A Rare Case of NUT Carcinoma and Review of the Literature

Abstract Nuclear protein in testis (NUT) carcinoma is a rare, aggressive, poorly differentiated malignant neoplasm. NUT carcinoma (NC) is hallmarked by its chromosomal translocation involving the NUT/NUTM1 gene, which leads to a fusion oncoprotein that blocks epithelial differentiation and maintains proliferation in tumor cells. The translocation occurs with members of the BET (bromodomain and extraterminal domain) protein family, with 70% of the cases forming the NUTM1-BRD4 fusion. It most frequently involves the thoracic cavity followed by the head and neck, with a preference for midline areas of the body, especially the sinonasal tract and mediastinum. This led to NC formerly being known as NUT midline carcinoma. However, studies have shown that NC can occur widely throughout the body, thus leading to the updated name. NUT carcinoma is histologically defined as a tumor of primitive appearing round monomorphic cells with possible foci of abrupt keratinization. Given its rarity and its morphologic and immunohistochemical overlap with other tumors, NC has been largely underdiagnosed and misdiagnosed in the past few decades. However, with the improvement of genetic testing and the availability of an anti-NUT monoclonal antibody for diagnostic immunohistochemistry, the number of cases classified as NCs has vastly increased in the recent past.