Nodular lymphocyte-predominant Hodgkin lymphoma

NLPHL accounts for approximately 5% of Hodgkin lymphoma cases and has a distinct pathologic, immunophenotypic, and clinical profile compared to classical Hodgkin lymphoma (cHL). Pathology shows a nodular growth pattern with scattered 'popcorn cells' (also called LP cells or L&H cells) within a background of reactive B-cells, T-cells, and follicular dendritic cell meshworks—distinct from the inflammatory milieu of classical Reed-Sternberg cells. Immunophenotypically, popcorn cells are CD20+, CD79a+, BCL6+, OCT2+, and typically negative for CD15 and CD30 (unlike classical RS cells), reflecting a germinal center B-cell origin. Clinically, NLPHL most often affects men in their 30s-50s, presenting with asymptomatic peripheral (often cervical or axillary) lymphadenopathy; B symptoms and mediastinal involvement are uncommon. The disease has an indolent, relapsing-remitting course with excellent long-term survival, though late relapses can occur. A rare but important complication is transformation to diffuse large B-cell lymphoma (DLBCL), occurring in up to 3-5% of cases, which carries a worse prognosis and requires more aggressive therapy. Treatment for early-stage disease often involves radiation therapy alone or combined modality therapy; rituximab (anti-CD20) may be used given CD20 positivity, distinguishing it from classical HL where rituximab is not standard. Staging follows the Ann Arbor system. On boards, NLPHL is a classic distractor from classical HL--key differentiators are: CD20+/CD15-/CD30- popcorn cells vs CD15+/CD30+ Reed-Sternberg cells with CD20 typically negative, nodular vs diffuse/mixed pattern, and absence of significant inflammatory background cells (eosinophils, plasma cells) seen in classical HL.