Epstein-Barr virus associated B-cell lymphoma of brain developing in myelodysplastic syndrome with c-kit mutation (Try-557 -> stop)

The first case of B-cell lymphoma of brain in a patient with myelodysplasti c syndrome (MDS) was reported. A 68-year-old man was admitted because of an emia, fever, and thrombocytopenia and was diagnosed as having MDS (refracto ry anemia with excess of blasts) on the basis of the findings of bone marro w aspiration and chromosomal analysis. The patient was followed up without chemotherapy, but a brain tumor appeared after 3 years. Histologic and immu nohistologic examinations revealed diffuse large B-cell lymphoma. Mutations of the c-kit proto-oncogene (stem cell factor receptor) and the p53 tumor- suppressor gene were examined in the MDS lesion and malignant lymphoma (ML) by the polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) method followed by direct sequencing. The p53 mutation was not found in either MDS or ML, but a nonsense mutation (Try-557 --> stop) in ex on 11 of the c-kit, which might lead to dysfunction of tyrosine kinase acti vity, was detected in MDS. This is the first report of c-kif mutation in MR S. Epstein-Barr virus (EBV) genome was demonstrated in the nucleus of brain ML cells by in situ hybridization with EBV-encoded RNA-1 probe. Immunohist ochemistry showed that the tumor cells expressed latent infection gene prod ucts, including EBV nuclear antigen-2 and latent membrane protein-1. This p attern of latent gene expression was Lat ill, which is usually found in mal ignant lymphomas developing in immunocompromised hosts. These findings sugg est that a profound pancytopenia in MDS resulted in an immunodeficient cond ition, after which EBV-positive B-cell lymphoma of brain developed. (C) 200 0 Wiley-Liss, Inc.