Gene rearrangement and comparative genomic hybridization studies of classic Hodgkin lymphoma expressing T-cell antigens.
BACKGROUND
Reed-Sternberg cells in classic Hodgkin lymphoma are enigmatic and difficult to study because they are so sparse. Tissue microdissection allows for the isolation of single Reed-Sternberg cells. Isolated Reed-Sternberg cells show clonal immunoglobulin gene rearrangement indicating a B-cell origin. Rarely, Reed-Sternberg cells in classic Hodgkin lymphoma express T-cell antigens, suggesting a possible T-cell origin.


OBJECTIVE
To determine whether there is a difference in genotype between classic Hodgkin lymphoma and classic Hodgkin lymphoma expressing T-cell antigens and to document T-cell clonality.


METHODS
We studied 4 cases of Hodgkin lymphoma with a characteristic phenotype and immunoreactivity for CD2 and CD3. Single CD30+ Reed-Sternberg cells from each case were isolated by laser capture microdissection for immunoglobulin heavy chain and T-cell receptor-gamma genes by polymerase chain reaction studies. Comparative genomic hybridization was performed in all cases.


RESULTS
Two of 4 cases showed clonal rearrangement of the T-cell receptor-gamma; none showed immunoglobulin heavy chain rearrangement. Two control cases were negative for T cell receptor-gamma but 1 showed immunoglobulin heavy chain rearrangement. Comparative genomic hybridization analysis revealed significant overlap in genomic alteration in Hodgkin lymphoma cases regardless of genotype or phenotype and several regions of imbalance specific to CD3+ Hodgkin lymphoma cases. All patients are alive with no evidence of disease from 10 to 44 months.


CONCLUSIONS
Our findings suggest that a T-cell phenotype classic Hodgkin lymphoma can be supported by genotypic studies and that there may be cytogenetic differences between classic Hodgkin lymphoma and Hodgkin lymphoma expressing T-cell antigens.
Aguilera
Nadine S I
NS
Department of Hematopathology, Armed Forces Institute of Pathology, 6825 16th St, NW, Bldg 54, Room 2051, Washington, DC 20306-6000, USA. aguilera@afip.osd.mil
Chen
Jian
J
Bijwaard
Karen E
KE
Director-Myska
Alison E
AE
Barekman
Carol L
CL
Millward
Carl
C
Lichy
Jack
J
Abbondanzo
Susan L
SL
D000293:Adolescent; D000328:Adult; D002999:Clone Cells; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics*; D005838:Genotype; D006689:Hodgkin Disease / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D008198:Lymph Nodes / Q000473:pathology; D042282:Microdissection; D009693:Nucleic Acid Hybridization / Q000379:methods*; D016539:Reed-Sternberg Cells / Q000276:immunology* / Q000473:pathology