Disseminated Xanthogranuloma Harboring a GAB2::BRAF Fusion and MITF Pathogenic Variant Successfully Treated With Cobimetinib: A Rare Case Report

ABSTRACT Several activating mutations and gene fusions involving the mitogen‐activated protein kinase (MAPK) pathway have appeared in the literature regarding histiocytic neoplasms. We identified a GAB2::BRAF fusion in a cutaneous lesion of a 36‐year‐old male who developed central diabetes insipidus and reddish‐pink grouped papules on the bilateral axillary rims, inguinal region, and periocular skin. Skin biopsy obtained from an axillary lesion showed a CD68+, S100‐, and CD1a‐ histiocytic proliferation with foamy histiocytes and multinucleated Touton giant cells, compatible with xanthogranuloma. Next‐generation sequencing identified a GAB2::BRAF fusion involving Exon 2 of GAB2 and Exon 10 of BRAF . Our case further highlights this novel fusion in the MAPK signaling pathway as a possible driver of nonLangerhans cell histiocytosis (NLCH) and underscores the utility of performing molecular studies on skin biopsy specimens with NLCH to help identify potential targets for therapy.