Contribution of Epstein‐Barr virus to development of malignant lymphoma of the thyroid

Epstein-Barr virus (EBV)-related mRNA, their products and apoptosis were investigated in 32 cases of malignant lymphoma of the thyroid (MLT) and 30 cases of Hashimoto's thyroiditis (HT) by in situ hybridization, immunohistochemistry and nick end labeling method on routinely processed tissue sections. In MLT, EBV-encoded small RNA (EBER) were detected in three cases, consisting of a follicular, predominantly large cell type (FL), a diffuse, large cell type (DL) and a large cell, immunoblastic type (IBL). In EBER-positive cases, IBL that was positive for T cell marker, exhibited neither BamHl H Left Frame 1 (BHLF1) transcript, EBV-encoded latent membrane protein (LMP) nor BamHl Z Left Frame 1 (BZLF1) gene product (ZEBRA), whereas both BHLF1 and ZEBRA were found in a small portion of the tumor cells in the FL and DL that expressed B cell marker and LMP. Apoptotic cells were observed in only a few lymphocytes in HT, and in a few non-neoplastic lymphocytes and various numbers of lymphoma cells in MLT. The apoptotic cell ratio of MLT tended to be higher in lower grade lymphomas. These results suggest that EBV may participate in the malignant transformation from HT to MLT.