Recurrent SRF-RELA Fusions Define a Novel Subset of Cellular Myofibroma/Myopericytoma: A Potential Diagnostic Pitfall With Sarcomas With Myogenic Differentiation.

Cellular myofibroblastic tumors other than desmoid-type fibromatosis are often diagnostically challenging due to their relative rarity, lack of known genetic abnormalities, and expression of muscle markers which may be confused with sarcomas with myogenic differentiation. In this study we investigate the molecular alterations of a group of cellular myofibroblastic lesions with in the myofibroma and myopericytoma spectrum for better subclassification. Two index cases were studied by paired-end RNA sequencing for potential fusion gene discovery. One chest wall soft tissue tumor in a 3-month-old girl case showed a SRF-C3orf62 fusion, while the other, a forearm lesion in an 8-year-old girl, showed a SRF-RELA fusion. Further screening of 42 cellular examples of myofibroma/myopericytoma by fluorescence in situ hybridization identified additional 8 cases with recurrent SRF gene rearrangements, 6 of them showing identical SRF-RELA fusions. The cohort was composed of 7 females and 3 males, with a wide age range of 3 months to 63 years (mean=17). All tumors showed a densely packed growth of oval to spindle cells with fibrillary eosinophilic cytoplasm, arranged either in intersecting fascicles or with a distinct nested pattern around a rich vascular network. Despite the dense cellularity and variable mitotic activity none of the lesions displayed nuclear pleomorphism or necrosis. All tumors showed coexpression for SMA and desmin, in most cases with a strong and diffuse pattern of staining, while myogenin was consistently negative. No distant metastases were seen in the few cases with follow-up information. A control group of 34 well-characterized myofibroblastic and perivascular tumors, including 10 typical myofibromas and 3 myopericytomas, were also investigated for SRF gene abnormalities by fluorescence in situ hybridization and were negative. In summary, we report a subset of cellular variants of myofibroma and myopericytoma showing a smooth muscle-like immunophenotype and harboring recurrent SRF-RELA gene fusions, which mimic sarcomas with myogenic differentiation.