Several Considerations on the Pathology, Treatment, and Prognosis of Laryngeal NUT Carcinoma

Laryngeal NUT carcinoma (NC) is an exceptionally rare and highly aggressive malignancy defined by rearrangements of the NUTM1 gene, most commonly involving BRD4. Owing to its morphologic overlap with poorly differentiated squamous cell carcinoma, this entity is frequently underrecognized in routine practice, particularly in the larynx. In this editorial, we summarize current knowledge on the pathology, molecular biology, treatment strategies, and prognosis of laryngeal NC, with particular emphasis on diagnostic pitfalls and clinical outcomes reported in literature. Available evidence highlights a strikingly aggressive clinical course, with most patients experiencing early disease progression and death within the first year of diagnosis, despite multimodal treatment approaches. Rare cases of long-term survival suggest underlying biological heterogeneity, potentially related to fusion subtype. Given the absence of standardized treatment protocols, most reported patients have been managed with an aggressive multimodal approach combining surgery and (chemo)radiation; however, outcomes remain poor. Therefore, early recognition and systematic NUT immunohistochemical testing in poorly differentiated laryngeal carcinomas, especially in younger patients, are critical. Advances in molecularly targeted therapies may offer future opportunities to improve outcomes in this devastating disease.