Can polymerase chain reaction help distinguish benign from malignant lymphoid aggregates in bone marrow aspirates?

Objective.-Although morphologic and immunologic clues are helpful in distin guishing benign from malignant lymphoid aggregates in bone marrow biopsies, there remain some cases in which it is not possible to arrive at a definit ive diagnosis. Since the malignant aggregates are monoclonal B-cell prolife rations, we sought to determine whether performing polymerase chain reactio n for the immunoglobulin heavy-chain locus would be helpful in distinguishi ng these 2 entities. Methods and Results.-Scrapings from unstained bone marrow aspirate smears o r touch preparations of bone marrow biopsies from 15 patients with benign b one marrow lymphoid aggregates and 18 patients with malignant lymphoid infi ltrates were analyzed for rearrangements of the FR3 region of the immunoglo bulin heavy-chain gene locus by a heminested polymerase chain reaction proc edure. All specimens had amplifiable DNA, as shown by amplification of the ras proto-oncogene. None of the 15 cases of benign bone marrow lymphoid agg regates demonstrated clonality upon amplification of the immunoglobulin hea vy-chain gene locus. In contrast, 8 of the 18 malignant samples were positi ve (P = .01 by chi(2) test; sensitivity, 44%; specificity, 100%; positive p redictive value, 100%; negative predictive value, 60%). There was a tendenc y for there to be more lymphocytes in stained bone marrow aspirate smears f rom the cases of malignant lymphoid aggregates with a positive polymerase c hain reaction result than in those without demonstrable clonality (36.0 +/- 35.4% vs 9.8 +/- 8.0%, P = .13). Conclusions.-Polymerase chain reaction for the immunoglobulin heavy-chain g ene locus may help distinguish benign from malignant bone marrow lymphoid a ggregates. Although the presence of false-negative samples may be related t o the relative lack of lymphocytes in the bone marrow aspirates, other fact ors, such as the lack of amplification of the FR3 region of the immunoglobu lin heavy-chain gene locus in particular tumors, cannot be ruled out with c ertainty.