Myelodysplastic syndromes

• Myelodysplastic syndromes are stem cell d/o characterized by maturational defects resulting in ineffective hematopoiesis and risk of transformation into AML (called “preleukemia” syndromes)

• Clinical features

  • There may be cytopenias and dysmorphic changes in the peripheral smear with normal or hypercellular marrow

  • If there is anemia it’s usually macrocytic and there may be monocytosis

  • Most often in males 60-70 YOA

  • May be asymptomatic or present with weakness, hemorrhage, and/or infection

  • Chromosomal abnormalities are in up to 2/3 of patients and indicate a poor prognosis and increased risk of progressing to AML

  • Median survival depends on form of myelodysplasia and presence of karyotypic abnormalities

• Peripheral smear changes affect all 3 lineages (erythroid, myeloid, and megakaryocytic)

  • Erythroid

    • Ringed sideroblasts (erythroblasts with iron-laden mitochondria that can be seen as perinuclear granules with a Prussian-blue stain

    • Megaloblastoid maturation like that seen with B₁₂ or folate deficiency

    • Nuclear budding abnormalities (nuclei with misshapen, often polypoid outlines)

  • Myeloid

    • Neutrophils may contain decreased number of secondary granules or contain toxic granulations and Dohle bodies

    • Pseudo-Pelger-Huet cells (neutrophils with a nucleus with only 2 lobes) are often seen

    • Neutrophils may appear to completely lack nuclear segmentation

    • Myeloblasts may be increased but are <>

  • Megakaryocytes – may have single nuclear lobes or multiple nuclei (pawn ball megakaryocytes) instead of a single multilobed nucleus

• Classification

  • RA (refractory anemia)

    • <>

    • Good prognosis

  • RARS (refractory anemia with ringed sideroblasts)

    • Differs from RA only in that there are more ringed sideroblasts (> 15%)

    • Good prognosis

  • RAEB (refractory anemia with excess blasts)

    • <5%>

    • Median survival only 11 months (tends to progress to leukemia)

  • RAEB-T (refractory anemia with excess blasts in transformation)

    • Lots (21-29%) of blasts in marrow and blood

    • Very poor prognosis

  • CMML (chronic myelomonocytic leukemia)

    • <>

    • Same prognosis as RAEB not because of transformation to leukemia but because these people tend to die of infection

    • See monocytosis (this is how you tell this apart from CML; CML has basophila, CMML has monocytosis)

  • CMML-T (chronic myelomonocytic leukemia in transformation)

    • 21-29% blasts in marrow and blood

    • Will see monocytosis

    • Generally, the more blasts the worse the prognosis (more likely to go onto leukemia)

• Other processes that cause dysmyelopoietic maturation

  • Megaloblastic anemia of B₁₂/folate deficiency

  • Chemotherapeutic drugs

  • Alcohol

  • Heavy metal intoxication

  • AIDS and autoimmune d/o

  • Paroxysmal nocturnal hemoglobinuria

Category: Medical Subject Notes , Pathology Notes