Refractory Cytopenia with Multilineage Dysplasia

Refractory Cytopenia with Multilineage Dysplasia

Carla S. Wilson, MD, PhD

Peripheral blood smear from a patient with RCMD shows hypogranular neutrophils image and a dimorphic red cell population with prominent anisopoikilocytosis and hypochromic red blood cells.

More than 10% dysplastic erythroid precursors are seen in this bone marrow aspirate smear from a patient with RCMD, including abnormal nuclear shapes image, multinucleation image, and karyorrhexis image.



  • Myelodysplastic syndrome (MDS)

  • Refractory cytopenia with multilineage dysplasia (RCMD)


  • RCMD-ring sideroblasts (RS)


  • MDS with cytopenia(s) and dysplasia

    • 1 or more cytopenias

      • Anemia, neutropenia, &/or thrombocytopenia

    • Dysplasia in 2 or more myeloid lineages

      • Erythroid, granulocytic, and megakaryocytic

    • Blasts: < 1% in peripheral blood, < 5% in bone marrow

  • Includes the former category of RCMD-RS


Environmental Exposure

  • Benzene and other industrial solvents

  • Insecticides, pesticides

  • Cigarette smoking


  • Clonal expansion of a neoplastic hematopoietic stem/progenitor cell

    • Gene mutations

      • Maintain proliferation of early progenitor cells

      • Abnormal cell maturation

      • Proportional loss of mature cells

    • Progressive decrease in normal hematopoietic stem/progenitor cells

      • Role for tumor suppressor genes in disease onset

      • Abnormal T-cell mediated immune dysregulation

      • Secondary B-cell immune dysregulation

      • Abnormal marrow microenvironment

    • Ineffective hematopoiesis

      • Peripheral cytopenias

      • Increased apoptosis of late marrow precursors



  • Incidence

    • Accounts for 30-40% of MDS

  • Age

    • Disease of older individuals

      • Peak incidence for men is 70-74 years

      • Peak incidence for women is 75-79 years

  • Gender

    • Incidence is slightly higher in men


  • Symptoms relate to cytopenias

    • Commonly seek medical attention for symptoms of anemia

      • Fatigue, dyspnea, palpitations, headache, dizziness

    • Exaggerated bleeding

      • Thrombocytopenia and platelet dysfunction

    • Infection

      • Neutropenia and neutrophil dysfunction

  • Occasional mild hepatomegaly or splenomegaly

Laboratory Tests

  • Complete blood count and differential cell count

    • Degree of cytopenia required unless definitive morphologic or cytogenetic abnormalities

      • Hemoglobin < 10g/dL

      • Neutrophil count < 1.8 × 109/L

      • Platelet count < 100 × 109/L

  • Bone marrow evaluation

    • Cytogenetic evaluation is essential


  • Options, risks, complications

    • Therapeutic considerations are based on the following factors

      • Age and comorbidities, risk category

    • Higher risk disease in patients who cannot tolerate high-intensity therapy

      • Supportive care alone, new therapeutic agents

  • Drugs

    • Immunomodulatory drugs

    • Methyltransferase inhibitors

    • Azacytidine and decitabine

      • Prolongs survival in intermediate- to high-risk patients

  • Allogeneic hematopoietic stem cell transplantation

    • Only curative treatment

    • Reduced intensity conditioning regimens reduce morbidity


  • Majority of patients have intermediate IPSS risk score

  • Pathologic determinants of prognosis include

    • Type of karyotypic abnormalities

      • Complex karyotype or -7 are poor prognostic markers

    • Degree of cytopenias or dysplasia

    • Presence of circulating blasts and blast % in bone marrow

  • Overall median survival is 30-60 months

    • ˜ 10% develop AML at 2 years after diagnosis

    • Patients with complex karyotypes have similar survivals to patients with refractory anemia with excess blasts (RAEB)


Peripheral Blood

  • Unicytopenia or bicytopenia

    • Anemia is often macrocytic

      • Reduced polychromasia

    • Dysplasia

      • May need buffy coat if markedly leukopenic

  • < 1% circulating blasts

  • No monocytosis or pancytopenia

Bone Marrow

  • Typically hypercellular

    • ≥ 10% dysplasia in 2 or 3 lineages

      • Megakaryocyte dysplasia is based on assessment of ≥ 30 megakaryocytes in biopsy sections

      • Some studies suggest > 40% megakaryocytic dysplasia is better criterion than ≥ 10%

    • < 5% blasts

    • Abnormal architecture in biopsy sections

      • Abnormal localization of immature precursors (ALIP)

      • Abnormal paratrabecular location of megakaryocytes or erythroid precursors

      • Increased megakaryocytes with clustering

      • Disruption of erythroid colonies

  • Subset of cases may be hypocellular or fibrotic

    • Histiocytes often increased

  • Prussian blue iron stain

    • Evaluate aspirate smear or touch preparation

    • Increased stores &/or erythroid iron incorporation

      • Increased erythroid iron incorporation

      • Ring sideroblasts may comprise ≥ 15% of erythroid precursors

Only gold members can continue reading. Log In or Register to continue

Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Refractory Cytopenia with Multilineage Dysplasia
Premium Wordpress Themes by UFO Themes
%d bloggers like this: