Nodular Lymphocyte Predominance Hodgkin's Disease: A Monoclonal or Polyclonal B-Cell Disorder?

• Published in: Blood 1996-03, Vol.87 (6), p.2428-2434
• Main Authors: Pan, L.X., Diss, T.C., Peng, H.Z., Norton, A.J., Isaacson, P.G.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - genetics; B-Lymphocyte Subsets - pathology; Base Sequence; Biological and medical sciences; Cell Lineage; Clone Cells - pathology; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Genes, Immunoglobulin; Hematologic and hematopoietic diseases; Hodgkin Disease - classification; Hodgkin Disease - genetics; Hodgkin Disease - pathology; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - pathology; Lymphoma, Non-Hodgkin - genetics; Lymphoma, Non-Hodgkin - pathology; Medical sciences; Molecular Sequence Data; Neoplasm Proteins - genetics; Neoplasms, Second Primary - genetics; Neoplasms, Second Primary - pathology; Neoplastic Stem Cells - pathology; Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V87.6.2428.bloodjournal8762428

Nodular lymphocyte predominance Hodgkin's disease (NLPHD) is characterized by the presence of atypical putatively neoplastic cells (L & H cells) with a B-cell phenotype. A proportion of patients with NLPHD develop a simultaneous or subsequent large cell B lymphoma (LCD that is thought to evolve directly from the L & H cells of NLPHD. However, the clonal nature of L & H cells remains controversial, and the relationship between NLPHD and complicating LCL has not been fully established. In an attempl to determine the clonality of L & H cells and to clarify the link between NLPHD and complicating LCL, we used polymerase chain reaction (PCR) to analyze 33 cases of NLPHD, including 15 cases with simultaneous or subsequent LCL, for clonal immunoglobulin (Ig) heavy chain variable region (VH) gene rearrangements. PCR amplifications with consensus primers covering framework 2 or framework 3 to joining region were performed on paraffin-embedded tissue sections and, in 12 cases, on microdissection-enriched L & H cells. No clonal Ig rearrangements were detected. In eight of the 15 LCL, monoclonal IgVH regions were amplified, four of which were cloned and sequenced. Clone specific primers were designed based on the unique N region sequences. These allowed detection of LCL clones at a sensitivity up to 1,000 times greater than the consensus primers, as determined by dilution assays. However, no LCL clones were detected in the preceding NLPHD, including microdissection-enriched L & H cells. Our results suggest that populations of L & H cells do not carry monoclonal Ig rearrangements and provide no evidence for a clonal link between NLPHD and complicating LCL.