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.


TERMINOLOGY


Abbreviations



  • Myelodysplastic syndrome (MDS)


  • Refractory cytopenia with multilineage dysplasia (RCMD)


Synonyms



  • RCMD-ring sideroblasts (RS)


Definitions



  • 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


ETIOLOGY/PATHOGENESIS


Environmental Exposure



  • Benzene and other industrial solvents


  • Insecticides, pesticides


  • Cigarette smoking


Pathogenesis



  • 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


CLINICAL ISSUES


Epidemiology



  • 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


Presentation



  • 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



Treatment



  • 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


Prognosis



  • 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)


MICROSCOPIC PATHOLOGY


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

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Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Refractory Cytopenia with Multilineage Dysplasia
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