Title: Familial hemophagocytic lymphohistiocytosis: report of four cases in a Japanese family.
Abstract: Four cases of familial hemophagocytic lymphohistiocytosis(FHL) occurring in a Japanese family are reported. They presented with typical fever, hepatosplenomegaly, and convulsions in the first year of their lives. These children were products of unconsanguineous marriage, and all children in that family were affected by FHL. Family history was otherwise unremarkable. Pertinent laboratory findings included pancytopenia, liver dysfunction and hypofibrinogenemia in all four cases. Hypertriglyceridemia was recorded in the fourth child. Clinical course was fulminant in all four cases. They died between 30 and 78 days after the onset of the disease. Autopsy revealed maked hepatosplenomegaly, marked atrophy of systemic lymphoid organs, and varaible degrees of lymphohistiocytic infiltration in many internal viscera. The infiltralion was noted in almost every organ, but was most prominent in spleen, bone marrow, and central nervous system. Many of these histiocytes showed variable degrees of hemophagocytosis. Immunohistochemical studies of proliferating histiocytes have shown following results: Leu M1(+), Leu 4(-), Leu 8(-), HLA-DR(+), Leu-M5(+), S-100 protein (-), α-1-antichymo-trypsin (+), lysozyme (+), and epithelial membrane antigen (EMA) (-). These data indicate that proliferating histiocytes are carrying markers similar to those of sinus histiocytes in reactive lymph nodes, and that they do not carry markers of T-zone histiocytes. Lack of cellular atypia as well as negative staining patterns for EMA suggest benign nature of these histiocytes. However, a possibility of malignancy cannot be ruled out with certainty, as these histiocytes infiltrated and destroyed the parenchyma of brain in all four cases.