Images in cardiovascular medicine. Cardiac transplantation for giant sarcoma of the left ventricle.
Explore the source record for details and available documents.
Child↗
Biomedical subjects
T Spieker
Publications and source records attributed to T Spieker.
Neoplastic heart disease -- the Muenster experience with 108 patients.
BACKGROUND: Tumours of the heart are rare. Different histological subtypes are known. The most common tumour entity is benign cardiac myxoma. Malignant heart tumours are less common. Tumours originating in other organs such as the kidney may also affect the heart by tumour progression via the inferior caval vein. A large experience with surgical treatment of different types of heart tumours is presented. METHODS: Between January 1989 and April 2004, 108 patients with a heart tumour were included in a database. All patients underwent radical surgical resection, except for 2 patients who had malignant lymphoma of the heart. RESULTS: Histological findings included 78 myxomas (72.2 %), and 6 other benign cardiac tumours in 5.6 % of the patients. Primary malignant heart tumours were seen in 10 (9.2 %) and renal cell carcinoma with cardiac involvement in 6 (5.6 %) patients. Eight patients presented with tumour metastases inside the heart (7.4 %). Mean overall survival was 12.7 years for myxoma patients and 5.6 years for patients with other benign heart tumours. Patients with primary malignant heart tumours survived 5.5 years on average. CONCLUSIONS: Heart tumours are rare, but usually life-threatening. Radical surgical resection is the therapy of choice and may offer excellent long-term survival, even in cases with malignant heart tumours.
Adolescent↗
Survival and clonal expansion of mutating "forbidden" (immunoglobulin receptor-deficient) epstein-barr virus-infected b cells in angioimmunoblastic t cell lymphoma.
Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a peculiar T cell lymphoma, as expanding B cell clones are often present besides the malignant T cell clones. In addition, large numbers of Epstein-Barr virus (EBV)-infected B cells are frequently observed. To analyze the differentiation status and clonal composition of EBV-harboring B cells in AILD, single EBV-infected cells were micromanipulated from lymph nodes of six patients with frequent EBV(+) cells and their rearranged immunoglobulin (Ig) genes analyzed. Most EBV-infected B cells carried mutated Ig genes, indicating that in AILD, EBV preferentially resides in memory and/or germinal center B cells. EBV(+) B cell clones observed in all six cases ranged from small polyclonal to large monoclonal expansions and often showed ongoing somatic hypermutation while EBV(-) B cells showed little tendency for clonal expansion. Surprisingly, many members of expanding B cell clones had acquired destructive mutations in originally functional V gene rearrangements and showed an unfavorable high load of replacement mutations in the framework regions, indicating that they accumulated mutations over repeated rounds of mutation and division while not being selected through their antigen receptor. This sustained selection-free accumulation of somatic mutations is unique to AILD. Moreover, the survival and clonal expansion of "forbidden" (i.e., Ig-deficient) B cells has not been observed before in vivo and thus represents a novel type of viral latency in the B cell compartment. It is likely the interplay between the microenvironment in AILD lymph nodes and the viral transformation that leads to the survival and clonal expansion of Ig-less B cells.
Adult↗
Low prevalence of latently Epstein-Barr virus-infected cells in chronic gastritis.
The association of Epstein-Barr virus (EBV) with a proportion of gastric carcinomas is well established. The role of EBV in conditions predisposing to carcinoma such as chronic gastritis has remained undefined, however. We used in situ hybridization with radioactive and nonradioactive single-stranded RNA probes specific for the EBV small latent nuclear transcripts, EBER1 and EBER2, to analyze biopsy specimens from 242 patients with mild to severe chronic gastritis of Sydney classification types A, B, and C. A small number of EBV infected lymphocytes was detected in only nine cases, even in biopsies investigated with radioactive probes. Labeling of epithelial or stromal cells was not observed. The paucity of latently EBV-infected cells in chronic gastritis biopsies differs from the previously reported higher prevalence of virus carrying cells in inflammatory conditions at other sites of the gastrointestinal tract. These findings argue against a direct involvement of EBV in the pathogenesis of chronic gastritis. The low prevalence of EBV-positive cells suggests that local factors do not favor the entry and retention of circulating EBV-infected lymphocytes in gastric mucosa. Moreover, our findings indicate that EBV infection of gastric epithelial cells is not an early event in gastric carcinogenesis.
Adolescent↗
Molecular single-cell analysis of Hodgkin- and Reed-Sternberg cells harboring unmutated immunoglobulin variable region genes.
Hodgkin- and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease of the B lineage are the clonal progeny of antigen-experienced B cells harboring highly mutated immunoglobulin variable (V) region genes. Based on the detection of obviously destructive somatic mutations in a fraction of cases, we speculated that H/RS cells may be derived from a pre-apoptotic germinal center B cell. Seemingly contradicting this speculation, we present here the first case of classical Hodgkin's disease with H/RS cells harboring unmutated, potentially functional V region genes, which may indicate the derivation of the H/RS clone from a naive B cell. However, germinal center founder cells, which have not yet acquired somatic mutations, already have the intrinsic propensity to die by apoptosis. Thus, the rare occurrence of H/RS cells with unmutated V genes is expected if the H/RS cells are derived from the pool of pre-apoptotic germinal center B cells.
Aged↗
Molecular single-cell analysis of the clonal relationship of small Epstein-Barr virus-infected cells and Epstein-Barr virus-harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease.
Epstein-Barr virus (EBV) can be detected in the tumor cells of approximately 40% of cases of classical Hodgkin disease (cHD). Clonality studies suggest that infection of the neoplastic Hodgkin and Reed/Sternberg (HRS) cells occurs before tumor clone expansion. In EBV-positive cases, variable numbers of EBER-positive small B cells are sometimes also observed that immunohistologically differ from the neoplastic cells by lack of CD30 and latent membrane protein 1 expression. To analyze the clonal relationship between these EBV(+) cells and the HRS cells, single EBV-infected CD30(-) B cells, as well as HRS cells from 3 cases of EBV-positive cHD were micromanipulated, their immunoglobulin gene rearrangements amplified and then compared with each other. In 2 cases, all small EBV-infected cells were clonally unrelated to the HRS cells. In a third case, 2 of 29 small CD30(-) cells were found to carry HRS cell-specific rearrangements. Thus, small CD30(-) EBV-infected B cells in cHD belong to the HRS tumor clone rarely, if at all. In all cases, small clones unrelated to the HRS cell clones were identified among the small EBV(+) CD30(-) cells. The vast majority of small EBV(+) CD30(-) B cells was found to carry somatically mutated V region genes, indicating that in lymph nodes of patients with HD, like in the peripheral blood of healthy individuals, EBV persists in memory B cells.
Adult↗
Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma.
Members of the nuclear factor (NF)-kappaB family of transcription factors play a crucial role in cellular activation, immune responses, and oncogenesis. In most cells, they are kept inactive in the cytosol by complex formation with members of the inhibitor of NF-kappaB (IkappaB) family, whose degradation activates NF-kappaB in response to diverse stimuli. In Hodgkin's lymphoma (HL), high constitutive nuclear activity of NF-kappaB is characteristic of the malignant Hodgkin and Reed-Sternberg (H/RS) cells, which occur at low number in a background of nonneoplastic inflammatory cells. In single H/RS cells micromanipulated from histological sections of HL, we detect clonal deleterious somatic mutations in the IkappaBalpha gene in two of three Epstein-Barr virus (EBV)-negative cases but not in two EBV-positive cases (in which a viral oncogene may account for NF-kappaB activation). There was no evidence for IkappaBalpha mutations in two non-HL entities or in normal germinal center B cells. This study establishes deleterious IkappaBalpha mutations as the first recurrent genetic defect found in H/RS cells, indicating a role of IkappaBalpha defects in the pathogenesis of HL and implying that IkappaBalpha is a tumor suppressor gene.
Adult↗
Distribution and phenotype of Epstein-Barr virus-infected cells in inflammatory bowel disease.
Little is known about Epstein-Barr virus (EBV) infection of colon mucosa, particularly in inflammatory bowel diseases. Crohn's disease and ulcerative colitis are thought to differ in T-helper lymphocyte composition and cytokine secretion patterns. Some of the implicated cytokines are growth factors for EBV-infected cells. We examined colon mucosa for differences in the distribution and phenotype of EBV-infected cells. Colon tissues with Crohn's disease (n = 31) or ulcerative colitis (n = 25) and controls (n = 60) were characterized by in situ hybridization and immunohistology for six EBV gene products as indicators of latent and replicative EBV infection. The cells were additionally phenotyped by combined detection of the EBV transcripts and B- or T-cell antigens. B lymphocytes predominated as the site of latent EBV infection in the colon and were most numerous in ulcerative colitis. In active ulcerative colitis, EBV-positive lymphocytes accumulated under and within the epithelium and displayed evidence for replicative infection. The patterns of mucosal EBV gene expression indicate local impairment of virus-specific T-cell responses in active ulcerative colitis. Detection of EBV may help to discriminate between active ulcerative colitis and other inflammatory bowel diseases. Colon mucosa is a potential site of EBV replication and may be relevant for EBV transmission.
Antigens, CD20↗
EBV-infected B cells in infectious mononucleosis: viral strategies for spreading in the B cell compartment and establishing latency.
Infection of humans with Epstein-Barr virus (EBV) may cause infectious mononucleosis (IM). Analysis of single EBV-infected cells from tonsils of IM patients for rearranged immunoglobulin genes revealed two strategies of EBV for rapid and massive spread in the B cell compartment: the direct infection of many naive as well as memory and/or germinal center B cells and the expansion of the latter cells to large clones. In IM, the generation of virus-harboring memory B cells from naive B cells passing through a germinal center reaction likely plays no role. Members of clones can show distinct morphologies and likely also EBV gene expression patterns, and this ability implies a mechanism by which EBV-harboring cells can evade immune surveillance and establish a pool of persisting EBV-infected B cells.
Adolescent↗
Molecular analysis of single B cells from T-cell-rich B-cell lymphoma shows the derivation of the tumor cells from mutating germinal center B cells and exemplifies means by which immunoglobulin genes are modified in germinal center B cells.
T-cell-rich B-cell lymphoma (TCRBCL) belongs to the group of diffuse large cell lymphomas (DLL). It is characterized by a small number of tumor B cells among a major population of nonmalignant polyclonal T cells. To identify the developmental stage of the tumor progenitor cells, we micromanipulated the putative neoplastic large CD20(+) cells from TCRBCLs and amplified and sequenced immunoglobulin (Ig) V gene rearrangements from individual cells. In six cases, clonal Ig heavy, as well as light chain, gene rearrangements were amplified from the isolated B cells. All six cases harbored somatically mutated V gene rearrangements with an average mutation frequency of 15.5% for heavy (VH) and 5.9% for light (VL) chains and intraclonal diversity based on somatic mutation. These findings identify germinal center (GC) B cells as the precursors of the transformed B cells in TCRBCL. The study also exemplifies various means how Ig gene rearrangements can be modified by GC B cells or their malignant counterparts in TCRBCL: In one case, the tumor precursor may have switched from kappa to lambda light chain expression after acquiring a crippling mutation within the initially functional kappa light chain gene. In another case, the tumor cells harbor two in-frame VH gene rearrangements, one of which was rendered nonfunctional by somatic mutation. Either the tumor cell precursor entered the GC with two potentially functional in-frame rearrangements or the second VHDHJH rearrangement occurred in the GC after the initial in-frame rearrangement was inactivated by somatic mutation. Finally, in each of the six cases, at least one cell contained two (or more) copies of a clonal Ig gene rearrangement with sequence variations between these copies. The presence of sequence variants for V region genes within single B cells has so far not been observed in any other normal or transformed B lymphocyte. Fluorescence in situ hybridization (FISH) points to a generalized polyploidy of the tumor cells.
Adult↗
Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4-34 gene segment.
Primary central nervous system lymphomas (PCNSLs) have recently received considerable clinical attention due to their increasing incidence. To clarify the histogenetic origin of these intriguing neoplasms, PCNSLs from 10 HIV-negative patients were analyzed for immunoglobulin (Ig) gene rearrangements. All tumors exhibited clonal IgH gene rearrangements. Of the 10 cases, 5 used the V4-34 gene segment, and all of these lymphomas shared an amino acid exchange from glycine to aspartate due to a mutation in the first codon of the complementarity-determining region 1. No preferential usage of D(H), J(H), V(kappa), J(kappa), V(lambda), or J(lambda) gene segments was observed. All potentially functional rearrangements exhibited somatic mutations. The pattern of somatic mutations indicated selection of the tumor cells (or their precursors) for expression of a functional antibody. Mean mutation frequencies of 13. 2% and 8.3% were detected for the heavy and light chains, respectively, thereby exceeding other lymphoma entities. Cloning experiments of three tumors showed ongoing mutation in at least one case. These data suggest that PCNSLs are derived from highly mutated germinal-center B cells. The frequent usage of the V4-34 gene and the presence of a shared replacement mutation may indicate that the tumor precursors recognized a shared (super) antigen.
B-Lymphocytes↗
Multiple cutaneous B-cell pseudolymphomas after allergen injections.
Explore the source record for details and available documents.
Adult↗
Generalised acanthosis nigricans with vitiligo.
We report on a 19-year-old woman with generalised acanthosis nigricans of the inherited type and concomitant vitiligo. Cutaneous velvety thickening of the skin with intensification of skin markings and progressive development of hyperpigmented papillomatous, verrucoid lesions in the body folds started to develop in early childhood. These hyperpigmentations were continuously replaced by a progressive vitiligo, finally leaving most of the acanthosis nigricans lesions completely depigmented. Generalised, pachyderma-like acanthosis nigricans with concomitant vitiligo is an association which to the best of our knowledge has not yet been described.
Acanthosis Nigricans↗