Genomically driven NUTM1-NSD3 carcinoma of the lung: Opportunity for chemotherapy response

Abstract

Nuclear protein in testis (NUT) carcinoma is a rare, genetically-driven carcinoma defined by NUTM1 gene rearrangements. It frequently presents as an aggressive, poorly differentiated squamous cell carcinoma of the midline. NUT carcinoma originating in the lung is extremely uncommon. We present a unique case of a 23-year-old female diagnosed mucoepidermoid carcinoma of the lung found to harbor a rare NSD3-NUTM1 gene fusion on targeted sequencing. Despite multiple metastases at diagnosis, she exhibited dramatic response to first-line carboplatin and paclitaxel doublet chemotherapy. Interim PET-CT after three cycles showed near complete resolution of the left hilar mass and metastases. This response was sustained after six total cycles and continues after six months on maintenance chemotherapy. To our knowledge, this represents the first reported case of NUTM1-NSD3 fusion positive lung carcinoma displaying chemosensitivity, unlike the typically aggressive course of NUT cancers. Our case reveals the emerging molecular heterogeneity of these rare malignancies and suggests platinum doublets may be an effective treatment option warranting further study. Overall, it highlights the potential for precision diagnostics to uncover actionable targets and prognostic insights even in elusive cancers.