Expanding the histomorphologic spectrum of TFE3-rearranged perivascular epithelioid cell tumors

Perivascular epithelioid cell tumors (PEComas) are a family of mesenchymal neoplasms that have smooth muscle and melanocytic differentiation. They can be sporadic or associated with tuberous sclerosis complex and commonly present in the kidney as angiomyolipoma or in the lung as pulmonary clear cell sugar tumors or lymphangioleiomyomatosis. However, they can present at any visceral or soft tissue site. They usually have a benign clinical course, but rarely can behave in a malignant fashion. Most PEComas demonstrate abnormalities of TSC2, but a recently described subset harbor TFE3 rearrangements that seem to be mutually exclusive of TSC2 alterations. TFE3-rearranged PEComas demonstrate a distinct alveolar morphology that lacks spindle cells and smooth muscle differentiation. Distinction between these may have important therapeutic consequences. Herein, we present a case of a TFE3-rearranged PEComa without the customary morphology that required ancillary investigation with TFE3 immunohistochemistry and break-apart fluorescence in situ hybridization for proper categorization.