Common germinal-center B-cell origin of the malignant cells in two composite lymphomas, involving classical Hodgkin's disease and either follicular lymphoma or B-CLL.
BACKGROUND
Classical Hodgkin's disease (HD) and B-cell non-Hodgkin lymphoma (NHL) occasionally occur in the same patient. Such composite lymphomas represent interesting models to study the pathogenesis of B-cell lymphomas and the relationship between HD and B-cell NHL.


METHODS
We analyzed two composite lymphomas (a combination of classical HD with follicular lymphoma [FL] and a combination of classical HD with B-cell chronic lymphocytic leukemia [B-CLL]) by micromanipulation of single cells from tissue sections and amplification of immunoglobulin V region genes for the clonal relationship of the tumor cells.


RESULTS
In both cases, clonally related variable (V) genes with both shared as well as distinct somatic mutations were obtained from the two lymphomas, showing that in each of the cases the distinct tumor cells were members of a common germinal center (GC) B-cell clone. FL cells from two different lymph nodes of patient 1 showed a similar mutation pattern, suggesting that infiltration of these lymph nodes by tumor cells was not restricted to a particular FL cell or subclone. In the FL, a single cell was identified with a mutation signature indicating that premalignant cells can persist in the tissue.


CONCLUSIONS
The cases presented here further underline the close relationship between HD and B-cell NHL and the role of the GC in lymphomagenesis. Whereas the latter was already suggested for FL and HD, the present study indicates that also in the B-CLL subset characterized by mutated Ig genes, important steps in malignant transformation happen in the GC, and that HRS cells can derive from CD5-positive B cells.
Küppers
R
R
Institute for Genetics, University of Cologne, Germany. rkuppers@mac.genetik.uni-koeln.de
Sousa
A B
AB
Baur
A S
AS
Strickler
J G
JG
Rajewsky
K
K
Hansmann
M L
ML
D000368:Aged; D000369:Aged, 80 and over; D019070:Cell Lineage; D002999:Clone Cells; D017809:Fatal Outcome; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin / Q000235:genetics; D018858:Germinal Center / Q000276:immunology / Q000473:pathology*; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007150:Immunohistochemistry; D016130:Immunophenotyping; D015448:Leukemia, B-Cell / Q000235:genetics / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000473:pathology*; D016133:Polymerase Chain Reaction; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000473:pathology
D007135:Immunoglobulin Variable Region