Langerhans cell histiocytosis is primarily a disease of childhood, although it clearly also occurs in adults, including the elderly. Classically, it is divided into three types: (i) Letterer-Siwe disease, which is prone to occur early in life and marked by multifocal skin and/or systemic involvement; (ii) Hand-Schüller-Christian disease, in which skin lesions can be accompanied by diabetes insipidus, exophthalmos, and bony defects; and (iii) unifocal disease, or eosinophilic granuloma, which affects older children and adults and in which skin involvement can accompany lesions of bones and other organs. Variant forms include an eruptive type limited to the skin that occurs in both infants and adults , a pulmonary form in young adults related to cigarette smoking , a form localized to the genitalia of elderly adults , and a rare multifocal type with marked cytologic atypia, termed Langerhans cell sarcoma . Another form presents at birth or shortly thereafter as single or multiple cutaneous papules and nodules that develop rapidly, ulcerate, and involute spontaneously; this variant is termed congenital self-healing reticulohistiocytosis . The appearance of lesions can range from crusted hemorrhagic papules in a seborrheic distribution (seen most often in Letterer-Siwe and Hand-Schüller-Christian types) to ulcerated plaques, papules, and nodules. Disease associations can include acute lymphoblastic leukemia, neonatal infection, lymphoma, and virus-associated hemophagocytic syndrome. Prognosis largely depends on the number of organ systems involved, with the poorest survivals being associated with multisystem disease.
Biopsy specimens show aggregates of cells with eosinophilic cytoplasm and nuclei displaying grooves and folds, sometimes producing a reniform appearance . These cells have a distinct tendency to infiltrate the overlying epidermis. In Langerhans cell sarcoma, cells are larger and possess nuclei with abnormal chromatin, prominent nucleoli, and frequent mitotic figures. Extravasated erythrocytes and inflammatory cells, including eosinophils, are frequently identified. The cells have the immunophenotype of Langerhans cells, expressing S-100 protein, CD1a, vimentin, and HLA-DR, and they also stain with peanut agglutinin. However, unlike normal intraepidermal Langerhans cells, the neoplastic cells express CD4 and placental alkaline phosphatase and show a different adhesion molecule expression profile. With electron microscopic analysis, Birbeck granules can be identified in a variable percentage of tumor cells. Morphologically, Langerhans cell histiocytosis can usually be distinguished from potential mimics such as xanthoma disseminatum and cutaneous T-cell lymphoma, and the immunohistochemical profile of its constituent cells is decisive. ( Sternberg’s 5th ed)