RESUMEN
HTLV-1 is a retrovirus endemic to different parts of the world that causes a variety of symptoms, ranging from asymptomatic infection to severe diseases such as lymphoma/leukaemia and myelopathy. HTLV-1 is transmitted from mother to child through breastfeeding, sexually and via blood and organ donation. We describe 3 patients as examples of the distinct clinical problems related to HTLV-1: a 53-year-old woman with HTLV-1-associated myelopathy, a 43-year-old woman with acute T-cell lymphoma and a 34-year-old pregnant woman who is an asymptomatic carrier. It is not known how many people are infected in the Netherlands, but it is probably more prevalent among immigrants from the Caribbean and Surinam and likely to be underdiagnosed. Diagnosis is important because it alters treatment and because measures to prevent transmission can be implemented, e.g. refraining from breastfeeding and safe sex precautions.
Asunto(s)
Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Linfoma de Células T/virología , Paraparesia Espástica Tropical , Adulto , Lactancia Materna , Región del Caribe/etnología , Portador Sano , Femenino , Infecciones por HTLV-I/etnología , Infecciones por HTLV-I/transmisión , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Persona de Mediana Edad , Países Bajos/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo , Suriname/etnologíaRESUMEN
Human T cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia/lymphoma. The development of HAM/TSP, a chronic neuroinflammatory disease, is correlated to complex interaction between the host immune response and the infecting virus. Tax expression plays an important role in HAM/TSP pathogenesis by activating various cellular genes, including the cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Exosomes have emerged as an important factor of cell-to-cell communication contributing to diverse cellular processes, including immune modulation. Considering the potential role of exosomes in modulating the immune response and inflammation, the main objective of this study was to examine if HTLV-1-infected cells produce exosomes carrying viral proteins or inflammatory molecules, which can participate in the chronic inflammation that is observed in patients with HAM/TSP. Exosomes were isolated from HTLV-1-infected cell line, evaluated for the tax mRNA presence, and tested for the ability to activate peripheral mononuclear cells (PBMC) in inducing an inflammatory immune response. We observed that the proinflammatory cytokines, IFN-γ and TNF-α, were upregulated in T cells after treatment of the PBMC with Tax-carrying exosomes compared to the negative control. Interleukin-4, Granzyme B, and Perforin did not show alterations. Taken together, these results suggest that exosomes carrying tax-mRNA isolated from HTLV-1-infected cells might induce the production of proinflammatory cytokines and activate T helper (Th)1, and not Th2-immune response. If this finding is further confirmed, this study may have impact on investigations on the pathogenesis of HAM-TSP and the inflammatory response involved in this disease.
Asunto(s)
Exosomas/metabolismo , Productos del Gen tax/metabolismo , Virus Linfotrópico T Tipo 1 Humano/genética , Interferón gamma/metabolismo , Paraparesia Espástica Tropical/inmunología , ARN Mensajero/metabolismo , Adulto , Donantes de Sangre , Comunicación Celular/inmunología , Células Cultivadas , Exosomas/virología , Femenino , Sangre Fetal/citología , Humanos , Linfoma de Células T/patología , Linfoma de Células T/virología , Masculino , Paraparesia Espástica Tropical/virología , ARN Viral , Células TH1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Hydroa vacciniforme (HV)-like lymphoma is a rare, usually fatal Epstein-Barr virus-driven lymphoproliferative disease affecting children from Asia, Mexico, and South America. Cutaneous manifestations imitate HV, a benign photodermatosis in which systemic symptoms are not observed, and spontaneous regression occurs later in adolescence or young adulthood. We report a case of HV-like lymphoma in a 12-year-old girl, descendent from an ancient Amazon indigenous tribe that, as far as we know, represents the second Brazilian case ever reported in the medical literature.
Asunto(s)
Hidroa Vacciniforme/patología , Linfoma de Células T/patología , Brasil , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/patología , Femenino , Humanos , Hidroa Vacciniforme/virología , Linfoma de Células T/virologíaRESUMEN
Extranodal natural killer/T-cell lymphoma, nasal type (NK/TCL) is more prevalent in Asia and in some areas of South and Central America, but it is rarely seen in the United States and Europe. In this study, a series of 122 cases of NK/TCL from Brazil was analyzed with respect to clinicopathologic features. Clinical characteristics and geographic distribution were evaluated in 97 cases of nasal/nasopharyngeal region and 23 cases in extranasal sites including 6 nodal cases. Clinical staging and follow-up information was available in a subset of 21 patients. All cases harbored Epstein-Barr virus (EBV), 95% and 85% expressed cytoplasmic CD3 and CD56, respectively, and all cases were positive for at least 1 marker for cytotoxic granules. The global distribution of EBV subtypes showed predominance of strain subtype A, 89%, and subtype B, 11%. No dual infections were detected. TCR-γ TCR-gene rearrangement was observed in 7 cases; all of them extranodal. Three of TCR-γ(+) cases showed EBV subtype A. Two TCR-γ(+)/CD56(+) cases showed EBV subtype B. Geographic distribution of NK/TCL showed higher frequency in the southeast and northeast regions of Brazil. Striking differences among geographic regions were seen with the vast majority of EBV subtype B (86%) occurring in the south and southeast regions.
Asunto(s)
Herpesvirus Humano 4/clasificación , Linfoma Extranodal de Células NK-T/virología , Linfoma de Células T/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Distribución de Chi-Cuadrado , Niño , ADN Viral/aislamiento & purificación , Femenino , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Genes Codificadores de la Cadena gamma de los Receptores de Linfocito T , Herpesvirus Humano 4/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Estimación de Kaplan-Meier , Ganglios Linfáticos/patología , Ganglios Linfáticos/virología , Linfoma Extranodal de Células NK-T/genética , Linfoma Extranodal de Células NK-T/mortalidad , Linfoma Extranodal de Células NK-T/patología , Linfoma de Células T/genética , Linfoma de Células T/mortalidad , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico , Características de la Residencia , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Análisis de Matrices Tisulares , Adulto JovenRESUMEN
Skin lesions are frequent in human T-cell lymphotropic virus type 1 (HTLV-1) infection and may constitute an alert for the diagnosis of this condition. The most severe skin diseases related to this virus are adult T-cell leukemia/lymphoma (ATLL), an aggressive form of leukemia/lymphoma that fails to respond to chemotherapy, and infective dermatitis associated with HTLV-1 (IDH), a severe and recurrent form of eczema occurring in childhood. ATLL affects the skin in 43-72% of cases. In this review, the clinical, histopathological and immunohistochemical aspects of ATLL and IDH will be discussed, as well as the differential diagnoses, giving particular focus to the primary cutaneous ATLL. IDH may progress to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and to ATLL. Adult onset IDH and reactional and inflammatory dermatoses found in carriers and also in patients with HAM/TSP will be considered. Other dermatological diseases that occur more frequently in HTLV-1-infected individuals such as xerosis, acquired ichthyosis, seborrheic dermatitis and infectious and parasitic dermatoses will also be discussed.
Asunto(s)
Linfoma de Células T/patología , Linfoma de Células T/virología , Antivirales/uso terapéutico , Portador Sano , Diagnóstico Diferencial , Resistencia a Antineoplásicos , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Humanos , Ictiosis/diagnóstico , Ictiosis/virología , Inmunohistoquímica , Interferón-alfa/uso terapéutico , Linfoma de Células T/clasificación , Linfoma de Células T/inmunología , Linfoma de Células T/terapia , Escabiosis/diagnóstico , Piel/patología , Enfermedades Cutáneas Virales/diagnóstico , Infecciones por Treponema/diagnóstico , Zidovudina/uso terapéuticoRESUMEN
In this article we present 2 cases of necrotizing sialometaplasia (NS) associated with angiocentric lymphoma of the midline. Immunohistochemical analysis confirmed a T-cell origin, and in situ hybridization in one case revealed its relationship to Epstein-Barr virus. These findings suggest that vascular occlusion by the neoplastic cells produces ischemia, which leads to local infarction contributing to the salivary gland lesion. To our knowledge, the association between angiocentric lymphoma and NS has been previously reported in only one instance, and we suggest that this particular type of lymphoma should be added to the list of related conditions for NS.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Linfoma de Células T/complicaciones , Neoplasias Palatinas/complicaciones , Neoplasias de los Senos Paranasales/complicaciones , Sialometaplasia Necrotizante/diagnóstico , Sialometaplasia Necrotizante/etiología , Adulto , Infecciones por Virus de Epstein-Barr/diagnóstico , Femenino , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Hibridación in Situ , Linfoma de Células T/patología , Linfoma de Células T/terapia , Linfoma de Células T/virología , Masculino , Neoplasias Palatinas/patología , Neoplasias Palatinas/terapia , Neoplasias Palatinas/virología , Hueso Paladar , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/terapia , Neoplasias de los Senos Paranasales/virología , Glándulas Salivales/irrigación sanguínea , Glándulas Salivales/patología , Sialometaplasia Necrotizante/patología , Sialometaplasia Necrotizante/terapiaRESUMEN
It is well known that extranodal NK/T-cell lymphoma (NK/TCL) nasal type clusters in Asian countries. A large series of 78 cases of nasal NK/TCL from Peru is analyzed in the present study. Two histologic groups 1 (monomorphic) and 2 (polymorphic), were segregated according to the proportion of large cells (above and below 30%, respectively). Catalyzed signal amplification technique was performed for enhancement of immunohistochemistry reactivities. Epstein-Barr virus (EBV) sequences and types were investigated using polymerase chain reaction. Clinical characteristics, stage, outcome, and response to treatment were evaluated in both groups. Fourteen cases (18%) and 64 cases (82%) corresponded to groups 1 and 2, respectively. Except for nasal obstruction, more common in group 2, all other symptoms were similar in both groups. Local extension and staging were also comparable. Both groups showed CD3c+ CD2+ CD56+ CD3s- CD20- immunophenotype. All cases were positive for EBV. In this series type-2 EBV was found more frequent than type-1 EBV, contrarily to that observed in Asian series. However, about one-third of cases simultaneously harbored both viral types. Both groups received an average of 50-Gy dose of radiation therapy (RT), with or without chemotherapy. Complete therapeutic response was achieved in 89% of group 1 and in 74% of group 2, but this difference was not statistically significant. There were no significant differences between the groups regarding disease-free survival, failure-free survival, relapse, and overall survival. The overall survival, in both groups, was longer for patients treated with RT alone compared with those treated with combined RT therapy and chemotherapy. The present study has shown that dividing nasal NK/TCL in monomorphic and polymorphic variants, according to frequency of large cells, does not correlate with clinical and prognostic factors.
Asunto(s)
Células Asesinas Naturales/patología , Linfoma de Células T/diagnóstico , Neoplasias Nasales/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Herpesvirus Humano 4/genética , Humanos , Inmunohistoquímica/métodos , Inmunofenotipificación , Células Asesinas Naturales/virología , Linfoma de Células T/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Nasales/virología , Perú/epidemiología , Reacción en Cadena de la Polimerasa , Resultado del TratamientoRESUMEN
BACKGROUND: Nasal T/natural killer (NK)-cell lymphoma is an aggressive type of non-Hodking's lymphoma associated with Epstein-Barr virus (EBV) and striking geographical variations worldwide. AIM: To characterise nasal NK/T-cell lymphoma associated with genotypes of EBV in Chile, a Latin American country, where multiple strains of EBV, including two new recombinant strains, in healthy individuals were recently found. METHODS: Cases with diagnosis of primary nasal lymphoma were selected for histological and immunohistochemical analysis (CD3, CD3e, CD4, CD8, CD79a, CD56, CD57 and TIA-1) and in-situ hybridisation, serology and genotyping analysis for EBV. RESULTS: Out of 22 cases, 9 (41%) cases fulfilled the World Health Organization criteria for nasal NK/T-cell lymphoma; of these 7 (78%) cases were positive for EBV. Genotyping analysis revealed 6 cases of type 1 EBV and wildtype F at the BamHI-F region, 4 cases type "i" EBV at the BamHI-W1/I1 region; XhoI wild type was found in 2 and XhoI loss in 4 cases, respectively. Cosegregation analysis of the BamHI-W1/I1 region and XhoI restriction site showed the new recombinant strain type "i"/XhoI loss in 3 cases and type "i"/XhoI wild-type strain in 1 case. Most patients were treated with combined anthracycline-containing regimens. Half of the cases attained complete remission. CONCLUSION: Although nasal NK/T-cell lymphomas from Chile share similar clinicopathological features, high association with EBV and unfavourable prognosis with those described elsewhere, genotype analysis shows that the new recombinant type "i"/XhoI loss strain might contribute to explain the intermediate incidence of nasal NK/T-cell lymphomas in Latin America.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Células Asesinas Naturales/patología , Linfoma de Células T/virología , Neoplasias Nasales/virología , Adulto , Infecciones por Virus de Epstein-Barr/virología , Femenino , Genotipo , Herpesvirus Humano 4/clasificación , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Técnicas para Inmunoenzimas , Inmunofenotipificación , Hibridación in Situ/métodos , Linfoma de Células T/inmunología , Linfoma de Células T/patología , Linfoma de Células T/terapia , Masculino , Persona de Mediana Edad , Neoplasias Nasales/inmunología , Neoplasias Nasales/patología , Neoplasias Nasales/terapia , ARN Viral/genética , Resultado del TratamientoRESUMEN
Nasal T/NK-cell lymphomas are highly associated with Epstein-Barr virus (EBV). They are more frequent in Asia than in Western countries. In Central and South America there are few studies about nasal T/NK-cell lymphoma and they have shown a strong predominance of this phenotype in Native American descents, supporting the hypothesis of a racial predisposition for the disease. We studied the lymphomas involving midline facial region at a Brazilian institution. T/NK cell lymphomas (16/25) were more frequently found compared to B lymphomas (9 cases, all B large cell). T/NK cell lymphomas involved predominantly the nasal region. Histologically they showed angioinvasion and necrosis. All of them were positive for CD3 and CD56 and showed numerous tumor cells labeled by EBER-1. Although disease was localized in 61% at diagnosis, there was no tendency to cure. The racial distribution of patients with T/NK-cell phenotype was similar to that found in B-cell lymphomas. EBV was more frequently found in adenoids than in palatine tonsils. In inflammatory lesions of the nasal and palatal regions EBV was not found. In the present study the relative frequency of T/NK versus B cell sinonasal lymphomas was high and similar to that observed in other Latin American countries. However, there was not any racial association with T/NK-cell phenotype and the tumor showed an agressive behavior similar to that reported in Asia. The high frequency of EBV-positive lymphocytes in nasopharyngeal lymphoid tissue (adenoids) suggests that they could serve as a reservoir for the virus.
Asunto(s)
Linfoma de Células T/epidemiología , Neoplasias Nasales/epidemiología , Población Blanca/genética , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunohistoquímica , Linfoma de Células T/etiología , Linfoma de Células T/genética , Linfoma de Células T/mortalidad , Linfoma de Células T/patología , Linfoma de Células T/virología , Masculino , Registros Médicos , Persona de Mediana Edad , Neoplasias Nasales/etiología , Neoplasias Nasales/genética , Neoplasias Nasales/mortalidad , Neoplasias Nasales/patología , Neoplasias Nasales/virología , Fenotipo , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
A case of peripheral T-cell lymphoma affecting the small bowel of a 5-year-old boy is reported. The cells did not form a tumoral mass but infiltrated diffusely, arranged in an angiocentric pattern and associated with numerous ulcers, one of which perforated. Immunohistochemistry proved them to be CD45RO-, CD3-, and CD8-positive. CD20, CD4, and CD56 markers were negative. The presence of EBV in the lymphomatous cells was demonstrated by in-situ hybridization. Polymerase chain reaction study revealed T-cell receptor (TCR) gene rearrangement. Notably the hemophagocytic syndrome present on admission reverted after surgery. The authors are not aware of a previous report of intestinal T-cell lymphoma in a child.
Asunto(s)
Herpesvirus Humano 4/aislamiento & purificación , Neoplasias Intestinales/patología , Neoplasias Intestinales/virología , Linfoma de Células T/patología , Linfoma de Células T/virología , Preescolar , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
A 46-year-old woman with a previous diagnosis of sarcoidosis presented with morphologically typical large granular lymphocyte (LGL) leukemia/lymphoma with an aggressive clinical course. Epstein-Barr virus DNA was detected in peripheral blood mononuclear cells by PCR. The phenotype was typical of the T cell lineage (CD2+ CD3+ CD5+ CD7+ CD8+ TCRalphabeta+) but with the absence of the CD16, CD56, CD57 NK cell markers. In addition, the LGLs expressed CD122 (p75) in the absence of CD25 which is characteristic of LGLs. These leukemic LGLs did not exhibit NK activity. The clonal nature of this proliferation was demonstrated by the rearrangement of the TCRgamma gene. This phenotypically unusual but morphologically typical LGL leukemia/lymphoma may represent the clonal expansion of a minor normal subset of T-LGLs which do not express any NK cell markers, probably corresponding to in vivo activated T cells.
Asunto(s)
Biomarcadores de Tumor/análisis , Células Asesinas Naturales/patología , Leucemia de Células T/patología , Linfoma de Células T/patología , Subgrupos de Linfocitos T/patología , Linaje de la Célula/inmunología , ADN Viral/análisis , Femenino , Herpesvirus Humano 4/genética , Humanos , Inmunofenotipificación , Células Asesinas Naturales/inmunología , Leucemia de Células T/inmunología , Leucemia de Células T/virología , Linfoma de Células T/inmunología , Linfoma de Células T/virología , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunologíaAsunto(s)
Adulto , Humanos , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Leucemia de Células T/virología , Linfoma de Células T/virología , Biomarcadores , Leucemia de Células T/patología , Leucemia de Células T/fisiopatología , Linfoma de Células T/patología , Linfoma de Células T/fisiopatología , Pronóstico , Biomarcadores de TumorRESUMEN
Nasal T-lymphocyte/natural killer cell lymphomas (nT/NKLs) are a distinct group of neoplasms highly associated with Epstein-Barr virus (EBV), with a high prevalence in Asia but rare in Western countries. Recent studies indicate that these neoplasms are of cytotoxic T- or NK-cell derivation. Previous studies identifying a characteristic 30-base pair deletion within the 3' end of latent membrane protein-1 (del-LMP-1) in other EBV-associated lymphomas suggested a pathogenetic role for del-LMP-1 in those neoplasms. We examined 23 cases of nT/NKL from Mexico for expression of the cytolytic granular proteins TIA-1 and perforin (PRF), and for the presence of EBV by in situ hybridization (ISH). Polymerase chain reaction was performed to identify the EBV (EBNA-2) strain type and the status of the LMP-1 gene (del-LMP-1). Controls consisted of 11 sinonasal B-cell lymphomas (nBLs) and 30 reactive tonsils (RTs) from healthy Mexican individuals. The nT/NKLs expressed TIA-1 in 21 (91%) of 23 cases and PRF in 15 (65%) of 23 cases. In contrast, all of the nBLs were negative for TIA-1 and PRF. Twenty-two (96%) of 23 nT/NKLs were positive for EBV by ISH. In contrast, only 2 (18%) of 11 nBLs were positive for EBV by ISH. EBV strain Type A was identified in 21 (91%) of 23 cases, whereas strain Type B was present in 2 (9%) of the 23 nT/NKLs. A similar percentage (80%) of Type A was noted in 12 of the 15 RTs. del-LMP-1 was detected in 6 (26%) of 23 nT/NKLs, comprising 4 cases of Type A and 2 of Type B. del-LMP-1 was detected in 9 (45%) of 20 RTs. Our results indicated that TIA-1 and PRF were sensitive markers of nT/NKL. The presence of del-LMP-1 in comparable frequencies in the RTs and nT/NKLs suggested to us that this genotype was common in the Mexican population and argued against a definite pathogenetic role for del-LMP-1 in nT/NKL.
Asunto(s)
Eliminación de Gen , Herpesvirus Humano 4/genética , Linfoma de Células T/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Neoplasias Nasales/metabolismo , Proteínas , Proteínas de Unión al ARN/metabolismo , Proteínas de la Matriz Viral/genética , Adolescente , Adulto , Anciano , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Células Asesinas Naturales/patología , Linfoma de Células T/genética , Linfoma de Células T/patología , Linfoma de Células T/virología , Masculino , México , Persona de Mediana Edad , Neoplasias Nasales/genética , Neoplasias Nasales/virología , Perforina , Proteínas de Unión a Poli(A) , Reacción en Cadena de la Polimerasa , Proteínas Citotóxicas Formadoras de Poros , Antígeno Intracelular 1 de las Células TRESUMEN
Adult T-cell lymphoma (ATL) is a neoplastic disease associated in 80% of cases with HTLV-I (Human T Lymphotropic virus type I) infection. 1-2% of HTLV-I carriers may develop the disease during their lives. In our country, the prevalence of HTLV-I infection is about 1%. We report a 72 y.o. woman HTLV-I positive, confirmed by Western-Blot. presenting with massive adenopathies, cutaneous tumor involvement, acute course and showing Reed-Sternberg cells (RSCs) in lymph node biopsy. The response to chemotherapy was poor, with the patient dying seven months after diagnosis. ATL and Hodgkin's disease (HD) are discussed highlighting that RSCs are not pathognomonic of HD though in their absence such diagnosis can not be made. RSCs are found in other benign and malignant disorders and it is especially important to differentiate HD from the other processes in order to dispense the appropriate treatment. This is the first case of ATL with RSCs reported in Chile. Hence, in our country we suggest systematic determination of the presence of HTLV infection when histopathology is compatible with HD and Non Hodgkin Lymphoma.