Prognostic factors of hemophagocytic syndrome in adults: analysis of 34 cases.

Hemophagocytic syndrome (HPS) presents with fever, pancytopenia, liver dysfunction and increase in hemophagocytic histiocytes in various organs. Although there are two major classifications of HPS in adults, malignant and reactive histiocytosis, it is often very difficult to distinguish between these disorders. We analyzed the laboratory data of patients with HPS to evaluate prognostic factors. Of 34 patients, 14 survived, and 20 died. The median age of survivors was 29.6+/-11.5 yr significantly younger than those who died (54.7+/-17.8 yr). Twenty patients had no obvious underlying disease, the other 13 had hematological malignancies or viral infections. Comparison of laboratory data revealed that nonsurvivors had significantly lower Hb and platelet values on admission. During treatment, worsening of anemia and thrombocytopenia, increase of transaminase and biliary enzymes were similarly more prominent. Risk factors associated with death were: age over 30 yr, presence of disseminated intravascular coagulation, increased ferritin and beta2-microglobulin, anemia accompanied by thrombocytopenia and jaundice. Our data suggests that patients with HPS and any of these risk factors should be treated aggressively with sufficient chemotherapy and supportive care.

Age-related neoplasia in a lifetime study of ad libitum-fed and food-restricted B6C3F1 mice.

Longevity, body weight, and age-specific neoplasia were determined in 1,064 B6C3F1 mice as part of a coordinated study of food restriction (FR). Restricted animals were offered 60% of the diet consumed by the ad libitum (AL) group. Longevity data were derived from a set of 56 animals of each sex from each diet group, which were examined whenever dead or moribund. For cross-sectional data, a parallel set of 210 animals were sacrificed in groups of 12-15 at 6-mo intervals. Lifetime body weight was reduced in the FR mice approximately proportional to restriction (i.e., 40%). Food restriction increased the age at 50% survival (median) by 36% in both sexes and increased the maximal lifespan (mean age of oldest 10%) by 21.5% in males and by 32.5% in females. In 56 males of the longevity groups, there were 89 neoplasms in the AL subgroup versus 53 in FR; 56 AL females had 100, versus 58 in 55 FR females. Increase in lifespan of the restricted animals was achieved primarily by decrease in incidence and delay of onset of fatal tumors, of which lymphoma was the most prominent. This report catalogs all of the neoplasms (1,103) observed in longevity and cross-sectional groups, by diet, sex, and age. These data add to the existing knowledge base needed for future studies of dietary restriction and aging as well to evaluate nutrition of animals used in bioassays.

Histiocytic sarcomas and monoblastic leukemias. A clinical, histologic, and immunophenotypical study.

Eight histiocytic sarcomas, identified by examination of more than 2000 malignant lymphomas, are described. For comparison, tumor infiltrates from five monoblastic leukemias were also analyzed. The histiocytic sarcomas were all high-grade malignancies consisting of markedly pleomorphic large cells with many mitotic figures. At presentation, six of the patients had systemic symptoms (fever, fatigue, loss of weight), skin infiltrates, and lymphadenopathy. Despite aggressive chemotherapy, clinical remissions were short, and six patients died of disease .5-48 months (mean, 6.5 months) after diagnosis. The remaining two patients are alive and in partial or complete remission 7 and 12 months after diagnosis. Immunotypic examination showed that all the histiocytic sarcomas were positive for macrophage-related antigens and negative for antigens on B cells, T cells, myeloid cells, epithelial cells, and melanocytes. T-cell receptor and immunoglobulin genes were studied in three cases and were present in a germline configuration. One of the histiocytic sarcomas resembled Langerhans' cells in phenotype and morphology; it was classified as a Langerhans' cell sarcoma. The remaining histiocytic sarcomas did not express accessory cell-associated antigens, but more closely resembled "ordinary" tissue macrophages; they were positive for lysozyme and/or CD68, followed in frequency by CD11c, CD4, CD11b, CDw32, peanut agglutinin receptor, and CD13. Similar features were seen in the monoblastic leukemias. These conditions could only be distinguished from histiocytic sarcoma by clinical and morphologic, rather than immunophenotypic, criteria. Expression of oncoprotein p53 was studied in nine cases and was positive in six of six histiocytic sarcomas and one of three monoblastic leukemias. Rare malignancies show features consistent with the derivation from macrophages. Two entities may be distinguished: those that resemble antigen-presenting accessory cells and those that more closely resemble ordinary tissue macrophages. Recognition of these tumors is important clinically and requires assessment of clinical, morphologic, and immunophenotypic features, supplemented by analysis of T-cell receptor and immunoglobulin genes. Whether (or how) p53 gene mutations are implicated in their pathogenesis will be an important topic for future investigation.