Nodal T-cell lymphoma in an HTLV-I-endemic area: proviral HTLV-I DNA, histological classification and clinical evaluation

Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). The histology usually indicates a pleomorphic type, but is not consistent. To clarify the relationship between the histological classification and prognosis in ATLL, and to confirm the significance of clonal HTLV-I integration, we reclassified 572 cases with nodal T-cell lymphoma in which the T-cell phenotype and/or genotype was confirmed. In all cases the clonal integration of HTLV-I proviral DNA in the lymph nodes was examined by Southern blot analysis. In addition, anti-ATL antigen (ATLA) determination in the serum or PCR analysis of HTLV-I pX amplification in lymph nodes was also performed, 66/313 (21%) cases with ATLA had no evidence of clonal HTLV-T integration. 572 cases were classified into three groups: (A) cases with clonal integration (247 cases), (B) cases with ATLA without clonal integration of HTLV-I proviral DNA (66 cases), (C) cases without ATLA (259 cases). Histologically, groups B and C frequently demonstrated large cell type and angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) type; however, group A tended to show a pleomorphic type. Clinically, group A showed a poorer prognosis than groups B and C. In conclusion, group A cases were defined as ATLL (HTLV-I-associated T-cell lymphoma), whereas group B was classified as T-cell lymphoma, which had coincidently occurred in HTLV-I infected carriers. The simplified classification of REAL indicated clinical outcome: the prognosis of ATLL was poor, the unspecified type was intermediate, whereas the other types of lymphoblastic, AILD and anaplastic large cell type were all relatively favourable.