Original ArticlesNUT Carcinoma of the Salivary Glands Clinicopathologic and Molecular Analysis of 3 Cases and a Survey of NUT Expression in Salivary Gland CarcinomasAgaimy, Abbas MD*; Fonseca, Isabel MD†,‡; Martins, Carmo BSc, PhD§; Thway, Khin MD∥; Barrette, Ryan BSc¶; Harrington, Kevin J. BSc, MBBS, FRCP, FRCR, PhD#,**; Hartmann, Arndt MD*; French, Christopher A. MD¶; Fisher, Cyril MD∥Author Information *Institute of Pathology, University Hospital, Erlangen, Germany †Instituto de Anatomia Patológica, Faculdade de Medicina, Universidade de Lisboa ‡Serviço de Anatomia Patológica, Instituto Português de Oncologia Francisco Gentil §UIPM, Instituto Português de Oncologia Francisco Gentil, Lisboa, Portugal ∥Sarcoma Unit/Head and Neck Unit #Head and Neck Unit, Royal Marsden Hospital **Targeted Therapy Team, Institute of Cancer Research, London, UK ¶Brigham and Women’s Hospital/Harvard Medical School, Boston, MA Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Abbas Agaimy, MD, Pathologisches Institut, Universitätsklinikum Erlangen, Krankenhausstrasse 8-10, Erlangen 91054, Germany (e-mail: a[email protected]). The American Journal of Surgical Pathology: July 2018 - Volume 42 - Issue 7 - p 877-884 doi: 10.1097/PAS.0000000000001046 Buy Metrics Abstract NUT carcinoma (NC) represents a rare subset of highly aggressive poorly differentiated carcinomas characterized by rearrangement of the NUT (aka NUTM1, nuclear protein in testis) gene, most commonly fused to BRD4. Originally described as a mediastinal/thymic malignancy, NC has been reported at a variety of anatomic regions including the upper and lower aerodigestive tract. To date, only 7 NC cases of probable salivary gland origin have been reported. We herein describe 3 new cases (all affecting the parotid gland) in 2 women (39- and 55-y old) and 1 man (35-y old). Histologic examination showed poorly differentiated neoplasms composed of poorly cohesive small-sized to medium-sized cells with variable squamoid cell component that was focal and abrupt. Immunohistochemistry showed uniform expression of p63 and distinctive punctate expression of the NUT antigen in the tumor cell nuclei. Review of the reported salivary gland NC cases (total, 10) showed a male:female ratio of 1.5:1 and an age range of 12 to 55 years (median, 29 y). Site of the primary tumor was the parotid (7), sublingual (2), and submandibular (1) glands. All presented as rapidly growing masses treated by surgery followed by adjuvant radiotherapy/chemotherapy. Initial nodal status was positive in 8/10. At last follow-up (1 to 24 mo; median, 5 mo), 7/10 patients died of disease at a median of 5.5 months (1 to 24 mo) and only 2 were disease free at 7 and 14 months. Of 9 cases with genetic data, the fusion partner was BRD4 (n=7), non-BRD4/3 (n=1), or undetermined (n=1). None of 306 carcinomas spanning the spectrum of salivary carcinoma types screened by NUT immunohistochemistry was positive. This is the first small series on salivary NC highlighting the importance to include this rare disease in the differential diagnosis of poorly differentiated salivary gland carcinomas and in cases of presumable poorly differentiated carcinoma of unknown origin. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.