A prospective evaluation of normal mean platelet volume in discriminating hyperdestructive thrombocytopenia from hypoproductive thrombocytopenia.

Bone marrow (BM) examination is the gold standard test in discriminating between hyperdestructive thrombocytopenia and hypoproductive thrombocytopenia. However, this procedure is invasive. Mean platelet volume (MPV) is simple and may be used as an alternative diagnostic test in distinguishing these two types of thrombocytopenia. All thrombocytopenic patients (platelet count: <150.0 x 10(9)/l), except those with congestive splenomegaly, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulopathy, were enrolled into the study prospectively. The mean MPV of normal Thais (7.9 fl) was tested as a cutoff value. Any thrombocytopenic patient with MPV of >7.9 fl would be presumptively diagnosed as hyperdestructive thrombocytopenia, whereas one with MPV of 7.9 fl could predict hyperdestructive thrombocytopenia with a sensitivity of 82.3% (95% CI: 70.5-90.8), a specificity of 92.5% (95% CI: 79.6-98.4), a positive predictive value of 94.4% (95% CI: 84.6-98.8), a negative predictive value of 77.1% (95% CI: 62.7-88.0), and a likelihood ratio of 11.0. In conclusion, the mean MPV of normal Thais may be used as a cutoff value in distinguishing these two types of thrombocytopenia.

Multiple lymphoid nodules in bone marrow have the same clonality as underlying myelodysplastic syndrome recognized with fluorescent in situ hybridization technique.

Benign nodular lymphoid lesions are not rare in the bone marrow of patients with myelodysplastic syndrome (MDS). Herein, we report a case of MDS with clonal lymphoid aggregates in the bone marrow but without evidence of systemic lymphoma. The case of a 71-year-old man was evaluated for cytopenia. His bone marrow was initially hypocellular, with 10% blasts and a few small lymphoid aggregates. The diagnosis of refractory anemia with excess blasts was made. The disease progressed gradually, and he received erythropoietin and granulocyte colony-stimulating factor for a short time. Forty-two months later, acute leukemia (M1) developed, with 60% to 70% blasts in the bone marrow. The bone marrow also showed large aggregates of lymphocytes. Immunohistochemical study of these cells in the nodular lesions showed 50% CD3+ and 50% CD20+. Cytogenetic and molecular genetic studies revealed monosomy 7 and T- and B-cell clonal gene rearrangement. Fluorescent in situ hybridization study with centromere-specific probes of a bone marrow specimen showed monosomy 7 in both nodular lymphoid lesions and surrounding bone marrow cells, indicating that both processes originated from the same abnormal pluripotential progenitor.

Nodular lesions of monocytic component in myelodysplastic syndrome.

We report 4 unusual cases of myelodysplastic syndrome with distinct persistent nodular lesions noted on serial bone marrow examinations, even during remission. The lesions were predominantly composed of immature monocytes that stained positively for CD68. Trisomy 9 and 11 were demonstrated in the cells of the nodular lesions and surrounding marrow of 1 patient, indicating the same clonal origin. Evaluation of p53 glycoprotein, retinoblastoma protein (pRb), proliferation-related protein (Ki-67), multiple drug-resistant enzyme glutathione-S-transferase pi, and topoisomerase IIalpha (Topo IIalpha) revealed decreased topoisomerase expression within the nodular lesions compared with the surrounding marrow and absence of Ki-67 antigen within nodular lesions. Most cells in the lesion were not in a proliferative cycle, with very low expression of Topo IIalpha, which may explain the apparent drug resistance of these nodular lesions.

Is multidrug resistance (P-glycoprotein) an intrinsic characteristic of plasma cells in patients with monoclonal gammopathy of undetermined significance, plasmacytoma, multiple myeloma and amyloidosis?

Multiple myeloma is not a curable disease, and most patients relapse after plateau phase. Drug resistance is a major problem in effective chemotherapy in this kind of disease. Current approaches are aimed at reversing or preventing drug resistance late in the disease. We studied a drug resistance marker, P-glycoprotein (P-gp), in a total of 43 patients with monoclonal gammopathy. This group included eight with monoclonal gammopathy of undetermined significance (MGUS), five with plasmacytoma (PCM), nineteen with multiple myeloma (MM; six newly diagnosed, seven plateau, five refractory, one relapse) and eleven amyloidosis (seven newly diagnosed, four after treatment). Using 3-color flow cytometry, a plasma cell gate was selected on the basis of CD38+/45-(dim) staining and the population was examined for the expression of P-gp using two monoclonal antibodies (MRK16 and UIC2). P-gp expression was positive on marrow plasma cells in 42/43 patients. The resistance index (RI) in these cases (range 2.0-7.07) is comparable to that in the positive cell line KG-1A (3.05-3.08). In 2 of 5 patients with refractory MM, the RI for P-gp (5.4, 6.36) was higher than in plateau phase. These data suggest that relative resistance due to the P-gp mechanism is likely to be an intrinsic property of plasma cells in monoclonal gammopathies and may provide a partial explanation as to why these diseases always relapse. The results of our study support strategies for MDR reversal earlier in the course.

True malignant histiocytosis.

OBJECTIVE: To attempt to distinguish cases of true malignant histiocytosis from the clinical syndromes of so-called malignant histiocytosis with use of recent methods. DESIGN: We retrospectively studied the laboratory data and clinical course of Mayo patients who had clinical syndromes of so-called malignant histiocytosis and reviewed available paraffin-embedded tissue specimens to identify the nature of the malignant cells. MATERIAL AND METHODS: After elimination of cases of infection-associated hemophagocytic syndrome, we reviewed and studied seven cases of so-called malignant histiocytosis in patients who had undergone assessment at Mayo Clinic Rochester between 1973 and 1993. We identified histiocytes by using current morphologic, cytochemical, and immunohistochemical methods. The clonal nature of the malignant cells was identified with morphologic, cytogenetic, and molecular genetic studies. RESULTS: Only one of the seven cases had a true histiocytic origin. The malignant cells were T cells in three other cases (the cells were also CD30+ in two cases), CD30+ cells only in one case, epithelial cells in one case, and an undetermined cell type (stained positively only with antitrypsin) in one case. CONCLUSION: True malignant histiocytosis is an exceedingly rare disease, and only a few reports have clearly identified the histiocytic origin of the malignant cells. Previously, the lack of monoclonal antibodies specific to histiocytes and the absence of techniques for performing molecular genetic studies on paraffin-embedded tissue prevented the study of such cases. With newer techniques cases of true malignant histiocytosis can now be identified.

Primary plasmacytoma at the site of exit wounds after electrical injury.

We report a case of primary plasmacytoma occurring 12 years after electrical injury. Roentgenograms showed multiple well-circumscribed lytic lesions involving both the right and left tibial diaphyseal regions. Bone biopsy from the left tibial region showed sheets of monoclonal myeloma cells. No evidence of multiple myeloma was found. The patient was treated with local radiation to both tibias and had no evidence of recurrence 6 years later. In conclusion, we report the first case of primary plasmacytoma of both tibias that occurred after electrical injury 12 years before.

Levels of serum tumor necrosis factor alpha in relation to clinical involvement and treatment among Thai adults with Plasmodium falciparum malaria.

UNLABELLED: Concentrations of tumor necrosis factor alpha (TNF-alpha) in serum were measured in 17 Thai men infected with Plasmodium falciparum malarial infections to determine whether they were affected by severity of infections or exchange transfusions. Twelve patients were considered having complicated malarial infections, eight of whom had cerebral malaria. Five patients had uncomplicated malarial infections. The results showed that malarial infection markedly raised TNF-alpha level above normal values (mean +/- SEM 406 +/- 38 vs 15 +/- 5, p = 0.004). In complicated malaria, cerebral involvement appeared to significantly increase concentration of TNF-alpha when compared to values in uncomplicated malaria (mean +/- SEM 496 +/- 64 vs 339 +/- 12, p = 0.01). Degree of parasitemia, intravenous quinine (day 0 value vs day 7 value) and exchange transfusion did not significantly affect TNF-alpha levels. CONCLUSION: Serum level of TNF-alpha is increased in Plasmodium falciparum malarial infections and may be a useful index to predict severity of malarial infection, cerebral malaria in particular.

Pleomorphic large cell hemato-lymphoma (the so-called "malignant histiocytosis"): clinicopathological and immunophenotypic studies in 35 cases.

Thirty-five patients diagnosed with "malignant histiocytosis" from 1984 to 1989 were studied for clinical, laboratory, histopathological features as well as survival and response to therapy, Immunocytochemistry and immunophenotypic studies were performed in 12 cases using the paraffin immunoperoxidase method. The staining included alpha-1 antichymotrypsin, muramidase, immunoglobulins and monoclonal antibodies specific for T, B lymphocytes and macrophage. From the clinical features, responsiveness to therapy and survival, the patients were divided into 2 groups: the non-responders (25 cases) and responders (10 cases) groups. Very short median survival of 1.25 months was found in the non-responders, whereas, longer median survival of 14.15 months was found in the responder group. Important different clinical and laboratory features were observed among these two groups. Unresponsiveness to treatment; rapidly progressive pancytopenia, increased hemophagocytosis, presentation of immature cells in blood with extensive infiltration of malignant cells in the bone marrow; severe jaundice and deterioration of hepatic function accompanied by early extranodal involvement were almost exclusively observed initially in the non-responder group. Satisfactory response to treatment was observed only in the responder group. Similarity of histopathology, cytology and immunophenotype was observed in these two groups. The immunophenotypic study in 12 cases showed 5 cases of B-cell lymphoma, 3 cases of T-cell (with 1 Ki-1 -positive) lymphoma; 1 case of Ki-1 positive non-T, non-B anaplastic large cell lymphoma; and 3 cases of undetermined cell lineage. From this study, so-called "malignant histiocytosis" appears to be a disorder of heterogeneity. The immunophenotypes of malignant cells indicated that their origin belonged mostly to lymphoid cell lineage. Based on their clinical feature of the early hematogenous spread along with the distinct histopathological and immunophenotypic findings, the term "pleomorphic large cell hematolymphoma" is proposed to be used instead of the old misnomer, "malignant histiocytosis" (MH).

Exchange transfusion therapy in severe complicated malaria.

Nine cases of severe complicated falciparum malaria treated by exchange transfusion were studied. Eight patients survived and one patient died. Multisystemic complications were found in all cases. The CNS complications, acute renal failure, pulmonary insufficiency, jaundice, bleeding, sepsis, and DIC were found in 9, 7, 5, 7, 2, 4 and 1 cases, respectively. The fatal case presented with severe multisystemic complications together with 40% parasitemia. In eight survivors, whose parasitemia ranged from 0.3%, to 90%, had milder degrees of systemic complications. With the use of blood exchange 10-15 units, the parasitemia was decreased to less than 5% within 24 hours in all expect one who had parasitemia 90%. In comparison with the other 10 matched non-exchanged patients, there was no significant difference in survival rate between these two group (89% vs 80%). However, in the patients with ARDS the survival rate in the group who received the exchange transfusion therapy was superior (75% vs 0%). The exchange transfusion therapy is therefore strongly recommended in the treatment of malarial patients who present with parasitemia > 30% and severe systemic complications, particularly those who have severe acute renal failure or have lung complications. The amount of blood used for exchange transfusion should at least 1.2 times the blood volume for rapid removal of parasites and toxic metabolites from the circulation.