Myopericytomatosis: Clinicopathologic Analysis of 11 Cases With Molecular Identification of Recurrent PDGFRB Alterations in Myopericytomatosis and Myopericytoma.

Myopericytoma is a benign tumor of concentrically distributed perivascular myoid cells. Its molecular basis and relationship with myofibroma/myofibromatosis and other pericytic tumors are not fully understood. In our consultation/surgical files of over 1000 myopericytic lesions, we identified 11 cases with diffuse dermal/subcutaneous involvement by microscopic myopericytomatous nodules, a phenomenon we have termed myopericytomatosis. Myopericytomatosis affected mostly adults (female:male=8:3; median age, 37 y; range, 9 to 63 y) in the lower extremities (foot/ankle, 5; calf, 3; knee, 1; thigh, 1; neck, 1) over months to 25 years, ranging from 1.5 to 11.0 (median, 6.0) cm in size. Histologically, myopericytomatosis displayed diffuse infiltration by innumerable discrete myopericytoma/myofibroma-like nodules of bland spindled-to-ovoid cells (smooth muscle actin positive), in a mainly perivascular distribution. No mitoses, atypia, or necrosis was noted. All patients were treated by surgical excision (1 patient also received adjuvant radiation), with margins focally positive in 5 of 6 known cases. Of the 6 cases with follow-up of 0.2 to 13.7 (median, 3.4) years, 1 recurred locally twice, while 5 cases showed no recurrence. Targeted next-generation DNA sequencing identified PDGFRB alterations in all cases of myopericytomatosis and conventional myopericytoma tested (5 cases each), including mutations in 4 cases of myopericytomatosis (N666K in 3; Y562-R565 deletion in 1 case) and 3 myopericytomas (Y562C, K653E, and splice acceptor deletion in 1 case each), as well as low-level PDGFRB amplification in 2 cases of myopericytomatosis and 4 myopericytomas. No BRAF, NOTCH, or GLI1 alterations were detected. In summary, myopericytomatosis is a rare, strikingly diffuse, but apparently benign variant of myopericytoma that typically involves superficial soft tissue in adults with innumerable discrete microscopic myopericytomatous nodules. The strongly activating PDGFRB mutation N666K is noted in myopericytomatosis, but not in conventional myopericytoma, suggesting that PDGFRB mutation status may account for their pathogenetic differences. As PDGFRB alterations are present in myopericytoma/myopericytomatosis and infantile myofibromatosis/myofibroma, these entities indeed lie within a histogenetic continuum. Identification of PDGFRB alterations suggests tyrosine kinase inhibition as a potential therapeutic strategy in myopericytic neoplasms if needed.