A novel GAB2::BRAF fusion in cutaneous non‐Langerhans‐cell histiocytosis with systemic involvement

Several mutations and gene fusions involved in the mitogen‐activated protein kinase (MAPK) pathway have been reported in histiocytic neoplasms including Langerhans cell histiocytosis and non‐Langerhans‐cell histiocytosis (NLCH). We identified a GAB2::BRAF fusion in a cutaneous lesion from a 22‐year‐old woman who presented with central diabetes insipidus and red/brown papules on her face, oral mucosa, axilla, and groin. Skin biopsy showed a CD68+, S100−, and CD1a− histiocytic proliferation consistent with NLCH, best clinically classified as xanthoma disseminatum. Next‐generation sequencing identified a GAB2::BRAF fusion involving exon 2 of GAB and exon 10 of BRAF. This case implicates a novel fusion in the MAPK signaling pathway, not previously reported in histiocytic neoplasms, as a possible driver of NLCH. Our findings underscore the utility of performing molecular studies on skin biopsy specimens with NLCH to help identify potential targets for therapy.