Familial erythrophagocytic lymphohistiocytosis: immunophenotypic, immunohistochemical, and ultrastructural demonstration of the relation to sinus histiocytes.

Familial erythrophagocytic lymphohistiocytosis (FEL), a rare, rapidly fatal childhood disease, is characterized by fever, hepatosplenomegaly, pancytopenia, and widely disseminated lymphohistiocytic infiltrates with prominent erythrophagocytosis. Immunophenotypic, immunohistochemical, and ultrastructural studies of two siblings with FEL were performed in an effort to determine the nature of the proliferating histiocyte of FEL. These studies demonstrated that the FEL histiocytes lack S-100 protein, T6, and Birbeck granules, which are found in Langerhans and interdigitating dendritic cells. The FEL histiocytes express alpha 1-antichymotrypsin, Leu-M3, HLA-DR, and, variably, lysozyme and Leu-M1. Thus, the proliferating histiocyte of FEL is a member of the mononuclear phagocytic system and has a phenotype similar to that of the histiocytes that normally populate the sinuses of benign and reactive lymph nodes. These studies suggest that FEL may represent uncontrolled proliferation of sinusoidal histiocytes.