Detection of MYD88 L265P mutations in formalin-fixed and decalcified BM biopsies from patients with lymphoplasmacytic lymphoma.

Abstract

The diagnosis of bone marrow (BM) infiltration by Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) poses a diagnostic challenge in hematopathology. No definitive morphology or immunophenotype is able to distinguish between infiltration of paraffin-embedded BM sections by WM/LPL and other indolent lymphomas, in particular those of the splenic marginal zone (SMZL) which may also show plasmacytic maturation. An oncogenic gain-of-function mutation (L265P) in the human MYD88 gene has been found to be present in most cases of WM/LPL, yet is absent in most other cases of B-cell chronic lymphoproliferative disorders (LPD), including SMZL. Here, we compare two newly developed diagnostic protocols for detection of this mutation in paraffin-embedded archival tissues which are particularly applicable to decalcified BM biopsies. Sanger sequencing can easily detect levels of BM infiltration above 15% by WM lymphoplasmacytic cells, while the allele-specific PCR can detect the L265P mutation in BM infiltrations below 1% of lymphoma cells. We show that these methods are easily applicable to archival BM specimens and markedly improve diagnostic accuracy of BM infiltrations by indolent B-cell lymphomas.

• Authors: Ianina Belén Capaldi, Annette M May, Annette Schmitt-Graeff, Marie Follo, Konrad Aumann, Gian Kayser, Juan Carlos Perazzo, Martin Werner, Paul Fisch
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 97 Issue 1 Pg. 57-65 (Aug 2014) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 24842316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• MYD88 protein, human
• Myeloid Differentiation Factor 88
• Formaldehyde

Topics

• Base Sequence
• Biopsy
• Bone Marrow (pathology)
• Case-Control Studies
• DNA Mutational Analysis (methods)
• Formaldehyde
• Humans
• Lymphoma, B-Cell (genetics, pathology)
• Molecular Sequence Data
• Mutation
• Myeloid Differentiation Factor 88 (genetics)
• Paraffin Embedding
• Polymerase Chain Reaction (methods)
• Reproducibility of Results
• Waldenstrom Macroglobulinemia (genetics)