Classical Hodgkin's disease and follicular lymphoma originating from the same germinal center B cell.
OBJECTIVE
Classical Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. To clarify whether these different diseases share a common precursor cell, we analyzed the immunoglobulin rearrangements in tumor cells of the classical Hodgkin's disease and the follicular lymphoma that developed in the same patient 2 years apart.


METHODS
Polymerase chain reaction (PCR) for the detection of rearranged immunoglobulin genes was carried out on single Reed-Sternberg cells and on whole tissue DNA extracted from the follicular lymphoma. PCR products were sequenced and compared with each other and with germ line immunoglobulin variable segments. Immunoglobulin heavy- and light-chain transcripts were analyzed by radioactive in-situ hybridization.


RESULTS
The same monoclonal immunoglobulin gene rearrangement was found in both neoplasms. The variable region of the immunoglobulin heavy-chain genes of the Reed-Sternberg and of the follicular lymphoma cells were differently mutated, but six somatic mutations were shared by both lymphoma cells. Although the coding capacity of the immunoglobulin genes was preserved in both neoplastic cell populations, immunoglobulin heavy- (mu) and light- (kappa) chain expression was restricted to the follicular lymphoma cells, except for small amounts of kappa light-chain mRNA in some Reed-Sternberg cells.


CONCLUSIONS
The neoplastic cells of the Hodgkin's disease and the follicular lymphoma that occurred in this patient derived from a common precursor B cell. Its differentiation stage could be identified as that of a germinal center B cell. Thus, transforming events can be more important than the cell of origin in determining a disease entity.
Marafioti
T
T
Institute of Pathology and Consultation and Reference Center for Lymph Node Pathology and Haematopathology, University Hospital Benjamin Franklin, Free University Berlin, Germany.
Hummel
M
M
Anagnostopoulos
I
I
Foss
H D
HD
Huhn
D
D
Stein
H
H
D000328:Adult; D001402:B-Lymphocytes / Q000473:pathology*; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000032:analysis; D015322:Gene Rearrangement, B-Lymphocyte; D005838:Genotype; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
D004273:DNA, Neoplasm; D007136:Immunoglobulins