TLE1 Expression in NUT Carcinoma: A Case Report Highlighting a Potential Diagnostic Pitfall for the Pathologist

Abstract

NUT carcinoma is a rare, aggressive malignancy defined as a carcinoma with a chromosomal rearrangement affecting the nuclear protein in testis (NUTM1) gene. This small round blue cell tumor classically exhibits focal abrupt keratinization and immunohistochemical positivity for keratin and squamous markers. However, keratinization is not always present and reports of positivity for other markers that may obscure the diagnosis are increasing. It is also noteworthy that gene fusions involving NUTM1 are not restricted to NUT carcinoma. Herein, we report a NUT carcinoma arising in the mediastinum of a male patient in his 40 s with morphological and immunohistochemical overlap with Ewing family sarcoma and poorly differentiated synovial sarcoma given a round cell morphology, diffuse strong immunoreactivity for CD99, and patchy strong immunoreactivity for TLE1. Squamous differentiation by morphology and p40 expression were notably absent in this case. Classification as NUT carcinoma was ultimately possible when the morphological and immunohistochemical findings were considered in the context of a BRD4::NUTM1 gene fusion identified by next-generation sequencing. While the patient initially responded to palliative radiotherapy, he died approximately one month later. To our knowledge, this is the first report of TLE1 immunoreactivity in NUT carcinoma. This case highlights a potential diagnostic pitfall and emphasizes the need for molecular confirmation in equivocal situations.