Molecular Aid in the Classification of a Clear Cell Neoplasm with MITF::CREM Rearrangement

ABSTRACT: The advent of molecular techniques has significantly enhanced the classification of melanocytic and nonmelanocytic tumors with melanocytic differentiation. One notable development is the identification of tumors within the MITF pathway, including the rare MITF::CREM fusion-associated lesion. In this study, we present a case of a 16-year-old adolescent girl with a lesion located on the mid upper back. Histopathologic examination revealed a poorly circumscribed, hypercellular dermal-based neoplasm composed of epithelioid cells arranged in sheets and cords. Notably, clear cell changes were observed only after re-excision. Molecular analysis through genome and RNA sequencing confirmed the presence of an MITF::CREM fusion, marking this as a rare MITF-pathway fusion tumor. To date, such tumors have been infrequently reported in the literature. Accurate classification of melanocytic tumors is crucial for guiding management and predicting prognosis. This case highlights a rare subtype of clear cell tumor with melanocytic differentiation, underscoring the need for further case studies to better understand its potential behavior and clinical significance.