Molecular Pathogenesis of the Histiocytic and Dendritic Cell Neoplasms

Abstract

The histiocytic and dendritic cell neoplasms encompass a clinically heterogeneous group of disorders leading to tissue damage secondary to the accumulation and infiltration of pathologic cells thought to be derived from the dendritic or monocytic lineages with accompanying inflammation. The pathophysiology of these disorders is poorly understood. Studies over the past 15 y have identified a high-frequency of BRAF^V600E, MAP2K1, and other kinase alterations in the histiocytic neoplasms. This review highlights the onslaught of molecular advancements and discusses the impact these insights have had on our understanding of the molecular pathophysiology and therapeutic targets of these rare, enigmatic diseases.

Keywords: BRAF; Erdheim-chester disease; Histiocytosis; Langerhans cell histiocytosis; MAP kinase signaling; MAP2K1; MEK1/2 inhibitors; Vemurafenib.