Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Follicular dendritic cells (FDC) are restricted to the B-cell regions of secondary lymphoid tissue and to non-Hodgkin's lymphomas derived from the follicular center or the mantle zone. With their cytoplasmic ramifications they form a dense network which contains the B-lymphocytes. In situ, FDC are only detectable at the ultrastructural level or when stained with anti FDC-reagents. On the surface of their dendritic extensions they express transferrin receptors (CD71), the B-cell epitope CD20, class II antigens, the myelomonocytic molecule CD14, the glycoprotein gp50 (CD40), and several receptors for components of the complement system (CD11b, CD21, CD35). Subsequent to an antigen challenge, FDC trap and retain immune-complexes for a long period of time. In vitro FDC and neoplastic lymphocytes spontaneously form small cellular aggregates. This adhesion is mediated by the LFA-1-alpha/beta = ICAM-1, the VLA-4 = VCAM-1, and the ICAM-1 = C3bi- receptor ligand pathways on B-cells and on FDC, respectively. The loss of LFA-1- alpha/beta and ICAM-1 molecules may enable neoplastic lymphocytes to detach from FDC. The monoclonal B-cells now invade new compartments. In vitro, FDC have the capacity to activate resting B-cells and to save them from dying by apoptosis. Signals involved in this activation include cell-surface immunoglobulin and CD40. Immunocytochemistry and autoradiography with single cell suspensions of neoplastic B cells suggest that FDC also provide signals leading to the continued stimulation of lymphoma lymphocytes. During the early stage of HIV infection lymph nodes show an immense follicular hyperplasia, with a massive increase of the dendritic network of FDC. In the later stage of the disease, the continuous involution of the germinal centers is associated with a progressive destruction of FDC.
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PMID:Follicular dendritic cells in non-Hodgkin's lymphomas. 785 1

C receptor type 1 (CR1, CD35) is present in a soluble form in plasma (sCR1). Soluble CR1 was measured with a specific ELISA assay in normal individuals and in patients with different diseases. The mean serum concentration of sCR1 in 31 normal donors was 31.4 +/- 7.8 ng/ml, and was identical in plasma. An increase in sCR1 was observed in 36 patients with end-stage renal failure on dialysis (54.8 +/- 11.7 ng/ml, p < 0.0001), and in 22 patients with liver cirrhosis (158.3 +/- 49.9 ng/ml, p < 0.0001). The mean sCR1 levels dropped from 181 +/- 62.7 to 52.1 +/- 24.0 ng/ml (p < 0.001) in nine patients who underwent liver transplantation, and was 33.5 +/- 7.3 in 10 patients with functioning renal grafts, indicating that the increase in sCR1 was reversible. Soluble CR1 was elevated in some hematologic malignancies (> 47 ng/ml), which included B cell lymphoma (12/19 patients), Hodgkin's lymphoma (4/4), and chronic myeloproliferative syndromes (4/5). By contrast, no increase was observed in acute myeloid or lymphoblastic leukemia (10) or myeloma (5). In two patients with chronic myeloproliferative syndromes, sCR1 decreased rapidly after chemotherapy. The mean concentration of sCR1 was not significantly modified in 181 HIV-infected patients at various stages of the disease (34.8 +/- 14.4 ng/ml), and in 13 patients with active SLE (38.3 +/- 19.6 ng/ml), although in both groups the number of CR1 was diminished on E. There was a weak but significant correlation between sCR1 and CR1 per E in HIV infection and SLE (r = 0.39, p < 0.0001, and r = 0.60, p < 0.03 respectively). In vitro, monocytes, lymphocytes, and neutrophils were found to release sCR1 into culture supernatants. In vivo, sCR1 was detected in the serum of SCID mice populated with human peripheral blood leukocytes. The sCR1 levels correlated with those of human IgG (r = 0.97, p < 0.0001), suggesting synthesis of sCR1 by the transferred lymphocytes. The mechanisms underlining the increased levels of sCR1 and its biologic consequences remain to be defined.
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PMID:Circulating soluble CR1 (CD35). Serum levels in diseases and evidence for its release by human leukocytes. 833 53

Two-hundred and twenty-one bone marrow biopsies with lymphoid infiltrates were studied histologically and immunohistochemically, to assess the incidence and the pattern of follicular dendritic cells. Three monoclonal antibodies selective for follicular dendritic cells were used: CD21, CD35 and DR53, all reactive on paraffin-embedded material. Follicular dendritic cells were present in two of 38 benign lymphoid aggregates, 92 of 134 low grade B-cell lymphomas (45 of 62 lymphocytic, 16 of 27 lymphoplasmacytoid, 0 of six hairy cell leukaemias, five of six centrocytic, 19 of 21 centroblastic-centrocytic, seven of 12 low grade NOS), one of 23 high grade B-cell lymphomas, 0 of 10 T-cell lymphomas, 0 of three Hodgkin's disease and four of 13 suspicious infiltrates. Follicular dendritic cells were found in lymphomatous involvement with nodular, patchy and massive growth pattern, but not in interstitial ones. They formed follicle-like networks, whose number and size were directly correlated to the tumour mass. The origin and frequency distribution of follicular dendritic cells in bone marrow biopsy lymphomas is discussed and the diagnostic relevance of follicular dendritic cell immunostaining in routine bone marrow biopsy lymphoid infiltrates is assessed.
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PMID:Follicular dendritic cells in bone marrow lymphoproliferative diseases: an immunohistochemical study including a new paraffin-resistant monoclonal antibody, DR53. 873 43

Tumors of the follicular dendritic cell are uncommon, and most occur as primary lymph node tumors. We report a case of primary follicular dendritic cell tumor of the liver that was initially reported as an inflammatory pseudotumor. The neoplasm recurred as two separate tumor masses 30 months after complete resection of the "hepatic inflammatory pseudotumor." It showed a wide spectrum of morphologic features ranging from areas with fascicles of very bland spindle cells amidst a background population of lymphocytes, reminiscent of inflammatory pseudotumor, to areas of dispersed sheets of highly pleomorphic tumor cells with a relative paucity of reactive inflammatory cells. The diagnosis was confirmed by positive immunohistochemical staining with CD21, CD35, R4/23, and Ki-M4 and by ultrastructural demonstration of convoluted interdigitating cell processes joined by desmosomes. The background lymphocytes were oligoclonal, CD8-positive T cells. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was positive in the tumor cells in the original and recurrent tumors. More importantly, the cells showed identical episomal clonal EBV on Southern blot analysis, implying that the initial and recurrent tumors are due to clonal proliferation of EBV-positive neoplastic follicular dendritic cells. The tumor cells expressed latent membrane protein but not EBV-encoded nuclear antigen 2 (EBNA2) or ZEBRA. Such gene expression is very similar to that of Hodgkin's disease and nasopharyngeal carcinoma. The strong expression of latent membrane protein restricted to the tumor cells and the clonality of the EBV suggest that the virus may be involved in the pathogenesis of this tumor and not present merely as a "bystander."
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PMID:Follicular dendritic cell tumor of the liver. Evidence for an Epstein-Barr virus-related clonal proliferation of follicular dendritic cells. 877 85

Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neoplastic cells in Hodgkin's disease (HD). Although most data suggest their lymphoid origin, the nature of these cells still remains a subject of controversy. Recently, a number of RS cells have been found to express an antigen that is also present on follicular dendritic cells (FDCs), asserting FDCs as the possible progenitor cells of H-RS cells. This prompted us to investigate whether these CD21-positive cases had distinct clinicopathologic characteristics. In a series of 94 examined cases of HD, we identified 9 CD21-positive ones (4 of 37 cases of nodular sclerosis, 1 of 41 mixed cellularity, and 4 of 12 lymphocyte depletion HD) without any other B-cell marker on paraffin sections. The patients varied in age from 16 to 82 years (median, 50 years) and included six men and three women. They had superficial or mesenteric lymphadenopathy without hepatosplenomegaly. Peripheral blood leukocytosis was seen in three patients. The clinical course was indolent, and all patients but one achieved an initial complete response with HD-based treatment regimens, although three of them relapsed. Morphologically, two subgroups could be delineated. Six of the cases were characterized, besides by the classic RS cells, by a varying number of the cells with the distinctive walnutlike or cerebrumlike nuclei and cytologically with cytoplasmic processes. Their fine structural examination also revealed villous processes, but no desmosomes. The other three cases had multinucleated RS cells often with triangular nuclei, but not cytoplasmic processes. The percentage of CD21-positive tumor cells ranged from less than 10% to 60% among the H-RS cells. These RS cells were positive for CD30 (9 of 9), CD15 (7 of 9), CD68 (1 of 8), fascin (8 of 8), S-100 protein (1 of 7), and epithelial membrane antigen (2 of 8) on paraffin sections. Notably, of eight cases examined on frozen sections, two showed immunostaining for DRC1, CD35, R4/23, and Ki-M4p. Only CD35 was also detected in the other two cases. Genotypic investigation showed germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene in all eight cases examined. In situ hybridization showed Epstein-Barr virus sequences in four cases, three of which were examined by the terminal region analysis and showed the Epstein-Barr virus to be monoclonal. We concluded that in a small proportion (9.6%) of HD, H-RS cells might be derived from FDCs and that they appear to represent a distinct pathologic variant based on morphologic and phenotypic traits within the framework of HD.
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PMID:Hodgkin's disease expressing follicular dendritic cell marker CD21 without any other B-cell marker: a clinicopathologic study of nine cases. 1019 66

The chimeric anti-CD20 MAb rituximab has recently become a treatment of choice for low-grade or follicular non-Hodgkin's lymphomas (FL) with a response rate of about 50%. In this report, we have investigated the mechanism of action of rituximab on 4 FL and 1 Burkitt's lymphoma (BL) cell lines, 3 fresh FL samples and normal B cells in vitro. Rituximab efficiently blocks the proliferation of normal B cells, but not that of the lymphoma lines. We did not detect significant apoptosis of the cell lines in response to rituximab alone. All cell lines were targets of antibody-dependent cellular cytotoxicity (ADCC). On the other hand, human complement-mediated lysis was highly variable between cell lines, ranging from 100% lysis to complete resistance. Investigation of the role of the complement inhibitors CD35, CD46, CD55, and CD59 showed that CD55, and to a lesser extent CD59, are important regulators of complement-mediated cytotoxicity (CDC) in FL cell lines as well as in fresh cases of FL: Blocking CD55 and/or CD59 function with specific antibodies significantly increased CDC in FL cells. We conclude that CDC and ADCC are major mechanisms of action of rituximab on B-cell lymphomas and that a heterogeneous susceptibility of different lymphoma cells to complement may be at least in part responsible for the heterogeneity of the response of different patients to rituximab in vivo. Furthermore, we suggest that the relative levels of CD55 and CD59 may become useful markers to predict the clinical response. (Blood. 2000;95:3900-3908)
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PMID:Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. 1084 26

Structural alterations in the meshwork of follicular dendritic cells (FDCs) are frequently found in malignant lymphomas. Formaldehyde fixation and paraffin embedding, however, have long prevented consistent detection of FDCs. Wet heat-induced epitope retrieval in Dako Target Retrieval Solution (TRS) (pH 6.0) enabled the reliable detection of FDCs through CD21, CD23, and CD35 antigens in routinely processed tissues from 11 reactive and 69 neoplastic lymphoproliferations, thus allowing the distribution of the FDCs to be reevaluated. Germinal center FDCs in lymphoid hyperplasias and expanded FDC meshworks in the 8 mantle cell lymphomas, 7 low-grade MALT lymphomas, and 6 low-grade follicular lymphomas were intensely stained with all these markers. In 6 cases of B cell chronic lymphocytic leukemia, tumor cells were CD23+. In four cases of nodular lymphocyte predominance Hodgkin's disease (HD), expanded FDC meshwork's sharply delineating negative tumor cells and their rosetting T cell, were revealed mainly with the CD21 and CD35 antibodies. Follicular dendritic cells were also demonstrated in 11 cases of grade I nodular sclerosing HD, including follicular HD. Striking dendritic cell clusters were revealed with all 3 antibodies in 9 angioimmunoblastic T cell lymphomas. Sparse or no FDC meshworks were detected in the 4 cases of grade II nodular sclerosing HD, 5 follicular lymphomas with high-grade transformation, and 5 T cell-rich B cell lymphomas. CD35 immunostaining showed the most consistent labeling in the four FDC sarcomas studied in the current article. Reproducible demonstration of FDCs in routinely processed paraffin sections with CD21, CD23, and CD35 antibodies, as presented here, provides invaluable pieces of information in the diagnosis of lymphoproliferative disorders.
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PMID:Follicular dendritic cells in reactive and neoplastic lymphoid tissues: a reevaluation of staining patterns of CD21, CD23, and CD35 antibodies in paraffin sections after wet heat-induced epitope retrieval. 1139 28

A comprehensive clinical-and-laboratory examination of patients with non-Hodgkin's malignant lymphomas revealed a lack of correspondence between results of histological and immunophenotypical investigations. The most characteristic feature appeared to be the presence of CD10, CD11a, and CD35 antigens. Absence of CD95 antigen on tumour cells is regarded as an unfavourable prognostic sign in patients with follicular lymphomas as is presence of CD10 antigen on the above cells.
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PMID:[Clinical and hematological aspects of follicular lymphoma]. 1258 4

Occasionally, primary large B-cell lymphomas (LBLs) arising in the spleen present with a micronodular pattern involving the splenic white pulp but sparing the red pulp. Histologically, the nodules contain scattered large B cells in a background of numerous T cells and histiocytes. They can cause substantial difficulty in histologic diagnosis as the morphology can mimic reactive and inflammatory lesions as well as other lymphoid neoplasms. In this study, we examined the histology and immunophenotype of the micronodular T-cell/histiocyte-rich LBL (MTLBL) of the spleen with a view to establish the characteristics that may be helpful in diagnosis. Paraffin-embedded material from 17 cases of MTLBL was studied. Clinical features and histology were reviewed and immunohistochemistry was performed for immunoglobulins, CD20, CD79a, CD3, CD68, CD10, BCL6, BCL2, OCT-2, epithelial membrane antigen, CD30, CD138, and EBV markers. The median age of presentation was 56 years, and the most frequent presenting features were anemia and B symptoms. All cases showed a micronodular pattern of involvement. The tumor nodules comprised a mixture of numerous CD3+ T cells and CD68+ histiocytes and scattered large CD20+ B cells with immunoglobulin light chain restriction. They were positive for BCL6 and OCT2 but negative for CD10, CD138, and EBV markers. There was variable expression of epithelial membrane antigen, Bcl-2, and CD30. No follicle dendritic cell meshwork infrastructure underlying the nodules could be demonstrated by staining for CD21 or CD35 antigens. The prognosis was poor; seven of the 12 cases with follow-up were dead within 2 years. MTLBL is unique variant of T-cell/histiocyte-rich diffuse LBL, characterized by primary splenic presentation and a micronodular architecture. The main differential diagnoses include granulomatous inflammation, Hodgkin's lymphoma, follicular lymphoma, and peripheral T-cell lymphomas.
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PMID:Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen: histology, immunophenotype, and differential diagnosis. 1282 82

Histiocytic sarcoma is a rare malignant neoplasm that occurs in lymph nodes, skin, and the gastrointestinal tract. Many previously published cases were likely misdiagnosed examples of non-Hodgkin lymphoma. Only small numbers of bona fide examples exist in the world literature; cases arising primarily at extranodal sites are not well described and often seem to go unrecognized. To characterize these tumors further, 14 extranodal histiocytic sarcomas were analyzed. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring hospitals. Eight patients were female and 6 male (median age, 55 years; range, 15-89 years). All patients presented with a solitary mass, ranging in size from 1.8 to 12 cm (median 6.8 cm). Seven tumors arose in soft tissue (6 lower limb; 1 upper limb), 5 in the gastrointestinal tract (1 involving both stomach and colon, 1 ileum, 2 rectum, 1 anus), 1 in the nasal cavity, and 1 in the lung. Three gastrointestinal tract tumors also involved regional lymph nodes, and 1 involved the liver. Most cases had infiltrative margins. The tumors were generally composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin, and large nucleoli. Binucleated cells were common, and 6 cases contained tumor giant cells. Mitoses ranged from 1 to 64 per 10 HPF (median 11 per 10 HPF). Necrosis was present in 8 cases. Nearly all tumors showed a striking inflammatory infiltrate, most often of neutrophils or lymphocytes. All cases were reactive for LCA, CD45RO, and CD68 (KP1 and PG-M1); 13 of 14 (93%) expressed CD4, 12 of 14 (86%) lysozyme, 8 of 10 (80%) CD31, 7 of 14 (50%) S-100 protein, and 5 of 14 (36%) focal CD1a. Two tumors showed weak, focal cytoplasmic positivity for CD30, and 1 for epithelial membrane antigen. The tumors were negative for ALK-1, CD21, CD35, CD3, CD20, CD34, myeloperoxidase, HMB-45, and keratins. Gastrointestinal tract cases were negative for c-kit and desmin. Six patients were treated with postoperative radiation and 7 with chemotherapy (CHOP or ProMACE-MOPP). Follow-up was available for 10 patients (median, 24 months; range, 4 months to 11 years). Two tumors recurred locally, and 5 patients developed distant spread: 3 to lymph nodes, 1 to lung, and 1 to bone. At the last follow-up, 2 patients have died of disseminated disease, 4 and 5 months following initial diagnosis. The patients who died thus far had the largest primary tumors. Histiocytic sarcoma may arise primarily in soft tissue and shows reproducible histologic features, including abundant eosinophilic cytoplasm and a prominent inflammatory infiltrate. Metastatic carcinoma, metastatic melanoma, and large cell non-Hodgkin lymphomas should be excluded by immunohistochemistry. Histiocytic sarcoma has the potential for an aggressive clinical course, most often with lymph node involvement. However, a subset of cases presenting with clinically localized disease have a favorable long-term outcome. Tumor size may be a prognostic factor.
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PMID:Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy. 1531 12


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