Nodular Lymphocyte-predominant Hodgkin Lymphoma: Incidence, Pathogenesis, Management

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma subtype, representing a small fraction of Hodgkin lymphoma or an even smaller fraction of B-cell non-Hodgkin lymphoma, depending on the classification schema used. NLPHL is characterized by rare lymphocyte-predominant (LP) cells interspersed within a complex immunologic architecture. NLPHL immunoarchitecture has led to hypothesis-driven research suggesting the pathogenesis of NLPHL may be driven by aberrant immune responses to commensal microorganisms, including Moraxella catarrhalis and Rothia mucilaginosa. NLPHL commonly presents in younger adults with asymptomatic lymphadenopathy in early stages. Although late relapses are a well-known feature of this disease, the prognosis is outstanding, nearly mirroring the average life expectancy in Western populations. Management options must carefully weigh the benefits of treatment against the risks of long-term toxicities, including end-organ damage and secondary malignancies. Options utilizing least-toxic approaches include active surveillance, radiation therapy, and combination chemoimmunotherapy for higher-risk presentations. A recent prognostic score, the LP-IPS, derived from large multicenter datasets, may help personalize approaches for patients at higher risk of morbidity/mortality requiring therapy and identify lower-risk patients for active surveillance or low-toxicity approaches.