SENSITIVITY OF PCR IN DETECTING MONOCLONAL B-CELL PROLIFERATIONS

Aims-To evaluate the rapid detection of various forms of monoclonal B cell proliferations by using the polymerase chain reaction (PCR) to id entify clonal immunoglobulin heavy chain genomic rearrangements. Metho ds-Thirty four B cell lymphomas defined by morphology, immunophenotypi ng, and positive immunoglobulin heavy chain gene rearrangements detect ed by Southern blot analysis were examined. An additional 22 cases rep resenting miscellaneous lymphoproliferative and non-lymphoproliferativ e disorders were also studied. Results-Monoclonal rearrangements were identified in 19 (56%) cases of B cell lymphoma. The method was less s ensitive in the detection of follicular centre cell lymphomas (15 of 2 8, or 54%) than non-follicular centre cell lesions (four of six, or 67 %). Monoclonal rearrangement was not identified in 19 control cases, i ncluding T cell lymphomas, Hodgkin's disease, reactive lymphadenopathy and metastatic carcinoma. Three cases showed positive immunoglobulin gene rearrangement by PCR but were negative on Southern blotting. Two of these cases had definite clinical, morphological, and immunophenoty pic evidence of monoclonal B cell proliferation suggesting that PCR co uld, on occasion, pick up cases missed by Southern blotting and that t he two methods are complementary in clonal lymphoproliferative disease diagnosis. The third case represented a ''false positive'' PCR reacti on involving a colonic adenocarcinoma. Conclusions-PCR analysis, using the primer sequences outlined in this study, will detect about 55% of clonal lymphoproliferative proliferations with increased sensitivity for non-follicular centre cell lesions. With these levels of detection in mind, this testing strategy can still be especially useful in case s which prove diagnostically problematic with standard morphological a nd immunophenotypic analysis, and in instances where the quantity and type of diagnostic material is limiting (needle aspirates and cellular fluids).