Correspondence

A Common B-Cell Precursor in Composite Lymphomas

N Engl J Med 1999; 341:764-765September 2, 1999

Article

To the Editor:

Bräuninger et al. (April 22 issue)1 identified a common germinal-center B-cell precursor for both Reed–Sternberg cells and non-Hodgkin's lymphoma cells in two patients with composite lymphoma. We studied five patients who had classic composite lymphoma with features of Hodgkin's disease and non-Hodgkin's lymphoma in the same lymph node to determine whether the two neoplasms were clonally related.

One patient presented with a combination of nodular-sclerosis Hodgkin's disease and a high-grade B-cell lymphoma; the others had mixed-cellularity Hodgkin's disease and low-grade B-cell lymphoma. Single cells were isolated from formalin-fixed, paraffin-embedded sections after immunohistochemical staining for CD20, CD15, CD30, and CD3. The cells of interest were isolated by destroying the surrounding tissue with an ultraviolet laser and removed with a computer-assisted micromanipulator. The isolated cells were then submitted to seminested polymerase-chain-reaction amplification of IgH gene rearrangement with primers LJH and FR3A for the first round, followed by a second reaction with primers VLJH and FR3A. The use of paraffin-embedded tissue allows better examination of morphologic features than does the use of frozen sections. Moreover, DNA amplification of single cells isolated from routinely embedded and stained sections has been shown to be comparable to that of fresh-frozen, microdissected cells in terms of sensitivity (unpublished data).

We amplified clonal IgH gene rearrangements in cells from four of the five patients (Table 1Table 1Characteristics of Five Patients with Composite Lymphoma.). In Patients 1 and 2, we obtained identical clones from the Reed–Sternberg cells and the non-Hodgkin's lymphoma cells, suggesting that a single B cell was the precursor of both neoplastic components and supporting the hypothesis of a shared precursor that underwent neoplastic transformation. Patients 3 and 5 had different clonal rearrangements for the two neoplastic components, suggesting that they were clonally unrelated. We do not think that this result is due to therapy, as proposed by Bräuninger et al.,1 because the Hodgkin's disease and the non-Hodgkin's lymphoma occurred simultaneously. Finally, in Patient 4, we could not detect a clonal amplification product of the Reed–Sternberg cells. This result could be due to a high number of somatic hypermutations in the primer binding sequences.

In conclusion, we believe it unlikely that composite B-cell lymphomas invariably have a single precursor, since other, even non–germinal-center B cells, may take part in the genesis of composite lymphomas.

Katrin Kerl, M.D.
Christophe Girardet, M.D.
Bettina Borisch, M.D.
University of Geneva School of Medicine, CH-1211 Geneva, Switzerland

1 References

1. 1

   Brauninger A, Hansmann M-L, Strickler JG, et al. Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma. N Engl J Med 1999;340:1239-1247
   Full Text | Web of Science | Medline

Citing Articles (6)

Citing Articles

1. 1

   H. ELMAHY, I. HAWLEY, J. BEARD. (2007) Composite splenic marginal zone lymphoma and classic Hodgkin lymphoma – an unusual combination. International Journal of Laboratory Hematology 29:6, 461-463
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2. 2

   A Zettl, T Rudiger, A Marx, H K Muller-Hermelink, G Ott. (2005) Composite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases. Histopathology 46:2, 217-228
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3. 3

   Massimo Libra, Valli De Re, Annunziata Gloghini, Patrick Michael Navolanic, Antonino Carbone, Mauro Boiocchi. (2004) Second Primary Lymphoma or Recurrence: A Dilemma Solved by VDJ Rearrangement Analysis. Leukemia & Lymphoma 45:8, 1539-1543
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   Roman K Thomas, Claudia Wickenhauser, Dieter Kube, Hans Tesch, Volker Diehl, Jürgen Wolf, Martina Vockerodt. (2004) Repeated Clonal Relapses in Classical Hodgkin's Lymphoma and the Occurrence of a Clonally Unrelated Diffuse Large B Cell Non-Hodgkin Lymphoma in the Same Patient. Leukemia & Lymphoma 45:5, 1065-1069
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   Alessia Caleo, Abel S??nchez-Aguilera, Sandra Rodr??guez, Ana M. Dotor, Luis Beltr??n, Aitor F. de Larrinoa, Francisco J. Men??rguez, Miguel A. Piris, Juan F. Garc??a. (2003) Composite Hodgkin Lymphoma and Mantle Cell Lymphoma. The American Journal of Surgical Pathology 27:12, 1577-1580
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   Cristiana Bellan, Stefano Lazzi, Maurizio Zazzi, Anna Vittoria Lalinga, Nazareno Palummo, Piero Galieni, Teresa Marafioti, Tiziana Tonini, Caterina Cinti, Lorenzo Leoncini, Stefano A. Pileri, Piero Tosi. (2002) Immunoglobulin Gene Rearrangement Analysis in Composite Hodgkin Disease and Large B-Cell Lymphoma: Evidence for Receptor Revision of Immunoglobulin Heavy Chain Variable Region Genes in Hodgkin-Reed-Sternberg Cells?. Diagnostic Molecular Pathology 11:1, 2-8
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