The host T cell response controls the proliferation of EBV-infected B cells and the spread of the virus. Early in the course of the infection, IgM antibodies are formed against viral capsid antigens. Later the serologic response shifts to IgG antibodies, which persist for life. More important in the control of the EBV-positive B cell proliferation are cytotoxic CD8+ T cells. Virus-specific CD8+ T cells appear in the circulation as atypical lymphocytes, a finding that is characteristic of mononucleosis. In otherwise healthy persons, the fully developed humoral and cellular responses to EBV act as brakes on viral shedding. In most cases, however, a small number of latently infected EBV-positive B cells escape the immune response and persist for the life of the patient. As described later, impaired T cell immunity places patients at high risk for EBV-driven B cell proliferations.
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MORPHOLOGYThemajoralterationsinvolvetheblood,lymphnodes,spleen,liver,andoccasionallyotherorgans.Thereisperipheralbloodleukocytosis;thewhitecellcountisusuallybetween12,000and18,000cells/µL.Typicallymorethanhalfofthesecellsarelargeatypical lymphocytes, 12to16µmindiameter,withanoval,indented,orfoldednucleusandabundantcytoplasmwithafewazurophilicgranules(
Fig.12.12 ).Theseatypicallymphocytes,whicharesufficientlydistinctivetosuggestthediagnosis,aremainlyCD8+ Tcells.
Lymphadenopathy iscommonandismostprominentintheposteriorcervical,axillary,andgroinregions.Onhistologicexamination,theenlargednodesarefloodedbyatypicallymphocytes,whichoccupytheparacortical(Tcell)areas.AfewcellsresemblingReed-Sternberg(RS)cells,thehallmarkofHodgkinlymphoma,oftenareseen.Becauseoftheseatypicalfeatures,specialtestsaresometimesneededtodistinguishthereactivechangesofmononucleosisfromlymphoma.
Thespleen isenlargedinmostcases,weighingbetween300and500g,andexhibitsaheavyinfiltrationofatypicallymphocytes.Asaresultoftherapidincreaseinsplenicsizeandtheinfiltrationofthetrabeculaeandcapsulebythelymphocytes,suchspleensarefragileandarepronetoruptureafterevenminortrauma.
Atypicallymphocytesusuallyalsoinfiltratetheportalareasandsinusoidsoftheliver.Scatteredapoptoticcellsorfociofparenchymalnecrosisassociatedwithalymphocyticinfiltratealsomaybepresent—apicturethatcanbedifficulttodistinguishfromthatinotherformsofviralhepatitis.