Abstract
PURPOSE: Diagnostic delays are common for patients with NUT carcinoma (NC), a cancer driven by NUT fusion oncoprotein. Rapid diagnosis is crucial for the best outcomes. We investigated NC's presenting features and associations with diagnostic delays. METHODS: We manually reviewed medical records from US participants in the NC Registry (2007-2024). Baseline features were analyzed descriptively, and multivariable logistic regression was used to examine odds ratios for delays. RESULTS: We analyzed 132 patients (median age 37 years). At presentation, 55% had metastatic disease and 64% had a thoracic primary. The median interval from symptom onset to diagnosis was 10 weeks (range, 1-165 weeks). The initial histopathologic diagnosis was poorly differentiated/squamous cell cancer in 52%, insufficient malignant cells in 14%, carcinoma in 12%, and NC in 22%. Immunohistochemistry (IHC) testing revealed NUT in 100%; 93% were keratin+, 88% p63+, 89% p40+, and 72% had Ki-67 ≥50%. IHC was used to diagnose NC in 79%. Nonthoracic primaries were associated with a longer time between symptom onset and NC diagnosis (odds ratio, 3.25). Of 32 patients who started treatment before diagnosis, 78% were on agents appropriate for NC. After a diagnosis of NC, 33% participated in clinical trials. CONCLUSION: NC almost always presents as squamous/poorly differentiated non-small cell lung or head and neck cancer. Overall, 78% of patients were initially diagnosed as non-NC. Efforts to raise awareness, recognition, and rapid diagnosis of NC by both oncologists and pathologists are critical if we are to improve outcomes.