•Hypofibrinogenemia and hyperlipidemia (hypertriglyceridemia)

•Impaired immunity of the humoral and cellular immune response, hypogammaglobulinemia, anergy to specific antigens, although B- and T-lymphocyte subsets may be present in normal distribution

•Natural killer cells are decreased and/or have decreased cytolytic function due usually to defects in synthesis, transport, or exocytosis of cytolytic granules

8.4.5Clinical Course

•Intermittent fever

•Progressive pancytopenia

•Liver dysfunction with jaundice

•Hemorrhage

•Meningitis

•Often lethal outcome within weeks or a few months without treatment

8.4.6Differential Diagnosis

•Secondary hemophagocytic syndrome

•Juvenile xanthogranulomatosis of the skin:

–In newborns and small children

–Usually a benign course

•Xanthoma disseminatum of the skin during the perinatal period:

–With multiple, dark red and dark blue skin infiltrations, which disappear spontaneously within 3–4 months

–Leukemia

–Neuroblastoma

8.4.7Therapy

•Chemotherapy with vinblastine, etoposide, cyclosporine, and corticosteroids may result in transient improvement, followed by allogeneic stem cell transplantation

•Supportive treatment with intravenous immunoglobulins, antibiotics or specific treatment when an underlying disease/infection is diagnosed

•Salvage treatment with anti-TNF antibody (infliximab) maybe indicated

8.5Malignant Histiocytosis

8.5.1Incidence

•Disease of adults, occasionally also in children and adolescents

•Predominant in men

8.5.2Pathology

•Monocyte-related leukemia or dendritic cell-related histiocytic sarcoma

–Proliferation of atypical, malignant histiocytes and precursor cells; often involves lymph nodes but can involve any organ

–Progressive extension of disease similar to Hodgkin disease (differential diag- nosis: Hodgkin disease stage IV, anaplastic lymphoma)

8.5.3Clinical Presentation

•Fever

•Lymphadenopathy, hepatosplenomegaly

•Maculopapular and nodular skin infiltration of atypical histiocytes

•Pancytopenia due to hypersplenism

•Often rapid onset and progressive disease with multiorgan involvement

8.5.4Therapy

•Intensive chemotherapy with combinations of vincristine, doxorubicin, cyclo- phosphamide, and prednisone, or M-BACOD (high-dose methotrexate, bleomy- cin, doxorubicin, cyclophosphamide, Oncovin, and dexamethasone); regimens designed to treat high-risk lymphoid malignancies appear most effective

•Stem cell transplantation may be indicated