Pronostico desfavorable de linfoma t/nk: reporte de casos

El linfoma de células T/NK tiene una frecuencia de presentación inusual, caracterizado por una progresión rápida y de mal pronóstico. Ocurrencia aludida a regiones de Asia y Latinoamérica por la fuerte incidencia de infección por el virus de Epstein- Barr. Su presentación puede ser nasal o en otra localización. Los esquemas de tratamiento suelen conllevar respuestas insuficientes, empero protocolos con base en L-Asparaginasa reflejarían mejores resultados. El presente reporte corresponde a 4 casos de este tipo de linfoma, 2 de tipo nasal y 2 de diversa presentación. Todos evolucionaron desfavorablemente, en parte por el mal pronóstico atribuido y también por el diagnóstico suscitado en etapas avanzadas de enfermedad concatenadas a dificultades económicas para sostener el tratamiento, factores intervinientes en nuestro medio.

NK/T cell lymphoma is an unusual neoplasm, characterized by fast progression and poor prognosis. It is present in regions of Asia and Latin America associated to a high incidence of Epstein-Barr virus infection. Its presentation can be nasal or in another location. Treatment schemes usually lead to insufficient responses, however protocols based on L-Asparaginase would reflect better results. This report concerns 4 cases of this lymphoma, 2 nasal type and 2 of a different presentation. Patients responses were unfavorable, partly due to the poor prognosis att r ibuted and also due to the diagnosis raised in advanced stages of the disease as well as to economic difficulties to sustain treatment, intervening factors in our country.

Relato de caso: linfoma de células t/nk extranodal tipo nasal / Case Report: Extranodal Nk/T-Cell Lymphoma, N a s a l Ty p e / Reporte de caso: linfoma extranodal de células t/nk de tipo nasal

Introdução: O linfoma não-Hodgkin é dividido em linfomas de células B e linfomas de células T, e o linfoma extranodal de células T / NK do tipo nasal está dentro do último grupo.Relato de caso: Paciente do sexo masculino de 30 anos, relata que há 6 meses, de forma progressiva e de início insidioso, apresenta tumor cervical à direita de crescimento progressivo, pelo qual foi encaminhado ao ambulatório de cabeça e pescoço onde apresentou seus principais sinais e sintomas adenopatia cervical direita, sintoma B e tumoração ao nível da nasofaringe, envolvendo o teto, parede posterior e face lateral; se movimenta com auxílio, com extenso conglomerado linfonodal supraclavicular direito, eritematoso, com calor local, além de áreas de ulceração e secreção serosa.Conclusão: O diagnóstico e tratamento precoces desta doença são as únicas ferramentas para melhorar o mau prognóstico e o grave impacto na qualidade de vida dos pacientes que a padecem

Introduction: Non-Hodgkin's lymphomas are divided into B-cell lymphomas and T-cell lymphomas, and extranodal NK/T-cell lymphoma, nasal type, is in the latter group.Case report: A 30-year-old male patient, for six months, progressively and with an insidious onset, has had a right-sided cervical tumor with progressive growth. He came to a head and neck outpatient clinic where the main signs and symptoms detected were right cervical lymphadenopathy, B-symptoms, and a tumor in the nasopharynx affecting the roof, posterior wall, and lateral wall. The patient moves with assistance and has an enlarged, erythematous warm right supraclavicular lymph node conglomerate. In addition, he has some ulcerated areas with serous drainage.Conclusion: Early diagnosis and treatment of this disease are the only tools to improve these patients' poor prognosis and severely deteriorated quality of life.

Introducción:El linfoma no Hodgkin se divide en linfomas de células B y linfomas de células T; y en este último grupo se encuentra el linfoma extraganglionar de células T / NK de tipo nasal.Caso clínico: Un paciente masculino de 30 años refiere que durante 6 meses de forma progresiva, y con un início insidioso, presenta una tumoración cervical en el lado derecho de crecimiento progresivo, por lo que acude a la consulta externa de cabeza y cuello, donde los signos y síntomas principales fueron adenopatía cervical derecha, síntoma B, y una tumoración a nivel de nasofaringe, que afecta el techo, la pared posterior y la cara lateral. Se moviliza con ayuda, con un extenso conglomerado ganglionar supraclavicular derecho, eritematoso, con calor local. Además, también muestra algunas áreas de ulceración y secreción serosa. Conclusión: El diagnóstico y tratamiento precoz de esta enfermedad son las únicas herramientas para mejorar el mal pronóstico y el deterioro severo en la calidad de vida de los pacientes que la padecen

Identificación de macrófagos y virus Epstein-Barr en biopsias de pacientes con Síndrome de Sjögren

RESUMEN El síndrome de Sjögren (SS) es una enfermedad crónica mediada inmunológicamente. La presencia de macrófagos y el virus Epstein-Barr (VEB) se ha relacionado con su desarrollo y severidad. Los macrófagos contribuyen al proceso autoinmune local y la infección viral promueve el quiebre de la auto-tolerancia. Objetivos. Identificar la presencia de Macrófagos en el infiltrado inflamatorio y VEB en células inflamatorias, correlacionándolos con las características histológicas de glándulas salivales labiales. Metodología. En biopsias de glándulas salivales labiales (8 pacientes y 7 individuos controles) se realizó inmunohistoquímica antiCD-68 para identificar macrófagos. El conteo de macrófagos y células inflamatorias se efectuó en relación a su distribución en las glándulas salivales. La presencia del virus fue evaluada mediante hibridación in situ e inmunohistoquímica para LMP1. Se utilizó el test t no pareado y de Mann-Whitney para comparar los grupos, y coeficiente de correlación de Pearson para correlacionar con parámetros histológicos. Resultados. Se observó un mayor número de macrófagos en el infiltrado inflamatorio de pacientes (p=0,001**). Los macrófagos se distribuyeron difusamente en las glándulas de controles y en los focos inflamatorios de pacientes. En ambos grupos no se detectó la presencia del virus Epstein-Barr. Conclusión. Los pacientes con síndrome de Sjögren presentaron mayor presencia de macrófagos y su incremento es a expensas del foco inflamatorio.

ABSTRACT: Sjögren's syndrome (SS) is an immunologically mediated chronic disease of complex etiopathogenesis. Macrophages and Epstein-Barr virus are among the factors related to its development and severity. Macrophages contribute to the local autoimmune process and viral infection promotes the breakdown of self-tolerance. Objectives. Identify the presence of macrophages in the inflammatory infiltrate and Epstein-Barr virus in inflammatory cells, correlating them with the histological features of labial salivary glands. Methodology. In labial salivary glands biopsies of 8 patients and 7 control individuals, anti-CD-68 immunohistochemistry was performed to identify macrophages. The macrophages and inflammatory cells were counted in relation to their distribution in the salivary glands. The presence of the virus was evaluated by in situ hybridization for viral RNA and immunohistochemistry for latent membrane protein type 1. The comparison between both groups was made using the unpaired t-test and Mann-Whitney test. The correlations with histological parameters were established with the Pearson´s correlation coefficient. Results. A greater number of macrophages was observed in the inflammatory infiltrate of SS patients (p=0,001**). Macrophages in control individuals were diffusely distributed in the gland, while, SS in patients, they were mainly located in inflammatory foci. In both groups, no inflammatory or epithelial cells infected by the Epstein-Barr virus were identified. Conclusion. Patients with Sjögren's syndrome had a greater presence of macrophages and their increase is at the expense of the inflammatory focus.

Prevalence of epstein-barr virus infection in palatine tonsils hyperplasia through the immunoexpression of the LMP-1 marker / Avaliação da prevalência de infecção por epstein-barr vírus na hiperplasia de tonsilas palatinas através da imunoexpressão do marcador LMP-1

Introduction: LMP-1 (latent membrane protein 1) is a membrane protein found in EBV and can be identified through immunohistochemistry. Objectives: To evaluate the prevalence of EBV virus in tonsillar tissue samples correlating with tonsil size, age and gender. Methods: An LMP-1 immunohistochemical study was performed in slides from patients with tonsil hyperplasia. Results: The sample consisted of 120 slides, 66 were from male. The average tonsillar size was 6.0 cm2 (1.5-14.0) and the average age was 6.5 years (2-18). Overall, 72 patients were positive for the virus, the majority being male (51%) and preschoolers (51.4%). For comparative analysis, the sample was divided: group 1 (positive immunohistochemistry) and group 2 (negative immunohistochemistry). The average age was 6.74 years (± 4.14) and 6.19 years (± 3.82) for group 1 and 2, respectively. Group 1 had 37 preschoolers, 23 school-age children and 12 adolescents. Group 2 had 28 preschoolers, 14 school-age children and 6 adolescents (p=0.71). To evaluate the presence of virus, the slides were divided according to area: G (≥6cm²) and P (<6cm²). In G group, 54 slides were positive, while in P group, 18 were positive. Group 1 presented 54 of G group slides and 18 of P group slides, with no statistical difference, but with a tendency to positivity (p=0.09). Conclusion: Most of the sample was positive for the presence of Epstein-Barr virus. There was no difference in the virus presence or absence when correlated with the tonsillar size, age or sex

Introdução: LMP-1 (proteína latente de membrana-1) é uma proteína de membrana encontrada no Epstein-Barr vírus (EBV) e que pode ser identificadaatravés da imunoistoquímica. Objetivo: Avaliar a prevalência do EBV em amostras de tecido tonsilar correlacionando com o tamanho da tonsila, idade e sexo. Método: Realizou-se um estudo imunoistoquímico de LMP-1 para EBV em lâminas de pacientes com hiperplasia de tonsilas. Resultados: A amostra foi composta por 120 lâminas, sendo 66 (55%) de pacientes do sexo masculino. O tamanho médio tonsilar foi 6,0 cm2 (1,5-14,0) e a idade média 6,5 anos (2-18). Ao todo, 72 pacientes (60%) tiveram positividade para o vírus, a maioria meninos (51%) e pré-escolares (51,4%). A amostra foi dividida em: grupo 1 (imunoistoquímica positiva) e grupo 2 (imunoistoquímica negativa). A idade média foi de 6,74 anos (±4,14) e 6,19 anos (±3,82), para o grupo 1 e 2, respectivamente. O grupo 1 apresentou 37 pré-escolares, 23 escolares e 12 adolescentes. O grupo 2 foi composto por 28 pré-escolares, 14 escolares e 6 adolescentes, sem diferença estatística (p=0,71). Para avaliar a presença do EBV, as lâminas foram divididas de acordo com a área: G (≥6 cm²) e P (<6 cm²). No grupo G, 54 lâminas foram positivas, enquanto no grupo P, 18, sem diferença estatística, mas com tendência a positividade (p=0,09). Conclusão: A maior parte da amostra foi positiva para o Epstein-Barr vírus. Não houve diferença significante na positividade ou não do vírus quando correlacionada com o tamanho tonsilar, a idade e o sexo dos pacientes.

A pediatric case of Bartonella henselae and Epstein Barr virus disease with bone and hepatosplenic involvement / Un caso pediátrico de enfermedad por Bartonella henselae y virus de Epstein Barr con afectación ósea y hepatoesplénica

Abstract Background: Cat scratch disease (CSD) is an infectious disorder caused by Bartonella henselae. The infection usually presents as local lymphadenopathy, fever, and mild constitutional symptoms. Systemic or severe disease is reported in 5-20% of patients with CSD. We report a case of disseminated CSD with osteomyelitis and hepatosplenic disease and a review of the literature. Case report: A previously healthy 5-year-old male presented with prolonged fever and abdominal pain, followed by low back pain. The serologic test showed positive IgG for B. henselae and IgM and IgG for Epstein Barr virus (EBV). The abdominal ultrasound showed hepatic and splenic hypoechoic lesions, and the magnetic resonance imaging (MRI) revealed spondylitis of the D6 vertebra. He received treatment with azithromycin for 4 weeks and rifampicin for 6 weeks. The symptoms disappeared, and the abdominal ultrasound was normal nine months later. Conclusions: Disseminated CSD is infrequent. The diagnosis requires a high rate of suspicion. Laboratory findings of Bartonella infection are often non-specific. Serologic test, polymerase chain reaction of B. henselae in blood or biopsied material of the site of involvement and imaging test can be performed to confirm the diagnosis. The diagnosis of disseminated B. henselae was based on significantly elevated blood titers, radiologic findings, and epidemiologic history. Treatment of CSD depends on the disease presentation. Azithromycin is used as a first-line agent for lymphadenopathy. The optimum treatment and its duration have not been established in atypical or complicated CSD, including patients with osteomyelitis and hepatosplenic disease.

Resumen Introducción: La enfermedad por arañazo de gato (EAG) es una patología infecciosa originada por Bartonella henselae. Habitualmente se presenta como linfadenopatía local, fiebre y síntomas constitucionales leves. El 5-20% de los pacientes con EAG manifiestan una afectación sistémica. Se presenta un caso de EAG diseminada, con osteomielitis y enfermedad hepatoesplénica, y se hace una revisión de la literatura sobre la EAG. Caso clínico: Paciente de sexo masculino de 5 años, previamente sano, que presentó fiebre prolongada y dolor abdominal, seguidos de dolor en la parte baja de la espalda. En la serología, presencia de IgG frente a B. henselae y de IgM e IgG frente al virus de Epstein-Barr. En la ecografía abdominal se observaron lesiones hipoecoicas en el hígado y el bazo, y la resonancia magnética mostró espondilitis de D6. Recibió tratamiento con azitromicina 4 semanas y rifampicina 6 semanas. Los síntomas desaparecieron y la ecografía abdominal a los 9 meses fue normal. Conclusiones: La EAG diseminada es infrecuente. El diagnóstico requiere un alto grado de sospecha. Los hallazgos de laboratorio en la infección por Bartonella suelen ser poco específicos. Para confirmar el diagnóstico pueden hacerse serología, reacción en cadena de la polimerasa para B. henselae en sangre o en biopsia de tejidos afectados, y estudios de imagen. El diagnóstico de EAG diseminada se basa en títulos elevados en la sangre, hallazgos radiológicos e historia epidemiológica. El tratamiento depende de la forma de presentación. En los casos de linfadenopatía se utiliza azitromicina. En la EAG atípica o complicada, que incluye osteomielitis y afectación hepatoesplénica, no están bien establecidos el tratamiento ni su duración.

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Rotura esplénica espontánea secundaria a mononucleosis infecciosa / Spontaneous splenic rupture secondary to infectious mononucleosis

Resumen La rotura esplénica es una complicación rara pero potencialmente fatal de la mononucleosis infecciosa. Presentamos el caso de una mujer de 18 años que consultó por dolor abdominal de siete días de evolución, asociado a fiebre y pérdida de conciencia brusca y transitoria. En el hemograma presentaba una anemia y linfocitosis. Se realizó una tomografía computada de abdomen y pelvis que mostró un extenso hemoperitoneo, con el bazo rodeado por un hematoma, y numerosas adenopatías cervicales, mesentéricas e inguinales. Se efectuó una laparoscopía que demostró abundante hemoperitoneo con coágulos a lo largo de la gotera parietocólica izquierda. El bazo estaba completamente decapsulado y rodeado por una colección hemática con sangrado en napa. Se realizó una esplenectomía total sin complicaciones. El estudio histopatológico esplénico mostró una atenuación de la pulpa blanca y expansión de la pulpa roja con áreas de hemorragia y necrosis. La IgM anti-cápside para virus de Epstein Barr fue positiva. La paciente evolucionó de manera favorable.

Abstract Splenic rupture is a rare but potentially fatal complication of infectious mononucleosis. We report the case of an 18-year-old woman, who presented a 7-day history of abdominal pain, sudden temporary loss of consciousness and fever. Admission blood tests showed anemia, and lymphocytosis. Computed tomography of the abdomen and pelvis demonstrated extensive hemoperitoneum and numerous cervical, mesenteric and inguinal enlarged lymph nodes. Laparoscopy was performed and abundant hemoperitoneum with blood clots along the left parietocolic gutter were observed. The spleen was completely decapsulated and surrounded by a hematoma and the subcapsular tissue was bleeding. Total splenectomy was performed without complications. Splenic histology demonstrated white pulp attenuation and expansion of the red pulp with focal hemorrhage and necrosis. IgM anti-viral capsid antigen of Epstein Barr virus was positive. The patient had a satisfactory recovery.

Lipschütz ulcer and Epstein-Barr virus infection: a case report / Úlcera de Lipschütz e infecção pelo vírus Epstein-Barr: um relato de caso

Aims: Lipschütz ulcer (LU), also known as acute vulvar ulcer, is a rare cause of vulvar ulcerations of nonvenereal origin. Our aim is to alert about this manifestation of the disease and to prevent unnecessary treatment. Case description: we present a 15 years old female, without relevant family and past history, admitted in the emergency room with a painful vulvar ulcer, preceded by five days of fever and sore throat. On physical examination, she had enlarged, and erythematous tonsils and bilateral anterior cervical lymphadenopathy and the genital examination revealed vulvar oedema and a deep ulcer with necrotic plaques in labium minus. The exclusion of transmitted sexual disease led to a diagnosis of Lipschütz ulcer. She started symptomatic treatment, oral antibiotic and corticoid therapy. She was discharged from the hospital after 6 days of admission and returned to a consult one month later when it was observed an almost complete resolution of the lesions. No recurrences occurred until 3 months. Conclusion: LU is a misdiagnosed pathology, probably because doctors, in general, are not familiarized with that, and since the diagnosis is made by exclusion. Infectious, such as Epstein-Barr Virus infections, are proposed etiologies.

Objetivo: a úlcera de Lipschütz, ou úlcera vulvar aguda, é uma causa rara de ulceração de origem não venérea. O nosso objetivo é alertar para essa manifestação da doença e prevenir tratamentos desnecessários. Descrição: adolescente, sexo feminino, 15 anos, sem história pessoal ou antecedentes familiares de relevo. Recorreu ao Serviço de Urgência por febre e odinofagia, com cinco dias de evolução, associada a uma úlcera vulvar dolorosa, que surgiu no próprio dia. O exame clínico revelou amígdalas hipertrofiadas e eritematosas, linfadenopatia cervical anterior, e o exame ginecológico apresentou edema da vulva e uma úlcera profunda, com placas necróticas nos lábios menores. A exclusão de uma doença sexualmente transmissível levou ao diagnóstico de úlcera de Lipschütz. Ficou internada no Serviço de Pediatria e iniciou tratamento sintomático, antibioterapia por sobreinfeção da úlcera e corticoterapia tópica. Teve alta após seis dias de hospitalização e foi reavaliada em consulta um mês depois, com resolução completa do caso. Não apresentou recorrência da úlcera até aos três meses seguintes. Conclusão: a úlcera de Lipschütz é uma doença subdiagnosticada, muito provavelmente porque os médicos não estão familiarizados com ela e por ser um diagnóstico de exclusão. A infeção pelo vírus Epstein-Barr é uma das etiologias propostas.

Síndrome de Behçet ou úlcera de Lipschütz: desafio diagnóstico / Behçet's syndrome or Lipschütz ulcer: diagnostic challenge

A ocorrência de úlceras genitais em adolescentes e mulheres jovens tem impacto emocional para as pacientes e seus familiares, pela frequente associação com uma possível etiologia de transmissão sexual. Porém, úlcera de Lipschütz e síndrome de Behçet não têm etiologia infecciosa e devem ser lembradas como possíveis diagnósticos diferenciais. O diagnóstico dessas duas patologias é clínico e pode ser desafiador. Dessa forma, foi realizada uma revisão na literatura com o objetivo de comparar as duas entidades. A úlcera de Lipschütz é causada por uma vasculite local e caracteriza-se pelo surgimento súbito de úlceras na vulva ou vagina inferior. Já a doença de Behçet é causada por vasculite sistêmica, com episódios de remissão e exacerbação, que pode envolver quase todos os sistemas orgânicos. Em ambos os casos, é essencial o referenciamento para reumatologia. O tratamento objetiva suprimir exacerbações, controlar a dor e prevenir infecção secundária.(AU)

The occurrence of genital ulcers in adolescents and young women have an emotional impact for the patient and their families, due to the frequent association of its etiology with a sexually transmitted disease. However, Lipschütz ulcer and Behçet's syndrome do not have an infectious etiology and should be remembered as a possible differential diagnoses. As the diagnosis of these two pathologies is clinical and can be challenging, a review of literature was carried out. The objective of this review of literature was to compare both diseases. Lipschütz ulcer is caused by local vasculitis and is characterized by the sudden appearance of ulcers in the vulva or lower vagina. Behçet's syndrome is caused by systemic vasculitis, with episodes of remission and exacerbation, which can affect almost all organ systems. In both cases, referral to rheumatology is essential. Treatment aims to suppress exacerbations, control pain and prevent secondary infection.(AU)

Úlcera de Lipschütz: reporte de un caso y revisión bibliográfica / Lipschütz Ulcer: a case report and a literature review

Resumen: ANTECEDENTES: Las úlceras de Lipschütz son lesiones vulvovaginales dolorosas, de aparición aguda y desaparición espontánea en 2 a 6 semanas, no dejan secuelas ni son recurrentes a largo plazo. Su etiopatogenia es incierta, alrededor de 70% se consideran idiopáticas. En los estudios más recientes se ha demostrado su asociación con agentes infecciosos, sobre todo con el virus de Epstein-Barr. El diagnóstico se establece por exclusión y su tratamiento se basa en el control sintomático, cicatrizantes, analgésicos y antisépticos. CASO CLÍNICO: Paciente de 15 años, con úlceras vulvares de aparición súbita acompañadas de cuadro catarral. Se indicó tratamiento local con cicatrizante, antiséptico y antiinflamatorio; al cabo de tres semanas se observó la desaparición de las lesiones y la negatividad de las pruebas que descartó el origen infeccioso. Se estableció el diagnóstico de úlcera de Lipschütz. CONCLUSIONES: La úlcera de Lipschütz es infrecuente y los niños son quienes más la padecen. Debido al carácter de desaparición espontánea y a la juventud de las pacientes, es decisivo establecer el correcto diagnóstico diferencial.

Abstract: BACKGROUND: Lipschütz Ulcers are painful, acute onset and self-limiting vulvovaginal lesions that can frequently be associated with prodromal symptoms, disappearing in 2-6 weeks without any sequelae. 70% of cases present idiopathic etiopathogenesis, and are related to Epstein-Barr virus, among others. The diagnosis is made by exclusion and its treatment is based on symptomatic control and the promotion of correct healing, using analgesics, cicatrizers and antiseptics. CASE REPORT: A 15-year-old girl reported the acute apparition of ulcerative vulvar lesions coinciding with systemic catarrhal symptoms. Local treatment with healing, antiseptic and anti-inflammatory lotions was prescribed, and after three weeks, she was reevaluated, observing the disappearance of the lesions and the negativity of the tests to rule out infectious origin, for which she was diagnosed with a Lipschütz ulcer. CONCLUSIONS: Lipschütz ulcer is rare and children are the ones who suffer most from it. Due to the spontaneous disappearance character and the youthfulness of the patients, it is decisive to establish the correct differential diagnosis.

Enfoque del paciente con adenopatías generalizadas. Importancia de la estrategia didáctica del estudio de casos clínicos: a propósito de un paciente con linfoma de Hodgkin asociado a una infección por el virus de Epstein-Barr

Se muestra el caso de un paciente con 56 años de edad, con un síndrome adenomegálico generalizado que presentó un linfoma de Hodgkin de celularidad mixta, asociado al virus de Epstein-Barr. El paciente previo al inicio del linfoma presentó episodios prolongados de estrés emocional, lo que posiblemente contribuyó a la disminución de la vigilancia inmunológica. El caso fue abordado por los estudiantes de quinto semestre en la asignatura Acto médico, una estrategia didáctica interdisciplinaria. Este artículo presenta los aspectos a tener en cuenta en el enfoque clínico de los pacientes con adenopatías desde una perspectiva integradora de la inmunología, la clínica y los diagnósticos diferenciales. Se resalta el valor del estudio de los casos clínicos con varios métodos diagnósticos como estrategia didáctica. Finalmente, se realiza una revisión de la literatura sobre el linfoma Hodgkin orientada al papel en el que participa la infección por el virus de Epstein-Barr, relacionada con la inmunosupresión por estrés.

SUMMARY We present the case of a 56-year-old patient with a generalized adenomegalic syndrome who presented a mixed cellular Hodgkin's lymphoma associated with Epstein Barr Virus. The patient had had great emotional stress prior to the onset of lymphoma, which possibly contributed to the decrease in immunological surveillance. The case was addressed by the students of the fifth semester in the subject "Medical Act", an interdisciplinary didactic strategy. We present the aspects to be taken into account in the approach of the clinician of patients with adenopathies from an integrative perspective of immunology, clinical and differential diagnoses; and the value of the study of clinical cases with several diagnostic approaches as a didactic strategy is highlighted. Finally, we present a literature review about Hodgkin lymphoma and the role which plays stress related Epstein Barr Virus infection.

Caracterización clínica y epidemiológica del carcinoma nasofaríngeo y su relación con el virus Epstein-Barr / Nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, clinical and epidemiological description

RESUMEN Fundamento: El carcinoma nasofaríngeo es el tumor maligno más frecuente del cavum. Estos tumores se diferencian de otros carcinomas epidermoide de la cabeza y cuello por su histología característica y su relación con el virus de Epstein-Barr. Objetivo: Caracterizar clínica y epidemiológicamente el carcinoma de nasofaringe y su relación con el virus Epstein-Barr, en el Instituto Nacional de Oncología y Radiobiología, Ciudad de la Habana, en el período de enero a diciembre de 2012. Metodología: Se realizó un estudio retrospectivo; se trabajó con un total de 16 historias clínicas. Se observaron variables como edad, sexo, tipo histológico, estadiamiento clínico, presencia del virus Epstein-Barr en el tumor, tratamiento aplicado, respuesta al tratamiento, recaída y estado del paciente. Resultados: El 50 % tenían entre 45-55 años de edad, 75 % eran hombres, el 50 % diagnosticados con tipo 3, 100 % negativo a la inmunohistoquímica para virus Epstein-Barr, predominó la etapa III con 43.75 %, el 56.25 % de los casos se trataron con radio-quimioterapia más quimioterapia, el 50 % tuvo respuesta completa, la recaída fue de 37.50 % y el 68.75 % de los pacientes estaba vivo a los 60 meses. Conclusiones: En esta pequeña población con carcinoma nasofaríngeo, la totalidad de la población fue negativa a la presencia de virus Epstein-Barr por técnicas de inmunohistoquímica, por lo que su negatividad se hizo representativa en los tipo 3 y etapas avanzadas y no tuvo impacto en la respuesta al tratamiento y la supervivencia global.

ABSTRACT Background: Nasopharyngeal carcinoma is the most common malignant tumor of the cavum. These tumors differ from some other epidermoid carcinomas of the head and neck by their histology features and their Epstein-Barr virus relationship. Objective: To describe clinically and epidemiologically the nasopharyngeal carcinoma and its relationship with the Epstein-Barr virus, at the National Institute of Oncology and Radiobiology, Havana City, from January to December 2012. Methodology: A retrospective study was conducted; with a total of 16 medical records. Variables such as age, sex, histological type, clinical staging, and presence of Epstein - Barr virus in the tumor, applied treatment, response to treatment, relapse and patient status were observed. Results: 50 % were between 45-55 years old, 75 % were men, 50 % diagnosed with type 3, 100 % negative to Epstein-Barr virus immunohistochemistry, stage III predominated with 43.75 %, 56.25 % of the cases were treated with radio-chemotherapy plus chemotherapy, 50 % had a complete response, relapse was 37.50 % and at 60 months 68.75 % of the patients were still alive. Conclusions: In this small population with nasopharyngeal carcinoma, the entire population was negative to the presence of Epstein-Barr virus applying immunohistochemical techniques, so its negativity became representative in type 3 and advanced stages and had no impact on the treatment response and overall survival.

Impacto del virus Epstein Barr en el cáncer gástrico en el Perú / Impact of the Epstein Barr virus on gastric cancer in Peru

El virus de Epstein Barr (VEB) es responsable del 10% del cáncer gástrico (CG) y se correlaciona con mejor tasa de sobrevida. En Perú, no existen estudios sobre prevalencia y características clínicas de CG VEB positivo. Objetivos: Determinar la prevalencia y las características clínico patológicas del CG VEB positivo. Materiales y métodos: 111 muestras de GC fueron examinadas centralmente por hibridización cromogénica in situ del RNA del VEB (EBER CISH). Resultados: El 8,4% de los casos fueron positivos para VEB. La mayoría de los casos VEB positivos tuvieron más de 60 años, varones y la localización, antro / píloro fue la más frecuente. La mayoría de los casos fueron de tipo intestinal y un patrón tubular con una tendencia a un mejor pronóstico en comparación con los casos de VEB negativo. Conclusión: CG VEB positivo es una entidad con una prevalencia de 8,4% en Perú con características clínicas y morfológicas distintivas.

Epstein Barr Virus (EBV) is responsible of 10% of Gastric Cancer (GC), correlating with better survival rates. In Peru, there were not studies about prevalence and clinical characteristics of CG EBV positive. Objective: Determine prevalence and clinicopathological characteristics of GC EBV positive. Materials and methods: 111 GC tumour samples were centrally screened by Chromogenic in situ hybridization (CISH) technique for EBV-encoded RNA (EBER) transcript. Results: 8.4% of cases were positive for EBV. Most cases EBV positive were more than 60 years old; male, antrum/pylorus had more frequent localizations. Most cases had an intestinal type and tubular patter and a tendency to better prognostic in comparison EBV negative cases. Conclusion: EBV positive GC is an entity with a prevalence of 8.4% in Peru with distinctive clinical and morphological characteristics.

Detección del virus Epstein Barr en escolares adolescentes en la ciudad de Cali, Colombia / Detection of epstein barr virus in adolescent students in the city of cali, colombia

Objetivo: Detectar el virus Epstein-Barr en estudiantes de secundaria entre los 14 y 17 años de la ciudad de Cali, Colombia y su posible asociación con la edad, sexo y grado escolar. Métodos: Estudio retrospectivo de corte transversal en donde se analizaron 374 muestras de saliva, tomadas entre el año 2015 y 2016, mediante PCR convencional y PCR en Tiempo real. Se evalúo la asociación entre la detección del ADN viral y las características demográficas, además de un análisis de razón de oportunidades para evaluar la medida de la asociación. Resultados: El ADN viral fue detectado en el 45% (167/374) de las muestras orales, encontrándose una presencia viral mayor en los escolares de los grados octavo y noveno (p=0,004); en donde los estudiantes de 14 años presentaron un riesgo de 2,4 veces mayor para la detección del virus (IC 95%:1,12-4,9) en comparación con los estudias de más edad. Conclusión: En el presente estudio se evidencio la exposición del VEB en la cavidad oral de estudiantes de secundaria, lo cual hace necesario que se tomen acciones de vigilancia que permitan monitorear las implicaciones de estos hallazgos en la salud de los escolares.

Objective: To detect the Epstein Barr virus in adolescent students between 14 and 17 years old in the city of Cali, Colombia and its possible association with age, gender and school grade. Methods: Retrospective cross-sectional study where 374 mouthwash samples collected between the years 2015 and 2016 was analyzed through conventional and real-time PCR. Association between viral DNA detection and sociodemographic characteristics were evaluated. The odds ratio analysis was used to assess the extent of this association. Results: The viral DNA was present in 45% (167/374) of the samples, with a higher DNA detection in the students of eighth and ninth grades (p=0.004); where the 14 years old students present a 2.4 times higher risk of detecting the virus (IC 95%: 1,12-4.9) in comparison with older students. Conclusion: In the present study, the Epstein Barr virus exposition in the oral cavity was evidenced, which make necessary to take actions on surveillance that allow monitoring the implications of these fndings in the teenage student's health.

Síndrome de Alice no país das maravilhas e reativação de infeção por Epstein-Barr / Alice in wonderland syndrome and reactivation of infection by Epstein-Barr

INTRODUÇÃO: O síndrome de Alice no País das Maravilhas (SAPM) é uma entidade rara que pode ocorre no contexto de várias condições clínicas, sendo a infeção por vírus Epstein-barr (EBV) a mais comum nas causas infeciosas. Apresenta-se um caso de SAPM associado a infeção a EBV alertando para a necessidade de investigação etiológica destes casos. RELATO DE CASO: Criança de 8 anos, com síndrome de Asperger que, no contexto de amigdalite aguda e febre, surgiu com episódios paroxísticos de alguns minutos de metamorfopsias (macro e micropsia), distorção da perceção das vozes e sensação de medo. A ressonância magnética e o eletroencefalograma foram normais, e o exame citoquímico do líquor foi normal mas a polimerase chain reaction (PCR) foi positiva para vírus EBV. As serologias para EBV, repetidas 3 e 10 semanas após a avaliação inicial, confirmaram uma reativação da infeção por este agente. O doente ficou assintomático após 2 semanas e não houve recidivas. CONCLUSÕES: A investigação de metamorfopsias ou síndrome de SAPM é mandatória pois podem indiciar patologia grave, nomeadamente lesão cerebral ou epilepsia focal. Embora a doença seja rara a etiologia infecciosa deve ser excluída mesmo em doentes com perturbação prévia do comportamento.

INTRODUCTION: Alice in wonderland syndrome (AWS) is a rare condition which may occur as a sign of multiple conditions, with the most frequent infectious etiology being Epstein-barr virus (EBV) infection. We present a case of an AWS caused by EBV infection to alert for the need to investigate these cases. CASE REPORT: 8-year-old boy with Asperger syndrome who developed, in the context of tonsillitis and fever, brief paroxystic episodes of metamorfopsias (macro and micropsia), with voice perception distortion and fear. Physical exam was otherwise normal. Brian magnetic resonance and electroencephalogram were normal, liquor cytochemical exam was normal but Epstein-barr virus (EBV) polimerase chain reaction was positive. EBV blood serologies, repeated 3 and 10 weeks after the initial evaluation, confirmed the reactivation of this agent's infection. Symptoms succumbed 2 weeks after its beginning, with no relapses. CONCLUSIONS: Metamorfopsias or AWS impose etiological investigation because they may occur due to severe disease, namely cerebral lesion or focal epilepsy. Although it is a rare disease, infectious causes should be excluded, even in patients with previous disturbed behavior.

Investigação da presença e da influência do Epstein-Barr vírus na severidade da papilomatose laríngea / Investigation of the presence and influence of Epstein-Barr virus on the severity of laryngeal papilomatosis

A papilomatose laríngea é uma neoplasia benigna causada pelo papilomavírus humano (HPV), sendo os tipos 6 e 11 os mais comuns, e que ocorre em dois grupos etários, juvenil e adulto. A possível coinfecção viral tem sido sugerida em lesões de cabeça e pescoço; nesse sentido, o Epstein Barr vírus (EBV), que também apresenta tropismo por células epiteliais vem sendo estudado neste grupo de lesões. Os objetivos deste estudo foram genotipar os HPVs, investigar a presença de EBV-DNA por PCR e EBV-RNA por hibridização in situ. Além disso, associar a presença de EBV com a imunoexpressão de CD21, os resultados obtidos com a escala laringoscópica de Derkay et al. (1998) e com os dados clinicopatológicos. Oitenta casos de papilomatose laríngea, juvenil (n=36) e adulta (n=44), foram retrospectivamente analisados e subdivididos em grupos de menor e maior severidade, baseando-se na escala de Derkay. Todas as amostras foram HPV posivitas, com 49 casos HPV 6, 26 casos HPV 11, 4 casos HPV 6 e 11, e 1 caso HPV 16. A presença de EBV-DNA foi detectada em 9 amostras, entretanto EBV-RNA não foi não foi identificado em nenhuma amostra. Assim como a presença do EBV-DNA, a imunoexpressão de CD21 não se associou estatisticamente com quaisquer variáveis. A presença de HPV 6 foi mais comum em PLA e, o HPV 11 foi mais comum (p=0,02) e maior em casos de maior severidade (p=0,04), no grupo juvenil. A presença do EBV provavelmente não desempenha papel importante na progressão/severidade desta patologia(AU)

Laryngeal papillomatosis is a benign neoplasm caused by the human papillomavirus (HPV), been types 6 and 11 the most commonly related, and is divided into two groups: juvenile and adult. Viral coinfection has been suggested in head and neck lesions; in this sense, Epstein Barr virus (EBV), which also presents tropism for epithelial cells, has been studied in this group of lesions. The aims of this study are to perform HPV genotyping, investigate EBVDNA presence by PCR and EBV-RNA by in situ hybridization; and associate EBV presence with CD21 immunoexpression. Finally, the results were associated with Derkay laryngoscopic score. Eighty cases of laryngeal papillomatosis, juvenile (n = 36) and adult (n = 44) were retrospectively subdivided into low-risk and high-risk of severity based on the Derkay index. All samples were HPV-positive, with 49 cases of HPV 6, 26 cases of HPV 11, 4 cases of HPV 6 and 11, and 1 case of HPV 16. The presence of EBV-DNA was detected in 9 samples, however EBV-RNA was not identified in any sample. As the presence of EBV-DNA, the CD21 immunoexpression was not statistically associated with any variables. The presence of HPV 6 was more common in ALP, HPV 11 was more common (p = 0.02) and higher in cases of higher severity (p = 0.04) in juvenile group. The presence of EBV probably does not play an important role in the progression/severity of this pathology(AU)

Análise comparativa do polimorfismo genético da glutationa transferase, do Helicobacter pylori e do vírus Epstein-Barr entre a área do tumor e as margens de ressecção proximal e distal do câncer gástrico / Comparative analysis of glutathione transferase genetic polymorphism, Helicobacter pylori and Epstein-Barr virus between the tumor area and the proximal and distal resection margins of gastric cancer

RESUMO Objetivo: comparar o polimorfismo dos genes Glutationa S-transferase teta 1 (GSTT1) e Glutationa S-transferase mu 1 (GSTM1) da área do tumor com as margens proximal e distal de espécimes de estômago ressecados de pacientes com câncer gástrico, e investigar a presença do DNA do vírus Epstein-Barr (EBV) e Helicobacter pylori. Métodos: coletamos prospectivamente amostras teciduais da área do tumor e das margens de ressecção proximal e distal dos estômagos de dez pacientes com adenocarcinoma gástrico submetidos à gastrectomia com linfadenectomia D2 e submetemos esses espécimes à extração de DNA. Comparamos a área do tumor com as margens proximal e distal dos estômagos ressecados para o polimorfismo dos genes GSTT1 e GSTM1 e investigamos a presença de DNA do EBV e H. pylori. Utilizamos o exon 5 do gene p53 como controle interno da reação de PCR multiplex. Resultados: em um paciente, detectamos genótipos GSTT1 e GSTM1 nulos na área do tumor, em contraste com a presença de ambos os genes nas margens proximal e distal. Encontramos DNA do EBV e H. pylori na área do tumor e também nas margens proximal e distal. Em outro paciente, a margem proximal foi negativa para GSTT1 e o DNA do EBV foi negativo na margem distal. Em três pacientes, o EBV-DNA foi negativo apenas na margem distal. Conclusão: este é o primeiro relato em que diferentes genótipos, infecção por EBV-DNA e H. pylori foram observados no mesmo paciente, indicando provável deleção desses genes em resposta à progressão tumoral e heterogeneidade intratumoral.

ABSTRACT Objective: to compare the polymorphism of the Glutathione S-transferase theta 1 (GSTT1) and Glutathione S-transferase mu 1 (GSTM1) genes from the tumor area with the proximal and distal margins of stomach specimens resected from patients with gastric cancer, and to investigate the presence of Epstein-Barr virus (EBV) DNA and Helicobacter pylori. Methods: we prospectively collected tissue specimens from the tumor area and from the proximal and distal resection margins of the stomachs of ten patients with gastric adenocarcinoma who underwent gastrectomy with D2 lymphadenectomy, and submitted these specimens to DNA extraction. We compared the tumor area with the proximal and distal margins of the resected stomachs for polymorphism of GSTT1 and GSTM1 genes and investigated the presence of EBV-DNA and H. pylori. We used the p53 exon 5 gene as an internal control of the multiplex PCR reaction. Results: in one patient, we detected null GSTT1 and GSTM1 genotypes in the tumor area, in contrast to the presence of both genes in the proximal and distal margins. We found EBV-DNA and H. pylori in the tumor area and also in the proximal and distal margins. In another patient, the proximal margin was negative for GSTT1, and EBV-DNA was negative in the distal margin. In three patients, EBV-DNA was negative only in the distal margin. Conclusion: this is the first report where different genotypes, EBV-DNA and H. pylori infection were observed in the same patient, indicating a probable deletion of these genes in response to tumor progression and intratumoral heterogeneity.

Linfoma NK/T extra nodal, tipo nasal, con compromiso cutáneo primario: reporte de un caso / Extranodal Natural Killer/T-Cell Lymphoma, nasal-type with primary cutaneous involvement: a case report

INTRODUCCIÓN: El linfoma extranodal natural killer/célula T (NK/T) de tipo nasal, es una neoplasia poco frecuente, con una alta letalidad, caracterizada por destrucción ósea alrededor de los senos paranasales, el septum nasal u obstrucción de la vía aérea. Puede presentar compromiso primario de la piel, vía aérea y otros órganos. OBJETIVO: Presentar un caso ilustrativo de una afección poco frecuente y de curso agresivo en población pediátrica, para facilitar la sospecha diagnóstica y el rápido reconocimiento por parte de los especialistas. CASO CLÍNICO: Adolescente de 14 años, que consultó por lesiones solevantadas en brazos y piernas, no dolorosas, sugerentes de paniculitis subcutánea, las cuales evolucionaron a máculas violáceas ulceradas. La biopsia de las lesiones fue compatible con linfoma NK/T de tipo nasal. Fue derivada a oncología pediátrica, donde recibió tratamiento quimioterápico. Pese a los esfuerzos médicos, la paciente falleció a los 8 meses producto de una infección pulmonar grave secundaria a inmunosupresión. CONCLUSIONES: El linfoma extranodal NK/T, tipo nasal es una neoplasia poco frecuente, que se comporta de forma agresiva, con una alta mortalidad sin tratamiento. Por lo que su reconocimiento es de gran relevancia para el diagnóstico precoz y rápida derivación a Hemato-Oncología.

INTRODUCTION: Extranodal natural killer/T-cell lymphoma (NK/T), nasal type, is an infrequent neoplasm with a high lethality, characterized by bone destruction around the sinus, nasal septum or obstruction of the airway. Also, may be primary skin involvement, airway and other organs. OBJECTIVE: Submit a rare condition in the pediatric population, in order to facilitate the diagnostic suspicion and quick recognition from specialists. CASE REPORT: a 14-year-old girl, who presented arm and leg lesions, painless, suggestive of subcutaneous panniculitis, which evolve to ulcerated purple maculae. Skin biopsy showed lesion compatible with NK/T lymphoma, nasal type. She was referred to pediatric oncology, where she received chemotherapy treatment. Despite medical efforts, the patient died eight months after due to a serious pulmonary infection secondary to immunosuppression. CONCLUSIONS: Extranodal NK/T-cell lymphoma, nasal type, is a rare neoplasm that behaves aggressively, with high mortality without treatment, therefore, its recognition has a high importance for early diagnosis and prompt referral to Hematology-Oncology.

Cáncer de cavum. Experiencia institucional / Cancer of cavum. Institutional experience

Los carcinomas epidermoides de cabeza y cuello son un grupo poco frecuente de neoplasias, en los Estados Unidos representan aproximadamente el 3% de todos los tumores. El cáncer de cavum se diferencia de otros tumores de cabeza y cuello por su epidemiología, histología, historia natural y respuesta al tratamiento. Presenta una marcada variación geográfica debido a su etiología multifactorial. En las áreas endémicas, la incidencia y la mortalidad han disminuido en los últimos 30 años. Esto probablemente se deba a cambios en el estilo de vida y avances en la radioterapia (RT) y quimioterapia (QT) sistémica (AU)

Epidermoid carcinomas of the head and neck are a rare group of tumors, in the United States they account for 3% of all cancers. Nasopharyngeal carcinoma differs from others head and neck squamous cells carcinomas in epidemiology, natural history, and response to treatment. Nasopharyngeal carcinoma displays a distinct racial and geographic distribution, which is reflective of its multifactorial etiology. The incidence and mortality has declined over the past 30 years in many endemic areas. This finding is probably a result of a combination of lifestyle modification and advances in radiotherapy and effective systemic agents (AU)

Presencia del marcador lmp-1 del virus epstein-barr en linfomas de caninos / Presence of lmp-1 protein of epstein-barr virus in lymphomas of canine origin

RESUMEN El virus Epstein-Barr (EBV) es un virus de alta prevalencia en humanos que se asocia con tumores de la línea linfoide B. En caninos se dispone de pocos reportes sobre la presencia del EBV y su rol en esta especie. El objetivo del presente estudio fue determinar la presencia de la proteína latente de membrana del EBV (LMP-1) en tejidos obtenidos de 20 linfomas de caninos cuyo diagnóstico se había realizado durante un periodo de 10 años, entre 2004 y 2014. Los linfomas se reclasificaron mediante las nuevas clasificaciones histopatológicas para linfomas y se sometieron a inmunohistoquímica (IHQ) con los anticuerpos anti-CD79a, anti-CD3, anticuerpos específicos para linfocitos B y T, además de un anti-LMP-1 como marcador de la presencia del EBV. Se encontró que el linfoma más común fue el linfoma nodal de zona T con un 75% de los casos. Al realizar la inmunomarcación se encontraron 18 casos positivos a CD3, 2 casos positivos a CD79a y 6 casos positivos a LMP-1, lo que representa el 30% de positividad del EBV en linfomas. El análisis Ji cuadrado demostró significancia estadística entre la presencia del virus y la presencia del linfoma lo que sugiere, no solamente que el virus está circulando en la población canina, sino que además puede tener relación con la ocurrencia de esta neoplasia. Con relación a las variables demográficas, sólo en la raza Golden Retriever se demostró relación con la presencia del linfoma, pero no con la presencia del virus.

ABSTRACT Epstein Barr virus (EBV) is a human high prevalent virus associated with lymphoid B cells tumors development. In canines, few reports have been published regarding the presence of the virus in dogs but its role in this species remains unclear. The aim of this study was to determine the presence of LMP-1 protein of EBV in 20 canine lymphomas tissues which were previously diagnosed in a period of time between 2004 -2014. Lymphomas were reclassified in accordance with the new histopathological classifications for lymphomas and were stained by IHQ with anti-CD79a, anti-CD3 and anti-LMP-1; in addition, specific antibodies for B lymphocytes, T lymphocytes and EBV biomarker, respectively. It was found that the most common lymphoma was T-zone lymphoma in 75% of the cases of the study. The distribution of the cases regarding the immunostaining was: 18 positive cases with anti-CD3, 2 positive cases with anti-CD79a and 6 positive cases with anti- LMP-1. Positive cases of LMP-1 as a biomarker of the presence of EBV corresponded to the 30% of the cases of the study. Chi-square test showed statistical significance between the presence of the virus and the presence of lymphomas, which suggests not only that the virus is circulating in the canine population but also that could have implications in the development of the disease. Regarding demographic parameters, only the Golden Retriever breed showed a relationship with the presence of lymphoma, but not with the presence of the virus.