A Rare Case of Oral-Maxillary NUT (Nuclear Protein in Testis) Carcinoma With Diffuse Osseous Metastasis and Hypercalcemia of Malignancy

Nuclear protein in testis (NUT) carcinoma is a rare and aggressive cancer arising from genetic rearrangements of the <i>NUTm1</i> gene. This leads to tumorigenesis, which commonly affects midline structures, including the head, neck, and thorax. It may originate from non-cutaneous epithelial tissues and resemble poorly differentiated squamous cell carcinomas. NUT carcinoma (NC) can typically be consistently identified through immunostaining for the NUT protein. Unfortunately, most cases are detected at an advanced stage, leading to unfavorable outcomes. The rarity of NC, combined with its aggressive behavior, late presentation, and limited understanding of its pathogenesis, presents considerable diagnostic and therapeutic challenges. We present and discuss our case of a 48-year-old male with NC of oral-maxillary origin with diffuse osteolytic metastasis. Uniquely, this is the first report of adult NC with severe hypercalcemia of malignancy (20.1 mg/dL) resistant to an aggressive multimodal treatment approach. We underscore the urgent need for the timely diagnosis of NC and the development of effective interventions for improving the outcome of this devastating malignancy.