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Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.

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Non-Hodgkin lymphomas with T-cell immunophenotype encompass a heterogeneous group of infrequent neoplasms that follow variable clinical courses but prevalently include aggressive behavior and high mortality rates. The involvement of the central nervous system (CNS) is an uncommon event in T-cell lymphomas, with wide variability among the different disease entities. CNS can be affected either at initial diagnosis or at recurrence, and both forms are considered "secondary CNS T-cell lymphoma". Given the low incidence of secondary CNS T-cell lymphoma, related literature is sparse, contradictory, and primarily constituted by small case series and single case reports. However, reported studies uniformly suggest high mortality rates related to this event. Therefore, to improve our ability to identify high-risk patients and offer them successful CNS prophylaxis or timely and effective treatment once the event has occurred may prevent CNS-related T-cell lymphomas deaths. For example, some entities like aggressive adult T-cell leukemia/lymphoma, extranodal natural killer/T-cell lymphoma, and other peripheral T-cell lymphomas with involvement of two or more extranodal organs are prone to CNS dissemination and should be considered for personalized CNS prophylaxis. The level of evidence suggesting an increased risk of CNS recurrence for other T-cell lymphomas and for other risk factors is lower. Published case series show that, following the example of aggressive B-cell lymphomas, patients with T-cell lymphomas and putative increased CNS risk receive different forms of prophylaxis, mostly methotrexate and cytarabine delivered by intrathecal and/or intravenous routes, with varied success. To date, achievements in the treatment of CNS involvement in patients with aggressive B-cell lymphoma were not replicated in secondary CNS T-cell lymphomas, and identification of effective therapies remains an urgent research target. This review is focused on clinical findings, diagnosis, treatment, and prognosis of patients with T-cell lymphoma experiencing CNS dissemination either at presentation or relapse. It aims to provide logical and, oftentimes, evidence-based answers to the most common questions on the most probable risk factors to CNS involvement in patients with T-cell lymphoma, the indications and strategies to prevent this life-threating event, and the management of patients with CNS disease.

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BACKGROUND: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. METHODS: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral) with available data were included in this study. RESULTS: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP); doxorubicin, ranimustine, and prednisolone (AMP); and vindesine, etoposide, carboplatin, and prednisolone (VECP)]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. CONCLUSIONS: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late probably due to lack of knowledge of adult T-cell leukemia/lymphoma by primary healthcare doctors and a Brazilian treatment protocol needs to be established.

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Abstract Background: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. Methods: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral) with available data were included in this study. Results: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP); doxorubicin, ranimustine, and prednisolone (AMP); and vindesine, etoposide, carboplatin, and prednisolone (VECP)]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. Conclusions: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late probably due to lack of knowledge of adult T-cell leukemia/lymphoma by primary healthcare doctors and a Brazilian treatment protocol needs to be established.

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Adult T-cell leukemia/lymphoma (ATL) is caused by the human T-cell lymphotropic virus type 1 (HTLV-1) which is endemic in countries of Caribbean and Central and South America. We performed a systematic search and review to identify publications on ATL in these countries to verify if this disease was getting recognition in these regions as well as the characteristics of the observed cases. The median age of 49.4 years was lower than that referred to in Japan. According to our findings in most Brazilian states and in some other countries, ATL is not being recognized and should be strongly considered in the differential diagnosis of T-cell leukemias/lymphomas. Failure to identify these cases may be due to the unsystematic realization of serology for HTLV-1 and phenotypic identification of non-Hodgkin lymphomas that may result from lack of resources. Detection of ATL cases has been more feasible with cooperation from foreign research centers. A huge effort should be made to improve the surveillance system for ATL diagnosis in most of the South- and Central-American and Caribbean countries, and this attitude should be embraced by public organs to support health professionals in this important task.

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Abstract Hodgkin-like ATLL is a rare variant of adult T-cell leukemia/lymphoma (ATLL), a disease caused by human T-cell lymphotropic virus type-1 (HTLV-1). At admission, a 46-year-old female presented with lymphadenomegaly, lymphocytosis, slight elevation of LDH blood level, and acid-alcohol resistant bacilli in sputum and was being treated for pulmonary tuberculosis (Tb). She had lymphocytosis in the previous 20 months. Serology for HTLV-1 was positive. Lymph node was infiltrated by medium-sized lymphocytes with scattered Hodgkin and Reed-Sternberg-like cells CD30+, CS1-4+, and CD79a+. Background cells were CD4+ and CD25+. A clinical diagnosis of favorable chronic ATLL was given. She was treated with chemotherapy but later progressed to acute ATLL and ultimately died. Hodgkin-like ATLL should be considered in the histological differential diagnosis with Hodgkin lymphoma since treatment and prognosis of these diseases are distinct. It is also important to search for HTLV-1 infection in patients with unexplained prolonged lymphocytosis.

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Hodgkin-like ATLL is a rare variant of adult T-cell leukemia/lymphoma (ATLL), a disease caused by human T-cell lymphotropic virus type-1 (HTLV-1). At admission, a 46-year-old female presented with lymphadenomegaly, lymphocytosis, slight elevation of LDH blood level, and acid-alcohol resistant bacilli in sputum and was being treated for pulmonary tuberculosis (Tb). She had lymphocytosis in the previous 20 months. Serology for HTLV-1 was positive. Lymph node was infiltrated by medium-sized lymphocytes with scattered Hodgkin and Reed-Sternberg-like cells CD30+, CS1-4+, and CD79a+. Background cells were CD4+ and CD25+. A clinical diagnosis of favorable chronic ATLL was given. She was treated with chemotherapy but later progressed to acute ATLL and ultimately died. Hodgkin-like ATLL should be considered in the histological differential diagnosis with Hodgkin lymphoma since treatment and prognosis of these diseases are distinct. It is also important to search for HTLV-1 infection in patients with unexplained prolonged lymphocytosis.

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Summary Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T-cells caused by human T-cell lymphotropic virus type 1 (HTLV-1). Twenty million people are believed to be infected throughout the world, mostly in Japan, Africa, the Caribbean, and South America, particularly in Brazil and Peru. ATL affects about 5% of infected individuals and is classified in the following clinical forms: acute, lymphoma, primary cutaneous tumoral, chronic (favorable and unfavorable), and smoldering (leukemic and non-leukemic). Although it is considered an aggressive disease, there are cases with a long progression. We emphasize the importance of clinical classification as an indispensable element for evaluating prognosis and appropriate therapeutic approach. Since several cases have been published in Brazil and this disease is still poorly known, we decided to make a review paper for dissemination of clinical, hematological and pathological aspects, diagnosis, and therapy. The best way to reduce the occurrence of ATL would be halting the transmission of the virus through breastfeeding.

Resumo A leucemia/linfoma de células T do adulto (LLcTA) é uma neoplasia de células T maduras CD4+ causada pelo vírus linfotrópico para células T humanas tipo 1 (HTLV-1). Acredita-se que existem cerca de 20 milhões de pessoas infectadas em todo o mundo, principalmente no Japão, na África, no Caribe e na América do Sul, particularmen te no Brasil e no Peru. A LLcTA acomete cerca de 5% dos indivíduos infectados e classifica-se nas seguintes formas clínicas: aguda, linfomatosa, tumoral primária de pele, crônica (favorável e desfavorável) e indolente (leucêmica e não leucêmica). Embora seja considerada uma doença agressiva, há casos com longa evolução. Salientamos a importância da classificação clínica como elemento im prescindível para avaliação do prognóstico e conduta terapêutica adequada. Como já foram publicados vários casos no Brasil e essa doença ainda é pouco conhecida, decidimos fazer um trabalho de revisão para divulgar os seus aspectos clínicos, hematológicos, anatomopatológi cos, diagnósticos e terapêuticos. O melhor meio de redu zir a ocorrência de LLcTA seria sustando a transmissão vertical do vírus pela amamentação.

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The typical characteristics of mesenchymal stem cells (MSCs) can be affected by inflammatory microenvironment; however, the exact contribution of HTLV-1 to MSC dysfunction remains to be elucidated. In this study, we demonstrated that MSC cell surface molecules VCAM-1 and ICAM-1 are upregulated by contact with HTLV-1, and HLA-DR was most highly expressed in MSCs co-cultured with MT2 cells. The expression levels of VCAM-1 and HLA-DR were increased in MSCs cultured in the presence of PBMCs isolated from HTLV-1-infected symptomatic individuals compared with those cultured with cells from asymptomatic infected individuals or healthy subjects. HTLV-1 does not impair the MSC differentiation process into osteocytes and adipocytes. In addition, MSCs were efficiently infected with HTLV-1 in vitro through direct contact with HTLV-1-infected cells; however, cell-free virus particles were not capable of causing infection. In summary, HTLV-1 can alter MSC function, and this mechanism may contribute to the pathogenesis of this viral infection.

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Here, we describe a 48-year-old woman infected by the human T-cell lymphotropic virus type 1 (HTLV-1) with spondyloarthritis, uveitis, bilateral episcleritis and neurogenic bladder. She had a history of a probable infective dermatitis associated with HTLV-1 (IDH) in childhood. After the use of adalimumab, she developed lymphocytosis and a cutaneous lymphoma associated with IDH. She had the diagnoses of IDH and of chronic adult T-cell leukemia/lymphoma, supported by the demonstration of proviral integration in the cutaneous lesion.

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OBJECTIVES: To evaluate the frequency of the different types of cutaneous lymphoma (CL) in 1 university hospital in Brazil and compare this frequency with those observed in other countries. METHODS: After review, 72 (84.7%) cases of primary cutaneous T-cell lymphoma (CTCL) and 13 (15.3%) cases of primary cutaneous B-cell lymphoma (CBCL) were included. RESULTS: Of the CTCLs, 40.3% were mycosis fungoides (MF); 26.4% were adult T-cell leukemias/lymphomas (ATLs); 23.6% were peripheral T-cell lymphomas, unspecified; and 8.3% were anaplastic large cell lymphomas. Of the MF cases, 17.2% progressed to transformed MF. Five-year survival for primary human T-cell lymphotropic virus type 1-negative CTCL, ATL, and CBCL was 64.0%, 42.1%, and 62.5%, respectively. MF and ATL were the most frequent primary CTCLs. CONCLUSIONS: The frequencies observed here are close to those observed in Peru but different from those of European countries. Unfortunately, the World Health Organization/European Organization of Research and Treatment of Cancer classification does not include primary cutaneous ATL.

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The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with neoplasias and inflammatory diseases, such as adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-infected individuals present a spontaneous T lymphocyte proliferation. This phenomenon is related to the HTLV-1-proviral load and the persistence of the infection. Viral proteins induce many cellular mediators, which can be associated with the abnormal cellular proliferation. The intracellular levels of glutathione (GSH) are important to modulate the cellular proliferation. The aim of this study was to investigate the correlation between the modulation of intracellular GSH levels and the spontaneous lymphocyte proliferation during the HTLV-1 infection. Intracellular GSH level can be modulated by using dl-buthionine-[S,R]-sulfoximine (BSO, GSH synthesis inhibitor) and N-acetylcysteine (NAC, peptide precursor). Our results demonstrated that BSO was capable of inducing a decrease in the spontaneous proliferation of PBMC derived from HTLV-1 carriers. On the other hand, the GSH precursor induces an increase in mitogen-stimulated cellular proliferation in infected and uninfected individuals. Similar results were observed by the inhibition of ABCC1/MRP1 protein, augmenting the mitogen-induced proliferation. This effect can be related with an increase in the GSH levels since ABCC1/MRP1 transports GSH to the extracellular medium. There was a significant difference on the expression of CD69 and CD25 molecules during the lymphocyte activation. We did not observe any alterations on CD25 expression induced by BSO or NAC. However, our results demonstrated that NAC treatment induced an increase in CD69 expression on unstimulated CD8(+) T lymphocytes obtained from HTLV-1 infected individuals, healthy donors and HTLV carriers. Therefore, our results suggest that the cellular proliferation promoted by the infection with HTLV-1 and the activation phenotype of CD8(+) T lymphocytes can be regulated by changing the intracellular GSH levels; suggesting the modulation of these intracellular levels as a new approach for the treatment of pathologies associated with the HTLV-1 infection.

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Leucemia/Linfoma T del Adulto (ATLL) es una enfermedad agresiva asociada con el virus linfotrópico de células T tipo I (HTLV-1) con presentación y curso clínico heterogéneo. El reporte describe cuatro casos con compromiso gástrico, considerando características clínicas y hallazgos endoscópicos, con la respectiva revisión de la literatura.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease associated with human T-cell lymphotropic virus type-I (HTLV-I) with heterogeneous clinical presentation and outcomes. We report four cases with gastric involvement. We describe clinical and endoscopic findings of cases and review literature.

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Adult T-cell leukemia/lymphoma is a lymphoproliferative disorder of mature T lymphocytes associated with infection with human T-cell lymphotrophic virus type I (HTLV-I). Adult T-cell leukemia/lymphoma is characterized by clinical and laboratory polymorphism that allows it to be classified into four distinct subgroups: smoldering, chronic, acute and lymphomatous types. We present here two cases of adult T-cell leukemia/lymphoma, respectively in the acute and lymphomatous forms of the disease. Case 1 was a 35-year-old woman who presented abdominal distension accompanied by hepatosplenomegaly, adenomegaly, skin lesions, positivity for anti-HTLV-I antibodies and leukocytosis with the presence of flower cells. Case 2 was a 38-year-old man who was admitted with generalized lymphadenomegaly, positivity for anti-HTLV-I antibodies, hypercalcemia and osteolytic lesions. In this paper, we correlate the clinical-laboratory findings of these two cases with data in the literature.

A leucemia/linfoma de células T do adulto é um distúrbio linfoproliferativo de linfócitos T maduros associado à infecção pelo vírus linfotrópico de células T humanas tipo I (HTLV-I). A leucemia/linfoma de células T do adulto tem polimorfismo clínico e laboratorial, que a classifica em quatro subgrupos distintos entre si: smoldering, crônica, aguda e linfomatosa. Apresentamos neste artigo, dois casos de leucemia/linfoma de células T do adulto, respectivamente, nas formas aguda e linfomatosa da doença. O caso 1: uma paciente de 35 anos apresentava distensão abdominal com hepato-esplenomegalia, adenomegalia, lesões cutâneas, anticorpos anti-HTLV-I positivo e leucocitose com presença de flower cell. O caso 2: homem de 38 anos, internado com linfadenomegalia generalizada, anticorpos anti-HTLV-I positivo, hipercalcemia e lesões osteolíticas. Neste artigo correlacionamos os achados clínicos e laboratoriais destes dois casos com dados da literatura.

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Os autores descrevem dois casos de complicações pulmonares pelo vírus linfotrópico de células T human (HTLV-I). Em seguida, apresentam uma breve revisão da literatura discutindo os aspectos mais importantes para o diagnóstico e terapêutica.

The authors describe two cases of pulmonary complications due to human T- lymphotropic virus type I (HTLV-I). Afterall they present a brief review of literature discussing important aspects for the diagnosis and therapeutic.

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