Is immunohistochemistry always the panacea to morphologic mimics? Two, distinct soft tissue tumors exhibiting...

Alveolar soft part sarcoma (ASPS) and certain perivascular epithelioid cell neoplasms (PEComas) exhibit overlapping histopathological features, including immunohistochemical expression of TFE3, as well as TFE3 gene rearrangement. PEComas with an epithelioid morphology are known to exhibit variable immunoexpression of muscle markers. At the same time, aberrant immunoreactivity of HMB45 immunostain, which is invariably, used to substantiate a diagnosis of a PEComa, has been reported in various other tumors. Herein, we discuss two rare cases of soft tissue tumors with overlapping morphological and immunohistochemical features. Case1: A 34-year-old male underwent a biopsy for a recurrent, right-sided nasal polyp. Biopsy showed polygonal tumor cells, containing prominent nucleoli, arranged in a "nesting-type"/alveolar growth pattern. Immunohistochemically, tumor cells displayed TFE3 positivity and an aberrant positivity for HMB45. Special stain (PAS-diastase) highlighted intracytoplasmic granules and crystals. Diagnosis of ASPS was offered. Furthermore, the tumor cells displayed TFE3 gene rearrangement. Case 2: A 29-year-old female underwent an aural polypectomy. Microscopic examination revealed a tumor with a "nesting-type"/alveolar arrangement of tumor cells with vacuolated cytoplasm, arranged around thin-walled blood vessels. Immunohistochemically, tumor cells were diffusely positive for HMB45 and TFE3 and focally for SMA. A diagnosis of a PEComa was offered. This report constitutes the first documentation of aberrant HMB45 immunoreactivity in case of ASPS, and one of the first reported cases of a PEComa in the ear. It emphasizes the value of integrating clinicopathological features with immunohistochemical and molecular results in differentiating two rare, but distinct soft tissue tumors with overlapping features. An exact diagnosis of both these tumor entities has therapeutic implications.