Abstract

Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (non-LCH) are rare disorders characterized by the accumulation of histiocytes (dendritic cells and macrophages). The discovery of recurrent BRAF p.V600E mutations in LCH samples established the neoplastic nature of these diseases and identified a potential therapeutic target. Since then, many other mutations and fusions of genes involved in the mitogen-activated protein kinase (MAPK) pathway have been reported in histiocytic neoplasms. Here we describe a GAB2-BRAF fusion identified in a cutaneous lesion from a 23-year-old woman who presented with central diabetes insipidus and red/brown papules on her face, oral mucosa, axilla, and groin. Skin biopsies showed a CD68+, S100-, and CD1a- histiocyte proliferation with Touton-type giant cells consistent with a non-LCH which was clinically classified as xanthoma disseminatum. Next-generation sequencing identified a GAB2-BRAF fusion involving GAB exon 2 and BRAF exon 10. Although previously described in other tumors, this is the first report of this fusion in a histiocytic neoplasm. She was treated with high-dose prednisone with partial response at 5-month follow-up. This case implicates a novel fusion mutation in the MAPK signaling pathway as a possible driver of non-LCH histocytoses, and underscores the utility of performing molecular studies on skin biopsies with non-LCH as a means of identifying potential targets for therapy.

Financial Disclosure:
No current or relevant financial relationships exist.