Richard A. Savage

Small noncleaved B cell burkitt-like lymphoma with chromosome t(8;14) translocation and epstein-barr virus nuclear-associated antigen in a homosexual man with acquired immune deficiency syndrome

This case report describes new manifestations of the acquired immune deficiency syndrome (AIDS) in a promiscuous homosexual man. Investigation of upper gastrointestinal bleeding in the patient lead to discovery of a high-grade, small, noncleaved cell (Burkitt-like) gastroduodenal lymphoma with visceral and extralymphatic extension. Specific phenotyping of the lymphoma revealed that it was a monoclonal B cell lymphoma of mu kappa isotype. An in vitro cell line was established that was Epstein-Barr virus nuclear-associated antigen-positive. The lymphoma cells displayed a t(8;14) translocation similar to endemic African Burkitt lymphoma. Epstein-Barr virus genomes were identified in the lymphoma and an axillary lymph node biopsy specimen by molecular hybridization. These data strongly suggest that Epstein-Barr virus actively infected this patient. However, he showed normal Epstein-Barr virus-specific serologic responses, indicating an immune defect against the virus.

Acute nonlymphocytic leukemia in patients receiving chemotherapy for nonmalignant diseases

The occurrence of acute leukemia in patients receiving chemotherapeutic agents for malignant disease has been well established. Recent reports have suggested that chemotherapeutic drugs used to treat inflammatory conditions may have an oncogenic potential. From 1969 to 1977, 11 patients with a variety of collagen-vascular diseases who developed acute nonlymphocytic leukemia were seen at the Cleveland Clinic. Rheumatoid arthritis was the most common underlying disease, in addition to giant cell arteritis, polyarteritis nodosa, chronic glomerulonephritis, and scleroderma. All patients were treated with alkylating agents, and 10 of the 11 received multiple cytotoxic agents. According to the French-American-British classification there were six examples of M4 (myelomonocytic leukemia), with single examples of M1 (myeloblastic leukemia without maturation), M2 (myeloblastic leukemia with maturation), M5a (monocytic leukemia, poorly differentiated), M5b (monocytic leukemia, differentiated), and M6 (erythroleukemia). Cytogenetic studies were abnormal in five patients studied, showing varying degrees of aneuploidy. All patients died, and the mean duration of time from the diagnosis of leukemia to death was four and one-half months, with only one complete remission.

Antigenic phenotype of splenic hairy cells

Hairy cell leukemia, a distinct clinical and morphologic lymphoproliferative disorder, is characterized by the proliferation of mononuclear cells of uncertain derivation. Attempts to identify the cell of origin have used studies either of functional capabilities or of membrane/cytoplasmic antigens. Only a few cases have been studied via monoclonal antibodies. Frozen sections of splenic tissue involved with hairy cell leukemia were studied with a variety of monoclonal antibodies having specificity for differentiation antigens using the avidin-biotinylated peroxidase complex technique. Conventional direct and indirect immunohistochemical study was used for immunoglobulin heavy and light chains. In all but one case, the neoplastic cells expressed monoclonal immunoglobulin. Although T cells were identified in persisting periarteriolar sheaths and occasionally admixed with red blood cells in pseudosinuses, phenotypic expression of intrathymic or peripheral T cell antigens by the proliferating neoplastic cells was not observed. Conversely, expression of B1 and HLA-Dr antigens by splenic hairy cells was documented in all 10 cases. Hairy cell leukemia cells did not express either monocyte antigens (M1 and MO2) or the antigens expressed by early (J5) and intermediate (B2) B cells or plasmacytoid lymphocytes and plasma cells (T10). These immunohistochemical results with monoclonal antibodies provide further evidence that hairy cell leukemia is characterized by a combination of antigens peculiar to mature B lymphocytes.

Immunoregulatory Leu-7+ and T8+lymphocytes in B-cell follicular lymphomas

Lymphocyte subpopulations were profiled in lymph nodes and tonsils showing follicular hyperplasia and in follicular lymphomas with monoclonal antibodies on frozen tissue sections. Immunoregulatory lymphocyte subsets identified with T8 and Leu-7 monoclonal antibodies were quantified within the follicular centers (FC) of the nonneoplastic tissue and neoplastic follicles of the lymphomas with an optical grid defining a unit surface area (USA) of 0.04 mm2. T8+ cells were essentially confined to the interfollicular areas, with a few cells occupying the FC of the nonneoplastic specimens (mean, two and five cells/USA for tonsils and benign lymph nodes, respectively). Although lymphomas exhibited a similar pattern of distribution of T8+ cells, 17 T8+ cells/USA were observed in the follicular small cleaved cell (FSCL) group and eight T8+ cells/USA within the follicular mixed small cleaved and large cell (FML) group. Leu-7+ cells were almost entirely confined to the FC of the nonneoplastic tissues and increased (mean, 17 and 19 cells/USA for tonsils and benign lymph nodes, respectively) compared with the T8+ population. Variable distributions of Leu-7+ cells were found in the FSCL group, with a mean of 16 cells/USA. Very few Leu-7+ cells were present in the FML group. Natural killer cells and/or cytotoxic/suppressor T lymphocytes may play an immunoregulatory role in modulating the growth of follicular lymphomas.