Histiocytic disorders: new haematopoietic neoplasms on the block

Abstract

The histiocytic disorders are rare diseases characterised by the accumulation of dendritic cell, macrophage and monocyte-derived cells in the skin, bone, lung, liver, haematopoietic organs and CNS. A wide range of presentations from benign cutaneous lesions to life-threatening multisystem disease is observed. Recent discoveries in genetic medicine have established that MAP kinase pathway activation by somatic mutation is almost universal in histiocytoses. This links histiocytosis with the family of myeloproliferative disorders and has opened up critical new therapeutic opportunities through the use of BRAF and MEK inhibitors. A revised classification no longer recognises Langerhans and non-Langerhans cell histiocytosis but proposes 5 disease groups: (1) Langerhans-related, (2) cutaneous and mucocutaneous; (3) malignant histiocytoses; (4) Rosai-Dorfman disease; and (5) haemophagocytic lymphohistiocytosis and macrophage activation syndrome. Guidelines for improved diagnosis based on modern imaging and molecular techniques will be discussed, together with the implication of these methods for treatment with targeted drugs.