Presenting Features and Causes of Diagnostic Delays: A Report From the NUT Carcinoma Registry

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.

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.

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.

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.