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Editorials
tation was found to be the most effective treatment choice for prolonged overall survival.12
Of particular interest in the study by Kawamoto et al.12 is their comparison of overall survival in patients with pediatric and adult-onset CAEBV with nasal and non- nasal ENKTL. Adult-onset CAEBV showed a worse over- all survival in comparison to pediatric onset CAEBV and ENKTL. In fact, adult-onset CAEBV had an overall sur- vival comparable to that of non-nasal ENKTL, which is generally more aggressive than its nasal counterpart.
In the pediatric age group, systemic EBV+ T-cell lym- phoma of childhood, a de novo CD8+ T-cell lymphoma with an aggressive clinical course, must be separated from CAEBV.1-3,8 One key feature that helps distinguish CAEBV from systemic EBV+ T-cell lymphoma of child-
hood is that the T cells in CAEBV are predominantly CD4+ and less frequently of cytotoxic CD8 origin. In addition, CAEBV can show clinical and histological over- lap with aggressive NK-cell leukemia and ENKTL. Age of onset, together with immunophenotypic differences help in the diagnosis: sCD3+, CD56-, CD8+ and/or CD4+ in sys- temic EBV+ T-cell lymphoma of childhood; sCD3-, cCD3+, CD16+, CD56dim, CD8- in aggressive NK-cell leukemia; and CD2+, CD5-, CD56+/-, cCD3+, EBER in ENKTL. The presence of T-cell clonality in systemic EBV+ T-cell lym- phoma can further help distinguish that entity from aggressive NK-cell leukemia, which lacks T-cell clones. Markers associated with NK-cell differentiation, such as CD16, can also be useful, as CD16 is positive in 75% of aggressive NK leukemia but usually absent in ENKTL.
Table 1. Characteristic features of Epstein-Barr virus (EBV)-positive (EBV+) T-cell and natural killer (NK)-cell lymphoproliferative disorders.
EBV-associated hemophagocytic lymphohistiocytosis (HLH)
• Non-neoplasticproliferationtypicallyseeninthepediatricagegroup
• AcutepresentationwithoutpriorhistoryofimmunodeficiencyorEBVinfection
• MostcommoninpatientsofAsiandescent
• T-cellmonoclonalityisoftendetectedbutisnotanindicationofmalignancy
• Hyperbilirubinemia(>1.8mg/dL)andhyperferritinemia(>20,300ng/mL)atdiagnosisarepoorprognosticfactors • HLH2004protocolisusedformanagement;lackofresponsemaynecessitatebonemarrowtransplantation
• Maybeself-limitinginsomecases
Chronic active EBV (CAEBV) infection
• Cutaneousandsystemicformsexist,althoughsymptomscanoverlap
• CutaneousCAEBVincludesseveremosquitobiteallergyandhydroavacciniforme-likelymphoproliferativedisorders • SystemicCAEBVpresentswithfever,lymphadenopathyandsplenomegaly,andtypicallyfollowsprimaryEBVinfection • Mostcommoninchildrenandyoungadults
• MostcommoninpatientsofAsianorHispanicdescent
• Follows a chronic, relapsing clinical course with a risk of progression to systemic EBV+ T- or NK-cell lymphoma
• CAEBVofT-celloriginhashighIgGtitersagainstEBVviralcapsidandearlyantigensandaworseprognosis
• Adult-onsetCAEBVisassociatedwithaworseprognosis
Systemic EBV+ T-cell lymphoma
• Acute, de novo T-cell lymphoma of EBV+ cytotoxic T cells
• Mostcommoninchildrenandyoungadults
• MostcommoninAsiansandinindigenouspopulationsofCentralandSouthAmerica
• Mostpatientsareimmunocompetent
• MostpatientsdevelopHLH
• Followsafulminantclinicalcoursewithpoorresponsetochemotherapyanddeathwithindaystoweeksofdiagnosis
Aggressive NK leukemia
• SystemicneoplasticproliferationofNKcellsfrequentlyassociatedwithEBV • Mostcommonlyinvolvesperipheralblood,bonemarrow,liverandspleen
• Mostcommoninyoungtomiddle-agedadultswithamedianageof40years • MostcommoninpatientsofAsiandescent
• MayevolvefromCAEBV,particularlyinyoungerpatients
• Followsafulminantclinicalcoursewithmulti-organfailureandpoorresponsetochemotherapy,withamediansurvivalof<2months
Extranodal NK/T cell lymphoma, nasal type
• Extranodal lymphoma of EBV+ cytotoxic T or NK cells associated with angiodestruction and prominent necrosis • Affectsimmunocompetentaswellasimmunocompromisedpatients
• Mostcommonlyinvolvestheupperaerodigestivetract,skin,softtissue,gastrointestinaltractandtestes
• Mostcommoninadultswithamedianageof44-54years
• MostcommoninAsiansandinindigenouspopulationsofCentralandSouthAmerica
• Clinicalcourseisvariable:somerespondwelltochemotherapyandup-frontradiationwhileotherssuccumbtodisseminateddisease
• Advanced stage, invasion of bone or skin, EBV+ cells in the bone marrow and a high proliferation index are unfavorable prognostic factors • Extranasaldiseaseishighlyaggressiveandisrefractorytotreatment
• Somecutaneouscasesmayhaveaprotractedclinicalcourse
Nodal peripheral T-cell lymphoma, EBV+
• Other EBV+ peripheral T-cell lymphomas (not further discussed in the report)
haematologica | 2018; 103(6)