NUT carcinoma is a rare, highly aggressive malignancy. Initially, it was regarded as occurring in the midline areas of the upper  respiratory tract, upper digestive tract, and mediastinum (i.e. central compartment of the thoracic cavity) of young adults and to lesser extents children and infants. It was therefore termed NUT midline granuloma. However, subsequent studies defined these carcinomas based on the presence of a NUT fusion gene in their malignant cells. As so defined, this malignancy occurs in individuals of all ages and, while most commonly developing in the cited respiratory, gastrointestinal, and mediastinal areas, occasionally develops in the salivary glands, pancreas, urinary bladder, retroperitoneum (i.e. space behind the peritoneum of the abdominal cavity), endometrium, kidneys, ovaries, and other organs. Consequently, the name of this disorder was changed form NUT midline carcinoma to NUT carcinoma by the World Health Organization, 2015. NUT carcinomas are characterized histologically as tumors containing
primitive epithelioid cells (i.e. derived from activated macrophages and resembling epithelial cells) admixed with foci of keratinization (i.e. tissue areas that are rich in keratin fibers); NUT carcinomas are considered variants of squamous cell carcinomas. Studies have found that ~66 tp 80% of NUT carcinomas harbor a BRD4-NUTM1 fusion gene while the remaining NUT carcinomas, sometimes termed NUT variant carcinomas, involve the BRD3-NUTM1 (~10 to 25% of cases)  or, rarely, the NSD3-NUTM1, ZNF532-NUTM1,, or ZNF592-NUTM1 fusion gene. It is thought that the latter fusions genes promote NUT carcinomas in manners at least somewhat similar to the BRD4-NUTM1 fusion gene.