Specificity of PCR-based clonality analysis of immunoglobulin heavy chain gene rearrangements for the detection of bone marrow involvement by low-grade B-cell lymphomas
✍ Scribed by Brinckmann, Roland; Kaufmann, Olaf; Reinartz, Barbara; Dietel, Manfred
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 223 KB
- Volume
- 190
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
A study was performed to investigate the utility of polymerase chain reaction (PCR)-based analysis of immunoglobulin heavy chain (IgH) gene rearrangements for the diagnosis of low-grade malignant B-cell lymphomas on formalin-®xed, EDTA-decalci®ed, and paraf®n-embedded bone marrow trephine biopsies. On amplifying two DNA samples per biopsy, no reproducible monoclonal PCR result was found in 32 patients with reactive lymphoid hyperplasias. In contrast, 5/14 patients with known low-grade B-cell lymphomas, but histomorphologically and immunohistochemically lymphoma-free bone marrow, showed a reproducible monoclonal IgH gene rearrangement. In three of these cases, sequence analysis revealed completely different ampli®cation products on comparing bone marrow and lymph node in®ltrations, while in the other two cases the products were identical. In one of the latter biopsies, an unequivocal lymphoma in®ltrate was found after step sectioning of the biopsy, while the other case remained lymphoma-free according to conventional criteria. A third group of three patients with known lymphomas and bone marrow ®ndings that were suggestive but not diagnostic of bone marrow involvement showed monoclonal PCR results in all three cases, with identical sequences in bone marrow and extramedullary lymphoma in®ltrates. These data suggest that a reproducible monoclonal IgH gene rearrangement is highly speci®c for the presence of malignant B-cells in bone marrow. In staging procedures for low-grade B-cell lymphomas, PCR yields no additional information in cases that are morphologically and immunohistochemically lymphoma-free after evaluation of representative sections. PCR may be useful in equivocal cases, provided that IgH gene rearrangements of extramedullary lymphoma and bone marrow are sequenced and compared.