Pathophysiology and Genetics of Pediatric Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

Cellular Pathophysiology

The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend that the defining pathologic feature of pediatric NLPHL is the presence of lymphocyte-predominant (LP) cells, which are malignant B-cells surrounded by a nodular background of non-neoplastic small B-lymphocytes, with LP cells constituting only a small fraction of the total cellular population within affected lymph nodes, typically representing 0.1-1% of cells 1, 2, 3
LP cells consistently express CD20, CD45, CD79a, BCL6, and PAX-5, which are all B-cell markers, and are uniformly negative for CD15 and CD30, distinguishing them from Reed-Sternberg cells of classical Hodgkin lymphoma 1, 2, 4, 5

The National Comprehensive Cancer Network recommends that CD3 is negative, confirming B-cell rather than T-cell lineage, and that the immunophenotype of LP cells is pathognomonic and critical for diagnosis 6

The National Comprehensive Cancer Network states that LP cells are clonal B-cells that harbor immunoglobulin heavy chain variable region (IGHV) gene rearrangements, confirming their origin from a single transformed germinal center B-cell, and that polymerase chain reaction (PCR) for IGHV gene rearrangements can establish clonality when diagnosis is uncertain 7
BCL6 expression in LP cells indicates active germinal center B-cell programming, which normally regulates B-cell differentiation 5

The American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend that excisional lymph node biopsy is mandatory to provide adequate tissue for architectural assessment and immunophenotyping, and that fine-needle aspiration alone is insufficient because the nodular architecture and immunoarchitectural patterns cannot be assessed 1, 2, 6, 7