Immunophenotypic and Molecular Analysis of a Novel Case of ACTG1::MITF Fusion Clear Cell Tumor With Melanocytic Differentiation

Abstract

Recently, a number of clear cell neoplasms with melanocytic differentiation have been reported. A more recently described fraction of these are microphthalmia-associated transcription factor (MITF) fused neoplasms. We report an additional case of an ACTG1::MITF fusion clear cell neoplasm on the right lateral thigh of a 74-year-old woman with detailed immunophenotypic and molecular analysis. Thus far, only 12 prior cases of MITF fusion clear cell tumors with melanocytic differentiation have been reported in the literature, of which 9 had an "ACTIN" fusion partner. Hence, more studies are needed to fully characterize the immunophenotypic, molecular, and clinical features of these tumors. This tumor had strong nuclear staining with MITF, complete absence of SOX10 staining, and weak blush positivity of the cytoplasm with S100. Mart-1 and HMB-45 showed focal positive staining. Furthermore, we compare the clinical, morphologic, and immunophenotypic features of our case and other MITF fusion tumors with other morphologically similar tumors such as clear cell sarcoma, CRTC1::TRIM11 fused neoplasms, NONO::TFE3 epithelioid and spindle cell neoplasms, MED15::ATF fused neoplasms, and PEComas. Although all these tumors share a common theme of MITF pathway overactivation, there are distinct clinical, morphologic, and immunophenotypic differences. In addition to detailing specific features of our case, we also discuss those differences that may help distinguish ACTG1::MITF fusions from other clear cell tumors. Considering the significant differences in clinical outcomes between these distinct classes of clear cell tumors, accurate distinction can significantly affect management options.

Keywords: clear cell tumor; clear cell tumor with melanocytic differentiation.