Molecular Diagnostics in Hematologic Malignancies

In hematologic malignancies, molecular testing of cytology specimens can be extremely useful in the context of tissue-based neoplasms such as lymphomas and myeloid sarcomas when the source of nucleic acids can be limited. FNA specimens are ideal for obtaining unprocessed high-quality nucleic acids essential for simultaneous assessment of a variety of genetic alterations as is usually the case with hematologic malignancies. Concurrent quantitative tumor burden assessed by multiparametric flow cytometry analysis on these samples enables a more informative interpretation of results. Clonality assays to detect monoclonal rearrangements in immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) beta or gamma receptor genes are invaluable for differentiating low-grade B-cell and T-cell lymphoproliferative disorders from reactive conditions. Assessment of characteristic gene translocations and gene mutations is fundamental for subclassification of small B-cell lymphomas and myeloid leukemias and prognostication of large B-cell lymphomas. Estimation of the degree of somatic hypermutation in IGHV is the standard of care for prognostication in CLL/SLL. Gene mutation analysis also affects the choice of therapy by identification of targets for treatment using approved FDA drugs and novel agents in clinical trials. In this context, screening of drug resistance mutations has emerged as a critical aspect of monitoring these patients akin to the assessment of measurable (minimal) residual disease. And lastly, monitoring of cancer-associated viruses such as EBV is crucial in various settings. Further details are elaborated in the chapter below.