Can polymerase chain reaction help distinguish benign from malignant lymphoid aggregates in bone marrow aspirates?
OBJECTIVE
Although morphologic and immunologic clues are helpful in distinguishing benign from malignant lymphoid aggregates in bone marrow biopsies, there remain some cases in which it is not possible to arrive at a definitive diagnosis. Since the malignant aggregates are monoclonal B-cell proliferations, we sought to determine whether performing polymerase chain reaction for the immunoglobulin heavy-chain locus would be helpful in distinguishing these 2 entities.


RESULTS
Scrapings from unstained bone marrow aspirate smears or touch preparations of bone marrow biopsies from 15 patients with benign bone marrow lymphoid aggregates and 18 patients with malignant lymphoid infiltrates were analyzed for rearrangements of the FR3 region of the immunoglobulin heavy-chain gene locus by a heminested polymerase chain reaction procedure. All specimens had amplifiable DNA, as shown by amplification of the ras proto-oncogene. None of the 15 cases of benign bone marrow lymphoid aggregates demonstrated clonality upon amplification of the immunoglobulin heavy-chain gene locus. In contrast, 8 of the 18 malignant samples were positive (P =.01 by chi(2) test; sensitivity, 44%; specificity, 100%; positive predictive value, 100%; negative predictive value, 60%). There was a tendency for there to be more lymphocytes in stained bone marrow aspirate smears from the cases of malignant lymphoid aggregates with a positive polymerase chain 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 gene locus may help distinguish benign from malignant bone marrow lymphoid aggregates. Although the presence of false-negative samples may be related to the relative lack of lymphocytes in the bone marrow aspirates, other factors, such as the lack of amplification of the FR3 region of the immunoglobulin heavy-chain gene locus in particular tumors, cannot be ruled out with certainty.
Ben-Ezra
J
J
Department of Pathology, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA 23298-0250, USA.
Hazelgrove
K
K
Ferreira-Gonzalez
A
A
Garrett
C T
CT
D001706:Biopsy; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D005335:Fever of Unknown Origin / Q000473:pathology; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D015658:HIV Infections / Q000473:pathology; D006801:Humans; D006942:Hypergammaglobulinemia / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology*; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000473:pathology; D009369:Neoplasms / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods*; D000090063:Proto-Oncogene Mas; D013921:Thrombocytopenia / Q000473:pathology