Table 2

Differential diagnostic considerations of EBV-positive DLBCL of the elderly

EntitySiteArchitectureImmunophenotypeSpecific findingsLight chainClonality
EBV-positive DLBCL, elderly N (70%) Effaced Pan B markers+ Geographic necrosis Monotypic Monoclonal 
E (30%) CD10/BCL6/MUM1+, EBER+,CD30+/− 
EBV-associated reactive atypical lymphoproliferations/infectious mononucleosis in elderly Not effaced Mixed B- and T-cell nature of HRS-like cells (CD3+/20+/30+n/a Polytypic Polyclonal 
EBER+ 
EBV-positive classical Hodgkin lymphoma Effaced CD20-/CD79a-/Pax5w+ HRS cells in reactive background Polytypic Polyclonal 
CD30+/CD15+, EBER+/− 
DLBCL, NOS, anaplastic variant Effaced Pan B markers+ Sinusodal or cohesive pattern Monotypic Monoclonal 
EBER-, CD30+ 
T-cell/histiocyte-rich large B-cell lymphoma Effaced Pan B markers+ Scattered B cells in benign T cells/histiocytes background Monotypic Monoclonal 
EBER, CD30+/−, CD15- 
Primary cutaneous DLBCL, leg type E (skin) Dermal infiltration Pan B-cell markers+, EBER- Diffuse sheets of centroblasts and immunoblasts Monotypic Monoclonal 
BCL2+/MUM1+/FOXP1+ 
Lymphomatoid granulomatosis polymorphic infiltration EBER+, LMP1 Angioinvasion, HRS-like cells in reactive background Noninformative Monoclonal 
Plasmablastic lymphoma of the elderly N (50%) Effaced CD38+, CD138+, MUM1+, CD20 Plasmablastic morphology Monotypic n/a 
E (50%) EBER+, LMP1, EBNA2- EBV latency I 
Angioimmunoblastic T-cell lymphoma Effaced CD10+, CXCL13+, PD1+ FDC expansion Polytypic Monoclonal in T cells 
Peripheral T-cell lymphoma, not otherwise specified Effaced CD3+/− with partial loss of T-markers, CD30+/−, CD15−/+ Large atypical cells Polytypic Monoclonal in T cells 
EBER−/+ Clear cytoplasm+/− 
EntitySiteArchitectureImmunophenotypeSpecific findingsLight chainClonality
EBV-positive DLBCL, elderly N (70%) Effaced Pan B markers+ Geographic necrosis Monotypic Monoclonal 
E (30%) CD10/BCL6/MUM1+, EBER+,CD30+/− 
EBV-associated reactive atypical lymphoproliferations/infectious mononucleosis in elderly Not effaced Mixed B- and T-cell nature of HRS-like cells (CD3+/20+/30+n/a Polytypic Polyclonal 
EBER+ 
EBV-positive classical Hodgkin lymphoma Effaced CD20-/CD79a-/Pax5w+ HRS cells in reactive background Polytypic Polyclonal 
CD30+/CD15+, EBER+/− 
DLBCL, NOS, anaplastic variant Effaced Pan B markers+ Sinusodal or cohesive pattern Monotypic Monoclonal 
EBER-, CD30+ 
T-cell/histiocyte-rich large B-cell lymphoma Effaced Pan B markers+ Scattered B cells in benign T cells/histiocytes background Monotypic Monoclonal 
EBER, CD30+/−, CD15- 
Primary cutaneous DLBCL, leg type E (skin) Dermal infiltration Pan B-cell markers+, EBER- Diffuse sheets of centroblasts and immunoblasts Monotypic Monoclonal 
BCL2+/MUM1+/FOXP1+ 
Lymphomatoid granulomatosis polymorphic infiltration EBER+, LMP1 Angioinvasion, HRS-like cells in reactive background Noninformative Monoclonal 
Plasmablastic lymphoma of the elderly N (50%) Effaced CD38+, CD138+, MUM1+, CD20 Plasmablastic morphology Monotypic n/a 
E (50%) EBER+, LMP1, EBNA2- EBV latency I 
Angioimmunoblastic T-cell lymphoma Effaced CD10+, CXCL13+, PD1+ FDC expansion Polytypic Monoclonal in T cells 
Peripheral T-cell lymphoma, not otherwise specified Effaced CD3+/− with partial loss of T-markers, CD30+/−, CD15−/+ Large atypical cells Polytypic Monoclonal in T cells 
EBER−/+ Clear cytoplasm+/− 

n/a, not available; FDC, follicular dendritic cell meshworks; Pan B-cell markers, CD19, CD20, CD22; Site E, extranodal; Site N, nodal.1,25,42-44,46,82,84-88 

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