Clinical and molecular features of pulmonary NUT carcinoma characterizes diverse responses to immunotherapy, with a...

Nuclear protein in testis (NUT) carcinoma is an uncommon malignant cancer characterized by NUTM1 rearrangement. We aimed to investigate the clinicopathological and molecular features and immunotherapy of pulmonary NUT carcinoma.

Immunohistochemistry (IHC) for NUT (C52B1) and programmed cell death ligand 1 (PD-L1: 22C3) and fluorescence in situ hybridization (FISH) for NUTM1 break and BRD4-NUTM1 fusion were performed on six pulmonary NUT carcinoma samples.

The 6 pulmonary NUT carcinoma samples were obtained from 5 males and 1 female, with ages ranging from 31 to 73 years (average, 46 years). Five tumors occurred in the lobes, with one in the trachea. Pathologically, all cases showed primitive-appearing round to epithelioid cells growing in nests and sheets. Squamous differentiation and abrupt keratinization were observed. All tumors expressed the NUT protein and p63, and 4 tumors showed focal synaptophysin, but PD-L1 expression was not observed. All cases displayed NUTM1 rearrangement, 5 had BRD4-NUTM1 fusion, and one had an unknown partner. Three patients presented regional lymph node involvement at diagnosis. Five patients underwent intensive radiation and/or chemotherapy. Furthermore, 2 patients (1 and 2) received a combination of PD-L1 inhibitor and chemotherapy. Patient 1 exhibited a poor response and soon showed tumor progression and metastasis; however, patient 2 responded remarkably and achieved pathologic complete response (pCR) without uncontrollable adverse events. The overall survival time was 2.9 months.

Pulmonary NUT carcinoma exhibits poorly differentiated morphological features with diffuse NUT staining, low PD-L1 expression, and NUTM1 rearrangement. Despite its poor prognosis, it presents a diverse response to immunotherapy. Immune checkpoint inhibitors (ICIs) need to be further explored in NUT carcinoma.