Chapter 22 - Tumors of the Hematopoietic System

Abstract

The discovery of genes associated with recurrent genetic abnormalities has resulted in several major transformations in the classification of hematopoietic malignancies over the past decades. The current World Health Organization classification schema incorporates numerous unique biomarkers and somatic mutations, which, in addition to conventional cytogenetics, define distinct clinicopathologic myeloid and lymphoid neoplastic entities. Examples include acute myeloid leukemia with mutated NPM1 or acute myeloid leukemia with biallelic mutation of CEBPA, which were once provisional entities but are now distinct well-defined disease subtypes. In addition to providing prognostic information, clinicians rely on the detection of these genetic aberrations to guide the use of unique, effective treatments targeting abnormal proteins and molecules. Examples include tyrosine kinase inhibitors in chronic myeloid leukemia, BCR-ABL1-positive, and myeloid and lymphoid neoplasms associated with rearrangements of PDGFRA and PDGFR, all-trans retinoic acid in acute promyelocytic leukemia, or IDH inhibitors in acute myeloid leukemia associated with mutated IDH1 or IDH2. These genetic defects also provide excellent biomarkers for monitoring of disease. As molecular diagnostic techniques, including high-throughput genomic sequencing, polymerase chain reaction, fluorescence in situ hybridization (FISH), and karyotyping, become commonplace in the practice of pathology, an ever-increasing list of provisional diagnostic entities have been, and will be, proposed. This chapter provides a current overview of the most common categories of hematopoietic neoplasms—the myelodysplastic syndromes, acute leukemias, myeloproliferative neoplasms, and mature lymphoid neoplasms.