Histiocytic disorders

The historic term 'histiocytosis' meaning 'tissue cell' is used as a unifying concept for diseases characterized by pathogenic myeloid cells that share histological features with macrophages or dendritic cells. These cells may arise from the embryonic yolk sac, fetal liver or postnatal bone marrow. Prior classification schemes align disease designation with terminal phenotype: for example, Langerhans cell histiocytosis (LCH) shares CD207(+) antigen with physiological epidermal Langerhans cells. LCH, Erdheim-Chester disease (ECD), juvenile xanthogranuloma (JXG) and Rosai-Dorfman disease (RDD) are all characterized by pathological ERK activation driven by activating somatic mutations in MAPK pathway genes. The title of this Primer (Histiocytic disorders) was chosen to differentiate the above diseases from Langerhans cell sarcoma and malignant histiocytosis, which are hyperproliferative lesions typical of cancer. By comparison LCH, ECD, RDD and JXG share some features of malignant cells including activating MAPK pathway mutations, but are not hyperproliferative. 'Inflammatory myeloproliferative neoplasm' may be a more precise nomenclature. By contrast, haemophagocytic lymphohistiocytosis is associated with macrophage activation and extreme inflammation, and represents a syndrome of immune dysregulation. These diseases affect children and adults in varying proportions depending on which of the entities is involved. Histiocytic disorders are characterized by proliferation of cells with macrophage or dendritic cell phenotype and intense inflammation. Clinical signs and symptoms depend on the specific disease and the tissues and organs affected.

Automated summary

Histiocytic disorders represent a group of diseases characterized by pathogenic myeloid cells with histological features similar to macrophages or dendritic cells. The diseases within this group, such as LCH, ECD, JXG, and RDD, are driven by activating mutations in the MAPK pathway. While these diseases share some malignant cell features, they are not hyperproliferative like cancer. Haemophagocytic lymphohistiocytosis, on the other hand, is associated with extreme inflammation and macrophage activation, representing a syndrome of immune dysregulation. These diseases can affect individuals of all ages with varying clinical manifestations depending on the specific disease.