Hodgkin's disease in the spleen

Summary 140 spleens involved by untreated Hodgkin's disease were studied utilizing conventional histological methods. Regardless of the sub-type of Hodgkin's disease, infiltrates of neoplastic cells were present either in the periarteriolar lymphoid sheath, the marginal zone or in both locations. Initially, infiltrates were confined to the splenic white pulp, later larger nodular foci of Hodgkin's disease developed by coalescence of several infiltrates. Neoplastic cells in Hodgkin's disease may reach the spleen by both retrograde lymphatic spread or the splenic artery; the presence of neoplastic cells in both T- and B-cell areas of the splenic white pulp implies a preference for Hodgkin's disease in the spleen with regard to a suitable microenvironment. This may be provided by certain macrophage subpopulations.     

Role of normal adherent cells in the regulation of the autologous mixed lymphocyte reactions in humans

The effect of normal adherent suppressor cells on the blastogenesis of human T lymphocytes in the mixed lymphocyte reaction (MLR) was studied in both allogeneic and autologous combinations. Non-T cells and Ia⁺ T lymphocytes were used as stimulator cells in both allogeneic and autologous MLR. The addition of adherent cells to the stimulators inhibited blastogenesis of T lymphocytes in both types of MLR when the stimulator population was made up of non-T lymphocytes but did not interfere with blastogenesis when Ia⁺ T lymphocytes were used as stimulator cells. The present data indicate that the T lymphocytes able to respond to Ia⁺ T cells (in the MLR, autologous or allogeneic) may be different from those which respond to non-T lymphocytes or may be less sensitive to the regulatory function of normal adherent cells.     

Immunophenotypic study of lymphocyte predominance Hodgkin''s disease

An immunophenotypic study of 17 cases of diffuse lymphocyte predominance Hodgkin's disease and 20 cases of nodular lymphocyte predominance Hodgkin's disease, along with eight of mixed cellularity and five of nodular sclerosing Hodgkin's disease, is reported. The atypical cells in nodular lymphocyte predominance Hodgkin's disease showed only minor differences from the published consensus. However, the atypical cells in diffuse lymphocyte predominance Hodgkin's disease showed an immunophenotype which was commonly B-cell positive (59%), but in a minority of cases LeuM1 (24%) or epithelial membrane antigen (12%) positive; none of the cases was Ber-H2 positive. These results do not differ greatly from our findings in nodular lymphocyte predominance Hodgkin's disease, but do diverge from the published consensus for diffuse lymphocyte predominance Hodgkin's disease. The question as to whether morphology or immunophenotype should form the primary diagnostic criterion for the definition of lymphocyte predominance Hodgkin's disease is discussed.     

Defective autologous mixed lymphocyte reactivity in multiple sclerosis.

T cells from patients with multiple sclerosis (MS) and normal controls were assessed for their ability to respond in the autologous mixed lymphocyte reaction (AMLR). Cells from stable MS patients demonstrated a significant defect in their proliferative response to non-T cells in comparison to normal controls. Despite the defective AMLR response, T cells from MS patients reacted as well as T cells from normal controls to allogeneic stimuli. Furthermore, MS non-T-cells were fully capable of stimulating allogeneic MLR responses by normal and MS T cells. Since the T4+ cell is the major subpopulation which proliferates in the AMLR, these studies suggest a functional defect in a subpopulation of T4+ cells in MS patients. Since the AMLR may represent an important mechanism by which immune responses are regulated, a defect in the ability of MS T cells to respond to autologous cells could account for several of the autoimmune features of the disease.     

Monocyte-dependent serum suppression of lymphocyte blastogenesis in Hodgkin's disease: An association with nephrotic syndrome

A factor inhibitory to PHA-induced lymphocyte blastogenesis was found to be present in the serum of a patient with advanced Hodgkin's disease and nephrotic syndrome. The inhibitory activity for both syngeneic and allogeneic lymphocytes was dependent on the presence of peripheral blood monocytes. The Raji-cell serum assay, as well as immunofluorescence and light and electron microscopy of the renal biopsy, showed no evidence of immune complexes. Nevertheless, a high serum IgE level as well as the finding that ultracentrifugation and heating at 56°C significantly reduced the inhibitory activity (P < 0.01) suggested the possibility that an immune complex might have mediated the suppressive activity. Treatment of the Hodgkin's disease with combined chemotherapy caused a marked reduction in the monocyte-dependent serum inhibitory activity which in turn coincided with a prompt remission of the nephrotic syndrome and marked regression of disease.     

Hypothermia in Hodgkin's disease after exploratory laparotomy

Summary Hypothermia is a rare complication of unknown origin in Hodgkin's disease which has been reported after the administration of antineoplastic agents, chlorpromazine and paracetamol. We report a highly febrile patient with stage IV-B Hodgkin's disease of mixed cellularity type who underwent exploratory laparotomy. Because of suspected septic shock high-dose prednisolone was given during surgery. Postoperatively the patient's body temperature fell progressively to 32.9° C and remained at less then 35.5° C for the following 5 days. There seems to be some functional disorder of thermoregulation in Hodgkin's disease. Physical factors during surgery or certain drugs, especially cytotoxics, corticosteroids, anesthetics or antipyretics may lead to prolonged hypothermia.Abbreviations Gamma-GT Gamma-glutaryl transpeptidase - MOPP combined chemotherapy consisting of nitrogen mustard, vincristine, procarbazine, and prednisolone - SGOT Serum-glutamate-oxalacetate transaminase - SGPT Serum-glutamate-pyruvate transaminase     

Vimentin expression by reed-Sternberg cells in Hodgkin's disease

Summary The expression of vimentin in Reed-Sternberg cells in 61 samples of Hodgkin's disease (HD) was examined using an avidin-biotin-peroxidase complex technique. Forty biopsies (66%) expressed vimentin, and expression was seen in all subtypes of HD. No immunophenotypic differences between vimentin-positive and vimentin-negative cases were noted. The significance of such expression is unclear, but may be related to the alterations in growth and differentiation that are typical of neoplastic cells.     

Impaired autologous mixed lymphocyte reaction (AMLR) reactivity of peripheral blood T cell subsets in rheumatoid arthritis

We examined AMLR reactivity of unseparated T cells and CD4+ and CD8+ T cell subsets in peripheral blood from 11 rheumatoid arthritis (RA) patients and 10 healthy controls. T cell subsets were isolated by negative selection using complement mediated cytotoxicity. AMLR reactivity of six patients (designated RA-L was reduced below the range of the controls' responses. Five patients (designated RA-N) exhibited normal AMLR reactivity. We observed impaired AMLR reactivity of CD4+ T cells from RA-L relative to RA-N and healthy controls (P < 0.05). CD4+ T cell reactivity of RA-L was reconstituted to normal with pharmacological doses of recombinant interleukin-2 (IL-2) (100 U/ml). In contrast, CD8+ T cells from RA-L in the presence of 100 U/ml IL-2 exhibited markedly impaired AMLR reactivity relative to RA-N and healthy controls (P < 0.05). Dose-response studies revealed partial reconstitution of CD4 T cells with physiological concentrations of IL-2 (10 U/ml). To examine the possibility that in vivo pre-activation of T cells in RA accounted for the findings, T cells or subsets were cultured alone for 7 days in the presence of 100 U/ml IL-2. A trend toward enhanced reactivity of CD4+ and CD8+ T cells in L-RA relative to N-RA and healthy controls was observed, but the differences were not statistically significant. There was no correlation between reactivity of T cells alone in the presence of IL-2 and AMLR reactivity. The results suggest the possibility that abnormal AMLR reactivity of CD4+ and CD8+ T cell subsets in RA may arise as a consequence of different pathophysiological mechanisms.     

Monocytoid B-cells occurring in Hodgkin's disease

In contrast with various forms of lymphadenitis, the presence of reactive monocytoid B-cells (MBCs) has only rarely been reported in Hodgkin's disease (HD). In order to analyse their occurrence in HD, we reviewed 120 cases before or after treatment. MBCs were identified morphologically and immunohistochemically in 8 cases (nodular paragranuloma, n=2; nodular sclerosis, n=2; and interfollicular mixed cellularity HD, n=4). Acute toxoplasmic, cytomegalovirus, or Epstein-Barr virus (EBV) infections were excluded by serological tests and immunohistochemistry. MBCs were negative by immunostaining for EBV encoded latent membrane protein, while Sternberg-Reed and Hodgkin's cells expressed positivity in 50% of cases. MBCs were only identified in cases with partial or incomplete lymph node infiltration by HD together with an activated B-zone of residual non-infiltrated tissue. The relation of MBCs and HD infiltrates followed three distinct patterns: large HD infiltrates without any connection to MBC foci; small areas containing various numbers of Sternberg-Reed and Hodgkin's cells at the border between MBC foci and surrounding lymphoid tissue; and HD infiltrates within at least some MBC clusters. The data obtained suggest that MBCs occurring in HD represent a transient phenomenon associated with a B-zone activation irrespective of treatment and that they are usually not histogenetically related to HD.     

Morphological and immunohistochemical studies of Hodgkin's disease in the spleen

Summary Hodgkin's disease in the spleen - with the exception of its B cell variant - behaves quite differently from non Hodgkin's lymphomas with respect to both its spread and microenvironment. Each type of HD appears to create its own microenvironment by the secretion of cytokines responsible for the characteristic cellular composition of the infiltrates and thereby alters the normal immunoarchitecture of the spleen profoundly. While some histological findings seem to imply the presence of a host response against HD especially in the nodular sclerosis subtype, morphological and immunohistochemical evidence in the spleen cannot conclusively substantiate this hypothesis.Visiting scientist from the Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan     

Reconstitution of impaired autologous mixed lymphocyte reactivity in rheumatoid arthritis.

We examined the ability of recombinant IL-2 to reconstitute the autologous mixed lymphocyte reaction (AMLR) defect in peripheral blood mononuclear cells (PBM) from patients with rheumatoid arthritis (RA). Our results revealed an ability to fully reconstitute RA AMLRs with pharmacologic concentrations (100 units/ml), but not physiologic concentrations (10 units/ml) of IL-2. Full reconstitution of RA AMLRs was achieved whether IL-2 was added as the initiation of culture or at 48 or 72 hours prior to termination of the cultures. Impaired IL-2 production was noted throughout the time course of the RA AMLRs. Neither an inhibitor of IL-1 nor IL-2 was detected in AMLR culture supernatants. Moreover, IL-1 in pharmacologic concentrations up to 50 units/ml failed to reconstitute impaired AMLR reactivity. In 2 patients whose AMLRs failed to reconstitute fully with 100 units/ml IL-2, addition of 10 units/ml IL-1 in combination with IL-2 fully reconstituted the AMLR defect. The results may suggest that defective IL-2 generation alone cannot fully account for impaired AMLR reactivity in RA patients.     

HLA-DP incompatibilities induce significant proliferation in primary mixed lymphocyte cultures in HLA-A, -B, -DR and -DQ compatible individuals: Implications for allogeneic bone marrow transplantation

The major part of the proliferative response in primary mixed lymphocyte cultures (MLC) is caused by HLA-DRB1 incompatibilities. In DRB1-matched pairs the proliferation induced by HLA-DRB3, -DQ and -DP mismatches may be unmasked. In most previous studies the influence of HLA-DP incompatibilities in primary MLC has been investigated in homozygous typing cells representing only a few Dw specificities. We were interested in determining the stimulatory capacity of isolated HLA-DP mismatches, ascertained by RFLP analysis, in primary MLC in HLA-A, -B, -DR and -DQ compatible, unrelated heterozygous individuals of many different Dw specificities. Thirty-eight MLCs performed with cells from related pairs and 67 with cells from unrelated pairs were evaluated. All but nine of the MLCs were analyzed in both directions, giving a total of 201 investigated reactions. The relative responses (RR) in the three MLCs performed between DP incompatible, related pairs were all positive (RR greater than or equal to 8%). Eighty of 82 MLCs performed with cells from DP incompatible, unrelated individuals were positive, whereas 37 of 46 MLCs between DP compatible, unrelated pairs were negative (RR less than 8%) (p less than 10(-10)). The magnitude of the RR was influenced by the number of DP mismatches. Thus, the mean RR was approximately twice as high in MLCs in which responder and stimulator cells differed by two DP antigens (mean RR 60.5%) compared with reactions with only one DP mismatch (mean RR 35.4%) (p less than 10(-3)). RFLP-defined HLA-DP incompatibilities predict a positive primary MLC in HLA-A, -B, -DR and -DQ matched individuals with a high degree of accuracy (98%).(ABSTRACT TRUNCATED AT 250 WORDS)     

T-cell rich B-cell non-Hodgkin's lymphoma: a progressed form of follicle centre cell lymphoma and lymphocyte predominance Hodgkin's disease

T-cell rich B-cell non-Hodgkin's lymphoma (T-cell rich B-cell lymphoma) is a morphological variant of diffuse large B-cell lymphoma. It is important to recognize this variant in the differential diagnosis of T-cell non-Hodgkin's lymphoma. The main differential diagnosis of T-cell rich B-cell lymphoma, nodular and diffuse lymphocyte predominance Hodgkin's disease (lymphocyte predominance Hodgkin's disease), is, however, even more difficult and differentiating criteria are still not satisfactorily defined. Moreover, T-cell rich B-cell lymphoma may not represent a clinicopathological entity. Twelve cases of T-cell rich B-cell lymphoma, selected on the basis of morphology and limited immunohistochemistry without previous knowledge of clinical data, were studied by immunohistochemistry and polymerase chain reaction for bcl-2 rearrangements to investigate the histogenetic background. In three of 12 cases, bcl-2 rearrangements were found, strongly suggesting a follicle centre cell origin. In three other cases, a documented history of definite nodular lymphocyte predominance Hodgkin's disease 29 months to 20 years prior to the diagnosis of the lymphoma was present. No differences in growth pattern, residual nodularity, tumour cell distribution, cellular morphology and composition, or immunophenotypical differences were noted in these six cases as compared to the remaining cases. These data underscore the histogenetic diversity in T-cell rich B-cell lymphoma and identify it as a progressed form of lymphoma derived from entities as diverse as follicle centre cell lymphoma and nodular lymphocyte predominance Hodgkin's disease. Moreover, it shows a complete morphological overlap with the diffuse form of lymphocyte predominance Hodgkin's disease and may actually encompass this disease entity.     

Recalcified plasma as nutrient additive in mixed lymphocyte culture

Animal or human blood protein is a costly but necessary additive to tissue culture. This supplemental protein is provided by the addition of pooled serum or heparinized plasma to standard tissue culture media. Many blood centers store CPDA-1 anticoagulated plasma, a form that does not provide optimal support of mixed lymphocyte culture (MLC). The optimal amount of CaCl2 (1 ml of 1 M CaCl2/100 g) added to citrate plasma and the use of glass vessels result in a completely clotted product that is comparable in MLC support to commercially available pooled human serum. Laboratories that have access to CPDA-1 plasma can replace the growing demand for serum with recalcified plasma without sacrificing quality.     

Autologous mixed lymphocyte reaction in man. VIII. Deficiency of autologous mixed lymphocyte reaction in patients with selective IgA deficiency

Autologous mixed lymphocyte reaction (AMLR) between T and non-T cells was studied in 12 patients with selective IgA deficiency. Seven of 12 patients demonstrated significantly (P less than 0.05) lower AMLR when compared to simultaneously studied age and sex matched controls. In the allogeneic MLR, T cells from patients responded normally to control non-T cells; however, non-T cells from patients were poor stimulators against normal responder T cells when compared to allogeneic MLR between different normal controls. The deficient AMLR in selective IgA deficiency further supports abnormal immune regulation and might explain the increased incidence of autoimmune phenomena and autoimmune diseases associated with selective IgA deficiency.     

Does nodular lymphocyte predominant Hodgkin's disease arise from progressively transformed germinal centres? A case report with an unusually prolonged history

A case is reported of nodular lymphocyte predominant Hodgkin's disease arising 13 years after the removal of a lymph node from the same site which showed marked progressive transformation of germinal centres. The morphological evidence for a histogenetic relationship between the two conditions is presented and discussed.