Lymph nodes - not lymphoma
Infectious / parasitic disorders
Epstein Barr virus

Topic Completed: 1 July 2013

Revised: 15 December 2019

Copyright: 2003-2019,, Inc.

PubMed Search: Epstein Barr virus [title] lymph nodes [title]

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Cite this page: DePond W. Epstein Barr virus. website. Accessed February 27th, 2020.
Definition / general
  • Causes infectious mononucleosis (typical cases); other viruses may cause atypical cases
  • Classic clinical features are teenager / young adult with fever, sore throat, cervical adenopathy and mild hepatitis; peripheral blood shows atypical lymphocytes (CD8+ cytotoxic T cells)
  • Lymph nodes should usually NOT be biopsied as diagnosis is clinical and serologic
  • Atypical cases (lymphadenopathy but no fever, no sore threat, no splenomegaly) may be biopsied to rule out lymphoma
  • Fatal cases of infectious mononucleosis are associated with monoclonal or biclonal EBV (Am J Clin Pathol 2002;117:582)
  • Associated with histiocytic necrotizing lymphadenitis (Kikuchi disease) in Taiwan (Am J Clin Pathol 2000;113:774)
  • EBV RNA also present in Peruvian patients in nonneoplastic lymph nodes in B and T cells (Mod Pathol 1993;6:729)
  • May cause post-transplant lymphoproliferative disorders (see Lymphomas - non B cell), also Hodgkin and some non-Hodgkin lymphomas
Case reports
Microscopic (histologic) description
  • Partial architectural effacement due to marked sinusoidal and capsular / extranodal infiltration by immunoblasts that often have Reed-Sternberg like features and atypia
  • Follicular hyperplasia with ragged or mottled edges, follicles have tingible body macrophages and marked mitotic activity
  • Polymorphous inflammatory cells
  • Early infections have prominent monocytoid B cell reaction and no epithelioid cells (Am J Surg Pathol 2005;29:595)
  • Necrosis is usually minimal, but may be extensive in immunocompromised
Microscopic (histologic) images

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Infectious mononucleosis involving lymph node

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EBV associated infectious mononucleosis

Cytology description
  • Greater than usual numbers of large immunoblastic lymphocytes
  • Polymorphic immunoblasts
  • Pattern is not specific (Diagn Cytopathol 1990;6:323)
Peripheral blood images

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Atypical lymphocytes

Positive stains
Negative stains
  • CD15 (for Reed-Sternberg like cells)
Differential diagnosis
  • Anaplastic large cell lymphoma: lymphomas have atypical cells throughout the lymph node, not confined to the sinuses as with EBV
  • Drug reactions
  • Hodgkin lymphoma: nodular distortion, mixed inflammatory cells
  • Other viral infections
  • Post vaccination
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