[Clinical spectrum of celiac disease].
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Biomedical subjects
Publications and source records attributed to S Daum.
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Epileptic seizures may be of a provoked origin in acute phases of multiple sclerosis (MS), while chronic epilepsy typically occurs in advanced stages of the disease. A case of seizure provocation during diagnostic transcranial magnetic stimulation (TMS) is described here with a corresponding central nervous system (CNS) lesion in cranial magnetic resonance imaging. A subsequent chronic epileptogenesis originating from the opposite cerebral hemisphere was observed without further TMS influence after several years. The case in its clinical rarity demonstrates that standard single pulse TMS may trigger epileptic seizures only under limited conditions. Single pulse TMS is still regarded a safe procedure in MS.
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BACKGROUND: Clonal T cell receptor (TCR) gene rearrangements and loss of T cell antigens such as CD8 and TCR-beta in intraepithelial lymphocytes (IELs) may indicate the development of an enteropathy-type intestinal T cell lymphoma (EITCL) in patients with refractory sprue. AIMS: To define the diagnostic value of these markers in duodenal biopsies from patients with villous atrophy as a result of various underlying disorders. PATIENTS AND METHODS: Duodenal biopsies from eight patients with coeliac disease and five patients with villous atrophy caused by defined disorders were compared with three patients with refractory sprue evolving into overt EITCL, two patients with ulcerative jejunitis, and with eight patients with overt EITCL, for expression of CD3, CD4, CD8, and TCR-beta in IELs using immunohistochemistry and for clonal TCR-gamma gene rearrangements using polymerase chain reaction. In addition, biopsies from six consecutive patients with refractory sprue of uncertain cause were examined. RESULTS: Clonal TCR-gamma gene rearrangements were found in all resected tumours of patients with EITCL, in 3/8 duodenal biopsies of patients with EITCL, in 2/2 patients with ulcerative jejunitis, in 2/3 patients with refractory sprue evolving into overt EITCL, and in 1/6 patients with refractory sprue. No rearrangements were found in biopsies from patients with refractory sprue caused by defined disorders or those with coeliac disease. Clonality in duodenal biopsies was associated with an abnormal phenotype of IELs in all cases and in all but one case in patients with evidence of underlying coeliac disease. Specificity for detection of an EITCL using immunohistology was 77% for CD8 and for TCR-beta staining, and 100% for detection of a clonal TCR-gamma gene rearrangement. Sensitivity was 62% for staining with CD8 and clonality investigation, while sensitivity reached 100% for TCR-beta staining in all investigated patients with EITCL. CONCLUSIONS: Clonal proliferations of phenotypically abnormal IELs in refractory sprue represent an early manifestation of EITCL, for which the term "sprue-like intestinal T cell lymphoma" is proposed. This constellation is also found in duodenal biopsies from patients with an overt EITCL and is not related to other sprue syndromes, resulting in a high specificity for detection of an EITCL or refractory sprue evolving into EITCL. Overt EITCL may develop directly from coeliac disease without a precursor lesion (refractory sprue with clonal IELs) being demonstrable in duodenal biopsies or via a "sprue-like intestinal T cell lymphoma". This latter entity is a complication of coeliac disease.
INTRODUCTION: Recently, patients with refractory sprue have been shown to contain a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes in their intestine. Whether this signifies early enteropathy-type intestinal T-cell lymphoma (EITCL) or a reactive condition is not clear. We report on a patient presenting with the findings of refractory sprue who subsequently developed overt EITCL. MATERIAL AND METHODS: Duodenal biopsies from 1997 (refractory sprue) and duodenal and jejunal biopsies from 1998 (intestinal T-cell lymphoma) were compared by immunohistochemistry and PCR for the detection of T-cell receptor (TCR)-gamma gene rearrangements. Clonal PCR products were sequenced. RESULTS: The duodenal biopsies from both 1997 and 1998 and the jejunal tumor biopsy showed villus atrophy and an increase of intraepithelial lymphocytes with an abnormal immunophenotype (CD3+, CD4-, CD8- and TCR-beta-). In all duodenal specimens including the one from 1997, and the jenunal tumor biopsy, an identical clonal amplificate was detected by enzymatic amplification of the TCR-gamma gene. CONCLUSION: These data suggest that refractory sprue containing a clonal proliferation of phenotypically abnormal intraepithelial lymphocytes may represent an early manifestation of EITCL. The detection of immunohistochemical negativity for several antigens normally found on intraepithelial lymphocytes such as CD8 or the TCR-beta chain in combination with clonal T-cell populations by PCR may be helpful in identifying refractory sprue with a malignant transformation.
AIMS: The classification of primary gastric T-cell lymphomas is uncertain due to the exceeding rarity of these tumours; many of the reported cases were felt to be similar to node-based lymphomas. We describe two cases of primary gastric T-cell lymphoma with evidence of origination from intraepithelial T-lymphocytes. METHODS AND RESULTS: Both tumours were restricted to the stomach; one displaying a large ulcerated mass, the other a widespread superficial tumour manifestation. Histologically the first tumour was composed of sheets of medium-sized lymphoid cells showing marked epitheliotropism at the edge of the ulcer, and a CD3+, CD4-, CD8-, CD20-, CD56-, CD103+, beta F1+ phenotype. The second case differed histologically and immunophenotypically from the first case. In addition to lamina propria and submucosal infiltration, the lymphoma contained an extensive intraepithelial component even in large areas without other evidence of tumour. The neoplastic cells ranged in size from small to medium and large. Immunohistology disclosed a CD3+, CD4+, CD8-, CD20-, CD56-, beta F1+ phenotype. Staining for CD103 could not be performed in this case since frozen material was not available. CONCLUSIONS: The prominent epitheliotropism, the marked intraepithelial growth and the expression of CD103 strongly imply a derivation of these primary gastric lymphomas from intraepithelial T-lymphocytes. Additional studies of larger series will clarify whether the findings described here are typical of primary gastric T-cell lymphomas.
BACKGROUND: Extracellular matrix (ECM) degradation may play a role in villus atrophy in coeliac disease (CD). AIMS: To compare the cellular expression of mRNA transcripts for the two major matrix degrading proteases, matrix metalloproteinase (MMP)-1 and MMP-3, their inhibitor, tissue inhibitor of metalloproteinases (TIMP)-1, and procollagen I in the intestinal mucosa of patients with untreated and treated CD and normal controls. PATIENTS/METHODS: Duodenal biopsy specimens from ten untreated CD patients, from six of these after a gluten free diet, and from ten control patients were hybridised with 35S-labelled RNA probes. The number of positive cells in the subepithelial region and lamina propria were counted microscopically. RESULTS: The numbers of cells positive for MMP-1 (p<0.005), MMP-3 (p<0.01), and TIMP-1 (p<0.05) mRNA were higher in the subepithelial region of CD mucosa than in that from controls. In the lamina propria, only cells positive for MMP-1 mRNA were increased in CD patients compared with controls (p<0.01). MMP-1 and MMP-3 mRNA expression returned to normal in CD patients after treatment with a gluten free diet (p<0.05), while TIMP-1 mRNA expression remained elevated. The number of procollagen I mRNA expressing cells did not change. Expression of MMP-1 and MMP-3 mRNA was mainly localised to subepithelial fibroblasts and macrophages. CONCLUSIONS: The decreased ratio of collagen I and TIMP-1 mRNA expressing cells to MMP-1 and MMP-3 mRNA expressing cells in untreated CD suggests a shift towards ECM degradation. ECM degradation by activated subepithelial fibroblasts and macrophages may be an important mechanism driving mucosal transformation in CD.
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Of all surgical interventions of intestinal non-Hodgkin's lymphomas 58% (15 or 26 patients) are performed in an emergency situation. In 42% of cases, examination by ultrasonography, endosonography, intestinoscopy. Sellink's enema, thoracic, abdominal/pelvic CT and bone marrow puncture could determine the stage preoperatively. This could also be done by examining the regional and juxtaregional lymph nodes or performing a liver biopsy intraoperatively. Crucial for the therapy is in all cases the adequate staging even in emergency situations. Only special knowledge of the intestinal non-Hodgkin's lymphoma can lead to the necessary stage-adapted multimodal therapy--operation/irradiation/chemotherapy.
Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from alpha beta intraepithelial T-lymphocytes. Since these lymphocytes may contain cytotoxic molecules, the question of whether this also holds true for ITCL arises. Twenty ITCL cases were examined for the presence of granzyme B, perforin, and T-cell-restricted intracellular antigen (TIA-1)/granule membrane protein of 17 kD (GMP-17). Two molecules with restricted expression in cytotoxic cells, granzyme B and perforin, were detected by immunocytochemistry and by in situ hybridization with an isotopically labelled RNA probe, respectively. Immunocytochemistry was also performed with the antibody 2G9, which recognizes two molecules, one expressed by cytotoxic cells (TIA-1) and the other found in granulocytes and cytotoxic cells (GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neoplastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectively, of ITCL, but not in the tumour cells of the control group, which consisted of intestinal B-cell lymphomas (five cases) and CD8-negative peripheral nodal T-cell lymphomas (six cases). At least one of these molecules was expressed in the tumour cells of all ITCL cases. 2G9 proved to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cases, but also found in high numbers of neoplastic cells in positive cases. In conclusion, ITCL appears to show cytotoxic differentiation in all cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithelial alpha beta cytotoxic T-lymphocytes.
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Intestinal T-cell lymphoma (ITCL) is a rare type of extranodal lymphoma derived from intraepithelial T-cells and generally exhibits macroscopically evident ulcerated lesions of the bowel wall composed of pleomorphic tumor cells. We report immunophenotypic and molecular genetic findings in an unusual small-sized intramucosal type of ITCL observed in a 74-year-old man presenting with enteropathy. Biopsies obtained from duodenum and jejunum showed a conspicuous accumulation of small-sized lymphoid cells forming intraepithelial clusters. The predominantly intraepithelial spread was accompanied by a spilling over to the lamina propria but not to deeper layers of the duodenal and jejunal wall, thus resulting in a purely intramucosal manifestation. This growth pattern and the immunophenotypic profile (CD3+, CD4-, CD8+, CD103+) suggested that the lesion may fall in the spectrum of ITCL. However, since the lymphoid cells cytomorphologically lacked neoplastic features and showed a small growth fraction. a reliable diagnosis of malignant lymphoma could not be established by histological and immunohistochemical methods. In this case a tissue-based polymerase chain reaction (PCR) analysis of T-cell receptor (TCR) beta and gamma gene rearrangements proofed to be essential in confidently distinguishing multifocal monoclonal intramucosal T-cell lymphocytosis from an intense reactive inflammatory infiltrate in celiac disease (CD). Our observation highlights that detection of clonal rearrangements of TCR genes is particularly useful in detecting ITCL composed of cytomorphologically innocuous T-cells because histologic diagnosis in such cases is at best presumptive.
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