Evaluation of B cell lymphoid infiltrates in bone marrow biopsies by morphology, immunohistochemistry, and molecular analysis

B Maes¹, R Achten¹, A Demunter¹, B Peeters², G Verhoef³, C De Wolf-Peeters¹

¹ Department of Pathology, University Hospital of Leuven, Minderbroedersstraat 12, 3000 Leuven, Belgium
² Department of Biochemistry, University Hospital of Leuven
³ Department of Haematology, University Hospital of Leuven

Correspondence to:
Dr Maes, Laboratory for Histochemistry and Cytochemistry, Minderbroedersstraat 12, 3000 Leuven, Belgium Brigitte.Maes{at}uz.kuleuven.ac.be

Aims—Morphological criteria to distinguish between reactive and neoplastic B cell lymphocytoid infiltrates in trephines have been defined but are not always reliable. Polymerase chain reaction (PCR) analysis of the CDR3 region of the immunoglobulin heavy chain (IgH) gene which, by demonstrating monoclonality, can provide additional arguments in favour of lymphoid malignancy is now frequently used for the detection and follow up of B cell lymphoma (NHL). The aim of this study was to investigate the usefulness of morphological findings in bone marrow biopsies in comparison with data obtained by PCR analysis.

Methods—Eighty nine bone marrow biopsies displaying lymphoid infiltrates were evaluated by morphology and immunohistochemistry as well as by CDR3-PCR using consensus framework 3 (FRW3) and JH primers.

Results—The presence of a clonal B cell proliferation was demonstrated by PCR analysis in 45 biopsies, including 21 samples considered to be positive, 17 to be suspicious, and seven to be negative by morphology. In the remaining 44 trephines we found no evidence of clonality, although 12 of these trephines were thought to be positive by morphology.

Conclusions—These results, revealing an incomplete correlation between CDR3-PCR data and immunomorphological findings, indicate that molecular analysis may be more sensitive and specific in general. However, false negative PCR results do occur, which emphasises the necessity to combine both diagnostic tools in the evaluation of lymphoid infiltrates.

Key Words: bone marrow biopsy • lymphoid infiltrate • polymerase chain reaction

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