Abstract

We present a rare case of clear cell tumor with melanocytic differentiation and ACTIN-MITF translocation.  A 46-year-old man presented with a lesion on the front of his left leg.  Physical examination revealed a dome-shaped, pink, soft nodule. Shave biopsy from the left pretibial region showed a dermal clear cell neoplasm composed of packets of clear cells enwrapped by delicate capillaries.  The majority of the tumor cells were small, with round normochromatic nuclei.  The tumor was MITF positive, and diffusely and weakly expressed HMB45.  AE1/3, CAM5.2, PAX8, SOX-10, S-100, Melan A, SMA, desmin, CD34, caldesmon, and TFE3 were negative. Molecular assay detected fusion of ACTB and MITF genes.  ACTIN-MITF fusion is a structural alteration which is reported to produce hyperactive MITF function.  Clear cell neoplasms showing melanocytic differentiation include clear cell sarcoma, PEComa, and subtypes of renal carcinoma. A hallmark of these tumors is the activation of a member of the MIT/TFE family of transcription factors. Cytogenetic translocations involving TFE3 and TFEB are described in multiple tumor types, but there has been little evidence to suggest similar regulation of MITF. Clear cell cutaneous neoplasms with melanocytic differentiation that are characterized by ACTIN (ACTB)-MITF gene fusions are rare. Previously, these tumors were likely diagnosed as PEComas or as paraganglioma/clear cell sarcoma-like dermal melanocytic tumor. Malignant potential must be considered, though malignancy is uncertain due to limited data. Related tumors with similar gene fusions are presently regarded as neoplasms of low malignant potential. Treatment appropriate for superficial cutaneous low-grade sarcoma is recommended.