistent reactivity for CK5, p63 and SOX10 and diffuse aberrant expression of TP53. CK7 expression was limited to a few luminal ductal cells. The androgen receptor and S100 were negative. Next generation sequencing (TruSight RNA fusion panel, Illumina) revealed the same YAP1-NUTM1 gene fusion in both tumors, which was subsequently confirmed by NUT-FISH and the monoclonal anti-NUT antibody. These cases represent a novel contribution to the spectrum of NUT-rearranged head and neck malignancies. This adnexal carcinoma variant should not be confused with the highly lethal NUT carcinoma based on NUT immunoreactivity alone.
Highlights
Gene rearrangements involving the NUTM1 gene (NUT) Midline Carcinoma Family Member 1 (NUTM1) gene mapped to chromosome 15q14 have emerged as a reliable genetic marker for a highly lethal poorly differentiated carcinoma with strong predilection for mediastinal and sinonasal midline structures, mainly of children and young adults [1, 2]
Given the young age of one of the patients and the risk for misclassification of his tumor as an aggressive NUT carcinoma on the basis of NUT immunoexpression alone, we believe reporting these cases is of utmost relevance for the differential diagnosis of NUT-positive neoplasms in head and neck routine surgical pathology practice
Porocarcinoma is considered the malignant counterpart of poroma and may arise either de-novo or from pre-existing benign poroma [12]
Summary
Gene rearrangements involving the NUT Midline Carcinoma Family Member 1 (NUTM1) gene ( known as Nuclear Protein in Testis or NUT) mapped to chromosome 15q14 have emerged as a reliable genetic marker for a highly lethal poorly differentiated carcinoma with strong predilection for mediastinal and sinonasal midline structures, mainly of children and young adults [1, 2]. Almost one half of all NUT carcinoma cases are located in head and neck sites [7]. Sinonasal cavities harbor half of the head and neck cases with the remainder distributed between other organs including the larynx, salivary glands and other exceedingly rare locations [4, 7,8,9]. Head and Neck Pathology (2020) 14:982–990 carrying a YAP1-NUTM1 translocation. Given the young age of one of the patients and the risk for misclassification of his tumor as an aggressive NUT carcinoma on the basis of NUT immunoexpression alone, we believe reporting these cases is of utmost relevance for the differential diagnosis of NUT-positive neoplasms in head and neck routine surgical pathology practice
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