Composite lymphoma of nodular lymphocyte-predominant and classical Hodgkin lymphoma-Epstein-Barr virus association suggests divergent pathogenesis despite clonal relatedness

SummaryNodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma are considered 2 distinct entities whose co-occurrence in 1 patient is extremely rare. We report a case of nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma concurrently affecting the same lymph nodes in a 48-year-old male patient. Amplification and sequencing of the rearranged immunoglobulin heavy chain genes in tumor cells isolated by laser-assisted microdissection revealed identical variable, diverse and joining segment rearrangements and somatic hypermutation events, demonstrating a clonal relationship between the 2 lymphomas. The Epstein-Barr virus-encoded RNA and latent membrane protein 1 were present in the Hodgkin/Reed-Sternberg cells of the classical Hodgkin lymphoma but not in the tumor cells of the nodular lymphocyte-predominant Hodgkin lymphoma, pointing to a common precursor cell but differences in the early steps of pathogenesis.