Cellular myofibromas with SRF fusions: clinicopathological and molecular study of 3 cases of a rare entity and a potential mimic of sarcoma

Cellular myofibromas/myopericytomas harboring recurring SRF fusions are recently characterized as rare and diagnostically challenging entities, which can mimic myogenic sarcomas. These tumors belong to the pericytic/perivascular myoid tumor family, which comprises a group of genetically heterogenous and sometimes morphologically overlapping entities. In this series, we describe 3 cases of SRF-rearranged cellular myofibromas/perivascular myoid tumors with a smooth muscle-like phenotype in children. The children ranged from 7 to 16 years of age, and all presented with a painless mass in the extremities, 2 of which were deep-seated. Histologically, the tumors demonstrated a smooth muscle-like morphology and immunophenotype with mild atypia and low-level mitotic activity. Prominent dense collagen deposition and coarse calcification was observed in 2 tumors. RNA sequencing revealed SRF fusions in all cases, with each tumor showing a different 3′ partner gene, RELA, NFKBIE, and NCOA3. Of these, NCOA3 has not been reported previously, and this expands the molecular spectrum by identifying a novel fusion partner for SRF. Given that histological features can be worrisome for a myogenic sarcoma, wider awareness of this emerging tumor is valuable to avoid potential misclassification.