Histologic and immunohistochemical findings in the differential diagnosis of chronic lymphocytic leukemia of B-Cell type and lymphoplasmacytic/lymphoplasmacytoid lymphoma

Summary 114 cases of malignant lymphoma consisting chiefly of lymphocytes were classified by histology as chronic lymphocytic leukemia of the B-cell type (B-CLL) or lymphoplasmacytic/lymphoplasmacytoid lymphoma (LP immunocytoma) and investigated with the immunoperoxidase-bridge (PAP) method for the presence of heavy and light immunoglobulin chains. Fifteen cases were excluded because they showed a completely negative reaction, which might have been an artifact. Of the remaining 99 cases, 46 revealed polyclonal immunoglobulin-positive plasma cells only and could be clearly classified as B-CLL. In 33 cases there were a moderate or large number of plasma cells or plasmacytoid cells with monoclonal intracytoplasmic positivity. Two heavy chain classes were demonstrated in three other cases, and both light chain types were detected in one case. These 37 cases were finally classified as LP immunocytoma. Ten cases contained only a few monoclonal plasmacytoid cells and were interpreted as borderline cases between B-CLL and LP immunocytoma. Six cases have not yet been clarified — there was an inexplicable discrepancy between their histology and immunostaining.In LP immunocytoma, the heavy chain class demonstrated most often was the chain (27 cases). Light chains of the type were about 2.5 times as common as chains.The differential diagnostic criteria for distinguishing B-CLL from LP immunocytoma are discussed and compared. PAS-positive tumor cells are an almost definite criterion of LP immunocytoma. At present, a critical evaluation of the results of PAP immunostaining is the most reliable way to clearly distinguish B-CLL from LP immunocytoma.Supported by the Kind-Philipp-Stiftung     

Human cytomegalovirus, human herpesvirus-6 and human herpesvirus-7 in neutropenic patients with fever of unknown origin

Objective  To investigate the appearance of cytomegalovirus (CMV) DNA, human herpesvirus-6 (HHV-6) DNA and human herpesvirus-7 (HHV-7) DNA in plasma as a sign of reactivation and possible causes of fever of unknown origin (FUO) during neutropenia.
Methods  From 134 patients with febrile neutropenia following cytotoxic chemotherapy during the years 1996–2000, 20 severely neutropenic patients (granulocyte count < 0.1 × 10⁹/L) were selected. Ten were patients with bacteremia and ten were patients with FUO. Five samples from each patient were selected at the start of chemotherapy, at the time of blood culture and fever, after 24 and 48 hours of fever, and, finally, after two to three days without fever. Virus DNA was detected by real-time quantitative and nested polymerase chain reaction (PCR).
Results  CMV-DNA was detected in two out of ten FUO-patients in all samples drawn during fever. From another FUO and during two bacteremia episodes, CMV-DNA was detected after 48 hours of fever. DNA from HHV-6 and HHV-7 was not detected in any of the 20 febrile episodes.
Conclusions  HHV-6 and HHV-7 as a possible explanation for FUO in severely neutropenic patients treated with cytotoxic chemotherapy seems not be very likely. However, CMV was identified in 5/20 patients and the febrile episodes in the two FUO-patients with constant DNA-emia may have been caused by a reactivation of CMV. This implies that CMV infection can be expected not only in transplant patients but also in chemotherapy-treated neutropenic patients.     

Immunologic reactivity of (C57BL/6 × A/Sn)F1 mice in mixed Mycoplasma-virus infection

Mixed infection of hybrid mice, highly resistant to Rauscher virus, with this virus andMycoplasma arthritidis was accompanied by progressive inhibition of populations of splenic rosetteforming (REC) and plaque-forming (PFC) cells and led to induction of malignant erythroblastosis, cytologically identical with Rauscher's leukemia. During mixed infection of the hybrid mice withAcholeplasma laidlawii and Rauscher virus the immune response was almost completely suppressed on the 21st day and considerable splenomegaly was observed, but by the 62nd day of infection the RFC and PFC populations and also the weight of the spleens had regained the control level. The possible role of mycoplasmas in the induction and development of Rauscher's leukemia is discussed.N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician O. V. Baroyan.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 9, pp. 327–329, September, 1979.     

A hybrid form of myeloid/NK-cell acute leukemia and myeloid/NK-cell precursor acute leukemia

Natural killer (NK)-cell leukemia/lymphoma is a rare entity that has been defined only in recent years. In the Revised European-American Lymphoma and World Health Organization classifications, only the mature NK-cell malignancies are included. However, at least 3 types of precursor NK-cell neoplasms have been reported in the literature. These include myeloid/NK-cell acute leukemia, myeloid/NK-cell precursor acute leukemia, and blastic NK-cell lymphoma/leukemia. These leukemias are characterized by the presence of blasts, which express CD56, in the peripheral blood, bone marrow, lymph nodes, and/or extranodal tissues. We report a case that is morphologically consistent with myeloid/NK-cell acute leukemia but immunologically is myeloid/NK-cell precursor acute leukemia. This case is unique in its cutaneous presentation without involvement of the peripheral blood. Extensive flow cytometric studies were performed on the skin biopsy and bone marrow aspirate specimens, which included many markers that had not been tested before in these entities. The clinical implications of these findings are discussed.     

B-cell function in patients with chronic lymphocytic leukemia

Summary Using a reverse hemolytic protein A plaque assay, spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin (Ig) secretion was determined in peripheral blood from 22 patients with B₁-chronic lymphocytic leukemia (CLL), one patient with B₂-CLL, and one patient with suppressor T-CLL. Diagnoses were established by cytological and histological criteria as well as several marker analyses. Lymphocytes from B₁- and B₂-CLL patients were unable to secrete Ig either spontaneously or after PWM stimulation. In T-CLL lymphocytes, spontaneous Ig secretion was suppressed very probably by the OKT-8-positive leukemic population, since, after cultivation with PWM, a normal Ig secretion could be demonstrated which was paralleled by a decrease in the OKT-8-positive cells. Cocultivation experiments with freshly isolated, unseparated lymphocytes from normal subjects and lymphocytes from patients were of no informational value, since isolated normal B-cells alone already showed a high rate of Ig secretion. However, coculture experiments with separated subpopulations after PWM stimulation revealed an intrinsic B-cell defect in lymphocytes from B₁-CLL patients, whereas their T-lymphocytes were found to be normal helper cells.

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Abbreviations CLL Chronic lymphocytic leukemia - PWM Pokeweed mitogen - ISC Immunoglobulin-secreting cells - Ig Immunoglobulin(s) Supported by the Deutsche Forschungsgemeinschaft (Ru 215/2)     

The ultrastructure of hybrid acute leukemia: a study of 15 cases

The objective of this study was to investigate the ultrastructural characteristics of hybrid acute leukemia (HAL). Fifteen cases of HAL were studied by transmission electron microscopy (TEM), focusing on organelles and myeloperoxidase (MPO) reaction of leukemic cells. By TEM, 5 out 15 cases of HAL were consistent with immunophenotyping (3 cases of biphenotypic type, and 2 cases of biclonal type with granulocytes and lymphocytes); 2 cases were suspected as HAL. On other hand, 5 cases of HAL were assigned to ALL, and 2 cases were misinterpreted as M5a and 1 as M4b. Most of the blast cells of biphenotypic HAL showed lymphoid features, except some cases containing MPO positive granules in blasts, while a few cases exhibited monocytic or nonspecific features. TEM offers advantages in the diagnosis of biclonal type HAL and biphenotypic HAL positive for MPO. However, it is difficult to differentiate MPO-negative cases of biphenotypic HAL from ALL and a few cases may be misinterpreted as M5 by TEM.     

Identification of Exocytosis Mediator Proteins in Peripheral Blood Neutrophils of Patients with Chronic Myeloid Leukemia

We demonstrated expression of plasma membrane proteins (syntaxin-4 and syntaxin-6) and specific/gelatinase granule membrane proteins (SNAP-25 and VAMP-2) in the peripheral blood neutrophils of patients with chronic myeloid leukemia. VAMP-1 associated with membranes of azurophilic and specific/gelatinase granules was absent in peripheral blood neutrophils of patients with chronic myeloid leukemia. Decreased capacity of neutrophils to exocytosis in chronic myeloid leukemia is probably caused by the absence of VAMP-1 in these cells.     

Regulation of mast cell signaling through high-affinity IgE receptor by CD45 protein tyrosine phosphatase

The transmembrane tyrosine phosphatase CD45 regulates the activity of src family protein tyrosine kinases (PTK) and thereby influences the signaling via such receptors as T and B cell antigen receptors associated with these PTK. However, its implication in signaling through the mast cell receptor with high affinity for IgE (FcepsilonRI) is less clear, although Lyn, a member of the src family, plays an important role in FcepsilonRI-mediated signaling. To define a role for CD45 in FcepsilonRI signal transduction, we established CD45 high expressing rat basophilic leukemia cell lines (RBL-CD45H) and cell lines expressing trace amounts of CD45 (RBL-CD45L). We demonstrate that although all RBL-CD45L cell lines degranulate following IgE- and antigen-induced FcepsilonRI aggregation, the response is significantly reduced at a low dose of antigen. The cells show a delayed and slowed Ca(2+) mobilization even though at a higher dose where the cells degranulate to a similar extent as RBL-CD45H. This diminished Ca(2+) response is restored by reconstitution of RBL-CD45L with a chimeric molecule containing the cytoplasmic phosphatase domains of rat CD45. Furthermore, tyrosine phosphorylation of FcepsilonRI, association of FcepsilonRI with Lyn and PTK activity associated with FcepsilonRI, all of which are enhanced upon FcepsilonRI aggregation in RBL-CD45H, are impaired in RBL-CD45L. Finally, we show that FcepsilonRI is physically associated with CD45 in RBL-CD45H prior to receptor aggregation. Thus, we propose that, although not indispensable in mast cell degranulation, CD45 positively regulates the signaling through FcepsilonRI by promoting the activation of FcepsilonRI-associated Lyn.     

Adult T cell leukemia/lymphoma with massive involvement of cardiac muscle and valves

An autopsy case of a 58-year-old woman with massive cardiac Involvement of adult T cell leukemia/lymphoma (ATLL) is reported. She developed cardiac failure due to aortic and mitral regurgitation with cardiac infiltration of ATLL cells, and underwent replacement of both aortic and mitral valves. Studies of the cut-surfaces revealed diffuse thickening of the subendocardial wall of the left chamber with widespread whitish-brown tumor infiltrates. In the regions surrounding the replaced aortic and mitral valves there was also massive tumor cell infiltration. The tumor cells infiltrating the cardiac muscle wall were T cell in origin and exhibited Leu-3a (CD4)-positive immunoreaction. Ultrastructurally, tumor cells contained markedly indented nuclei and some were attached directly to the muscle cells. These findings suggest that this was an unusual form of ATLL with widespread involvement of the heart.