Leucemia asociada al virus linfotrópico T humano tipo 1 (HTLV-1) y transmisión intrafamiliar de la infección en Santiago del Estero / Leukemia associated to human T cell lymphotropic virus type 1 (HTLV-1) infection and intrafamily transmission in Santiago del Estero

Resumen La leucemia/linfoma a células T del adulto (ATLL) es una enfermedad hematológica causada por el virus linfotrópico T humano tipo 1 (HTLV-1) que se desarrolla luego de 20 años de incubación, preferencialmente cuando la infección se adquiere por transmisión vertical. Este tiempo se reduce de 3 meses a 3 años cuando la transmisión del virus es por transfusión o trasplante de órganos. La ATLL aguda es de difícil diagnóstico por ser inusual y tener una rápida progresión a la muerte. En el Noroeste argentino, donde el virus es endémico, la ATLL es más frecuente, sin embargo, también se la detecta continuamente en el resto del país. El tratamiento de elección, en primera instancia, es el uso combinado de antivirales. Presentamos un caso de ATLL aguda desarrollada en un hombre de 59 años de Santiago del Estero a partir del cual se identificó transmisión intrafamiliar de la infección por HTLV-1.

Abstract Adult T-cell leukemia/lymphoma (ATLL) is an hematological disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) that develops after 20 years of incubation preferentially when the infection is acquired by vertical transmission. In cases of transmission by transfusion or organ transplant, this time is reduced from 3 months to 3 years. Acute ATLL is difficult to diagnose because it is unusual and has a rapid progression to death. In the Argentine Northwest, where the virus is endemic, ATLL is more frequent, however it is also detected continuously in the rest of the country. The treatment of choice, in the first instance, is the combined use of antivirals. We present a case of acute ATLL developed in a 59-year-old man from Santiago del Estero from which intrafamilial transmission of HTLV-1 infection was identified.

Falla hepática aguda fulminante como manifestación de leucemia de células T del adulto en paciente con infección por HTLV-1 / Acute Liver Failure as Presentation of Adult T-cell Leukemia in an HTLV-1 Patient

La falla hepática aguda es el desarrollo de injuria hepática severa con deterioro de la función de síntesis y encefalopatía. Dentro de la variedad de causas, las infiltraciones neoplásicas representan menos del 0,5%. Presentamos el caso de un paciente varón HTLV1 positivo que debuta con una clínica de hepatitis aguda, siendo posteriormente diagnosticado con diseminación de linfoma/leucemia de células T del adulto. Desafortunadamente el paciente presentó deterioro rápido y progresivo de la función hepática, falleciendo a los pocos días de la hospitalización

Acute liver failure is the development of severe hepatic injury with deterioration of liver synthesis function and encephalopathy. Among all the variety of causes, neoplastic infiltration represents less than 0.5%. We present the case of a male patient with a past medical history of HTLV-1 infection, who reports symptoms of acute hepatitis, being diagnosed with Adult T-cell leukemia/ lymphoma. Unfortunately, the patient had a rapid deterioration and passed away a few days after admission

Case for diagnosis. Infective dermatitis associated with HTLV-1: differential diagnosis of atopic dermatitis

Abstract: Infective dermatitis associated with HTLV-1 (IDH) is the main cutaneous marker of HTLV-1 infection. This disease occurs primarily in children and should be differentiated from other eczemas, especially from atopic dermatitis. The largest series of IDH are from Jamaica and Brazil. There are an estimated 15 to 20 million infected people in the world, and Brazil is one of the endemic regions. Studies suggest that IDH in children may be a marker for the development of T-cell leukemia/lymphoma (ATL) or myelopathy associated with HTLV-1/tropical spastic paraparesis (HAM / TSP) in adulthood.

Un caso de leucemia/linfoma T del adulto en Uruguay / Adult T-cell leukemia/lymphoma. Report of a case in Uruguay

La leucemia/linfoma T del adulto pertenece al grupo de neoplasias T maduras y constituye una entidad clínica de baja incidencia. Su etiopatogenia se asocia a la infección por el virus linfotrópico humano 1. En Uruguay se registra una incidencia muy baja de infección por este virus y no se ha comunicado a la fecha ningún caso de leucemia/linfoma T del adulto. Presentamos el caso de una inmigrante de Perú, quien se presentó con linfocitosis sostenida, múltiples parasitosis intestinales y compromiso cutáneo. El diagnóstico fue tardío y la paciente falleció antes de iniciar tratamiento oncoespecífico. Destacamos la importancia de la sospecha clínica de esta entidad y el estudio de la serología para el virus, en particular en casos, como el nuestro, procedentes de área endémica.

Adult T-cell leukemia/lymphoma belongs to the group of mature T-cell malignancies according to the WHO classification. It constitutes a rare entity and has a strong association with infection by human T-lymphotropic virus 1. In Uruguay, this viral infection is very infrequent and, to our knowledge, no case of adult T-cell leukemia/lymphoma has been previously reported. We describe the case of a woman, immigrant from Peru, who presented with persistent lymphocytosis, intestinal parasitic diseases, and skin involvement. The diagnosis was delayed and the patient died before initiating oncological treatment. We therefore emphasize the relevance of an early clinical suspicion and serology for this virus, especially in patients coming from endemic countries like Peru.

Linfoma duodenal asociado a infección por Strongyloides stercoralis. Dos manifestaciones de la infección por HTLV-1 / Duodenal Lynphoma associated to Strongyloides stercoralis infection. Two types of HTLV-1 infection

La infección por el virus linfotrópico de células T humanas tipo 1 (HTLV-1), es causante de la leucemia/linfoma de células T del Adulto (ATLL), siendo la afectación duodenal poco usual. La coinfección de HTLV-1 con Strongyloides stercolaris es común en los pacientes con HTLV- 1 debido a la inadecuada respuesta TH2 que presentan estos sujetos. Describimos a una paciente mujer de 48 años de edad, natural y procedente de la selva del Perú con historia familiar de infección por HTLV- 1 quien acude con diarrea crónica y baja de peso. Se le diagnosticó infección por HTLV-1 así como ATLL duodenal y estrongiloidiasis. Se inició tratamiento con ivermectina y quimioterapia, siendo estabilizada y dada de alta. Reportamos el presente caso debido a la poca frecuencia de coexistencia en duodeno de ATLL y estrongiloidiasis.

Infection by the Human T- Lymphotropic virus I (HTLV-1) causes Adult T cell Leukemia-lymphoma (ATLL), being the duodenal involvement rare. Commonly, patients co-infected with HTLV-1 and Strongyloides stercoralis are seen due to the lack of TH2 response found on these patients. We describe a 48-year-old woman, from the jungle of Peru, with a family history of HTLV-1 infection, who presented with a History of chronic diarrhea and weight loss. HTLV-1 infection with ATLL and strongyloidiasis were diagnosed. Ivermectin treatment and chemotherapy were initiated, being stabilized, and discharged. We report this case because of the unusual coexistence in the duodenum of ATLL and strongyloidiasis.

Comorbidity between HTLV-1-associated adult T-cell lymphoma/leukemia and verrucous carcinoma: a case report / Comorbilidad entre carcinoma verrugoso y linfoma/leucemia de células T del adulto asociado con HTLV-1: un reporte de caso

Abstract Background: Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described. Case report: We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2. Treatment and outcome: The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle. Clinical relevance: Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV).

Resumen Antecedentes: La leucemia/linfoma de células T del adulto se clasifica como una neoplasia de células T CD4+ periféricas desencadenada por el virus linfotrópico de células T humanas tipo 1 (HTLV-1). Los síntomas típicos se asocian a la infiltración leucémica; sin embargo, también se ha descrito la manifestación atípica y exagerada de carcinomas verrugosos. Caso clínico: Se presenta el caso de una paciente con lesiones múltiples en piel, necrosis isquemica del hallux y linfadenopatías. se realizaron biopsias que reportaron carcinoma epidermoide verrugoso y linfoma cutáneo. Se detectó esplenomegalia y adenopatías en mesenterio, región retroperitoneal, y cadenas ganglionares de las extremidades. la medula ósea presentó hallazgos compatibles con leucemia/linfoma de células T y ELISA positivo para HTLV-1/2. Tratamiento y resultado: La paciente presentó buena respuesta inicial al esquema CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona) con filgrastim. Sin embargo, presentó recaída de la enfermedad antes del segundo ciclo y falleció Relevancia clinica: La comorbilidad podría conducir al modelo de factores de riesgo asociados. De acuerdo con este modelo, la inmunodeficiencia secundaria causada por HTLV-1 puede inducir el desarrollo de carcinomas verrugosos; Alternativamente, la enfermedad podría deberse a una correlación entre el HTLV-1 y el virus del papiloma humano (VPH).

Western Blot e PCR em tempo real em pacientes com leucemia/linfoma de células T do adulto associado ao HTLV-1 / Western blot and real-time PCR in patients with HTLV-1-associated adult T-cell leukemia / lymphoma

Contexto: Um dos requisitos para garantir a instituição de um tratamento adequado aos pacientes acometidos por leucemia/linfoma associada ao HTLV-1 é a confirmação diagnóstica da infecção por HTLV-1. Essa confirmação, dá-se hoje por meio de exames laboratoriais, a saber: ELISA, WESTERN BLOT e PCR em tempo real (RT-PCR). O Elisa já se encontra incorporado ao SUS para investigação diagnóstica nesta doença, contudo, por conta de sua baixa acurácia, são necessárias outras provas confirmatórias que permitam um diagnóstico preciso da doença que possibilite que pacientes com possibilidade de tratamento, como é o caso dos pacientes com leucemia/linfoma acometidos pelo HTLV-1, recebam o melhor tratamento. O processo diagnóstico da infecção pelo HTLV se baseia na detecção de anticorpos anti-HTLV circulantes no sangue. Geralmente o processo se inicia através da realização do ELISA. Para confirmação do diagnóstico, é recomendada a realização de um teste complementar em casos com ELISA positivo. Além de confirmar o diagnóstico, os exames complementares também irão diferenciar entre HTLV-I e HTLV-II e descartar casos falso-positivos. As combinações tornam a sensibilidade e especificidade mais confiáveis. Dentre estes testes os mais utilizados são o Western Blot (WB), e o teste de biologia molecular (PCR). Evidências científicas: O Western blot é um teste imunoenzimático para detecção de anticorpos anti-HTLV-1 e HTLV-2, utilizado como teste confirmatório da infecção pelo HTLV após reatividade em teste de triagem e também para diferenciação entre a presença de HTLV-1 e HTLV-2. É o teste mundialmente mais aceito como exame confirmatório para HTLV. Os antígenos utilizados pelos testes mais modernos incluem as proteínas env recombinante GD21, presente nos dois vírus, e rgp46-I e rpg46-II, respectivamente específicas do HTLV-I e HTLV-II. Além das proteínas gag p19, p24, p26, p28, p32, p36, p53. Da mesma forma, a PCR em tempo real surge para melhorar a acurácia dos resultados, abrindo novas perspectivas sobre seu uso na prática clínica. Alguns estudos mostram que a sensibilidade da PCR-RT é de 100% e especificidade de 96,7 a 100%. Estudos que analisaram a sensibilidade comparativamente pelo tipo de vírus demonstram que a PCR-RT apresentou sensibilidade de 84,6% a 94,2% para o HTLV-1 e 76,9% a 90,7% para o HTLV-2. Decisão: Incorporar os procedimentos laboratoriais por técnicas de Western Blot e PCR em tempo real no diagnóstico de leucemia/linfoma de células T do adulto associado ao HTLV-1, no âmbito do Sistema Único de Saúde ­ SUS, dada pela Portaria SCTIE-MS nº 23 publicada no Diário Oficial da União (DOU) nº 106, de 06 de junho de 2016.

Leucemia/linfoma T del adulto en pacientes infectados con HTLV-1: reporte de dos casos de Colombia / Adult T-cell leukemia/lymphoma in HTLV-1 infected patients: report of two cases in Colombia

La leucemia/linfoma de células T del adulto ( Adult T-Cell Leukemia/Lymphoma , ATLL) es una neoplasia maligna de los linfocitos T CD4 maduros, que resulta de la infección con el virus T-linfotrópico humano de tipo 1 (HTLV-1), con varias manifestaciones sistémicas y cutáneas. Se presentan dos casos de leucemia/linfoma de células T del adulto en pacientes del suroccidente de Colombia, cuyos diagnósticos fueron confirmados por histología, inmunohistoquímica, citometría de flujo y pruebas ELISA y Western blot. También, se discute acerca del virus y cómo hacer el diagnóstico en países como el nuestro.

Adult T-cell leukemia/lymphoma (ATLL) is a malignant neoplasia of mature CD4+ T lymphocytes,resulting from infection with human T-lymphotropic virus type 1 (HTLV-1), with several systemic and cutaneous manifestations. We present two cases of adult T-cell leukemia/lymphoma, in patients from the Colombian Southwestern region, whose diagnoses were confirmed by histology, immunohistochemistry, flow cytometry, ELISA and Western blot tests. We also discuss about the virus and how to make this diagnosis in countries like Colombia.

Immunophenotyping of mature T/NK cell neoplasm presenting as leukemia.

Introduction : Mature T/NK cell lymphomas (MTNKL) presenting as leukemia are rare and show considerable overlapping of clinical, morphological and immunophenotypic features. AIM: Critical analysis of the morphology and immunophenotypic profile of MTNKL. Materials and Methods : We reviewed 380 consecutive cases of mature lymphoid neoplasm that presented as leukemia and were diagnosed on morphology and immunophenotyping of bone marrow and/or peripheral blood samples. Results : Peripheral blood and bone marrow involvement was seen in all cases. MTNKL constituted 4% (nine cases) of all mature lymphoid neoplasms presenting as leukemia. It included four cases of T-large granular leukemia (T-LGL), two of T-cell prolymphocytic leukemia small cell variant (T-PLL), two of adult T-cell leukemia/lymphoma (ATLL) and one of primary cutaneous gamma delta T-cell lymphoma (PCGDTCL). T-LGL revealed CD4-/CD8+ phenotype in three, and CD4+/CD8+ phenotype in one case. CD56 was absent in all the cases of T-LGL. One case of T- PLL small cell variant showed CD4+/CD8- phenotype, while the other revealed CD4-/CD8+ phenotype. Both cases of ATLL showed CD4+/CD8+/CD25+ phenotype. The single case of PCGDTCL showed CD4-/CD8- phenotype pattern. CD3 and CD5 were expressed in all MTNKL. CD7 was absent in three cases of T-LGL. TCRα/β was performed in three cases of T-LGL and was positive in all. TCRα/β was also seen in both the cases of T-PLL small variant. However, TCRα/β was seen in the single case of PCGDTCL. Conclusion : Mature nodal T/NK cell neoplasms are rare and MTNKL presenting as leukemia are even rarer. There is an overlap between the immunophenotypic profiles of different MTNKL subtypes and elaborate T/NK cell panels are required for their evaluation.

Myelopathy and adult T-cell leukemia associated with HTLV-1 in a young patient with hearing loss as the initial manifestation of disease / Mielopatia e leucemia de células T do adulto associada ao HTLV-1 em um paciente jovem com perda auditiva como manifestação inicial da doença

A young male developed hearing loss, vertigo, headache and facial palsy. Neurological examination did not show any abnormalities. Two years later, cervical lymphadenopathy, hepatosplenomegaly and atypical lymphocytes in peripheral blood revealed leukemia. At the same time, acquired ichthyosis was observed. Subsequently, neurological abnormalities revealed myelopathy associated with HTLV-1, due to vertical transmission.

Um jovem do sexo masculino desenvolveu perda auditiva, vertigem, cefaléia e paralisia facial. Exame neurológico sem alterações. Dois anos mais tarde, linfadenopatia cervical, hepatoesplenomegalia e linfócitos atípicos no sangue periférico divulgado leucemia. Concomitante, observou-se ictiose adquirida e, posteriormente, anormalidades neurológicas revelaram mielopatia associada ao HTLV-1, transmitido verticalmente.

Adult T-cell leukemia/lymphoma: report of two cases / Leucemia/linfoma de células T do adulto: relato de dois casos

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.

Use of flowcytometry in diagnosis of t-acute lymphoblastic leukemia in children hospital, Damascus - Syria

Acute Lymphoblastic Leukemia [ALL] is a malignancy of immature lymphoid cells, which comprises the highest incidence of acute leukemia in children. Many attempts were made to morphologically classify ALL. Most of these were unsuccessful either because of its technical difficulties, or because it lakes the clinical significance. Hence the immuno classification is more specific and shows that leukemia may occur in different stages of lymphoid maturation. T-ALL is a neoplasm of lymphoblasts committed to the T cell linage and observed in 20% of the children who suffer from ALL. Also it is more common in young adults, and in males rather than females. It manifests by low count of leukocytes and sometimes by existence of a mass. T-ALL is classified to different stages according to the number of antigens and their expression. Immunophenotyping was achieved for 50 samples collected from children visiting children hospital in Damascus with suspected ALL. 24% of ALL was classified as T-ALL. 83.3% of them were males and 16.7% were females. Occurrence of ALL was 41.7% in the group of 6 - 9 years of age. Also it was found that 58.3%, 25%, 16.7% of the studied samples represented as late T-ALL, Middle T-ALL, and Early T-ALL respectively

Acute T lymphoid and megakaryoblastic bi-lineal leukemia in a child.

A 1 1/2-year-old boy presented with fever, anemia, petechial rash and hepatosplenomegaly. Bone marrow examination showed two morphologically distinct blasts (small and large) which were confirmed on immunophenotyping to be of T-lymphoid and megakaryocytic lineages respectively. Patient was refractory to therapy. This is a rare combination of bi-lineal leukemia in a child.

Leucemia/linfoma de células T del adulto asociado al virus linfotrópico humano tipo I: presentación de cuatro casos con enfermedad de inicio cutáneo y revisión de la literatura / Leukemia/lymphoma of T cells in adults associated with human lymphotropic virus type I: presentation of four cases with initial cutaneous presentation and literature review

La leucemia/linfoma de células T del adulto es una enfermedad maligna de linfocitos T CD4+ maduros infectados con el virus linfotrópico humano tipo I. El presente trabajo es un estudio descriptivo de cuatro pacientes con leucemia/linfoma de células T del adulto asociados al virus VLTH-1, que presentaron lesiones cutáneas como manifestación inicial de su enfermedad. Algunos de estos pacientes fueron diagnosticados erróneamente como micosis fungoides. El virus linfotrópico humano tipo I se transmite por mecanismos similares al virus de la inmunodeficiencia humana. En nuestro país y otros países de América Latina, no se realiza de rutina el descarte el virus en donantes de sangre. Estos casos son los primeros publicados en Venezuela con enfermedad de inicio cutáneo. El objetivo de este trabajo es alertar al dermatólogo y familiarizarlo con las características clínicas e histopatológicas de esta enfermedad relativamente desconocida en nuestro medio

HTLV-I Associated infective dermatitis may be an indolent HTLV-I associated lymphoma

When present for a first time blood donation, a 28-year-old Brazilian white female reported a pruritic eczema of the scalp and retroauricular areas since childhood that had been frequently infected. Her mother had been diagnosed as having HTLV-I-associated myelopathy (HAM), and the patient was found to be a human T-lymphotropic virus type-I (HTLV-I) carrier. The patient had been breast-fed for 6 months. The patient had a complete examination, and a biopsy was taken from eczema in the retroauricular area. The byopsy indicated chronic lymphohistiocytic dermatitis with no abnormal lymphocystes. Eleven months later, the patient had an infliltration in the skin of the retroauricular area and a new biopsy revealed atypical lymphocytes. Nested polymerase chain reaction (PCR) was positive for HTLV-I and immunohistochemistry of the tissue at this time confirmed adult T-cell leukemia/lymphoma (ATLL). Retrospective immunohistochemistry showed that the first fragment submitted from the biopsy 11 months before was also compatible with the diagnosis of ATLL. This case fulfilled all major criteria for diagnosis of HTLV-I-associated infective dermatitis (HTLV-I-ID). We postulate that the patient has indolent ATLL associated with HTLV-I infective dermatitis since childhood. We recommended that tissue immunohistochemistry analysis be done in any patient with HTLV-associated infective dermatitis.