Myelodysplastic Syndromes

Key Features

Essentials of Diagnosis

• Cytopenias with hypercellular bone marrow

• Morphologic abnormalities in one or more hematopoietic cell lines

General Considerations

• Group of acquired clonal disorders of the hematopoietic stem cell, characterized by the constellation of cytopenias, a usually hypercellular marrow, morphologic dysplasia and genetic abnormalities

• Causes

  • Idiopathic (most common)

  • Prior exposure to cytotoxic chemotherapy or radiation therapy

• In addition to cytogenetics, sequencing can detect genetic mutations in 80–90% of patients

• Acquired clonal mutations identical to those seen in myelodysplastic syndrome can occur in the hematopoietic cells of ~10% of apparently healthy older individuals, defining the disorder of clonal hematopoiesis of indeterminate potential (CHIP)

• Myelodysplasia encompasses several heterogeneous syndromes; a key distinction is whether there is an increase in bone marrow blasts (> 5% of marrow elements)

  • MDS with excess blasts represents a more aggressive form of the disease, often leading to acute myeloid leukemia

  • Patients without excess blasts are characterized by the degree of dysplasia, eg, MDS with single lineage dysplasia and MDS with multilineage dysplasia

  • The morphologic finding of MDS with ringed sideroblasts is used to define a subcategory of lower risk syndromes

  • Patients with isolated 5q loss, which is characterized by the cytogenetic finding of loss of part of the long arm of chromosome 5, comprise an important subgroup of patients with a different natural history

  • Chronic myelomonocytic leukemia (CMML) is a proliferative syndrome, including sustained peripheral blood monocytosis > 1000/mcL (> 1.0 × 10⁹/L)

Demographics

• Occurs most often in patients aged > 60

Clinical Findings

Symptoms and Signs

• Asymptomatic, with incidentally found cytopenias

• Symptoms and signs are related to bone marrow failure

• Symptoms

  • Fatigue

  • Bleeding

• Signs

  • Fever

  • Infection

  • Wasting

  • Weight loss

  • Splenomegaly

  • Pallor

• Paraneoplastic syndromes of various sorts (prior to or following diagnosis)

Differential Diagnosis

• Acute myeloid leukemia (AML) (≤ 20% blasts)

• Aplastic anemia

• Anemia of chronic disease

• Vitamin B₁₂ or folate deficiency

• Megaloblastic anemia

• Myelofibrosis

• HIV-associated cytopenias

• Acute or chronic drug effect

Diagnosis

Laboratory Tests

• Anemia may be marked

• Mean cell volume is normal or increased

• Peripheral blood smear may show macro-ovalocytes

• White blood cell count usually normal or reduced; neutropenia is common

• Neutrophils may exhibit morphologic abnormalities, including deficient numbers of granules, or bilobed nucleus (Pelger-Huet abnormality)

• Myeloid series may be left shifted with small numbers of promyelocytes or blasts

• Platelet count is normal or reduced; hypogranular platelets may be present

Diagnostic Procedures

• Bone marrow aspirate and biopsy are characteristically hypercellular (but may occasionally be hypocellular)

• Signs of abnormal erythropoiesis include

  • Megaloblastic features

  • Nuclear budding

  • Multinucleated erythroid precursors

• Prussian blue stain ...