Acute bilineal leukemia: a rare disease with poor outcome.

Most cases of acute leukemia can be assigned to the myeloid, B or T lineage. In a few cases, definitive assignment cannot be achieved because blasts express antigens of more than one lineage. A subset of these, referred to as acute bilineal leukemias (aBLLs), is characterized by the presence of more than one population of blasts, each comprising a single lineage. We identified 19 cases of aBLL, including 10 mixed T and myeloid (T-My) and nine mixed B and myeloid (B-My); no mixed B and T cases were identified. Cytogenetic data were available for 16 patients. Three of seven patients with B-My had a t(9;22)(q34q11.2), two had 11q23 translocations and one had del(9). Two of nine patients with T-My had 2p13 translocations; five had other unrelated abnormalities. Of 16 patients with outcome data, only six achieved complete remission and only two remain free of disease 2.5 and 4.5 years after chemotherapy or stem cell transplantation. aBLL is a rare disease that combines B or T and myeloid blasts. Cytogenetic abnormalities of t(9;22) and 11q23 are common in, and may be restricted to, B-My cases, while T-My cases have frequent but generally non-recurring abnormalities. Both types of aBLL are associated with poor outcome.

Flow cytometry in the diagnosis of acute leukemia.

Acute leukemias are a heterogeneous group of malignancies with varying clinical, morphologic, immunologic, and molecular characteristics. Many distinct types are known to carry predictable prognoses and warrant specific therapy. Distinction between lymphoid and myeloid leukemias, most often made by flow cytometry, is crucially important. Several advances in flow cytometry, including availability of new monoclonal antibodies, improved gating strategies, and multiparameter analytic techniques, have all dramatically improved the utility of flow cytometry in the diagnosis and classification of leukemia. Acute leukemias reflect the pattern of antigen acquisition seen in normal hematopoietic differentiation, yet invariably demonstrate distinct aberrant immunophenotypic features. Detailed understanding of these phenotypic patterns of differentiation, particularly in myeloid leukemia, allows for more precise classification of leukemia than does morphology alone. However, morphologic and differentiation-based classifications of leukemia are limited in their prognostic value; cytogenetics and molecular genetics appear to be most important for identifying entities with distinct prognoses and clinical behavior. Increasingly, many of these genetically distinct subgroups of leukemia have been found to be closely associated with distinct immunophenotypes. For example, translocations such as t(8;21), t(15;17), and inv(16) in acute myeloid leukemia (AML), and t(1;19) and t(12;21) in acute lymphoblastic leukemia (ALL) have distinctive immunophenotypic profiles. Thus, in addition to classification into differentiation-based subtypes, detailed flow cytometric studies can define complex antigenic profiles that are associated with specific molecular defects and well-defined biology. In summary, multiparameter flow cytometry is an invaluable tool in the diagnosis, classification, and monitoring of patients with acute leukemia. Semin Hematol 38:124-138.

Ectopic cervical thymic tissue: diagnosis by fine needle aspiration.

Cervical thymic masses are congenital lesions that result from aberrant thymic migration during embryogenesis. Although most of these masses are asymptomatic, they may cause debilitating symptoms secondary to encroachment on adjacent aerodigestive structures. Preoperative diagnosis of ectopic thymic tissue is rare; most cases are clinically misinterpreted as branchial cleft remnants or cystic hygromas. Definitive diagnosis has relied on histopathologic examination in nearly all reported cases. However, the invasiveness of open incisional or excisional biopsy carries the risk of surgical and anesthetic complications. Inadvertent surgical thymectomy may result in cell-mediated immune deficiencies in infants and young children. The utility of fine needle aspiration is gaining wider acceptance in the diagnostic evaluation of neck masses. We describe an infant with an asymptomatic cervical thymic mass diagnosed by fine needle aspiration.

Automated RBC exchange transfusion:treatment for cerebral malaria.

BACKGROUND: Cerebral malaria is a life-threatening complication of Plasmodium falciparum infection. RBC exchange transfusion can reduce the level of parasitemia in this setting. Experience with automated RBC exchange for cerebral malaria may be limited, as most cases occur when the necessary equipment and blood components are not readily available. CASE REPORTS: Three patients were admitted with cerebral malaria. Parasites were found in more than 30 percent of RBCs in two cases and in more than 60 percent of RBCs in the third case. Many RBCs contained multiple organisms. In each case, antimalarial therapy was begun, and an automated RBC exchange was performed emergently with a cell separator. Exchange transfusion was repeated within 24 hours for two patients. Parasitemia levels were less than 1 percent in all patients 24 hours after the last exchange. The neurologic status of these patients returned to baseline, and they were discharged 7 to 18 days after admission. CONCLUSION: Automated RBC exchange transfusion can rapidly reduce the level of parasitemia and restore neurologic functioning in patients with cerebral malaria.

Correlation of serum prostate specific antigen and quantitative immunohistochemistry.

PURPOSE: Serum prostate specific antigen (PSA) in patients with prostate carcinoma is influenced by prostate size, transition zone volume, and tumor differentiation and volume. Immunohistochemistry studies have demonstrated an inverse correlation between PSA staining intensity and tumor grade, yet to our knowledge tissue expression of PSA has never been correlated with serum PSA. MATERIALS AND METHODS: In 47 radical prostatectomy cases serum PSA was corrected for gland size and tumor volume. Standard immunohistochemistry staining techniques were applied to specimens using monoclonal antibodies to PSA and cytokeratin CAM5.2. Color images of PSA and CAM5.2 immunohistochemistry stained slides were digitally acquired and analyzed using a standard image analysis system. Representative tumor foci in each slide were imaged with a 20x objective and 10x eyepiece. Staining extent and intensity of the tumor epithelium were measured, and stromal elements and luminal areas were excluded from analysis. For each case quantitative PSA staining intensity was expressed relative to keratin staining in adjacent benign epithelium. RESULTS: Gland volume and tumor volume independently correlated with serum PSA. Furthermore, tissue PSA intensity inversely correlated with histological grade of the tumor (p <0.00001). After gland size, tumor volume and grade were considered, corrected quantitative tissue PSA intensity did not significantly correlate with corrected serum PSA. CONCLUSIONS: Immunohistochemistry expression of tissue PSA in prostate carcinoma cannot be used to explain variations in serum PSA. This discrepancy may relate to differences between the amount of PSA produced by prostatic tumors and the amount secreted, and/or the sensitivity of detecting various tissue isoforms of PSA with immunohistochemistry.

A limited antibody panel can distinguish B-precursor acute lymphoblastic leukemia from normal B precursors with four color flow cytometry: implications for residual disease detection.

Multiparameter flow cytometry may be used to detect minimal residual disease in acute leukemia because leukemic cells often display aberrant phenotypes when compared to normal cells. One limitation of this approach in B-precursor ALL is that leukemic phenotypes are often qualitatively similar to normal marrow B progenitors, though it has long been recognized that the latter show a predictable pattern of antigen expression with differentiation. In this study we used four-color flow cytometry to define precisely the patterns of normal antigen expression on a series of normal bone marrows using two different four-color combinations of antibodies: CD19-APC/CD45-perCP/CD20-PE/CD10-FITC; and CD19-APC/CD45-perCP/CD9-PE/CD34-FITC. A series of dual parameter displays were created in which normal B precursors occupied predictable regions. We then tested these antibody combinations on a series of 82 cases of B-precursor ALL and found that in 76/82 cases (93%) the first combination demonstrated an abnormal population on at least one of the dual parameter displays, and that 72/77 cases tested (94%) showed an abnormality with the second combination. When taken together, 81/82 cases (99%) showed an abnormality. When purified blasts were serially diluted into normal marrows we found a sensitivity of detection of 1 cell in 10(4) normal marrow cells provided sufficient CD19+ cells were acquired to visualize the abnormal population as a discrete cluster. Because the pattern of antigen expression in normals is very reproducible, it is possible to create a fixed set of geometrical regions to define the normal; this makes analysis of an unknown sample very straightforward. We conclude that our approach could be employed as a simple method for the detection of minimal residual disease in B-precursor ALL, and unlike many other methods should prove applicable to virtually all cases of this malignancy.