Primary pleomorphic T-cell lymphoma of the spleen.
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Biomedical subjects
Publications and source records attributed to H J Stutte.
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Bone marrow aspirates and biopsies of 20 patients with malignant tumors (n = 6), bone marrow failure due to chemotherapy (n = 4), myelodysplastic syndromes (n = 5) and aplastic anemia (n = 5) were analysed before and after treatment with recombinant human interleukin-3. rhIL-3 led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells. In all patients marked eosinophilia and, in some, fibrosis was observed. These results show that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells and may contribute to the treatment of bone marrow failure.
As part of a phase I/II clinical trial with recombinant human Interleukin-3 (rhIL-3), bone marrow and peripheral blood cells from patients treated with rhIL-3 were assessed in vitro for effects on the cycling status and frequencies of erythroid, myelomonocytic and multilineage progenitor cells. Treatment with rhIL-3 induced a pronounced increase in S-phase rate of BFU-E, CFU-GEMM and day 14 CFU-GM. Circulating CFU-GEMM and day 14 CFU-GM were increased on day 7 of therapy whereas circulating BFU-E were reduced in the majority of patients. After i.v. bolus injection of IL-3 an acute effect on the peripheral blood count with neutrophilia and, after an initial nadir, monocytosis was observed. IL-6 serum-levels increased in 5 out of 14 patients after IL-3 administration with concomitant side effects in 2 patients in whom IL-6 levels increased above 75 pg/ml. In the majority of the patients a stimulation of peripheral leukocytes and platelets was observed during the 15 day treatment course. In conclusion rhIL-3 induces a multilineage response in vivo by stimulating proliferation of hemopoietic progenitor cells with a resulting elevation in peripheral blood counts.
Bone marrow biopsies of 23 HIV-1 infected patients and 29 patients with myelodysplastic disorders were examined histologically by immuno- and enzyme-histochemical techniques and morphometrical methods. The nucleolar organizer regions (AgNOR) were demonstrated and visually counted. Hypercellularity in marrows of AIDS patients is substantially caused by an increase of erythropoiesis and CD68+ macrophages/reticular cells. However, hypercellularity in preleukemia results from hyperplasia of all hematological cell lines and CD68+ bone marrow macrophages/reticular cells. AgNOR count is positively correlated with granulo- and erythropoiesis in preleukemia. In AIDS there is such a positive correlation between AgNOR count and granulopoiesis whereas an inverse relationship appears in erythropoiesis. The results suggest that HIV-associated bone marrow alterations differ from merely reactive changes and are related to myelodysplastic disorders.
In order to assess the effects of malignant tumors on the immune system, 25 spleens from patients with gastric carcinoma were studied by in situ immunohistochemical methods for lymphocyte subsets and cells of the mononuclear phagocyte system. Highly significant reductions of CD4+ T cells (P less than 0.001), Ki M2+ and Ki M-3+ MPS cells (P less than 0.02 and P less than 0.05), and a stage-dependent reduction of Ki 67+ B cell proliferation activity (P less than 0.05) were seen in spleens of patients with gastric cancer. These results, which were obtained by morphologic methods in a noninvolved lymphatic organ, reflect the systemic immunosuppressive and immunodepleting effects of malignant tumors that are probably mediated by tumor-associated cytokines.
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.
The case of an ileal carcinoid tumor metastatic to the spleen causing splenomegaly and symptoms that necessitated splenectomy is described. Morphological analysis reveals that viable tumor cells are present along the whole pathway of splenic circulation and, accordingly, may lead to metastatic deposits at different sites within the spleen.
Clinical and morphological findings in four patients with mixed mullerian tumors of the uterus showed, that these highly aggressive neoplasms are derived from the undifferentiated mullerian epithelium. Immunohistochemically, each component exhibits characteristic differentiation markers. The presence of cytokeratins or desmin signals an epithelial viz. rhabdomyosarcomatous differentiation, whilst the detection of vimentin in the absence of other markers demonstrates an undifferentiated mesenchymal component. This component appears to be responsible for the aggressive biological behavior of mixed mullerian tumors.
Lipomatous lesions of the uterus are rare but may lead to problems in the differential diagnosis of uterine tumors. A typical case of uterine lipoma illustrates the characteristic clinical and morphological findings. Additional immuno-histochemical studies delineate the histogenesis of uterine lipomas.
Twenty hamartomas of the spleen were studied by histological, immuno- and enzyme-histochemical methods. In all cases nodules of varying size resembling proliferation of splenic red pulp structures were present that exhibited considerable morphological variation with regard to plasmacytosis, extramedullary haematopoiesis and phagocytic activity of macrophages. Splenic red pulp structures could be identified by immuno- and enzyme-histochemical markers reacting with sinus endothelium, including Factor VIII related antigen, proteinase inhibitors and non-specific esterases. In conjunction with the absence of organized lymphoid tissue and of dendritic reticulum cells these studies allow the differentiation of splenic hamartomas from haemangiomas that may possess a deceptively similar morphological appearance.
One hundred and five formalin fixed renal allograft biopsies with a graft survival of more than 12 months have been examined by histological and immunohistochemical methods. 51 cases of vascular and 41 cases of tubulointerstitial allograft rejections were diagnosed by conventional light microscopy. 13 cases showed a combined type of rejection. The vascular and the interstitial type contain on average 64 respectively 79 CD 45 positive cells/mm2 surface of section. A mean of 70 cells/mm2 has been calculated for the combined type of rejection. The corresponding mean values of MT 1 positive T-lymphocytes are 46 in the vascular type, 52 in the combined type and 60 cells/mm2 in the tubulointerstitial type of allograft rejection. Apparently because of the great ranges there are no statistically significant differences between the observations in the different types of rejection. His equal for the concentration of Mac 387 positive macrophages and as well for the content of L26 positive B-lymphocytes in the different types of rejection. The concentrations of HLA-DR expressing cells in the interstitium are determined with a monoclonal anti-HLA-DR antibody, which detects a fixation resistant epitope of the DR-molecule. There is an average of DR positive cells/mm2 of 79 in vascular and 107 in interstitial rejection. The combined type of rejection contains 86 cell/mm2 on average, so that there is a statistically significant positive correlation, if you will order the observations in sequence of vascular, combined and interstitial type of rejection. In this case the observations of interstitial and vascular rejections differ statistically significant as well.(ABSTRACT TRUNCATED AT 250 WORDS)
A 32-year-old homosexual with AIDS, who until 1985 was a frequent traveller to South America and mediterranean countries, had recurrent bouts of fever, splenomegaly, arthralgias as well as granulocytopenia and anaemia. Liver and bone-marrow punctures were performed to exclude malignant lymphoma and (or) a mycobacterial infection. Both biopsies revealed Leishmania donovani. During administration of sodium stibogluconate (Pentostam) the fever disappeared for a time and there was clinical improvement, but further treatment was limited because of thrombocytopenia. In patients with AIDS who have splenomegaly with nonspecific fever, visceral leishmaniasis must be considered in the differential diagnosis even outside of endemic regions.
In six patients with systemic symptoms, four of which had lymphoplasmacytic infiltrates in the bone marrow splenectomy was performed because of suspected malignant lymphoma, with resolution of clinical symptoms. The spleen showed epithelioid granulomas, and neither splenic tissue nor clinical follow-up revealed evidence of malignant lymphoma. Immunohistochemical analysis documented an identical phenotype in epithelioid and giant cells as well as in large numbers of CD4 + lymphocytes and S100 + interdigitating reticulum cells within the granulomas. These cases are interpreted to represent epithelioid granulomatosis with primary and/or predominant manifestation in the spleen.
72 spleens from AIDS patients were studied by histologic and immunohistochemical methods. Apart from the opportunistic infections and malignancies typically occurring in AIDS patients (malignant lymphomas, Kaposi's sarcoma, mycobacterial infections, cryptococcosis, cytomegalovirus infections) morphological changes probably directly attributable to HIV infection were noted that progressed from follicular hyperplasia with nearly normal periarteriolar lymphoid sheaths to atrophy of follicles and severe cellular depletion of T cell areas with concomitant plasmacytosis and occurrence of small giant cells. At the same time the number of Protein S-100 positive cells markedly increased; in some cases almost all pulp cord macrophages expressed the antigen. In addition, the sinus endothelia strongly expressed protease inhibitors.
The case of an AIDS patient with visceral leishmaniasis diagnosed by bone marrow and liver biopsy is reported. Despite the infrequent association between HIV infection and leishmaniasis pathologists and clinicians alike should be alerted to the possibility of leishmaniasis occurring as yet another opportunistic infection in the setting of HIV-induced immunodeficiency.
Lymphocyte subpopulations and macrophages in 16 spleens from patients with Hodgkin's disease were analysed immunohistochemically using monoclonal antibodies of the Leu and the Ki M series. In non-involved splenic tissue there is an increase of T-lymphocytes with an increased T-helper/T-suppressor cell ratio, while Ki M-1, -2, -3 and -5-positive, i.e. phenotypically different macrophages, are reduced. These results indicate that involvement of the spleen in Hodgkin's disease is accompanied by changes with respect not only to lymphocyte subpopulations but also to cells of the mononuclear phagocyte system. The immunodeficiency associated with Hodgkin's disease is probably not solely due to lymphocyte dysfunction, since the disease may lead, at least in the spleen, to alterations in macrophages and accessory cells and this may contribute to the impairment of cell-mediated immunity.
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