Molecular Hematopathology

Molecular and cytogenetic analysis is a critical component of hematopathology practice. Correct diagnostic classification, prognosis and therapeutic decisions are often predicated on the presence or absence of tumor-specific genetic abnormalities. Understanding the wide range of abnormalities associated with hematologic neoplasia and interpreting a large number of molecular diagnostic techniques can pose challenges for hematopathologists. From chromosome translocations to complex RNA or DNA mutation patterns, the application of molecular diagnosis has greatly enriched our definitions of lymphoid and myeloid neoplasms. The incessant pace of new technological advances such as next-generation sequencing, as well as medical and scientific knowledge accumulation, requires the continuous updating of our knowledge to make judicious decisions regarding cost-effective yet comprehensive approaches to molecularly characterize hematologic cancers. This chapter encompasses an overview of the test design considerations, molecular diagnostic techniques, and rational application of these tests to non-Hodgkin lymphoma and myeloid malignancies in modern hematopathology practice. The field of benign hematology is also greatly expanding with the broader use of molecular analysis. Disorders of hemoglobins, erythrocytosis, and hemolysis have underlying constitutional genetic abnormalities enabling the diagnostic application of molecular testing in an increasingly sophisticated manner. These advances will also be summarized in this chapter.