Uterine plexiform tumorlets: multifocal and solitary cases with subsets expressing melanocytic markers.

AIMS Uterine plexiform tumorlets are traditionally regarded as microscopic epithelioid leiomyomas. They are typically solitary incidental findings but may be multifocal (plexiform leiomyomatosis). We aim to report novel immunohistochemical and morphological findings, specifically the presence of spindled and epithelioid cell nodules, in these lesions. METHODS AND RESULTS Three cases of plexiform leiomyomatosis and 16 solitary plexiform tumorlets were included. Two cases of plexiform leiomyomatosis and four solitary plexiform tumorlets demonstrated spindled and epithelioid cell nodules which in one of the former cases formed expansile masses up to 15mm. The nodules demonstrated mild cytological atypia and occasional mitotic activity, and they were associated with a myxoid stroma and a lymphohistiocytic infiltrate which imparted a granulomatous appearance to the microscopic lesions. The plexiform tumorlets (solitary and multifocal) consistently expressed desmin, smooth muscle actin, ER and PR, and they commonly co-expressed melanocytic and perivascular epithelioid cell (PEC) markers HMB45, MiTF and cathepsin K. The spindled and epithelioid cell nodules were generally negative for myoid markers and hormone receptors but they expressed p16, cyclin D1 and TFE3. All lesions tested were negative for cytokeratin, S100, melanA, inhibin, EMA, ALK and BCOR; fluorescence in situ hybridization was negative for ALK, TFE3 and BCOR rearrangements in one of the larger spindled and epithelioid cell nodules. CONCLUSIONS Plexiform tumorlets commonly co-express myoid and melanocytic markers and may represent part of the spectrum of gynaecological PEC-related lesions. Some cases are associated with spindled and epithelioid cell nodules that could potentially mimic other uterine myxoid neoplasms.