T‐cell malignancies in Brazil. Clinico‐pathological and molecular studies of HTLV‐I‐positive and ‐negative cases

Abstract

T-cell malignancies in Brazil have a high seroprevalence rate of HTLV-I antibodies. We have analyzed the disease features in 188 Brazilian patients with a T-cell disorder. These included 40 with T-lymphoblastic leukaemia or lymphoma (T-ALL/T-LbLy) and 148 with mature T-cell diseases: 5 T-prolymphocytic leukaemia, 53 adult T-cell leukaemia/lymphoma (ATLL), 54 cutaneous T-cell lymphomas, 29 pleomorphic T-cell lymphomas and 7 large granular lymphocyte leukaemia. The diagnosis was based on clinical, morphological and immunological features and HTLV-I serology. ATLL in Brazil has the same diseases features as in other endemic regions, the only apparent differences being: age, Brazilian patients being younger than Japanese, and ethnic grouping, one third of Brazilians being white Caucasians of European descent. We applied a scoring system based on the presence or absence of typical features associated with ATLL; hypercalcaemia, cell morphology, immunophenotype, histopathology and HTLV-I status, to see whether it may help in diagnosing cases of ATLL. All had high scores, whereas all other T-cell diseases scored low. Only 5 ATLL cases were HTLV-I-negative by serology, but they had otherwise typical features of ATLL, and their cells did not have HTLV-I proviral sequences by DNA analysis. Such cases suggest that ATLL may develop in a minority of individuals living in regions where it is endemic, without evidence of HTLV-I infection, and that other factors may contribute to the pathogenesis of the disease.

High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis

“…By contrast, Southern-blotting, which has a sensitivity of about 1/20, failed to detect any signal in HTLV-1 infected individuals without strongyloidiasis (Chen et al, 1995;Nakada et al, 1987;Yamaguchi et al, 1988). In addition, Ss has been found to signi®cantly shorten the incubation period of ATLL, which occurs 30 years earlier in HTLV-1 individuals with strongyloidiasis than in other HTLV-1 asymptomatic carriers (Cleghorn et al, 1995;Plumelle et al, 1997;Pombo de Oliveira et al, 1995;Yamaguchi et al, 1987). Indeed, a greater exposure to infectious agents including Ss has been proposed to explain the earlier onset of ATLL in Caribbean/African patients when compared to Japanese patients .…”

“…Infection early in life is crucial in the development of ATLL. However, the average age of onset is 60 years in Japan but only 40 in Jamaica, Trinidad and Brazil (Cleghorn et al, 1995;Pombo de Oliveira et al, 1995). In vivo, the HTLV-1 life cycle includes the proliferation of its host cell and persistent clonal expansion of circulating CD4 T-cells harboring the HTLV-1 provirus has been evidenced in all symptomatic and asymptomatic carriers (Cavrois et al, 1996a(Cavrois et al, ,b, 1998Leclercq et al, 1998).…”

Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV-I-associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical, pathological and immunovirological study of 14 cases and a review of the African ATL cases

“…This suggests that the prevalence of such diseases is greatly underestimated in African countries, 24,34,39,40,44 as has been the case in South American areas such as Brazil 53,54 and French Guiana. 55 For ATL and SS, this under-reporting appears to be due mainly to the acute character of the disease, with patients dying before a diagnosis can be made, but also to the paucity of dermatologists and to the fact that HTLV-I serological confirmatory tests (Western blot), immuno-phenotyping and/or viro-molecular investigations are not readily available.…”

Adult T Cell Leukemia / Lymphoma in Chile

“…Later on, several reports came from Latin American countries, specially from Brasil, Colombia, Peru, Argentina and from Afro-Caribbean inmigrants to the United States and Europe (Pombo de Oliveira 1995, Blank 1996, Rodriguez 1994, Gioseffi 1995, Bunn 1983, Catovsky 1982, Gibbsw 1987, Manns 1993. In Chile, the first case of ATL of the acute form was documented in 1985, although without virological confirmation (Pereira 1985) and later on, it was published a case of a chilean man from Valparaiso that was living in Spain (Montserrat 1989).…”