NUT CARCINOMA IN CHILDREN: THE EXPERT EUROPEAN EXPERIENCE

Background and Aims: NUT-carcinoma is a rare, probably underdiagnosed and highly aggressive tumor defined by the presence of a somatic NUTM1 rearrangement. The tumor occurs mainly in adolescents and young adults. We analyzed the clinical, radiologic, and biological features of pediatric patients (≤18 years) with NUT-carcinoma. Methods: This retrospective multicenter international study was based on review of medical records of 24 childrenwith NUT-carcinoma from 5 countries with specific rearrangement or positive anti-NUT nuclear staining. Results: Twenty-four patients with a median age of 14.6 years (range: 3.9–18 years) were analyzed. Thoracic/mediastinal tumors were the primary in 14 patients, and head and neck in 7 cases. One patient had multifocal tumor with unknown primary, another a vocal cord and the last one a pancreas primary. Sixteen patients (67%) presented with regional lymph node involvement and 17 patients (71%) with distant metastases, in most cases lung (38%), distant lymph nodes (38%) and bone marrow (30%). Approximately half of patients were initially misdiagnosed and diagnosis was corrected after NUT immunochemistry or NUT fusion sequencing. Chemotherapy was administered in all patients; nine patients underwent major surgery and 19 radiotherapy. Median overall survival was 0.75 years (range 0.2-11 years) median event free survival 0.4 years (range 0.1-11 years), one patient is currently treated for a subsequent relapse (1.9 years after diagnosis). Three long-term survivors (11, 9.1 and 6.6 years after diagnosis) were identified, these cases were associated with non-metastatic cervical disease and non-metastatic disease with BRD3-NUT-fusion. Conclusions: As in adults, NUT-carcinoma in pediatric patients is poorly sensitive to conventional therapy in most cases. In a minority of patients long-term survival is possible with multimodal treatment. Early diagnosis of undifferentiated or poorly differentiated carcinomas to identify the specific rearrangement of NUT-gene is necessary to initiate the optimal diagnostic and therapeutic strategy.