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EBV-associated classical Hodgkin lymphoma

Monday 9 February 2015

EBV-related CHL

There is strong evidence supporting an association of Classical Hodgkin lymphoma (CHL) with EBV. There is strong evidence between an altered EBV humoral immune response and development of CHL.

In epidemiologic studies the overall prevalence of EBV in CHL in immune competent individuals is approximately 50% (40-70%) with higher incidence in African and South American countries and lower incidence in some European countries. In HIV infected individuals EBV associated HL can be greater than 80%. EBV association is also more prevalent in children than adults and shows little effect on survival.


- Extranodal hean and neck EBV+ CHL

  • Extranodal CHL is uncommon with most CHL occurring in lymph node or contiguous to lymph node.
  • HL in the head and neck is uncommon comprising 1-4% of all lymphomas in this location.
  • In the head and neck, Waldeyer ring is the most common site of CHL involvement. EBV has been reported in as high as 67% of HL of Waldeyer ring, possibly owing to the fact that this location is a reservoir for EBV.
  • There was no consensus as to the most prevalent subtype occurring in Waldeyer ring between studies.
  • Interestingly, lymphocyte rich classical HL, a relatively rare subtype overall in HL, has been reported as the most prevalent type of Waldeyer ring CHL in one study.
  • CHL occurs outside Waldeyer ring with rare case reports in other location in the head and neck.
  • The morphology and immunophenotype of CHL is similar to that in the lymph node. All subtypes including mixed cellularity, nodular sclerosis, lymphocyte rich and lymphocyte depletion are described in the head and neck.


Morphologically, the cases are classified and subtyped by the 2008 WHO classification. These lymphomas show effacement of the normal architecture with a mixture of inflammatory cells in the background including histiocytes, eosinophils, plasma cells and small lymphocytes.

The malignant cells are in the minority and are large often multinucleated with prominent nucleoli and often abundant cytoplasm.

Differential diagnosis

The histology can be very similar to that of infectious mononucleosis, with extensive infiltrate in the interfollicular area with numerous epithelioid histiocytes; and atypical large cells with mummified cells are small lymphocytes; classic Reed-Sternberg cells.

Hodgkin-like transformation of a small B cell lymphoma such as small lymphocytic lymphoma/chronic lymphocytic leukemia, which may be EBV associated, may occur. In this setting, the clinical history is important.

Some treatment-related lymphoproliferative disorders may also resemble Hodgkin lymphoma, such as methotrexate-related EBV-associated lymphoproliferative disorders, which are similar to post transplant lymphoproliferative disorders (PTLD), and must be excluded if a diagnosis of CHL is entertained.


By immunohistochemistry, the large malignant cells are immunoreactive with CD30 and CD15 but negative for CD45. PAX5 is positive the majority of cases.

When associated with EBV, EBER is positive with a variable number of cases showing LMP-1 staining.

CD20 and CD3 should be negative in the malignant cells.

If CD20 is positive in many of the cells, B cell lymphoma unclassified with features intermediate between DLBCL and classical Hodgkin lymphoma should be considered.

The small lymphocytes in the background are T cells and stain with pan T cell antigens.