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