Linfoma de células NK/T subtipo nasal ­ relato de caso / Nasal subtype NK/T cell lymphoma ­ case report

RESUMO O linfoma de células NK/T subtipo nasal tem baixa incidência e alta agressividade, mostrando-se necessário diagnóstico precoce. Tal se mostra desafiador devido à sua manifestação clínica inicial, semelhante a quadro infeccioso de vias aéreas superiores. Por meio deste estudo observacional descritivo, relatam-se casos deste linfoma acometendo paciente masculino e outro feminino, ambos com diagnóstico tardio e com envolvimento de vias aéreas superiores sem resposta à antibioticoterapia. À exame de imagem, apresentaram lesão expansiva em cavidade nasal e o diagnóstico se deu por meio de estudo histológico com marcadores imuno-histoquímicos de células NK atípicas e presença de vírus Epstein-Barr (EBV). PALAVRAS-CHAVE: Linfoma de células NK/T tipo nasal, Epstein-Barr vírus, linfoma não-hodgkin, linfoma de células T periférico

ABSTRACT Nasal subtype NK/T cell lymphoma has a low incidence and high aggressiveness, and early diagnosis is necessary. This is challenging due to its initial clinical manifestation, similar to an upper airway infection. Through this descriptive observational study, we report cases of this lymphoma affecting a male and a female patient, both with late diagnosis and involvement of the upper airways without response to antibiotic therapy. On imaging scan, they presented an expansive lesion in the nasal cavity and the diagnosis was made through histological study with immunohistochemical markers of atypical NK cells and the presence of Epstein-Barr virus (EBV). KEYWORDS: NK/T-cell lymphoma nasal type, Epstein-Barr virus, Lymphoma non Hodgkin, T-cell lymphoma

Extranodal NK/T-cell lymphoma, nasal type with extensive cardiopulmonary involvement

Extranodal NK/T-cell lymphoma, nasal type (ENKTL-NT) is a rare type of Non-Hodgkin's lymphoma, which usually presents with extranodal involvement and affects the nasal/upper aerodigestive tract in the classical presentation. Herein, we report the case of a 31-year-old, previously healthy, male patient diagnosed with ENKTL-NT with the involvement of the lung parenchyma and heart. Unfortunately, due to the rapid disease progression, the diagnosis was performed only at the autopsy. The authors highlight the rare clinical presentation of this type of lymphoma, as well as the challenging anatomopathological diagnosis in necrotic samples.

Vías moleculares patogénicas del linfoma T/NK extranodal de tipo nasal asociadas con virus de Epstein Barr: Revisión narrativa / Molecular pathways related to Epstein Barr virus in extranodal NK/T cell lymphoma, nasal type: Narrative review

El virus de Epstein Barr (VEB) se encuentra presente en el 100% de los casos de linfoma T/NK extranodal de tipo nasal (ENKTL) y juega un papel importante en la etiopatogenia de esta enfermedad. El objetivo de esta revisión es actualizar el conocimiento de las vías moleculares genéticas y epigenéticas utilizadas por el VEB en la oncogenesis del ENKTL. Para ello se realizó una revisión de la literatura, en las bases de datos de PubMed y Google Scholar, sobre los mecanismos que utilizan las proteínas virales como la proteína de membrana latente (LMP1) y el antígeno nuclear Epstein Barr 1 (EBNA1) para activar proteínas antiapoptóticas del huésped y pro-teínas relacionadas a proliferación celular, a través de las vías moleculares JAK/STAT (Janus quinasas/señales de transducción y activación de proteínas de transcripción), NF-κB (el factor nuclear potenciador de las cadenas ligeras kappa de las células B activadas) EZHZ2 (Enhancer of Zeste 2 Polycomb repressive Complex 2) y PI3K/Akt (Fosfoinositido 3 quinasa/proteína quinasa B); también se revisó el papel de las proteínas virales BNLF2a, BILF y BDLF3 en la evasión inmune del virus. También LMP1 aumenta la expresión de PDL-1 (ligando de la muerte celular programada), contribuyendo a la disminución de la respuesta inmunológica. A nivel epigenético se abordan los cambios del perfil de metilación en las áreas promotoras de genes supresores de tumor y se explica la función de los miARN de VEB que participan inhibiendo genes supresores de tumor o activando genes que aumentan la proliferación.

Epstein Barr virus (EBV) is present in 100% of cases of nasal-type extranodal NK/T cell lymphoma (ENKTL). It plays an important role in the etiopathogenesis of this disease. The objective of this review is to update the knowledge of the genetic and epigenetic molecular pathways used by EBV in the oncogenesis of ENKTL. To this end, a literature review was carried out in the PubMed and Google Scholar databases on the mechanisms used by viral proteins such as latent membrane protein (LMP1) and Epstein Barr 1 nuclear antigen (EBNA1) to activate host antiapoptotic proteins avoiding cell death and activating cell proliferation, through the molecular pathways JAK/STAT (Janus kinases/signal transduction and activation of transcription proteins), NF-κB (the nuclear factor enhancing the kappa light chains of activated B cells) EZHZ2 pathways (Enhancer of Zeste 2 Polycomb repressive Complex 2) and PI3K/Akt (Phosphoinositide 3 kinase protein kinase B). The role of the viral proteins: BNLF2a, BILF and BDLF3 in the virus immune evasion. It is currently recognized that LMP1 increases the expression of PDL-1 (programmed cell death ligand), contributing to the decrease in the immune response. Thus, the epigenetic changes in the methylation profile in the promoter areas of tumor suppressor genes, was also reviewed. Finally role of EBV miRNAs participate in inhibiting tumor suppressor genes or activating genes that increase proliferation.

Linfomas cutáneos: serie de casos en México / A case series of cutaneous lymphomas in Mexico

Resumen Introducción: Los linfomas cutáneos primarios son un grupo heterogéneo de neoplasias de células T y B que se presentan en la piel, sin ninguna evidencia de enfermedad extracutánea en el momento del diagnóstico, y muestran diferencias considerables en histologia, fenotipo y pronóstico. Se consideran neoplasias poco frecuentes. Casos clínicos: Se presentan cinco casos de linfomas cutáneos diagnosticados en el Hospital Infantil de México Federico Gómez durante el periodo de 2010 a 2018. Las presentaciones clínicas más frecuentes en estos pacientes fueron dermatitis, costras hemáticas y úlceras necróticas. El inmunofenotipo más común fue el linfoma cutáneo no Hodgkin T/NK extranodal nasal primario. El esquema de tratamiento que se utilizó en la mayoría de los pacientes fue SMILE. El promedio de tiempo al diagnóstico fue de 7 meses. Conclusiones: El pronóstico depende del estadio de la enfermedad al diagnóstico, grado de afectación de la piel y presencia o ausencia de enfermedad extracutánea. Los linfomas cutáneos primarios son neoplasias poco frecuentes. Debido al diagnóstico tardío, el estadio de la enfermedad suele ser avanzado, por lo que, generalmente, el comportamiento es agresivo.

Abstract Background: Primary cutaneous lymphomas are a rare heterogeneous group of T and B cell skin neoplasms without any evidence of extracutaneous disease at the time of diagnosis, which show considerable differences in histology, phenotype and prognosis. Case reports: Five cases of cutaneous lymphomas treated at the Hospital Infantil de México Federico Gómez from 2010 to 2018 are described. The most frequent clinical presentations in these patients were dermatitis, blood scabs, and necrotic ulcers. The most common immunophenotype was non-Hodgkin T/NK primary nasal extranodal cutaneous lymphomas. The treatment scheme used in most patients was SMILE. The average time to diagnosis was 7 months. Conclusions: The prognosis depends on the stage of the disease at diagnosis, the degree of skin involvement, and the presence of extracutaneous disease. As primary cutaneous lymphomas are infrequent neoplasms, the stage of the disease is usually advanced and generally shows an aggressive behavior due to a late diagnosis.

Linfoma de células T/NK extranasal primario en íleon / Natural Killer/T cell primary extranasal ileum lymphoma

RESUMEN El linfoma extranodal de células T/NK extranasal (NKTL) primario del tracto gastrointestinal es poco frecuente y tiene carácter agresivo. Presentamos el caso de un paciente inmunocompetente de 51 años que ingresa por dolor abdominal de dos meses de evolución. En la colonoscopía, se hallaron ulceraciones ileales, por lo que se le realizaron estudios para descartar enfermedad de Crohn y tuberculosis intestinal, posteriormente presentó obstrucción intestinal. En la laparotomía exploratoria, se encontró un conglomerado ganglionar en mesenterio. La anatomía patológica confirmó el diagnóstico de NKTL primario en íleon. Se inició quimioterapia y el paciente pidió alta voluntaria dada su precaria condición. Dos meses después del alta el paciente fallece. Este linfoma ha sido reportado principalmente en Asia y posiblemente sea el primer caso reportado en Perú. Tiene un pronóstico funesto con una supervivencia global de ocho meses. Por ello, es necesario un diagnóstico precoz e iniciar la terapia oportunamente.

ABSTRACT Primary extranodal Natural Killer / T cell lymphoma (NKTL) on gastrointestinal tract is an uncommon and aggressive neoplasm. We present the case of a 51-year-old immunocompetent patient with a 2-month history of abdominal pain. Colonoscopy findings showed ileal ulcerations, so studies were carried out to rule out Crohn's disease and intestinal tuberculosis. Later, he developed intestinal obstruction. Exploratory laparotomy found a nodal conglomerate in the mesentery. Anatomical pathology confirmed the diagnosis of primary NKTL on the ileum. Chemotherapy was initiated but the patient asked for voluntary discharge because of his precarious condition. Two months after discharge the patient died. This lymphoma has been reported mainly in Asia and is possibly the first case in Peru. It has a dismal prognosis with overall survival of 8 months. Therefore, it is necessary to get an early diagnosis and begin therapy in a timely manner.

Linfoma Extranodal de Células T/NK en Cavidad Oral. Reporte de un Caso en Chile / Extranodal Lymphoma of T / NK Cells in Oral Cavity. Case Report in Chile

RESUMEN: El linfoma extranodal de células T/NK es una neoplasia maligna agresiva que se caracteriza por una destrucción de estructuras de la línea media de la cara como paladar y fosa nasal. Presentamos el caso de un paciente de sexo masculino, 48 años de edad, consumidor de cocaína, que consulta en la Facultad de Odontología de la Universidad de Chile en Septiembre del 2015 por síntomas de disfagia, rinorrea y que presenta al examen clínico un tumor ulcerado que compromete paladar duro y blando, de un mes de evolución. Se confirma diagnóstico de linfoma de células T/NK con una batería de pruebas inmunohistoquímicas. Esta patología, aunque infrecuente, siempre debe ser considerada dentro los diagnósticos diferenciales en tumores ulcerados en esta localización.

ABSTRACT: Extranodal T / NK cell lymphoma is an aggressive malignant neoplasm characterized by destruction of midline structures of the face such as the palate and nasal fossa. We present the case of a male patient, 48 years old, cocaine user, who consults at the Faculty of Dentistry of the Universidad de Chile in September of 2015 due to symptoms of dysphagia, rhinorrhea and presenting to the clinical examination an ulcerated tumor which compromises hard and soft palate, a month of evolution. Diagnosis of T / NK cell lymphoma is confirmed with a battery of immunohistochemical tests. This pathology, although infrequent, should always be considered within the differential diagnoses in ulcerated tumors of this location.

SMILE en linfoma de células NK/T extranodal en recaída / SMILE in relapsed extranodal NK / T cell lymphoma

Introducción: El linfoma extranodal de células NK/T, tipo nasal es una variedad agresiva que se presenta con mayor frecuencia en Asia Oriental y América Latina. El régimen de tratamiento SMILE, basado en dexametasona, metotrexato, ifosfamida, L-asparaginasa y etopósido, mostró tasas de respuestas objetivas adecuadas en estudios de fase 1/2. Objetivo: presentar el primer reporte de la aplicación del protocolo SMILE en Cuba. Presentación del caso: paciente de 47 años de edad, blanca que presentó recaída temprana de linfoma extranodal de células NK/T tipo nasal en partes blandas de la pared anterior izquierda del tórax. Recibió quimioterapia SMILE por 4 ciclos y en la evaluación al final del tratamiento se comprobó que hubo una respuesta completa de la enfermedad(AU)

Introduction: Extranodal lymphoma of NK / T cells, nasal type is an aggressive variety that occurs most frequently in East Asia and Latin America. The SMILE treatment regimen, based on dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide, showed adequate objective response rates in phase 1/2 studies. Objective: to present the first report of the application of the SMILE protocol in Cuba. Case presentation : 47-year-old white patient who presented early relapse of extranodal lymphoma of nasal NK / T cells in soft parts of the left anterior wall of the thorax. He received SMILE chemotherapy for 4 cycles and the evaluation at the end of the treatment showed that there was a complete response of the disease(AU)

Nasal-type extranodal T-cell/NK lymphoma in association with hemophagocytic syndrome

Abstract: Extranodal NK/T-cell lymphoma nasal type is a rare disease that mainly affects the nasal cavity and paranasal sinuses of males in the fifth decade of life. It has aggressive and locally destructive behaviour, and can be complicated by the hemophagocytic syndrome, conferring high lethality to the disease. This article describes a case of NK/T-cell lymphoma nasal type in a previously healthy patient, exemplifying its rapid and fulminant course.

Linfoma nasal de células T/NK (granuloma letal de la línea media), una neoplasia agresiva: reporte de un caso / Nasal T/NK-cell lymphoma (lethal midline granuloma), an aggressive neoplasia: report of a case

RESUMEN El linfoma nasal de células T/NK es una neoplasia agresiva, infrecuente, con predilección por el sexo masculino. Representa el 1,5% del total de linfomas no Hodgkin, el grupo etáreo más afectado es entre 40 a 80 años. Su etiología es desconocida, pero se ha asociado con el virus de Epstein Barr. Se presenta el caso de una paciente mujer de 40 años, con dolor e induración de fosa nasal derecha asociado a secreción fétida, seropurulenta de 3 meses de evolución. Estudio histopatológico, reporta linfoma nasal de células T/NK. La paciente recibe quimioterapia, con mejoría clínica sustancial. El linfoma T/NK es una neoplasia con sintomatologia inespecífica, predominio que afecta nasofaringe, amígdalas y base de la lengua. Entre las manifestaciones encontramos dolor de garganta, obstrucción nasal, rinorrea, epistaxis y cefalea. El diagnóstico se sospecha con imágenes, pero es necesaria la confirmación histológica con marcadores de inmunohistoquímica CD45Ro, CD43, CD3, CD2, CD45Ro entre otros. Muchos casos suelen detectarse en fase tardía, cuando ya son evidentes los signos radiológicos de destrucción ósea. El diagnóstico diferencial incluye lesiones infecciosas o inflamatorias, la bola fúngica fue el diagnóstico inicial realizado en esta paciente. El tratamiento suele realizarse con radioterapia y quimioterapia.

ABSTRACT Nasal T-cell / NK lymphoma is an uncommon aggressive neoplasm with male predilection. It represents 1.5% of the total number of non-Hodgkin's lymphomas, the most affected age group is 40-80 years. Its etiology is unknown but has been associated with the Epstein Barr virus. We present the case of a female patient of 40 years, with pain and induration of the right nostril associated with fetid secretion, seropurulent of 3 months of evolution. Histopathological study, reports T-cell / NK nasal lymphoma. The patient receives chemotherapy, with substantial clinical improvement. T / NK lymphoma is a neoplasm with predominant non-specific symptomatology, affecting the nasopharynx, tonsils and base of the tongue. Among the manifestations we find sore throat, nasal obstruction, rhinorrhea, epistaxis and headache. Diagnosis is suspected with imaging, but histological confirmation with immunohistochemical markers CD45Ro, CD43, CD3, CD2, CD45Ro, among others is required. Many cases are usually detected in the late phase, when radiological signs of bone destruction are already visible. The differential diagnosis includes infectious or inflammatory lesions, the fungal ball was the initial diagnosis made in this patient. Treatment is usually done with radiotherapy and chemotherapy.

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.

Linfoma de células T-natural killer tipo nasal en la piel: presentación de un caso / Nasal- type natural killer/ T-cell lymphoma involving the skin: a case report

El año 1994 marcó una línea temporal de avance y desarrollo en la investigación de cierto grupo de linfomas, caracterizados por la afectación, generalmente extranodal, en la línea media facial, la nasofaringe y la piel. La Organización Mundial de la Salud, y su más reciente revisión en el 2016, los agrupó dentro del apartado de neoplasias maduras de células T y natural killer como linfomas extraganglionares. Se presenta a una paciente, blanca, de 71 años de edad, con diagnóstico de un linfoma cutáneo de células T/natural killer tipo nasal, angiocéntrico en estadio avanzado. Se trata de un linfoma poco común, pero con curso clínico agresivo, con múltiples factores de mal pronóstico y escasa respuesta al tratamiento, que ocasionó el desenlace fatal de la paciente.

Accurate diagnose and management of advanced nasal type extranodal nk/t cell lymphoma. a case report

ABSTRACT Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare entity in otorhinolaryngology. Its management requires skilled physicians in order to suspect this disease and making a proper diagnosis at early stages. This paper reports the case of a 31-year-old male patient, with one month of nasal obstruction, recurrent sinusitis, palatal ulceration and a necrotizing lesion. Histopathology reported lymphoid infiltrate polymorph angiocentric growth pattern and extensive areas of necrosis. Immunohistochemistry confirmed the phenotype for T/NK cells: positive CD3, BCL2, CD4 and CD56. IgG for Epstein-Barr virus was also positive. The initial staging was T4, N1, M0, Eastern Cooperative Oncology Group (ECOG) scale was 1, with intermediate risk, and low International Prognostic Index (IPI); based on this results, the patient was referred to oncology to initiate treatment. After a ten-month follow-up, the patient's condition improved, with complete remission of nasal and palate injuries; no relapse has occurred to date. This case is a clear example of the importance of early diagnostic through multiple biopsies in order to establish a specific treatment to decrease complication rates and improve prognosis.

Linfoma T/NK extraganglionar tipo nasal: caso clínico / Extranodal T/NK-Cell lymphoma nasal type: clinical case

El linfoma T/NK extraganglionar tipo nasal es un linfoma extraganglionar, habitualmente expresa el fenotipo NK y VEB positivo. Cursa ocasionando necrosis y angioinvasión afectando de manera preferente estructuras mediofaciales. Característicamente es muy agresivo. Presentamos un caso con una sobrevida de siete meses a partir de los primeros síntomas y realizamos revisión de la literatura.

Extranodal NK/T-cell lymphoma nasal type, is an extranodal lymphoma, usually with an NK-cell phenotype and EBV possitive. It causes necrosis and angioinvasion, and it is most commonly presenting in the midfacial area. Characteristically it is very aggressive. A case with survival of seven months from the first symptoms is reported and a review of the literature is made.

Multifocal primary cutaneous extranodal NK/T lymphoma nasal type

Abstract Nasal type extranodal NK/T-cell lymphoma is a distinct entity according to the World Health Organization classification. Although 60% to 90% of patients with this disease present with a destructive mass in the midline facial tissues, it may also primarily or secondarily involve extranasal sites, like the skin. We report the case of a 77-year-old patient that came to our department with erythematous plaques of the right leg and eczematous lesions of the trunk. These lesions were biopsied and the patient was diagnosed with extranodal NK/T-cell lymphoma, nasal type. He was treated with multi-agent systemic chemotherapy but died 5 months after diagnosis. This case highlights the rarity and variability of cutaneous features of this disease and its aggressive course and poor prognosis.

Linfoma de células T/Natural Killer extranodal, tipo nasal / Extranodal Natural Killer /T-cell lymphoma, nasal type

Introducción: El linfoma de células T/Natural Killer (T/NK) extranodal, tipo nasal, es un linfoma extra-ganglionar poco frecuente, con extensión a lo largo de la línea media facial, rápidamente progresivo, catastrófico y de mal pronóstico, por lo que también se le conoce como "granuloma letal de la línea media". Objetivo: El propósito de este artículo es revisar la literatura disponible y actualizada sobre el linfoma de células T/NK extranodal, tipo nasal: manifestaciones clínicas, estándares de enfoque, diagnóstico, pronóstico y tratamiento. Diseño: Revisión Narrativa de la literatura. Metodología: Revisión de la literatura mediante búsqueda selectiva por términos MeSH: Extranodal Natural Killer /T cell lymphoma, nasal type, lethal midline granuloma, de las bases de datos: MEDLINE, Current Contents, Cochrane, Pubmed y Scielo, entre los años 2000 y 2014. Resultados: Se revisaron 36 artículos según los requerimientos de los objetivos. El linfoma de células T/NK es una neoplasia rápidamente progresiva, destructiva y de mal pronóstico excepto en los casos donde el diagnóstico ha sido oportuno. Conclusiones: El diagnóstico y tratamiento tempranos del linfoma de células T/NK extranodal, tipo nasal, son las únicas herramientas para mejorar el mal pronóstico y gran afectación en la calidad de vida de los pacientes con esta enfermedad.

"Introduction: Extranodal nasal Natural Killer (NK) /T-cell lymphoma, nasal type, is an extranodal lymphoma, infrequent, with extension along facial midline, rapidly progressive, catastrophic and with poor prognosis, also known as "lethal midline granuloma". Objectives: The purpose of this article is to review the current literature available about Extranodal nasal NK/T-cell lymphoma, nasal type: Clinical manifestations, approach standards, diagnosis, prognosis and treatment. Methodology: Literature review by selective MeSH search terms: Extranodal Natural Killer / T cell lymphoma, nasal type, lethal midline granuloma of databases: MEDLINE, Current Contents, Cochrane, PubMed and SciELO, between 2000 and 2014. Results: 36 articles were reviewed according to the requirements of the objectives. Extranodal NK/T cell lymphoma, nasal type, is a rapidly progressive neoplasia, destructive and with poor prognosis except in cases where diagnosis has been timely. Conclusions: Early diagnosis and treatment of Extranodal NK/T cell lymphoma, nasal type, are the only tools to improve the poor prognosis and high impairment in quality of life of patients with this disease.

Linfoma extranodal NK de celulas T tipo nasal: reporte de caso / Extranodal NK/T cell lymphoma, nasal type: report of case

El linfoma extranodal de c‚lulas T/NK tipo nasal es una entidad rara, cuya etiolog¡a est  asociada al virus Epstein-Barr, su comportamiento agresivo (20% de sobrevida a 5 a¤os) y es predominante en hombres. Se manifiesta por una lesi¢n tumoral mediofacial destructiva de vasos y necrosis prominente. El diagn¢stico es cl¡nico e inmunohistopatol¢gico y se caracteriza por una marcada agiocentricidad y necrosis tisular, acompa¤ada de infiltrado inflamatorio de linfocitos, histiocitos, c‚lulas plasm ticas y a veces eosfin¢filos. Su inmunofenotipo caracter¡stic es CD2(+), CD56(+), CD3 epsilon (+), CD3 superficie (-), CD7(-), CD16(-), CD30 +/-. A pesar de ser radiosensible, tiene un mal pron¢stico, generalmente, como consecuencia de complicaciones del tratamiento. Se reporta un caso representativo de linfoma extraodal de c‚lulas T/NK tipo nasal de una paciente mujer de 58 anos procedente de Cusco.

Nasal T-cell and natural killer (NK) cell extranodal lymphoma is a rare entity whose etiology is associated with Epstein-Barr, has an aggressive behavior (20% 5-year survival), predominantly in men. Expressed by a midface destructive lesion tumoral of vessels and prominent necrosis. diagnosis is clinical and immunohistochemical is characterized by a marked angiocentricity, and tissular necrosis accompanied by inflamatory infiltrate of lymphocytes, histiocytes, plasma cells and sometimes eosinophils. Its characteristic inmunophenotype is CD2(+), CD56(+), CD3 epsilon (+), CD3 superficie (-), CD7(-), CD16(-), CD30 +/-. Despite being radiosensitive, generally has a poor prognosis due to treatment complications. We report a representative case of nasal T-cell and natural killer cell extranodal lymphoma of a female patient of 58 years from Cusco.

Clinical and otorhinolaryngological aspects of extranodal NK/T cell lymphoma, nasal type / Aspectos clínicos e otorrinolaringológicos do linfoma extranodal de células NK/T tipo nasal,

INTRODUCTION: Extranodal NK/T-Cell lymphoma, nasal type (NKTLN) is a disease that mainly affects the nasal cavity and the paranasal sinuses. Early nasal symptoms are nonspecific, simulating sinus infection. With disease progression, necrosis of the nasal mucosa increases, hindering histological diagnosis. Thus, multiple biopsies may be necessary until definitive diagnosis. Most studies on NKTLN address the hematological and immunological aspects of the disease. OBJECTIVES: To present data from a Brazilian quaternary hospital, with emphasis on the clinical aspects of the disease, and to correlate the findings with the most recent literature data. METHODS: Case study of seven patient files. RESULTS: Patients were evaluated on their medical history, number of biopsies necessary, association with Epstein-Barr virus, treatment, and outcome. All patients had nonspecific nasal complaints and underwent at least three cycles of antibiotic therapy. The earlier a biopsy was performed, the fewer biopsies were required to diagnose the disease and start treatment. However, this fact did not translate into better prognosis. CONCLUSION: The otolaryngologist plays a fundamental role in the prognosis of NKTLN and can shorten time between symptom onset and treatment of the patient. .

INTRODUÇÃO: O linfoma extranodal de células NK/T tipo nasal (LNKTN) é uma doença que acomete preferencialmente a cavidade nasal e os seios paranasais. Os sintomas nasais iniciais são inespecíficos, mimetizando um quadro de infecção nasossinusal. Com a progressão da doença, aumenta a necrose da mucosa nasossinusal, dificultando o diagnóstico histológico e podendo ser necessárias múltiplas biópsias até o diagnóstico definitivo. A maioria dos estudos sobre o LNKTN aborda aspectos imunológicos e hematológicos da doença. OBJETIVO: Apresentar a casuística de um hospital quaternário brasileiro, destacando os aspectos clínicos dos pacientes e correlacionando aos achados mais recentes da literatura. MÉTODO: Estudo de casos de sete pacientes. RESULTADOS: Pacientes foram avaliados quanto a aspectos de sua história clínica, número de biópsias necessárias, associação ao EBV, tratamento e evolução. Todos iniciaram o quadro com queixas inespecíficas nasais e foram submetidos a pelo menos três ciclos de antibióticos. Quanto mais precocemente a biópsia foi realizada, menos biópsias foram necessárias para se obter o diagnóstico e iniciar o tratamento. Entretanto, esta situação não refletiu num melhor prognóstico dos pacientes. CONCLUSÃO: O otorrinolaringologista tem papel fundamental no prognóstico do LNKTN, podendo encurtar o tempo entre o início dos sintomas e o tratamento do paciente. .

Extranodal Nasal NK/T-Cell Lymphoma: A Rare Oral Presentation and FASN, CD44 and GLUT-1 Expression

Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignant tumor with distinctive clinicopathological features, characterized by vascular invasion and destruction, prominent necrosis, cytotoxic lymphocyte phenotype and a strong association with Epstein-Barr virus. Here is reported an extranodal nasal NK/T-cell lymphoma case, involving the maxillary sinus, floor of the orbit, and interestingly extending to the oral cavity through the alveolar bone and buccal mucosa, preserving the palate, leading to a primary misdiagnosis of aggressive periodontal disease. Moreover, this work investigated for the first time the immunohistochemical expression of fatty acid synthase (FASN) and glucose transporter 1 (GLUT-1) proteins in this neoplasia. FASN showed strong cytoplasmatic expression in the neoplastic cells, whereas GLUT-1 and CD44 were negative. These findings suggest that the expression of FASN and the loss of CD44 might be involved in the pathogenesis of the extranodal nasal NK/T-cell lymphoma, and that GLUT-1 may not participate in the survival adaptation of the tumor cells to the hypoxic environment. Further studies with larger series are required to confirm these initial results.

O linfoma de células natural killers (NK)/T extranodal é um tumor maligno agressivo com características clinicopatológicas distintas, caracterizadas por invasão e destruição vasculares, necrose proeminente, fenótipo linfocítico citotóxico e uma forte associação com o vírus Epstein-Barr. Relatamos aqui um caso de linfoma de células NK/T nasal extranodal, envolvendo o seio maxilar, assoalho de órbita, e interessantemente estendendo-se para a cavidade oral através do osso alveolar e mucosa vestibular, preservando o palato, levando a um diagnóstico inicial equivocado de doença periodontal agressiva. Ainda, nós investigamos pela primeira vez a expressão imunoistoquímica das proteínas Fatty acid sinthase (FASN) e glucose transporter 1 (GLUT-1) nesta neoplasia. FASN revelou uma forte expressão citoplasmática nas células neoplásicas, enquanto GLUT-1 e CD44 foram negativas. Estes achados sugerem que a expressão de FASN e a perda de CD44 podem estar envolvidas na patogênese do linfoma de células NK/T nasal extranodal, e que GLUT-1 não deve participar da adaptação das células tumorais ao ambiente de hipóxia. Estudos adicionais com séries maiores são necessários para confirmar nossos resultados iniciais.

Ocular masquerade syndrome associated with extranodal nasal natural killer/T-cell lymphoma: case report / Síndrome ocular mascarada associada ao linfoma extranodal nasal natural killer/células T: relato de caso

A 33-year-old woman complained of unilateral eyelid edema and blurred vision. Initial ophthalmic examination disclosed anterior chamber reaction with keratic precipitates on the cornea, without posterior abnormalities. Anterior uveitis was treated. Despite that, patient showed rapidly progressive unilateral vision loss with optic nerve swelling. Systemic workup was inconclusive, as well as cranial magnetic resonance imaging and cerebrospinal fluid examination. Based on the hypothesis of optic neuritis, intravenous methylprednisolone pulse was performed with no success. During the following days, the patient presented pericardial effusion and cardiac tamponade, progressing to death. Necropsy was performed and diagnosis of extranodal natural killers/T-cell lymphoma, nasal type with ocular involvement was confirmed by immunohistochemistry.

Paciente feminina de 33 anos apresentando edema palpebral unilateral com baixa acuidade visual. Ao exame oftalmológico inicial apresentava reação de câmara anterior com precipitados ceráticos corneano, sem alterações no fundo de olho. Foi instituído tratamento para uveíte anterior e solicitado exames sistêmicos para investigação. Após alguns dias, paciente apresentou piora da acuidade visual, com edema de disco óptico unilateral. Sendo então solicitada ressonância nuclear magnética de crânio. Ambos exames de imagem e investigação sistêmica foram inconclusivos. Em vista da piora progressiva da acuidade visual e sob hipótese diagnóstica de neurite óptica, foi iniciado pulso intravenoso de metilprednisolona por 3 dias sem sucesso. A paciente apresentou dos dias seguintes, derrame pericárdico e tamponamento cardíaco, evoluindo para óbito. A necrópsia confirmou o diagnóstico de linfoma extranodal de células T e natural killers do tipo nasal com envolvimento ocular, através de imunoistoquímica.

Virus de Epstein-Barr y piel / Epstein-Barr virus and skin

La infección por el virus de Epstein-Barr puede afectar de manera muy variada al ser humano en sus diferentes etapas de la vida. Algunas veces las manifestaciones son asintomáticas o con síntomas poco específicos y otras puede presentarse como una enfermedad de severidad y duración variable, que puede desarrollar un proceso maligno. Hasta el momento se ha estudiado muy poco sobre la relación del virus de Epstein-Barr y piel, por lo que se trata de hacer una revisión de esta enfermedad y sus diferentes expresiones en la piel.

Epstein-Barr virus infection can occur in different manners, affecting humans throughthe different stages of life. Sometimes, manifestations are asymptomatic or non specific;conversely it can occur as a disease of variable severity and duration, and occasionallyeventuate into malignancy. So far little has been studied on the relationship betweenEpstein-Barr virus and skin; therefore we present this review of the disease and its various expressions upon the skin.