Nonvisceral YAP1::TFE3- Rearranged Inflammatory Spindle Cell PEComa in Somatic Soft Tissue : Clinicopathologic and...

Inflammatory spindle cell PEComa is a rare PEComa variant with rare cases harboring YAP1::TFE3 fusion recently reported in the lungs. These tumors share identical YAP1::TFE3 fusion breakpoints and overlapping morphology with clear cell stromal tumor of the lung ( CCST-L ), but differ by demonstrating a myomelanocytic immunophenotype. We report the first 3 nonvisceral cases of inflammatory spindle cell PEComa with YAP1::TFE3 fusion. All occurred in female patients, aged 51 to 76 years, involving the vulva, presacral region, and thigh, and ranged from 3.8 to 5.0 cm (median: 4.0 cm). Histologically, all were well circumscribed with a fibrous capsule containing lymphoid cuffs, and were composed of fusiform to plump spindle cells arranged in short fascicles and vaguely storiform patterns, admixed with prominent inflammatory infiltrates. Extensive stromal calcifications, focal necrosis and occasional mitotic figures, including one atypical mitosis, were present in one case. Immunohistochemically, all cases were positive for smooth muscle actin and HMB45, and negative for cytokeratins, ERG, CD31, S100, and ALK. Targeted RNA sequencing identified YAP1::TFE3 fusions in all tumors, with 2 showing identical breakpoints to CCST-L ( YAP1 exon 4- TFE3 exon 7), and 1 showing a breakpoint involving YAP1 exon 3- TFE3 exon 7. We report the first 3 cases of YAP1::TFE3 -rearranged, nonvisceral inflammatory spindle cell PEComa occurring in somatic soft tissue sites, expanding the anatomic spectrum of this recently characterized entity. Inflammatory spindle cell PEComa should be considered in the differential diagnosis of spindle cell neoplasms with prominent admixed inflammation.