A chromosomal translocation involving the MYC gene is characteristic of Burkitt lymphoma (BL) and represents a molecular disease marker with diagnostic and clinical implications. The detection of MYC breakpoints is hampered by technical problems, including the distribution of the breakpoints over a very large genomic region of approximately 1,000 kb. In this article, we report on the testing and validation of a segregation fluorescence in situ hybridization (FISH) assay for MYC breakpoints on a large series of BLs. A contig of overlapping genomic clones was generated, and two probe sets flanking the MYC gene were selected. Both probe sets were tested in an interphase FISH segregation assay on 8 B-cell lymphoma cell lines and 32 lymphoma samples with proved 8q24/MYC abnormalities and validated in 47 BLs from The Netherlands, Brazil, and Uganda. MYC translocation breakpoints were identified in 98% of the tumors of the test series and in 89% of the cases of the validation series. In 89% of all positive samples, the breakpoints were located between 190 kb 5' and 50 kb 3' of MYC. Nine cases had more distant breakpoints, and in one patient an insertion of MYC into the IGH region was detected. In two of the three BLs lacking CD10 expression, no breakpoint could be detected, suggesting that CD10 is a discriminative marker of BL. We did not find consistent differences between BL and atypical BL in incidence of an MYC breakpoint.
A substantial proportion of HIV-positive MSM with AIN completely cleared their lesions with topical 5-FU treatment. In those with partial response, pretreatment with topical 5-FU might facilitate subsequent ablative therapy.
EGFR and KRAS quality assurance schemes in pathology: generating normative data for molecular predictive marker analysis in targeted therapy Thunnissen, E.; Bovée, J.V.M.G.; Bruinsma, H.; van den Brule, A.J.C.; Dinjens, W.; Heideman, D.A.M.; Meulemans, E.; Nederlof, P.; van Noesel, C.; Prinsen, C.F.M.; Scheidel, K.; van de Ven, P.M.; de Weger, R.; Schuuring, E.; Ligtenberg, M.
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Epithelioid cell granulomas have been reported in association with a wide range of neoplasms including malignant lymphomas. In lymphoma, this refers mainly to Hodgkin disease and T-cell-derived non-Hodgkin lymphomas where a granulomatous reaction is probably evoked by aberrant cytokine production in the tumor cells or other cells composing the tumor background. Here we report on four cases of sporadic Burkitt lymphoma with unusual florid granulomatous reaction. In all samples, the tumor cells were admixed with numerous epithelioid cells that formed clusters and granulomatous lesions. No microorganisms could be detected at the tissue level, and there were no clinical or laboratory indications of an underlying immunodeficiency. The lymphomas harbored a specific morphology and immunophenotype of Burkitt lymphoma, and the presence of translocation breakpoint in MYC gene was confirmed by interphase fluorescence in situ hybridization. In all four patients, the lymphoma was associated with Epstein-Barr virus infection, detected by EBER in situ hybridization and the latency I phenotype as defined by lack of expression of LMP1. All four patients were treated with polychemotherapy, achieved a complete remission, and are alive without evidence of disease. We draw attention to this unusual phenomenon as it caused difficulties in interpretation and delayed diagnosis and hypothesize on the possible role of Epstein-Barr virus products.
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