Non-Hodgkin malignant lymphomas and Hodgkin's disease in first-degree relatives

The occurrence of malignant lymphomas in 3 siblings is described. The cases include the first report of Hodgkin's disease and non-Hodgkin malignant lymphoma in dizygotic twins. Another remarkable feature was the development of malignant lymphoma, when the siblings were at the same age. Although a transmissible agent or environmental factors cannot be excluded in this family, our observations may suggest a mutual genetic predisposition in Hodgkin's disease and non-Hodgkin malignant lymphoma.     

DNA synthesis in unstimulated blood lymphocytes of patients with untreated malignant lymphomas or other malignant tumors.

Blood lymphocyte DNA synthesis, as expressed by 24-h uptake of 3H-thymidine in culture of mononuclear peripheral blood leucocytes has been reduced prior to treatment in 18 patients with Hodgkin's disease, 11 with non-leukaemic lymphosarcoma, 13 with reticulosarcoma and 20 with various solid tumors, and compared to 37 normal control subjects.The 3H-thymidine uptake was significantly increased in all the patient groups, but no significant difference existed between them. Increased uptake of 3H-thymidine did not appear to correlate with the degree of dissemination in any of the patient groups or with the presence or absence of general symptoms in malignant lymphoma. It is concluded that increased DNA synthesis in peripheral blood lymphocytes is a feature not limited to Hodgkin's disease, but found in non-Hodgkin's malignant lymphomas and other malignancies to about the same extent.     

Concanavalin a receptors on the cell membrane of Trypanosoma cruzi.

Epimastigotes and trypomastigotes of T. cruzi obtained from acellular culture as well as bloodstream trypomastigotes agglutinate with concanavalin A (Con A). Con A-binding sites were also localized on the cell membrane by using the Con A-horseradish peroxidase-diaminobenzidine method. Passage of epimastigotes and trypomastigotes from acellular culture through DEAE-cellulose column did not affect Con A-binding sites as detected by agglutination and electron miscroscopy.     

Blood B and T lymphocytes and in vitro cellular immune reactivity in untreated human malignant lymphomas and other malignant tumors.

Peripheral blood lymphocytes and their in vitro reactivity have been recorded prior to treatment in 18 patients with Hodgkins disease, 11 with lymposarcoma, 13 with reticulosarcoma, 20 with various solid tumors and 37 normal control persons. The mean total numbers of lymphocytes, those of T lymphocytes,and the mean reactivity to PHA and ConA were reduced in all groups except lymphosarcoma, although with varying degrees of statistical significance. The percentages of T and B lymphocytes appeared to be normal in all groups, but the ranges of values were somewhat greater than among the normal controls. The mean total numbers of B lymphocytes were normal in all patient groups. All reductions seemed to be more pronounced in patients with disseminated than in those with localized disease, but none of these differences was statistically significant. All patient groups appeared to have reduced reactivity in MLC, while the ability to stimulate control lymphocytes was nearly normal. The results fail to indicate an in vitro immunological abberation specific to Hodgkin's disease. It seems that human malignant, neoplastic diseases are associated with a relatively selective reduction of the total numbers and reactivity of blood T lymphocytes. Various explanations of the reactivity impairment are proposed. The pathogenesis of the reduction of the total number of blood T lymphocytes remains obscure.     

Behavior of total serum complement in Hodgkin''s disease and other malignant lymphomas

Using the method of Mayer and collaborators for the determination ofcomplement in the blood serum, 67 normal persons, 72 patients with Hodgkin’s disease, 28 with other types of lymphoma and 65 with cancer involvement of various organs were studied.

Fifty-eight of 72 Hodgkin’s disease patients were found to have an elevatedlevel of complement, 12 a normal level and 2 a below-normal level. Elevatedlevels were found also in patients with other lymphomas and cancer.

An association between elevated complement, increased sedimentationlevel, decreased serum properdin, positive C-reactive protein and elevatedbeta globulin in the serum was noted.

The conclusion reached is that an elevation of complement in the serumindicates that Hodgkin’s disease is in an active phase. As to the nature ofthe disease, the statistics assembled seem to give no clue.

Submitted on March 7, 1958 Accepted on July 22, 1958     

Non-Hodgkin malignant lymphomas and Hodgkin's disease in first-degree relatives. Evidence for a mutual genetic predisposition?

The occurrence of malignant lymphomas in 3 siblings is described. The cases include the first report of Hodgkin's disease and non-Hodgkin malignant lymphoma in dizygotic twins. Another remarkable feature was the development of malignant lymphoma, when the siblings were at the same age. Although a transmissible agent or environmental factors cannot be excluded in this family, our observations may suggest a mutual genetic predisposition in Hodgkin's disease and non-Hodgkin malignant lymphoma.     

Identification and characterization of a new surface membrane antigen found predominantly on malignant B lymphocytes.

A monoclonal antibody, 1D10, was derived that identifies a new antigenic epitope on the surface of malignant B lymphocytes. Normal resting and stimulated lymphocytes do not express the antigen. The majority of individuals with acute Epstein-Barr virus infection express the antigen on their lymphocytes, and in these patients, the T lymphocyte may also be antigen positive. The antigen was found on B-lymphoid neoplasia from the early pre-B cell stage through terminally differentiated plasma cells, a characteristic not reported for other B cell-associated antigens. Studies on homozygous typing cells and cells from individuals with known HLA phenotypes indicate that the antigen does not segregate in a pattern characteristic for major histocompatibility antigens. The molecule is a heterodimeric polypeptide with the molecular weight and isoelectric points of the alpha and beta chains being 32,000 d/4 and 28,000 d/6, respectively. Evidence is presented that the 1D10 molecule is not HLA-DR, -DP, or -DQ. By extrapolation, we suggest that this novel molecule may represent HLA D-region gene expression of a gene(s) not normally expressed. Potential candidates are D-region pseudogenes. We conclude that the antigenic epitope identified by the 1D10 monoclonal antibody is unique among previously described B-lymphocyte antigens. Further studies of the factors controlling the expression of this molecule, as well as studies designed to look at the possible cellular function, may provide insights for understanding crucial events in the malignant transformation of lymphocytes.     

Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma

To test the possibility that interleukin-9 (IL-9), the human homologue of the mouse T-cell growth factor P40, may be involved in the pathogenesis of human lymphomas, we examined IL-9 expression in a variety of tumors both by Northern blot analysis and by in situ hybridization. Of 18 B-cell non-Hodgkin's lymphomas and 11 peripheral T-cell lymphomas, none expressed IL-9 message. By contrast, IL-9 message was found in two of six cases of large cell anaplastic lymphoma (LCAL) and in 6 of 13 cases of Hodgkin's disease (HD). In HD the strongest signals were observed in Hodgkin (H) and Sternberg-Reed (SR) cells, but IL-9 mRNA was also detected in small lymphocytic cells. A search for IL-9 message in a panel of 20 cell lines derived both from hematopoietic and nonhematopoietic tumors confirmed the unique association of IL-9 expression with HD and LCAL in as much as the only two cell lines with IL-9 message were derived from cases of HD and LCAL. These results suggest that IL-9 is not involved as an autocrine growth factor in the pathogenesis of most B- and T-cell lymphomas, but that it may play a role in HD and LCAL.     

Membrane difference in peripheral blood lymphocytes from patients with chronic lymphocytic leukemia and Hodgkin's disease.

Lymphocytes were isolated from the peripheral blood of 21 normal persons and 66 patients with chronic lymphocytic leukemia (CLL), CLL in remission, Hodgkin's disease, Hodgkin's disease in remission, various other tumors, or cardiovascular diseases; The lymphocytes were studied for cap formation and agglutinability by concanavalin A, and for cell attachment to the surface of a petri dish. The frequency of cap formation was lowest in lymphocytes from patients with untreated Hodgkin's disease (2.1 plus or minus 0.8%), next lowest in lymphocytes from patients with CLL who were or were not under treatment (7,0 plus or minus 1;3%), and also low in Hodgkin's disease in remission (10.6 plus or minus 1.2%). The frequencies of cap formation by lymphocytes from patients with various other tumors (19.1 plus or minus 2.5%), with CLL in remission (24.0 plus or minus 0.9%), and with nonmalignant diseases (26.0 plus or minus 2.2%) were more similar to the frequency found in lymphocytes from normal persons (29.4 plus or minus 2.8%). Lymphocytes from all the patients, including those in remission, showed a higher degree of agglutinability by concanavalin A than lymphocytes from normal persons. Cell attachment to a petri dish was highest with CLL, next highest with CLL in remission, and low for normal persons and all the other patients. Lymphocytes from normal persons that consisted predominantly of thymus-derived cells gave similar results to isolated normal bone marrow-derived cells. The results indicate that there were different changes in the surface membrane of lymphocytes from patients with CLL, CLL in remission, Hodgkin's disease, and Hodgkin's disease in remission, and that the patients in clinical remission still showed abnormalities in their lymphocytes.     

Bone marrow biopsy in patients with malignant neoplasms other than lymphomas or leukemia.

104 patients with various cancer, excluding malignant lymphoma and leukemia, underwent bone marrow biopsy using a Jamshidi needle, regular type. In 100 patients an adequate pice of bone marrow was obtained. In 24 patients metastases were detected in the bone marrow. Metastases were found in 10 of 38 (26.3%) patients with breast cancer, in 5 of 17 (29.4%) patients with lung cancer, in 5 of 10 (50%) patients with cancer of the prostate, in 1 patient with rhabdomyosarcoma, 1 with chordoma and in 2 of 14 patients who underwent biopsy in search of unknown cancer. 71% of the patients with positive findings in the bone marrow had clinical signs of bone involvement, 80% had positive X-ray film and 78.9% had positive skeletal isotope survey. Hemogram, serum alkaline phosphatase, serum calcium level and sedimentation rate were of no value in predicting whether the marrow was involved or not. No complications were documented following biopsy. The use of the Jamshidi bone marrow biopsy needle for staging and early detection of metastases in a select group cancer patients is suggested.     

T and B lymphocytes in lymph nodes and spleen of patients with Hodgkin's disease.

Lymphocyte surface markers of 100 tissue specimens (67 lymph nodes and 33 spleens) of 40 patients with Hodgkin's disease were studied by means of spontaneous E-rosette formation and direct immunofluorescence method. The occurrence of active and total T cells was signigicantly higher (p less than 0.001) in the tumor-involved lymph nodes and spleens, while the frequency of B cells was practically the same in the histologically negative lymph nodes and spleens. In the tumorous spleen of 6 untreated patients the frequency of active and total T cells was higher in the tumorous tissue specimens than in the surrounding histologically negative tissue specimens. No correlation has been found between the simultaneously investigated peripheral T and B cell counts, clinical stage and the histological type of the tumor.     

Effect of sera from patients with Hodgkin's disease on normal donor lymphocytes containing parallel tubular structures

Summary Normal donor peripheral blood mononuclear cells incubated for 24 h with sera from patients with Hodgkin's disease were investigated by electron microscopy for the presence of parallel tubular structures (PTS) and/or amorphous electrondense granules (large granular lymphocytes = LGL). In comparison with normal human serum, 14 out of 29 sera of the patients induced a marked increase in the percentage of LGL. From a limited number of experiments it was likely that this increase is paralleled by an increase in Fc receptor-bearing cells after the incubation. This serum effect did not show a correlation with the number of Fc receptor-positive lymphocytes in the peripheral blood of the patients.A difference in the induction effect could be demonstrated between the sera from patients with a favourable and those with an unfavourable clinical course, but this distinction was not absolute. The presence of absence of splenic involvement by Hodgkin's disease does not apparently influence the effect of the sera.From experiments using sera positive for immune complexes or anti-Epstein-Barr virus antibodies, it seems unlikely that these factors are responsible for the observed increase in LGL.