RESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal syndrome of abnormal T-cell activation and cytokine production, which can be familial or secondary in nature. Although HLH can occur concomitantly with lymphomas, the development of HLH alongside Hodgkin lymphoma in children is unusual. Here we report the diagnostic evaluation and clinical course of 2 pediatric cases of HLH secondary to lymphocyte-depleted classic Hodgkin lymphoma. These cases highlight the need to be vigilant for this rare presentation and the difficulties in managing these patients.
Asunto(s)
Enfermedad de Hodgkin/complicaciones , Linfohistiocitosis Hemofagocítica/etiología , Niño , Manejo de la Enfermedad , Enfermedad de Hodgkin/diagnóstico , Humanos , Linfocitos/patología , Linfohistiocitosis Hemofagocítica/diagnósticoRESUMEN
Epstein-Barr virus (EBV) persistently infects more than 90% of the human population and is etiologically linked to several B cell malignancies, including Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and diffuse large B cell lymphoma (DLBCL). Despite its growth transforming properties, most immune-competent individuals control EBV infection throughout their lives. EBV encodes various oncogenes, and of the 6 latency-associated EBV-encoded nuclear antigens, only EBNA3B is completely dispensable for B cell transformation in vitro. Here, we report that infection with EBV lacking EBNA3B leads to aggressive, immune-evading monomorphic DLBCL-like tumors in NOD/SCID/γc-/- mice with reconstituted human immune system components. Infection with EBNA3B-knockout EBV (EBNA3BKO) induced expansion of EBV-specific T cells that failed to infiltrate the tumors. EBNA3BKO-infected B cells expanded more rapidly and secreted less T cell-chemoattractant CXCL10, reducing T cell recruitment in vitro and T cell-mediated killing in vivo. B cell lines from 2 EBV-positive human lymphomas encoding truncated EBNA3B exhibited gene expression profiles and phenotypic characteristics similar to those of tumor-derived lines from the humanized mice, including reduced CXCL10 secretion. Screening EBV-positive DLBCL, HL, and BL human samples identified additional EBNA3B mutations. Thus, EBNA3B is a virus-encoded tumor suppressor whose inactivation promotes immune evasion and virus-driven lymphomagenesis.
