Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare distinct B-cell neoplasm comprising approximately 5% of all Hodgkin lymphomas. The 2022 WHO classification reclassified NLPHL as 'nodular lymphocyte-predominant B-cell lymphoma' (NLPBCL) reflecting its biological similarity to indolent B-cell lymphomas rather than classical Hodgkin lymphoma. The neoplastic cells are lymphocyte-predominant (LP) cells (formerly L&H or popcorn cells) — large B-cells with multilobated nuclei resembling popped popcorn kernels, abundant cytoplasm, single prominent nucleolus — embedded in nodular meshwork of follicular dendritic cells with surrounding small B-cells, T-cells (PD1+ rosettes), and histiocytes.

Immunophenotype distinguishes NLPHL from classical Hodgkin lymphoma: LP cells express CD20+ (strong, all cells), CD45+, CD79a+, BCL6+, EMA+ (50-80%), J chain+, OCT2/BOB1+ strong (transcription factors), and notably NEGATIVE for CD15 and CD30 (the classical HL markers). Surrounding immune environment includes prominent CD3+ CD57+ PD1+ T-cell rosettes around LP cells. Six histological growth patterns described (Fan classification): A (classic nodular), B (serpiginous nodular), C (nodular with prominent extranodular LP cells), D (T-cell rich), E (diffuse with T-cell/histiocyte rich large B-cell lymphoma-like), F (diffuse with B-cell rich pattern). Variant patterns C-F associate with worse prognosis and higher transformation risk.

Epidemiology: incidence 0.1-0.2 per 100,000 per year, male predominance 3:1, bimodal age distribution (peak 30-40 years and second peak 60-70 years). Clinical presentation: localized peripheral lymphadenopathy (cervical, axillary, inguinal), bulky disease uncommon, mediastinal involvement rare (10-15%, contrast to classical HL), B-symptoms uncommon (10-20%), advanced stage uncommon at presentation (60-70% are stage I-II). Splenic involvement in 5-10%. Diagnosis requires excisional biopsy with characteristic LP cell identification and immunohistochemistry. Differential diagnosis: classical Hodgkin lymphoma lymphocyte-rich subtype, T-cell/histiocyte-rich large B-cell lymphoma, follicular lymphoma, reactive follicular hyperplasia. Staging by PET-CT, CT chest/abdomen/pelvis, bone marrow biopsy (low yield), CSF analysis usually not needed. Treatment by stage and risk: limited stage IA without risk factors — involved-site radiotherapy alone (30 Gy) with excellent outcomes (10-year PFS 80-85%); rituximab monotherapy as alternative for selected patients; advanced or unfavorable stage — R-CHOP, R-ABVD, or R-CHVPP regimens for 4-6 cycles with consolidation radiotherapy; relapsed/refractory disease — rituximab retreatment, radiation salvage, autologous stem cell transplantation for transformation. Long-term surveillance important due to risk of late relapses and transformation to aggressive lymphoma. Overall prognosis excellent: 10-year overall survival >90%, but late relapses and transformation possible.