Origin, diagnosis and treatment of periocular Histiocytic disorders- state-of-the-art review

Historically classified as benign or malignant, histiocytic disorders are a diverse group of conditions characterised by abnormal accumulation of cells from the mononuclear phagocytic system. Diagnosis primarily relies on histopathological examination, but recent molecular and histological advances have refined classification into five subtypes: (1) Langerhans-related histiocytosis, (2) cutaneous and mucocutaneous histiocytosis, (3) Rosai-Dorfman disease, (4) haemophagocytic lymphohistiocytosis (HLH) and macrophage-activation syndrome and (5) malignant histiocytosis. Treatments include local excision, systemic corticosteroids, and chemotherapy targeted to specific mutations (such as inhibitors to BRAF mutations). The prognosis remains variable, with Langerhans cell histiocytosis often showing favourable outcomes and, due to systemic involvement, HLH and malignant histiocytoses carrying a poor prognosis. This review provides an updated understanding of histiocytic disorders affecting the orbit, and highlights advances in understanding of pathogenesis, diagnosis, and therapeutic approaches. KEY MESSAGES: WHAT IS KNOWN : Histiocytic disorders are a diverse group of conditions characterised by abnormal accumulation of cells from the mononuclear phagocytic system in tissue throughout the body, and often in the orbit and periocular structures, with a wide spectrum of clinical presentations. WHAT IS NEW : This review of histiocytic disorders follows the newest classification of disease, addressing each group methodically. An update is provided of the molecular and genetic understanding of histiocytic disorders which present new diagnostic tools and treatment targets. Up-to-date published management of the disorders are reviewed.