Neoplastic WBC I

• Leukemia arises in the bone marrow
• Leukemia can be classified by stage of maturation: acute vs. chronic
• Leukemia can also be classified as myeloid vs. lymphoid
• Lymphoma arises in lymphoid tissue
• In leukemia, normal bone marrow is taken over by leukemic cells
• Leukemia may also be marked by cytopenias in peripheral blood
• Bone marrow core biopsy is the most important test to diagnose leukemia
• Bone marrow aspirate is used to look at individual cell morphology
• The definition of leukemia is >20% blasts in peripheral blood or bone marrow
• A distinguishing feature of blasts in AML is the presence of Auer rods which are composed of abnormal lysosomes
• Acute promyelocytic leukemia with PML::RARA fusion is a subtype of AML that can lead to DIC
• APL can present hypergranular or microgranular with bilobed nuclei
• APL is genetically defined by translocation: t(15;17)
• APL can be treated with ATRA and arsenic
• >80% of leukemic cells are monocytic lineage
• In acute erythroid leukemia, >30% of cells are immature erythroid cells
• Acute Megakaryoblastic Leukemia is associated with trisomy 21 and involves >20% blasts in bone marrow or blood
• APL with PML:RARA fusion has a favorable prognosis with early ATRA administration
• Therapy-related myeloid neoplasms have a poor prognosis
• FLT3 mutation is associated with a worse AML prognosis
• NPM1 mutation is associated with a good AML prognosis
• AML overall has a 15-30% survival rate
• Myelodysplastic syndrome is a clonal hematopoietic stem cell disease associated with increased risk for AML
• Myelodysplastic syndrome is a disease of older adults, has an increased risk of increased % of blasts and is mutationally defined by Biallelic TP53 inactivation
• Dysplasia is when 10% of cells in a particular lineage show dysplastic changes
• Aspirate smears or touch/roll preparations of core biopsy are best for evaluating dysplasia
• 50-70% of MDS cases have at least one cytogenetic abnormality
• Dysplasia RBC Precursors

  Karyorrhexis

  Nuclear budding

  Multinucleation

  Megaloblastic change

  Mitosis in later maturational stages

  Ring sideroblasts
• Granulocyte Dysplasia

  Hypogranularity

  Nuclear segmentation

  Abnormally large granules

  Auer rods
• Megakaryocyte dysplasia

  Too small

  Nuclear hypolobation

  Multinucleation/widely separated nuclear lobes
• Compared to the older MDS classification system, the newer system has an updated category for mutations