NSD3::NUTM1 fusion evidenced on RNA sequencing in poorly differentiated thyroid cancer: a report of two cases

Background Nuclear protein in testis (NUT) carcinomas are aggressive, poorly or undifferentiated cancers, generally arising from midline structures. This subtype of squamous cell carcinoma is rare and has a poor prognosis. NUT cancers are defined by NUTM1 fusions. Rearrangements of the NUTM1 gene have rarely been described in primary thyroid cancer and are mainly reported in patients ≤ 45 years old. NSD3::NUTM1 translocation is the most common NUTM1 fusion transcript reported in thyroid cancer. As they are very infrequent, NUTM1 fusions are not routinely sought in poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC). Case presentation We report two PDTC patients > 65 years old with locally advanced disease and 18 FDG-avid distant metastases. NSD3::NUTM1 translocation was evidenced in both patients by RNA sequencing using the next-generation sequencing (NGS) panel of our institution. Conclusion We suggest including the search for NUTM1 fusions in the RNA sequencing panel for advanced and refractory thyroid cancers. Established facts Nuclear protein in testis (NUT) carcinomas are rare, aggressive, poorly or undifferentiated cancers with a poor prognosis, generally arising from midline structures in young patients. NUT cancers are defined by NUTM1 fusions that can be evidenced by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) or RNA sequencing. NUTM1 fusions have rarely been described in primary thyroid cancer, usually in patients ≤ 45 years old. NSD3::NUTM1 translocation is the most common NUTM1 fusion transcript reported in thyroid cancer. As they are very infrequent, NUTM1 fusions are not routinely sought in poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancers (ATC). Novel insights We report two patients > 65 years old with locally invasive refractory PDTC and NSD3::NUTM1 translocation. NSD3::NUTM1 translocation might be more systematically sought in locally advanced PDTC/ATC with no point DNA mutations or other rearrangements. This strategy would better identify these patients, whose pathological diagnosis and clinical management may be challenging.