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Previous Volume 337:453-458 August 14, 1997 Number 7 Next

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ABSTRACT

Background The atypical cells of nodular lymphocyte-predominant Hodgkin's disease, designated lymphocytic and histiocytic (L&H) cells, have a B-cell phenotype. To clarify the clonality of these cells, we studied rearranged immunoglobulin genes for the variable region of the heavy chain (V_H genes) in individual L&H cells from 11 patients with nodular lymphocyte-predominant Hodgkin's disease. We also studied the expression of immunoglobulin light chains by those cells in six of the same patients.

Methods Single CD20+ L&H cells were isolated from frozen sections by a technique of micromanipulation. The rearranged V_H genes of these cells were amplified by the polymerase chain reaction (PCR), sequenced, and compared with germ-line V_H genes. Immunoglobulin light-chain messenger RNA (mRNA) was detected by in situ hybridization.

Results Of 615 L&H cells isolated from all the frozen sections, 160 yielded PCR products. In each of the 11 patients, the L&H cells that could be evaluated had identically rearranged V_H genes, whether they were isolated from the same nodule, different nodules, or different blocks of tissue. All the V_H sequences derived from the L&H cells were highly mutated (7.5 to 27.2 percent). In two cases the coding capacity of the V_H genes was completely or partially disrupted by mutations. Intraclonal diversity was found in six cases, and monotypic immunoglobulin light-chain mRNA was found in six.

Conclusions The L&H cells of nodular lymphocyte-predominant Hodgkin's disease represent a monoclonal expansion of B cells. The high load of V_H gene mutations and signs of intraclonal diversity suggest a relation between L&H cells and germinal-center B cells at the centroblastic stage of differentiation.

Source Information

From the Institute of Pathology, University Hospital Benjamin Franklin, Free University Berlin, and the Consultation and Reference Center for Lymph Node Pathology and Haematopathology, Berlin, Germany (T.M., M.H., I.A., H.-D.F., H.S.); the Institute of Hematology, University of Perugia, Perugia, Italy (B.F.); the Laboratoire Central d'Anatomie–Pathologie, Hôpitaux de Toulouse, Centre Hospitalier Universitaire Purpan, Toulouse, France (G.D.); the Department of Histopathology, University College London Medical School, London (P.G.I.); and the Secondo Servizio di Anatomia Patologica, Sezione di Emolinfopatologia, Università di Bologna, Bologna, Italy (S.P.).

Address reprint requests to Professor Stein at the Institute of Pathology, Benjamin Franklin University Hospital, Free University Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.

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L&H Cells in Lymphocyte-Predominant Hodgkin's Disease
Küppers R., Rajewsky K., Braeuninger A., Hansmann M.-L., Hummel M., Stein H., Marafioti T., Anagnostopoulos I.
Extract | Full Text  
N Engl J Med 1998; 338:763-765, Mar 12, 1998. Correspondence

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