Antibodies to HTLV-I in Nigerian blood-donors, their relatives and patients with leukaemias, lymphomas and other diseases

Antibodies to HTLV-I have been detected in sera from 15 (2.0%) of 736 adult blood-donors in Nigeria, in 4 (20.0%) of 20 patients with chronic lymphatic leukaemia, 3 (10.0%) of 30 with non-Hodgkin's lymphoma, one of 12 with Burkitt's lymphoma and one of 7 with acute lymphoblastic leukaemia. The frequency of positivity was higher (3.6%) in the blood-donors from the guinea and wooded savanna of northern Nigeria than in those from the rain-forest and mangrove swamps of southern Nigeria (1.8% in Lagos and 0.7% in Calabar). Two of the 3 seropositive patients with lymphoma had clinical presentation and courses similar to those of Japanese and Caribbean patients with adult T-cell leukaemia/lymphoma.     

Hypercalcemia, unusual bone lesions, and human T-cell leukemia-lymphoma virus in adult T-cell lymphoma

Extensive generalized and subperiosteal bone resorption was demonstrated in a patient with adult T-cell lymphoma and marked hypercalcemia of unclear pathogenesis. Antibody to the human T-cell leukemia-lymphoma virus (HTLV) was present in the serum of the patient, consistent with the recently reported association of adult T-cell lymphoma, hypercalcemia, and HTLV. The unique feature of this case was the presence of bone radiographic and pathologic findings consistent with hyperparathyroidism, in the absence of elevated parathormone levels. These findings contrast with the few previously reported cases of adult T-cell lymphoma with hypercalcemia, which showed lytic, sclerotic, or osteoporotic bone lesions. The authors suggest that the patient's malignant T-lymphocytes may have produced an osteoclast-activating-factor-like substance or a parathormone-like substance, which caused the striking bone changes. The exact role of HTLV in the pathogenesis of such cases remains to be determined.     

HTLV-positive and -negative T-cell lymphomas. Morphological and immunohistochemical differences between European and HTLV-positive Japanese T-cell lymphomas

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.     

Adult T-Cell Leukemia/Lymphoma and Cluster of HTLV-I Associated Diseases in Brazilian Settings

We studied the transmission routes of human T-cell lymphotropic virus type I (HTLV-I) within families of 82 Brazilian patients diagnosed with adult T-cell leukaemia/lymphoma (ATL). Diagnosis of ATL in 43 male and 39 female patients was based on clinical and laboratory criteria of T-cell malignancy and detection of HTLV-I monoclonal integration. Samples were tested for HTLV antibodies and infection was confirmed as HTLV-I by Western Blot and/or polymerase chain reaction (PCR) assays. Overall 26/37 (70%) of mothers, 24/37 (65%) of wives, 8/22 (36%) of husbands, 34/112 (30%) of siblings and 10/82 (12%) offspring were HTLV-I infected. In 11 ATL patients, mothers were repeatedly HTLV-I seronegative, but HTLV-I pol or tax sequences were detected in 2 out of 6 cases tested by PCR. ATL patients with seronegative mothers related the following risk factors for HTLV-I infection: 6 were breast-fed by surrogate mothers with unknown HTLV-I status, 4 had a sexually promiscuous behaviour and 1 had multiple blood transfusions at a young age. Familial aggregation of ATL and other HTLV-I associated diseases such as HTLV-I myelopathy (HAM/TSP) and or uveitis, ATL in sibling pairs or in multiple generations was seen in 9 families. There were 6 families with ATL and TSP sibling pairs. In 3 families at least one parent had died with lymphoma or presenting neurological diseases and 2 offspring with ATL. Further to the extent of vertical and horizontal transmission of HTLV-I infection within ATL families, our results demonstrate that mothers who provide surrogate breast-milk appear to be an important source of HTLV-I transmission and ATL development in Brazil.     

Adult T-cell leukemia/lymphoma and cluster of HTLV-I associated diseases in Brazilian settings.

We studied the transmission routes of human T-cell lymphotropic virus type I (HTLV-I) within families of 82 Brazilian patients diagnosed with adult T-cell leukaemia/lymphoma (ATL). Diagnosis of ATL in 43 male and 39 female patients was based on clinical and laboratory criteria of T-cell malignancy and detection of HTLV-I monoclonal integration. Samples were tested for HTLV antibodies and infection was confirmed as HTLV-I by Western Blot and/or polymerase chain reaction (PCR) assays. Overall 26/37 (70%) of mothers, 24/37 (65%) of wives, 8/22 (36%) of husbands, 34/112 (30%) of siblings and 10/82 (12%) offspring were HTLV-I infected. In 11 ATL patients, mothers were repeatedly HTLV-I seronegative, but HTLV-I pol or tax sequences were detected in 2 out of 6 cases tested by PCR. ATL patients with seronegative mothers related the following risk factors for HTLV-I infection: 6 were breast-fed by surrogate mothers with unknown HTLV-I status, 4 had a sexually promiscuous behaviour and 1 had multiple blood transfusions at a young age. Familial aggregation of ATL and other HTLV-I associated diseases such as HTLV-I myelopathy (HAM/TSP) and or uveitis, ATL in sibling pairs or in multiple generations was seen in 9 families. There were 6 families with ATL and TSP sibling pairs. In 3 families at least one parent had died with lymphoma or presenting neurological diseases and 2 offspring with ATL. Further to the extent of vertical and horizontal transmission of HTLV-I infection within ATL families, our results demonstrate that mothers who provide surrogate breast-milk appear to be an important source of HTLV-I transmission and ATL development in Brazil.     

Clinical and Laboratory Features of Adult T-cell Leukaemia Lymphoma in Barbados

We describe the clinical and pathological features of 23 Afro-Caribbean patients with adult T-cell leukaemia/lymphoma admitted to the Queen Elizabeth Hospital, Barbados over a 5 year period. There were 9 males and 14 females, with a median age of 38 years (range 14-84). Twelve had acute leukaemia, 10 lymphoma (including 4 with solitary extra nodal lesions) and 1 smouldering subtype. Two patients had a past history of tropical spastic paraparesis/HTLV 1 associated myelopathy (TSP/HAM). The prognosis was poor, with only 3 complete responses to chemotherapy (CHOP) lasting from 9 to 36 months. We conclude that ATLL in Barbados is similar to the disease in the other Caribbean islands and Japan, except that in Barbados the age of onset is over a decade younger than in Japan.     

Antibodies against human T-cell leukemia/lymphoma virus (HTLV) and expression of HTLV p19 antigen in relatives of a T-cell leukemia patient originating from Surinam

Serum and peripheral blood cell samples from eleven relatives of a T-cell leukemia patient with human T-cell leukemia/lymphoma virus (HTLV)-associated disease, were investigated for the presence of HTLV antibody and antigen expression. In addition to the patient, three family members were seropositive and a wide range in HTLV antibody titer was observed. The father of the patient showed the highest titer (173,000) and carried HTLV p19+ cells in his peripheral blood. Upon induction of proliferation of these cells by short-term culture in the presence of phytohemagglutinin (PHA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA), an increase from 1% to 28% HTLV p19+ cells was observed confirming previous findings that HTLV p19 expression was correlated with proliferative activity of the host cells. In none of the other seronegative or seropositive relatives of the patient HTLV p19 expression was revealed when tested in freshly isolated mononuclear cells, upon short-term incubation in PHA + TPA or after prolonged culture for 2 or 3 passages in medium containing T-cell growth factor. The results from HLA typing studies did not provide any evidence for HTLV related abnormalities in haplotype expression. Our data confirmed the earlier notion of a prevalence of HTLV infection within families of patients with HTLV-associated disease. It is furthermore obvious from our results that a normal individual may possess high titer HTLV antibody and circulating HTLV p19+ cells without showing signs of disease.     

Chewing of Betel,Areca and Tobacco: Perceptions and Knowledge Regarding their Role in Head and Neck Cancers in an Urban Squatter Settlement in Pakistan

Epstein-Barr virus (EBV) infection is highly associated with specific subtypes of malignant lymphoma. In our ‍previous report on nodal malignant lymphoma in Thailand, we found that 64% of classical Hodgkin’s lymphoma ‍(cHL), 51% of non-Hodgkin’s lymphoma, T-cell (NHL-T), and 13% of non-Hodgkin’s lymphoma, B-cell (NHL-B) ‍were EBV-related. In the present research, we conducted a retrospective study of primary extranodal non-Hodgkin’s ‍lymphoma of the sinonasal tract (e-NHL-ST) and primary extranodal non-Hodgkin’s lymphoma of the nasopharynx ‍(e-NHL-NP) in Southern Thailand, between 1997 and 2004. EBV-encoded RNA (EBER) expression by in situ ‍hybridization was performed in all cases and a T-cell receptor (TCR)-g gene rearrangement study was performed in ‍NHL-T cases. There were 18 cases of e-NHL-ST and 42 cases of e-NHL-NP detected by histologic and ‍immunohistochemistry examinations. The percentages of e-NHL-ST and e-NHL-NP as compared to nodal malignant ‍lymphoma were 3.7% and 6.8%, respectively. Sixteen cases (88.9%) of e-NHL-ST and 7 cases (16.7%) of e-NHL-NP ‍were NHL-T, and the remainder were NHL-B. All of the NHL-T cases in both sites were EBER-positive. Two (5.4%) ‍of the NHL-B cases in the nasopharynx showed EBER positive. Monoclonal bands of the TCR-ã gene were detected ‍in 71.4% of the extranodal NK/T-cell lymphomas, nasal type, patients; 50.0% of peripheral T-cell lymphoma, ‍unspecified, patients; and one case of angioimmunoblastic T-cell lymphoma. This study indicates a very strong ‍association of NHL-T in the sinonasal tract or nasopharynx with EBV infection, the link apparently being weaker in ‍NHL-B patients. The study also indicates that most cases of extranodal NK/T-cell lymphoma, nasal type, are not the ‍germline configuration of the TCR genes.     

Epstein-Barr Virus-Associated Extranodal Non-Hodgkin's Lymphoma of the Sinonasal Tract and Nasopharynx in Thailand

Epstein-Barr virus (EBV) infection is highly associated with specific subtypes of malignant lymphoma. In our ‍previous report on nodal malignant lymphoma in Thailand, we found that 64% of classical Hodgkin’s lymphoma ‍(cHL), 51% of non-Hodgkin’s lymphoma, T-cell (NHL-T), and 13% of non-Hodgkin’s lymphoma, B-cell (NHL-B) ‍were EBV-related. In the present research, we conducted a retrospective study of primary extranodal non-Hodgkin’s ‍lymphoma of the sinonasal tract (e-NHL-ST) and primary extranodal non-Hodgkin’s lymphoma of the nasopharynx ‍(e-NHL-NP) in Southern Thailand, between 1997 and 2004. EBV-encoded RNA (EBER) expression by in situ ‍hybridization was performed in all cases and a T-cell receptor (TCR)-g gene rearrangement study was performed in ‍NHL-T cases. There were 18 cases of e-NHL-ST and 42 cases of e-NHL-NP detected by histologic and ‍immunohistochemistry examinations. The percentages of e-NHL-ST and e-NHL-NP as compared to nodal malignant ‍lymphoma were 3.7% and 6.8%, respectively. Sixteen cases (88.9%) of e-NHL-ST and 7 cases (16.7%) of e-NHL-NP ‍were NHL-T, and the remainder were NHL-B. All of the NHL-T cases in both sites were EBER-positive. Two (5.4%) ‍of the NHL-B cases in the nasopharynx showed EBER positive. Monoclonal bands of the TCR-ã gene were detected ‍in 71.4% of the extranodal NK/T-cell lymphomas, nasal type, patients; 50.0% of peripheral T-cell lymphoma, ‍unspecified, patients; and one case of angioimmunoblastic T-cell lymphoma. This study indicates a very strong ‍association of NHL-T in the sinonasal tract or nasopharynx with EBV infection, the link apparently being weaker in ‍NHL-B patients. The study also indicates that most cases of extranodal NK/T-cell lymphoma, nasal type, are not the ‍germline configuration of the TCR genes.     

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

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 disease 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-Inegative 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.     

A bibliography of the leukaemias in Africa, 1904-1985

A bibliography of leukaemias in Africa is presented from 1904 to 1985. The literature is listed chronologically and is classified geographically (north, south, east and west Africa) and by leukaemia type. The epidemiology of leukaemias in Africa is discussed briefly, especially as to the rarity of acute lymphoblastic leukaemia under the age of four years, the frequency of chloroma, the young age of presentation of chronic granulocytic leukaemia, the frequency of chronic lymphatic leukaemia in adults, especially women, under 45 years in tropical Africa, and the frequency of infection by the human T-cell leukaemia-lymphoma (or lymphotropic) virus type I and of adult T-cell leukaemia-lymphoma.     

Orofacial lymphomas in seropositive patients manifesting the type I human lymphotropic virus (HTLV-I)

Eleven cases of extranodal orofacial lymphomas (EOFL), consisting of 4 HTLV related and 7 HTLV unrelated EOFLs, have been investigated with regard to their immunohistological and clinical features. The HTLV related EOFLs were found to be of the T-cell phenotype and were associated with a poorer prognosis than the HTLV unrelated EOFLs, most of which were of B-cell origin. The comparatively high incidence of T-cell type in our series was considered to be related to the high percentage of HTLV carriers in our district, an area in which adult T-cell leukemia lymphoma has been found to be endemic.     

Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion

The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed.     

Antibodies against three purified structural proteins of the human type-C retrovirus,HTLV, in Japanese adult T-cell leukemia patients,healthy family members,and unrelated normals

The immunological relationship of human T-cell leukemia/lymphoma virus (HTLV) and the virus found in Japanese adult T-cell leukemia/lymphoma (ATL) was investigated in detail by testing the specific binding of serum antibodies from Japanese ATL patients and normal Japanese donors to the purified HTLV proteins p24, p19, and p15. Sera were prescreened for antibodies to p24. Of those positive, 67% of the ATL sera and 78% of the normal sera were further shown to have antibodies against p19. In both groups 17% had antibodies to p15. Generally, the average antibody titers were twice as high in ATL as in normal sera. Competition radioimmunoprecipitation assays done with various sera and involving HTLV-producing cells, virus-positive cells from a Japanese ATL patient, and virus-positive cultured T cells of one of his healthy family members as competing materials demonstrated no differences between the p24, p19, and p15 found in these cells. These results provide strong and detailed immunological evidence that the human retrovirus isolates first made from US patients with cutaneous T-cell malignancies, and those made later in Japanese ATL are either identical or very closely related strains of the same virus, HTLV, a finding verified in other detailed analyses of the HTLV genomes of the respective isolates. To date only HTLV-II, isolated from a US case of hairy-cell leukemia of a T-cell type, is a distinct additional human retrovirus class.     

Peripheral T-cell lymphoma in a patient with acquired immune deficiency syndrome

A case of pulmonary T-cell lymphoma in an Acquired Immune Deficiency Syndrome (AIDS) patient is presented. Morphologically, it belonged to the large cell, immunoblastic category of the Working Formulation and demonstrated a helper/inducer phenotype. Clinically there was no association with manifestations of human T-lymphotropic virus (HTLV)-I related lymphoma and the patient was seronegative for HTLV-I and HTLV-II antibodies. High-grade B-cell lymphomas occur with an increased frequency in patients with AIDS but the occurrence of a peripheral T-cell lymphoma in AIDS has not been documented before. The case is discussed in the context of current concepts of AIDS-related lymphomagenesis.     

Human T-cell leukemia virus-I and hematologic malignancies in Panama

Serum samples were obtained in a 2-year period (November 1, 1984-December 31, 1986) from 136 Panamanian patients with hematologic malignancies identified by a population-based registry designed for studies investigating human T-cell lymphotropic virus (HTLV)-I. Only three patients had clinical and serologic findings of HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The authors conclude that although classical HTLV-I-associated ATLL occurs in the Panamanian population, it is not as prevalent as in other Caribbean populations.     

Effect of tumor promoters on human T cell leukemia/lymphoma virus (HTLV)-structural protein induction in adult T-cell leukemia cells

We assayed the capacity of tumor promoters to induce human T-cell leukemia/lymphoma virus (HTLV) structural proteins p19 and p24 from the HTLV genome-carrying adult T-cell leukemia (ATL) cell lines, MT-1 and KH-2Lo, and fresh ATL cells. Among the tested substances, 12-O-tetradecanoyl phorbol-13-acetate (TPA), 12-hexadecanoyl-phorbol-13-acetate (HPA) and teleocidin induced HTLV structural protein p19 and p24. This suggests that certain environmental substances, especially those known to be tumor promoters, may activate the HTLV-gene in ATL cells.