MGA::NUTM1 fusion sarcoma: expanding the spectrum of NUT-rearranged sarcomas with extensive review of the literature.

Objectives: We sought to present a rare case of MGA::NUTM1 fusion sarcoma, with a discussion of the differential diagnoses and approach to diagnosing these ultra-rare cases, which represent an emerging subset of NUTM1-rearranged mesenchymal neoplasms characterized by varied clinical behavior. Our review of the literature (17 cases) indicated bimodal age distribution, variable anatomical distribution, and frequent metastasis in these cases. Differential diagnosis has included synovial sarcoma and BCOR-associated sarcoma. The reported survival rates vary widely, from 1 month to 15 years.

Methods: Here we report the case of a 16-year-old girl who presented with a large pelvic-abdominal mass and metastatic disease on a positron emission tomography/computed tomography scan. Based on TLE-1 positivity, the mass was initially diagnosed as synovial sarcoma at an outside center.

Results: Histologically, the patient's tumor showed monomorphic spindle to epithelioid cells within dense hyalinized stroma. Immunohistochemistry demonstrated diffuse nuclear NUT positivity along with TLE-1 and BCOR expression. Next-generation sequencing confirmed MGA::NUTM1 fusion, with additional alterations in TP53, CCND2, and PIK3CD. Despite chemotherapy, the patient's disease progressed, highlighting poor therapeutic response in these cases.

Conclusions: This case highlights the overlapping and distinguishing features between MGA::NUTM1 fusion sarcomas and other common entities. Because survival in the reported MGA::NUTM1 fusion sarcomas varies widely, we hypothesized that more aggressive cases harbor second-hit alterations in the tumor suppressor genes (eg, our case had TP53 missense mutations). As the true biological nature of MGA::NUTM1 fusion sarcomas is still evolving, exploring this hypothesis by studying the second-hit alterations will be worthwhile in future cases and studies. The current lack of effective targeted therapies underscores the need for further research into novel treatment strategies for this disease.