Primary Nuclear Protein in Testis (NUT) Carcinoma of the Lung: Clinical, Genetic, and Pathological Characterization

Abstract

Background: Nuclear protein in testis(NUT) carcinoma of the lung is an extremely rare malignancy, predominantly affecting adolescents and young adults, and is associated with poor prognosis. To date, no comprehensive review has synthesized clinical, imaging, pathological, and genetic features, as well as management strategies for patients with primary NUT carcinoma of the lung. Method: This study retrospectively analyzed a cohort of five adult patients with pulmonary NUT carcinoma treated at the First Affiliated Hospital, College of Medicine, Zhejiang University, between 2020 and 2023. Clinical, imaging, pathological, and genetic data were collected and analyzed. Treatment decisions, therapeutic responses, and overall survival (OS) were closely monitored. Additionally, tumor genome sequencing data were subjected to a thorough analysis. Results: The median age at diagnosis for patients in this cohort was 44 years (range: 20–74 years), with 60% (3/5) testing positive for the BRD3-NUTM1 fusion gene. Most patients (60%, 3/5) had a confirmed distant metastasis status based on pathology or imaging at the time of diagnosis. In all cases, the primary lung mass was centrally located, predominantly in the lower lobes. Airway neobiological masses were the primary manifestations in two patients, while three cases showed bilateral mediastinal lymphadenopathy. Immunohistochemistry (IHC) analysis revealed that all patients were positive for P40 or P63. Among the five patients, patient 1 received chemotherapy, resulting in an OS of only 10 months. Patients 2 and 4 underwent chemoimmunotherapy, achieving OS durations of 15 and 8 months, respectively. Patients 3 and 5 underwent surgery due to early diagnosis, resulting in OS durations of more than 9 and 28 months, respectively. Conclusion: Diagnosis and management of NUT carcinoma of the lungs pose significant challenges. IHC, fluorescence in situ hybridization (FISH), and RNA-sequencing play crucial roles in distinguishing poorly differentiated lung squamous cell carcinoma from NUT carcinoma. Surgical resection substantially improves survival rates for patients with early-stage NUT midline carcinoma of the lung. However, for those with advanced pulmonary NC, specialized nationwide clinical studies are imperative, as current treatment modalities are unlikely to achieve long-term survival.