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A total of 56 cases of malignant lymphoma presumed to be of peripheral T-cell origin were investigated with regard to histological and immunohistochemical features. The goal of the study was to determine whether virus-associated T-cell lymphomas can be morphologically or immunohistochemically distinguished from presumably virus-negative T-cell lymphomas. The cases came from endemic and non-endemic regions of Japan, the United Kingdom (including 4 Caribbean cases) and the Federal Republic of Germany. Sera of all Japanese and Caribbean patients and 8 German patients were tested for antibodies to adult T-cell leukaemia virus-associated antigen HTLV-A. In all cases sections were examined blind by 5 well-trained histopathologists. In most cases cryostat sections could be prepared from fresh tissue specimens and stained with a large panel of monoclonal antibodies. All HTLV-A-positive cases were morphologically classifiable as the pleomorphic type of T-cell lymphoma. Approximately 70% of the tested cases of pleomorphic T-cell lymphoma, however, showed a positive serum reaction for HTLV-A. All other types of peripheral T-cell lymphoma (T-immunoblastic lymphoma, chronic lymphocytic leukaemia of T type, T-zone lymphoma, "AILD type" and lymphoepithelioid cell lymphoma) were HTLV-A-negative and mostly observed in European patients. Thus virus-associated T-cell lymphomas appear to be invariably of the pleomorphic type; but pleomorphism is not specific to HTLV-A-positive cases. This was also evident from the results of an experiment in which 2 Japanese histopathologists attempted to recognize HTLV-A positivity in a blind study of pleomorphic T-cell lymphomas. A maximum of about 80% of cases were correctly identified, with about 10% false-positive diagnoses (in HTLV-A-negative or presumably negative cases) and 10% false-negative diagnoses. The immunohistochemical analysis revealed not only many common features but also 2 distinct differences between HTLV-A-positive and -negative T-cell lymphomas. All but one of the HTLV-A-positive cases showed reactivity with anti-Tac and all cases in the virus-positive group were negative for TU14. All other cases were Tac-negative and approximately 65% of these cases exhibited reactivity with TU14. Preliminary cytogenetic observations suggest that there are also differences in specific chromosome aberrations.