FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 340:1239-1247 April 22, 1999 Number 16 Next

	Full Text PDF Editorial by Manis, J. P Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed–Sternberg cells originate from B cells.

Methods We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell–rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed–Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced.

Results In both patients, the Reed–Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed–Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type.

Conclusions In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed–Sternberg cells in classic Hodgkin's disease.

Source Information

From the Department of Pathology, University of Frankfurt, Frankfurt am Main, Germany (A.B., M.-L.H.); the Department of Pathology, Mayo Clinic, Rochester, Minn. (J.G.S.); the Department of Dermatology, Universitätsspital Zürich, Zurich, Switzerland (R.D., G.B.); and the Institute for Genetics, University of Cologne, Cologne, Germany (K.R., R.K.).

Address reprint requests to Dr. Küppers at the University of Cologne, University Hospital, LFI E4 R706, Joseph-Stelzmannstr. 9, 50931 Cologne, Germany, or at rkuppers{at}mac.genetik.uni-koeln.de.

Full Text of this Article

Related Letters:

A Common B-Cell Precursor in Composite Lymphomas
Kerl K., Girardet C., Borisch B.
Extract | Full Text  
N Engl J Med 1999; 341:764-765, Sep 2, 1999. Correspondence

This article has been cited by other articles:

• Steinhoff, M, Assaf, C, Anagnostopoulos, I, Geilen, C C, Stein, H, Hummel, M (2006). Three coexisting lymphomas in one patient: genetically related or only a coincidence?. J. Clin. Pathol. 59: 1312-1315 [Abstract] [Full Text]  
• Abramson, J. S. (2006). T-cell/histiocyte-rich B-cell lymphoma: biology, diagnosis, and management.. The Oncologist 11: 384-392 [Abstract] [Full Text]  
• Re, D., Kuppers, R., Diehl, V. (2005). Molecular Pathogenesis of Hodgkin's Lymphoma. JCO 23: 6379-6386 [Abstract] [Full Text]  
• Renne, C., Willenbrock, K., Kuppers, R., Hansmann, M.-L., Brauninger, A. (2005). Autocrine- and paracrine-activated receptor tyrosine kinases in classic Hodgkin lymphoma. Blood 105: 4051-4059 [Abstract] [Full Text]  
• Straus, D. J., Portlock, C. S., Qin, J., Myers, J., Zelenetz, A. D., Moskowitz, C., Noy, A., Goy, A., Yahalom, J. (2004). Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Blood 104: 3483-3489 [Abstract] [Full Text]  
• Savage, K. J., Monti, S., Kutok, J. L., Cattoretti, G., Neuberg, D., de Leval, L., Kurtin, P., Cin, P. D., Ladd, C., Feuerhake, F., Aguiar, R. C. T., Li, S., Salles, G., Berger, F., Jing, W., Pinkus, G. S., Habermann, T., Dalla-Favera, R., Harris, N. L., Aster, J. C., Golub, T. R., Shipp, M. A. (2003). The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 102: 3871-3879 [Abstract] [Full Text]  
• Wlodarska, I., Nooyen, P., Maes, B., Martin-Subero, J. I., Siebert, R., Pauwels, P., De Wolf-Peeters, C., Hagemeijer, A. (2003). Frequent occurrence of BCL6 rearrangements in nodular lymphocyte predominance Hodgkin lymphoma but not in classical Hodgkin lymphoma. Blood 101: 706-710 [Abstract] [Full Text]  
• Franke, S., Wlodarska, I., Maes, B., Vandenberghe, P., Achten, R., Hagemeijer, A., De Wolf-Peeters, C. (2002). Comparative Genomic Hybridization Pattern Distinguishes T-Cell/Histiocyte-Rich B-Cell Lymphoma from Nodular Lymphocyte Predominance Hodgkin's Lymphoma. Am. J. Pathol. 161: 1861-1867 [Abstract] [Full Text]  
• Bosshart, H., Ansell, S. M., Jelinek, D. F., Wettstein, P. J., Witzig, T. E. (2002). T Helper Cell Activation in B-Cell Lymphomas. JCO 20: 2904-2905 [Full Text]  
• Jundt, F., Anagnostopoulos, I., Forster, R., Mathas, S., Stein, H., Dorken, B. (2002). Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood 99: 3398-3403 [Abstract] [Full Text]  
• Pileri, S A, Ascani, S, Leoncini, L, Sabattini, E, Zinzani, P L, Piccaluga, P P, Pileri, A Jr, Giunti, M, Falini, B, Bolis, G B, Stein, H (2002). Hodgkin's lymphoma: the pathologist's viewpoint. J. Clin. Pathol. 55: 162-176 [Abstract] [Full Text]  
• Xu, Y, Wiernik, P H (2001). Systemic lupus erythematosus and B-cell hematologic neoplasm. Lupus 10: 841-850 [Abstract]  
• Brauninger, A., Spieker, T., Willenbrock, K., Gaulard, P., Wacker, H.-H., Rajewsky, K., Hansmann, M.-L., Kuppers, R. (2001). Survival and Clonal Expansion of Mutating "Forbidden" (Immunoglobulin Receptor-Deficient) Epstein-Barr Virus-Infected B Cells in Angioimmunoblastic T Cell Lymphoma. JEM 194: 927-940 [Abstract] [Full Text]  
• Seitz, V., Hummel, M., Anagnostopoulos, I., Stein, H. (2001). Analysis of BCL-6 mutations in classic Hodgkin disease of the B- and T-cell type. Blood 97: 2401-2405 [Abstract] [Full Text]  
• Frisch, M., Biggar, R. J., Engels, E. A., Goedert, J. J., for the AIDS-Cancer Match Registry Study Group, (2001). Association of Cancer With AIDS-Related Immunosuppression in Adults. JAMA 285: 1736-1745 [Abstract] [Full Text]  
• Franke, S., Wlodarska, I., Maes, B., Vandenberghe, P., Delabie, J., Hagemeijer, A., De Wolf-Peeters, C. (2001). Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic imbalances. Blood 97: 1845-1853 [Abstract] [Full Text]  
• Kuppers, R., Brauninger, A., Muschen, M., Distler, V., Hansmann, M.-L., Rajewsky, K. (2001). Evidence that Hodgkin and Reed-Sternberg cells in Hodgkin disease do not represent cell fusions. Blood 97: 818-821 [Abstract] [Full Text]  
• Stein, H., Marafioti, T., Foss, H.-D., Laumen, H., Hummel, M., Anagnostopoulos, I., Wirth, T., Demel, G., Falini, B. (2001). Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription. Blood 97: 496-501 [Abstract] [Full Text]  
• Spieker, T., Kurth, J., Kuppers, R., Rajewsky, K., Brauninger, A., Hansmann, M.-L. (2000). Molecular single-cell analysis of the clonal relationship of small Epstein-Barr virus-infected cells and Epstein-Barr virus-harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease. Blood 96: 3133-3138 [Abstract] [Full Text]  
• Shimodaira, S., Hidaka, E., Katsuyama, T. (2000). Clonal Identity of Nodular Lymphocyte-Predominant Hodgkin's Disease and T-Cell-Rich B-Cell Lymphoma. NEJM 343: 1124-1125 [Full Text]  
• Falini, B., Fizzotti, M., Pucciarini, A., Bigerna, B., Marafioti, T., Gambacorta, M., Pacini, R., Alunni, C., Natali-Tanci, L., Ugolini, B., Sebastiani, C., Cattoretti, G., Pileri, S., Dalla-Favera, R., Stein, H. (2000). A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood 95: 2084-2092 [Abstract] [Full Text]  
• Kanzler, H., Kuppers, R., Helmes, S., Wacker, H.-H., Chott, A., Hansmann, M.-L., Rajewsky, K. (2000). Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and Reed-Sternberg cells in Hodgkin's disease. Blood 95: 1023-1031 [Abstract] [Full Text]  
• Muschen, M., Rajewsky, K., Brauninger, A., Baur, A. S., Oudejans, J. J., Roers, A., Hansmann, M.-L., Kuppers, R. (2000). Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma. JEM 191: 387-394 [Abstract] [Full Text]  
• Staudt, L. M. (2000). The Molecular and Cellular Origins of Hodgkin's Disease. JEM 191: 207-212 [Full Text]  
• Kuppers, R., Klein, U., Hansmann, M.-L., Rajewsky, K. (1999). Cellular Origin of Human B-Cell Lymphomas. NEJM 341: 1520-1529 [Full Text]  
• Gopal, A. K., Schuetze, S. M., Maloney, D. G., Weiden, P. L. (1999). Large Cell Non-Hodgkin's Lymphoma and Hodgkin's Disease Arising Synchronously in a Patient With Chronic Lymphocytic Leukemia: Importance of Immunocytochemistry. Blood 94: 2537-2537 [Full Text]  
• Kerl, K., Girardet, C., Borisch, B. (1999). A Common B-Cell Precursor in Composite Lymphomas. NEJM 341: 764-765 [Full Text]  
• Kamel, O. W. (1999). Unraveling the Mystery of the Lymphoid Follicle. Am. J. Pathol. 155: 681-682 [Full Text]  
• Montesinos-Rongen, M., Roers, A., Kuppers, R., Rajewsky, K., Hansmann, M.-L. (1999). Mutation of the p53 Gene Is Not a Typical Feature of Hodgkin and Reed-Sternberg Cells in Hodgkin's Disease. Blood 94: 1755-1760 [Abstract] [Full Text]  
• Manis, J. P (1999). Precursors of Hodgkin's Disease and B-Cell Lymphomas. NEJM 340: 1280-1282 [Full Text]