1/12. Increased spontaneous in vitro apoptosis in double negative T cells of humans with a fas/apo-1 mutation.We describe a 17 year old patient suffering from Canale-Smith syndrome (CSS) including chronic lymphadenopathy, splenomegaly, hypergammaglobulinemia and recurrent Coombs positive hemolytic crises. The parents are not consanguine, all other family members including two brothers are healthy. Peripheral blood mononuclear cells of the patient showed an increased rate of CD3 positive, CD4/CD8 double negative t-lymphocytes. in vitro assays showed these cells to have an increased rate of spontaneous apoptosis. Though expression of Fas/Apo-1 (CD95) and Fas-ligand (FasL) was detected on rna- and protein level we found Fas/Apo-1 mediated apoptosis being significantly reduced. Sequencing of the fas/apo-1 gene proved the patient RT and his father to carry a point mutation at position 804 located in exon 9 (death domain) leading to an amino acid substitution. For developing of CSS, a fas/apo-1 mutation seems to be necessary but not sufficient. An additional independent mechanism must be involved in the pathogenesis of human lpr<-phenotype.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
2/12. Gain of chromosome 3/3q in B-cell chronic lymphoproliferative disorder is associated with plasmacytoid differentiation with or without IgM overproduction.trisomy 3 has been reported to be associated with marginal zone B-cell lymphoma. However, its occurrence and significance in other B-cell chronic lymphoproliferative disorders has not been fully defined. We report five cases of B-cell chronic lymphoproliferative disorders showing gain of chromosome 3 or 3q. The patients were elderly males who presented with splenomegaly with or without hepatomegaly and lymphadenopathy. The diagnoses included chronic lymphocytic leukemia (3 cases), prolymphocytic leukemia (1 case), and waldenstrom macroglobulinemia (1 case). Distinctive feature in this group of patients was the plasmacytoid appearance of the leukemic lymphocytes, with an associated IgM hypergammaglobulinemia in three patients. The relationship between the gain of chromosome 3 and plasmacytoid differentiation in B-cell chronic lymphoproliferative disorders is discussed.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
3/12. autoimmune lymphoproliferative syndrome presenting with glomerulonephritis.autoimmune lymphoproliferative syndrome (ALPS) is characterized clinically by chronic non-malignant lymphoproliferation and autoimmunity and is caused by a genetic defect in programmed cell death (apoptosis). Most patients with ALPS have heterozygous mutations in the Fas gene. We describe an 11-year-old Brazilian boy with hepatosplenomegaly, lymphadenopathy, hemolytic anemia, and hypergammaglobulinemia since early infancy. T cell lines from the patient were defective in Fas-mediated apoptosis. He was diagnosed as having ALPS and found to have a novel Fas gene mutation (IVS4 1G>A). In addition, he presented with glomerulonephritis in infancy. An aunt and uncle who had the same Fas mutations also had histories of glomerulonephritis. Although glomerulonephritis is common in Fas-deficient mice, it is infrequent in human ALPS. Corticosteroid therapy ameliorated the glomerulonephritis in our patient, as well as his lymphoproliferation, anemia, and hypergammaglobulinemia. This study suggests that glomerulonephritis is one of the characteristic features of ALPS.- - - - - - - - - - ranking = 2keywords = hypergammaglobulinemia (Clic here for more details about this article) |
4/12. Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like clinicopathological findings in elderly patients. Report of three cases.Three cases of Epstein-Barr virus (EBV)-related lymphoproliferative disorders in elderly patients showing autoimmune disease-associated lymphadenopathy-like clinicopathological findings have been reported. Clinically, they were characterized by systemic lymphadenopathy, "B" symptoms, polyclonal hypergammaglobulinemia, elevated serum LDH and transient presence of various autoantibodies, and absence of atypical lymphocytosis in peripheral blood. One case was associated with idiopathic thrombocytopenic purpura. The clinical course was self-limiting. Histologically, they exhibited numerous lymphoid follicles with hyperplastic germinal centers and atypical interfollicular widening with prominent vascular proliferation. In the paracortical area, there was a mixed infiltrate comprising small to medium-sized lymphocytes and plasma cells, and variable numbers of eosinophils and T- and B-immunoblasts. in situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the germinal center as well as in the interfollicular area. polymerase chain reaction demonstrated that neither clonal rearrangement of T-cell receptor gamma-gene nor immunoglobulin heavy-chain rearrangement was detected in two of the cases examined. Although acute EBV infection rarely occurs in older adults, EBV related to reactive lymphoproliferative disorder should be added to the differential diagnosis of autoimmune disease-associated lymphadenopathy and node-based peripheral T-cell lymphoma in elderly patients.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
5/12. The autoimmune lymphoproliferative syndrome (Canale-Smith) in adulthood.The autoimmune lymphoproliferative syndrome (ALPS) or Canale-Smith syndrome is a recently described clinical entity consisting of chronic, non-malignant lymphadenopathy and hepatosplenomegaly together with hypergammaglobulinemia, positive autoantibodies and/or overt autoimmune diseases. It is caused by a genetic defect in the mechanism of programmed cell death (apoptosis) and is characterized by the presence of double-negative (TCR alpha/beta CD4- CD8-) T lymphocytes (DNT). Although well known in pediatric patients, ALPS is an unusual diagnosis in adults. The oldest reported patient was aged 54. We describe another two adult patients in whom a presenting autoimmune disease led to the diagnosis of ALPS.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
6/12. Histological varieties of Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like clinicopathological findings in middle-aged and elderly patients: a study of six cases.Six cases were studied to further clarify clinicopathological findings of Epstein-Barr virus (EBV)-related lymph node lesions showing autoimmune disease-like clinicopathological findings (EBVAID) in middle-aged and elderly patients. The patients, four males and two females, ranged in age from 53 to 74 years, with a median age of 62 years. Clinically, they were characterized by systemic lymphadenopathy, "B"symptoms, polyclonal hypergammaglobulinemia, elevated serum lactate dehydrogenase and a transient presence of various autoantibodies, as well as an infrequent presence of atypical lymphocytosis in peripheral blood. Two cases were associated with idiopathic thrombocytopenic purpura. The clinical course was self-limiting. Histologically, three patterns could be delineated: pattern A, follicular hyperplasia with pronounced arborizing vasculature in the expanded paracortex (n=3); pattern B, follicular hyperplasia with pronounced interfollicular B-immunoblastic/plasma cell proliferation (n=2); and pattern C, paracortical hyperplasia containing numerous large transformed lymphocytes (n=1). in situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the germinal center and in the interfollicular area. polymerase chain reaction analysis demonstrated that neither clonal rearrangement of T-cell receptor gamma-chain nor immunoglobulin heavy-chain rearrangement was detected in the three cases examined. Although EBVAID appears to be rare in middle-aged and older adults, EBVAID exhibits histological variations and should be added to the differential diagnosis of various atypical or malignant lymphoproliferative disorders, in particular autoimmune-disease-associated lymphadenopathy and angioimmunoblastic T-cell lymphoma with a hyperplastic germinal center in middle-aged and elderly patients.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
7/12. Oligoclonal immunoglobulin heavy chain gene rearrangement in a childhood immunoblastic lymphoma. Presentation as a polyphenotypic atypical lymphoproliferative reaction.The authors describe a diagnostically difficult case of childhood lymphoma that presented as an atypical polyphenotypic lymphoproliferative reaction. Initial immunophenotyping revealed the presence of IgG, IgA, kappa, and lambda within the neoplastic lymphocytes. The patient had circulating plasmacytoid lymphocytes and a polyclonal hypergammaglobulinemia. The patient died of widespread immunoblastic lymphoma in two months. Postmortem tumor dna showed a oligoclonal pattern of immunoglobulin heavy chain gene rearrangement. Blots for T-cell receptor beta-chain rearrangement showed germline bands. Epstein-Barr virus dna was present within tumor cells, but there was no history of prior immunosuppression or serologic evidence of Epstein-Barr virus infection. The apparent polyclonal nature of the immunoproliferation delayed the institution of chemotherapy.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
8/12. A lymphoproliferative disorder of T gamma cells with the phenotype of cytotoxic/suppressor T-cell.A 25-yr-old Japanese male showed unique T gamma cell proliferation different from cases reported previously. His clinical and hematological features were characterized by persistent high fever and the appearance of large lymphocytes with abundant cytoplasm and azurophilic granules in the peripheral blood (11% of the leukocyte differential count) and the ascitic fluid. These lymphocytes showed the ability to bind the Fc portion of IgG and they beared the antigen of cytotoxic/suppressor T-cell defined by monoclonal antibodies. T-cells from this patient suppressed the immunoglobulin production of normal B-cells by pokeweed mitogen, although a polyclonal hypergammaglobulinemia was observed in the serum. Chromosomal abnormality indicated the malignant nature of the proliferating T gamma cells in this patient. The clinical, hematological, and immunological findings characterized the disease of this patient as a distinct entity among the lymphoproliferative disorders of T-cell origin.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
9/12. mycosis fungoides/Sezary's syndrome progressing to immunoblastic sarcoma. A T-cell lymphoproliferation with both helper and suppressor phenotypes.Multiparameter studies of an unusual patient exhibiting cutaneous manifestations of both mycosis fungoides and Sezary's syndrome are presented. The neoplastic cells of dermal and nodal infiltrates and peripheral blood expressed both helper and suppressor immunologic phenotypes. Cytofluorographic analysis of cells isolated from lymph node and peripheral blood showed a population of neoplastic cells that were stained with the monoclonal antibodies OKT 3, 4, 8, and 11. Immunoperoxidase staining of frozen sections with monoclonal antibodies Leu 1, 2, and 3 provided a topographical identification of an identically marking population of cells in dermis and lymph node. In light of current models depicting normal T-cell lineage, the authors suggest that the neoplastic population in this patient, expressing both helper and suppressor phenotypes, reflected a phenotypic stage of immunologic maturation (OKT 6-, OKT 10-, OKT 3 , OKT 11 , OKT 4 , OKT 8 ) in which the neoplastic cells had not yet segregated into distinctive T-cell subsets. While excess helper activity was suggested by serum hypergammaglobulinemia, in vitro helper and suppressor function was not determined. The range of studies employed illustrates the wide variety of technics required to adequately characterize complex clinico-immunopathologic disorders, as represented by this case, and the wealth of information that can be gleaned.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
10/12. Proteinaceous (angiocentric sclerosing) lymphadenopathy: a polyclonal systemic, nonamyloid deposition disorder.Proteinaceous lymphadenopathy with hypergammaglobulinemia (PLWH) is an exceedingly rare disease of unknown etiology. Described primarily as a pathologic entity, relatively little is known about its clinical manifestations or its response to therapy. The disease is often referred to and treated as an unusual form of plasma cell dyscrasia or light chain deposition disease. We have recently encountered a young patient with PLWH who presented with generalized lymphadenopathy, marked liver function abnormalities, hypocomplementemia, cryoglobulinemia, decreased T4/T8 ratio, and ophthalmopathy. Contrary to the notion that PLWH is a clonal disorder, we found no evidence of clonality in this patient. The most characteristic finding in this and in another patient, previously seen at our institution, was marked angiocentric hyaline sclerosis of the small and mid-sized blood vessels of involved lymph nodes and organs. Based on these findings, we propose the term angiocentric sclerosing lymphadenopathy, which more accurately defines this clinicopathologic entity that appears to be distinct from light chain deposition disease and other plasma cell dyscrasias.- - - - - - - - - - ranking = 1keywords = hypergammaglobulinemia (Clic here for more details about this article) |
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