Thyroid Carcinoma With NSD3::NUTM1 Fusion and Secondary TERT Promoter Mutation: A Case Report and Literature Review

Int J Surg Pathol. 2024 Sep 16:10668969241271966. doi: 10.1177/10668969241271966. Online ahead of print.

Abstract

Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive tumor characterized by translocation of the NUTM1 gene. To date, only about 20 NUT carcinomas arising from the thyroid have been reported in the literature, with the majority showing immunohistochemical markers indicative of squamous differentiation. We present a 29-year-old man with NUT carcinoma arising from thyroid follicular cells. Notably, the tumor cells expressed markers characteristic of thyroid follicular cells such as thyroglobulin, TTF1 and PAX8, without obvious histological and immunohistochemical features of squamous differentiation. Molecular analysis revealed a concurrent TERT promoter mutation (C228T) together with the NSD3::NUTM1 fusion, a combination not previously documented in NUT carcinoma. The tumor highlights the need to include NUT carcinoma in the differential diagnosis of thyroid cancer, especially when it presents with unconventional histopathological features, even in the absence of signs of squamous differentiation.

Keywords: NUT carcinoma; NUTM1 mutation; TERT promoter mutation; thyroid cancer.