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.

Recurrence of Extranodal Natural Killer/T-cell Lymphoma Presenting as Tarsal Tunnel Syndrome.

This case report is a rare form of lymphoma recurrence which presented as tarsal tunnel syndrome. The patient had been previously treated for the malignancy and was presumed to be in remission; however, standard radiology imaging protocols failed to include the distal extremities on these scans. The patient presented to the orthopedic clinic with tarsal tunnel symptoms and a mass in the tarsal tunnel. A complete evaluation resulted in a diagnosis of recurrence of the malignancy. This case illustrates the importance of a thorough medical history and personal review of imaging studies, and how a systematic approach can produce the correct diagnosis for any unknown lesion. Furthermore, this case may prompt oncologists to consider obtaining whole-body fluorodeoxyglucose positron emission tomography computed tomography when evaluating for recurrence in patients.

[Extranodal NK-T-cell lymphoma, nasal type in granulomatosis with polyangiitis. A case report]. / Linfoma T/NK nasal en granulomatosis con poliangeítis. Reporte de un caso.

BACKGROUND: Granulomatosis with polyangiitis (GP) is a systemic necrotizing vasculitis with multi-organ involvement that primarily affects the respiratory tract and the kidneys. Fever in these patients is an indicator of activity; however, if it arises in isolation, the physician should exclude other causes. CLINICAL CASE: Male patient admitted due to an unexplained fever and weight loss; it was diagnosed GP by a history of pauci-immune glomerulonephritis, fixed pulmonary nodules and chronic sinusitis of four years of evolution; however, the fever persisted despite treatment and in the absence of infection. It was performed an oropharynx lesion biopsy and the diagnosis was extranodal NK-T-cell lymphoma, nasal type, and positive for CD56 and granzyme. CONCLUSION: Extranodal NK-T-cell lymphoma, nasal type is a rare entity, of poor prognosis, that should be considered as a diagnosis in patients with GP unresponsive to steroid. That is the reason why biopsy of the lesion and immunohistochemistry are required.

Introducción: la granulomatosis con poliangeítis (GP) es una vasculitis sistémica necrosante con afección multiorgánica que afecta principalmente el tracto respiratorio y los riñones. La fiebre en estos pacientes se considera indicador de actividad, pero si se presenta de forma aislada, deben descartarse otras causas. Caso clínico: paciente de sexo masculino que ingresó por fiebre de origen desconocido y pérdida de peso; se le diagnosticó granulomatosis con poliangeítis por antecedente de glomerulonefritis pauciinmune, nódulos pulmonares fijos y sinusitis crónica de cuatro años de evolución; sin embargo, la fiebre persistió a pesar del tratamiento y en ausencia de infección. Se realizó biopsia de úlcera faríngea que reportó linfoma de células T/NK de tipo nasal ulcerado positivo para CD56 y granzima. Conclusión: el linfoma T/NK nasal es una rara entidad, de mal pronóstico, que debe considerarse en pacientes con GP que no responden a esteroide, por lo que requieren biopsia de la lesión e inmunohistoquímica.

Extensive extranodal adult T-cell lymphoma presenting with a lytic arthropathy of the ankle.

A case is presented of a 44-year-old human T-cell lymphotropic virus-1 seropositive Afro-Caribbean man whose adult T-cell lymphoma presented with an ankle arthropathy. Over a period of weeks he developed subcutaneous tumor masses, osteolytic lesions, sinonasal involvement, and spinal disease culminating in death 4 months after his diagnosis. The case highlights the extranodal manifestations, generally, and rheumatological complications, specifically, of this very aggressive form of lymphoma with review of the relevant literature. Consideration should be given to the possibility of this condition in individuals originating from known endemic areas, notably, the Caribbean, southwestern Japan, South and Central America, parts of southeastern United States, and equatorial Africa.