Wiley, Journal of Cutaneous Pathology, 8(49), p. 727-730, 2022
DOI: 10.1111/cup.14231
Full text: Unavailable
AbstractSeveral 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.