Histiocytoses

The histiocytoses are characterized by the infiltration of affected tissues with cells of monocyte/macrophage lineage.

Disorders of dendritic cells

Langerhans’ cell histiocytosis—may present with (1) disease affecting a single organ—typically skin (rash) or bone (pain and soft tissue swelling, or asymptomatic radiographic lesions); or (2) multisystem disease—characteristic features include ear discharge, diabetes insipidus, and lung involvement (diffuse micronodular shadowing on chest radiography, with progression to cyst formation and a honeycomb lung appearance). Diagnosis requires identification of Langerhans’ cells within lesional inflammatory cell infiltrate, with demonstration of either the CD1a surface antigen on immunohistochemistry or the presence of Birbeck granules on electron microscopy. Most cases eventually resolve spontaneously. Immunosuppressive and/or cytotoxic drugs are given when there is progressive organ injury, but the most effective and least toxic approach to treatment is not known.

Disorders of macrophages

Haemophagocytic lymphohistiocytosis—this may be (1) primary—an autosomal recessive disorder, caused in some cases by mutation in one of several genes involved in down-regulation of the T-cell response via apoptosis; or (2) secondary—the condition may be associated with a range of infectious, malignant and other disorders. Manifestations include fever, a variety of neurological conditions, splenomegaly, hepatomegaly, lymphadenopathy, pancytopenia, abnormal liver function, and coagulopathy. Diagnosis requires histopathological demonstration of haemophagocytosis in an appropriate clinical context. Aside from supportive care, standard treatment of primary disease is with (1) etoposide and corticosteroids, or (2) antithymocyte globulin, corticosteroids, and ciclosporin.

Malignant histiocyte disorders

Acute myelomonocytic and acute monocytic leukaemia—see Chapter 22.3.4.