histiocytosis

Histiocytosis refers to a group of rare disorders characterized by abnormal proliferation and accumulation of histiocytes, immune cells derived from monocytes and macrophages or dendritic cells. The most studied form is Langerhans cell histiocytosis (LCH); historically, cases were grouped under histiocytosis X.

Classification is based on the cellular origin of the proliferating histiocytes: Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytoses, which include disorders such as Erdheim-Chester disease and Rosai-Dorfman disease.

LCH commonly involves bone, skin, pituitary, lymph nodes, and lungs. Symptoms vary by sites and may include bone pain, skin rashes, diabetes insipidus, lymphadenopathy, or organ dysfunction. Non-LCH histiocytoses show organ involvement that depends on the specific entity.

Diagnosis rests on tissue biopsy. LCH cells express CD1a and Langerin (CD207) and are typically S-100 positive; Birbeck granules may be seen on electron microscopy. Mutations such as BRAF V600E and MAP2K1 are common in LCH and support targeted therapy decisions; non-LCH have variable mutation patterns.

Imaging, including skeletal surveys, MRI, CT, and PET-CT, maps disease extent, particularly bone lesions in LCH.

Treatment and prognosis depend on extent and organ involvement. Single-system LCH may be treated with local measures or observation; multi-system disease often requires systemic chemotherapy (vinblastine and prednisone) and supportive care. Targeted therapies (BRAF inhibitors for BRAF-mutant disease or MEK inhibitors) offer options for select patients. HLH, when present as a related immune syndrome, uses immunochemotherapy and, in suitable cases, stem cell transplantation.

Histiocytosis comprises rare, heterogeneous disorders. LCH is more common in children but occurs in adults, with prognosis ranging from excellent to poor depending on burden and response to therapy.