This is an uncommon classical Hodgkin lymphoma variant (5% of CHL), which is characterized by a predominant reactive lymphocyte infiltrate without significant histiocytes, plasma cells, and eosinophils that are characteristic of the mixed-cellularity variant.  The difficult differential diagnosis is separating this entity from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) as both usually have a nodular pattern.  Prior to good immunohistochemical characterization many cases of lymphocyte-rich and NLPHL were misclassified.  EBV infection is present in approximately 40% of cases.  The immunophenotype of lymphocyte-rich Hodgkin lymphoma is the same is other classical Hodgkin lymphomas.  

 

The immunophenotype combined with identification of Reed-Sternberg cells is the main way to differentiate from nodular lymphocyte predominant Hodgkin lymphoma.  CD21 (follicular dendritic marker) is helpful to highlight the nodules (which contain the neoplastic cells) and small/regressed germinal centers usually at the periphery of the nodules (do not contain the neoplastic cells).  Historically, 30% of cases were misclassified (NLPHL vs. LRCHL), and cannot be reliably differentiated without immunohistochemistry.

 

Characteristic Immunohistochemical Features

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References