Immunoglobulin gene rearrangement analysis in cerebrospinal fluid of patients with lymphoproliferative processes.
OBJECTIVE
To determine the sensitivity and specificity of clonal immunoglobulin heavy chain gene rearrangement (IGHR) analysis in the distinction of benign and malignant lymphoproliferative diseases.


METHODS
A retrospective analysis was conducted of patients in whom a malignant lymphoproliferative process was suspected. Cells of CSF samples were collected by centrifugation, resuspended in 100 microl of the supernatant and boiled. A 10 microl aliquot of this lysate served as template for semi-nested polymerase chain reaction using variable and joining region consensus primers. PCR products were analyzed by polyacrylamide gel electrophoresis. Cytopathological diagnosis and flow cytometry results were recorded. Sensitivity and specificity of IGHR analysis, cytopathology and flow cytometry were calculated.


RESULTS
Eleven patients (12 specimens) had involvement of leptomeninges at the time of lumbar puncture. Another 25 cases (27 specimens) had normal CSF findings or were diagnosed with benign lymphoproliferative conditions. Sensitivity of CSF cytopathology, flow cytometry and IGHR analysis were 0.27 [95% confidence interval 0.06, 0.61], 0.1 [0.003, 0.45] and 0.58 [0.28, 0.85]. Specificity was 1 [0.86, 1], 0.95 [0.77, 1.0] and 0.85 [0.66, 0.96].


CONCLUSIONS
IGHR analysis appears to be a useful addition to morphological and flow cytometry analysis of cerebrospinal fluid in the evaluation of CNS lymphoproliferative processes.
Baehring
Joachim M
JM
Pappas Center for Neuro-Oncology, Yawkey 9E, Massachusetts General Hospital, Boston, MA 02114, USA. joachim.baehring@yale.edu
Hochberg
Fred H
FH
Betensky
Rebecca A
RA
Longtine
Janina
J
Sklar
Jeffrey
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D023061:Gene Order; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000134:cerebrospinal fluid* / Q000235:genetics; D007136:Immunoglobulins / Q000134:cerebrospinal fluid / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000134:cerebrospinal fluid / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; D012333:RNA, Messenger