eMedicine Specialties > Hematology > Stem Cells and Disorders

Myelodysplastic Syndrome: Differential Diagnoses & Workup

Author: Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Coauthor(s): Ulrich Woermann, MD, Consulting Staff, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland
Contributor Information and Disclosures

Updated: Apr 28, 2009

Differential Diagnoses

Other Problems to Be Considered

Idiopathic thrombocytopenic purpura
Pancytopenia
Thrombocytopenia

Workup

Laboratory Studies

• Significant changes are found in the peripheral blood counts and morphology of patients with myelodysplastic syndrome (MDS), and bone marrow abnormalities are also present.
• The peripheral blood counts may reflect a single cytopenia (anemia, thrombocytopenia, or neutropenia) in the early phase or bicytopenia (2 deficient cell lines) and pancytopenia (3 deficient cell lines) in later stages.
  • Anemia varies in degree from mild to severe.
  • It is usually macrocytic (mean cell volume of >100 fL) with oval-shaped RBCs (macro-ovalocytes).
  • It is usually dimorphic (>2 populations), consisting of a normal or a hypochromic microcytic population (RARS) coexisting with the macrocytes.
  • Punctate basophilia is observed in RBCs.
  • Neutropenia may vary from mild to severe.
  • Morphologic abnormalities are often observed in the granulocytes. These can include bilobed or unsegmented nuclei (pseudo–Pelger-Huet abnormality) or hypersegmentation on the nuclei (6-7 lobes) similar to megaloblastic diseases.
  • Granulation abnormalities vary from an absence of granules to abnormal distribution inside the cytoplasm (Dohle bodies).
  • Platelet counts are decreased (rarely increased) and demonstrate morphologic size abnormalities and cytoplasm abnormalities, such as giant hypogranular platelets and megakaryocyte fragments.
• In most cases, bone marrow changes include hypercellularity with trilineage dysplastic changes. A small number of patients may have a hypocellular marrow. This often overlaps with aplastic anemia. Increased marrow fibrosis may be confused with other MPDs.
  • Dysplastic changes in RBC lineage (dyserythropoiesis) are characteristic.
  • In the absence of vitamin B-12 or folate deficiencies, bone marrow changes usually manifest similar changes in asynchronous maturation of nuclei and cytoplasm as described in megaloblastic anemias.
  • Other changes include binuclearity or multinuclearity in the erythroid cell precursor cells and the presence of ringed sideroblasts (iron accumulation in the mitochondria). This property was used by FAB to classify 2 types of RA, with (RARS) versus without ringed sideroblasts (RA).
  • Dysplastic changes in WBC lineage (dysmyelopoiesis) show myeloid hyperplasia with an increased number of myeloblasts and an expanded myelocyte and metamyelocyte population (midstage bulge). This separates it from acute leukemia (leukemic hiatus or absence of mid stage). The percentage of myeloblasts have been used by the FAB classification separating RA (<5%), RAEB (5-20%), RAEB in transformation (>20, <30%), and AML (>30%). (See recent WHO modification,⁸ as well as Reviewing the ICD-10 classification of haematological neoplasms on its way to ICD-11.)
  • Morphologic abnormalities are evident in nuclear-cytoplasm dissociation in maturation and when the pseudo–Pelger forms are also present in bone marrow.
  • Dysthrombopoiesis in the platelet production cell lineage consists of micromegakaryocytes (dwarf forms) with poor nuclei lobulation and giant platelets budding off from their cytoplasm.
• Cytogenetic studies of the bone marrow cells indicate mutations into clonal cell lines, with abnormal chromosomes in 48-64% in different series.
• Using higher-resolution techniques (fluorescent in situ hybridization), some practitioners claim a 79% rate of chromosomal abnormalities in primary myelodysplastic syndrome (MDS) patients.
  • Chromosomal abnormalities are clonal and include 5q-, monosomy 7 (-7) or 7q-, trisomy 8 (+8), and numerous other less frequent abnormalities.
  • Multiple combinations may be present, which indicate a very poor prognosis.
  • A single abnormality, except those involving chromosome 7, usually indicates good prognosis and survival.

Other Tests

• Cytogenetic techniques have evolved from individual chromosome identification by banding techniques to the new, more sensitive color-coded methods.
  • Separating individual chromosomes is dependent on the ability to induce the cell into mitosis to identify abnormalities.
  • The new technique uses fluorescent in situ hybridization and color-coded chromosomes to enable observation of the intact cell without requiring mitosis.
• A newer WHO classification is helpful in evaluating patients with myelodysplastic syndrome (MDS) in predicting subgroup differences in prognosis and response to treatment.
  • Refractory anemia is now divided to a group without (RCMD-) or with multi-lineage dysplasia (RCMD+), with (RCMD+/+RS) or without ringed sideroblasts (RCMD/-RS).
  • A new subcategory in RA includes patients with isolated 5q- and <5% blasts called the 5q- syndrome. Identification of the syndrome or presence of this particular cytogenetic abnormality is useful because the majority of these patients will respond to the new drug lenalidomide (Revlimid).
• Unclassified by the WHO are the group of patients with myelodysplastic syndrome (MDS) whose conditions overlap with severe aplastic anemia and paroxysmal nocturnal hemoglobinuria. A group of myelodysplastic syndrome (MDS) patients with the FAB-RA subtype who may have a hypoplastic marrow, usually human leukocyte antigen (HLA)-DR15 phenotype, are young (<60 y), and may have negative cells to CD55 and CD59 respond to immunosuppression with anti-thymocyte globulin (ATG) or cyclosporin.⁹

Histologic Findings

The presence of dysplastic changes in the peripheral blood smear and trilineage dysplasia and hypercellular marrow in the absence of vitamin deficiency is diagnostic of myelodysplastic syndrome (MDS). The presence of typical chromosomal abnormalities supports the diagnosis and contributes to determining the prognosis of myelodysplastic syndrome (MDS).

Staging

Because patients with myelodysplastic syndrome (MDS) have heterogeneous clinical manifestations and varying clinical outcomes, staging the patients according to their prognosis and approaching therapy depending on the severity and stage is necessary. Also, the FAB classification as discussed previously is not an adequate staging mechanism (see Mortality/Morbidity).

An international group of experts called the International Prognostic Scoring System (IPSS) convened and determined new criteria for staging myelodysplastic syndrome (MDS).¹⁰

Table 1. IPSS Score for Staging Myelodysplastic Syndrome (MDS)¹⁰

Open table in new window

*Good is no abnormality (46,XX or 46,XY), -Y, del(5q), del(20q); intermediate is other abnormalities, such as trisomy 8 (+8); and poor is complex (33 abnormalities or chromosome 7 abnormality [ie, 7q- or -7]).

• The first prognostic factor is the amount or percentage of myeloblasts in the patient's bone marrow study. Each increase of 10% over the reference range is equivalent to a half point.
• The number of cytopenias is scored by the presence of 2-3 (anemia plus thrombocytopenia or neutropenia or pancytopenia), which is worth a half point. The presence of none or a single cytopenia indicates a good prognosis.
• The total score is added, and the patient is staged according to the following:
  • Low: 0
  • Intermediate 1: 0.5-1
  • Intermediate 2: 1.5-2
  • High: Greater than or equal to 2.5

Classification of the subtypes or categories of myelodysplastic syndrome (MDS) has changed from the FAB classification to the most recent WHO classification.

Table 2. Categories of FAB Classification Versus WHO Classification for Myelodysplastic Syndrome (MDS)

Open table in new window

WHO classifies CMML into the following:

• Juvenile and proliferative CMML under MDS/MPDs have more than 13,000/μL monocytes plus splenomegaly.
• CMML under myelodysplastic syndrome (MDS) is limited to monocytosis of less than 13,000/μL with trilineage dysplasia.

• Search for CME/CE on This Topic »

• Myelodysplastic Syndrome (Pediatrics: General Medicine)
• Myelodysplastic Syndromes Associated With Isolated Del (5q) (Pathology)
• Acute Myeloid Leukemia With Myelodysplasia-Related Features (Pathology)
• Aplastic Anemia (Hematology)

• Outcome of Stem Cell Transplant for Myelodysplastic Syndrome Unaffected by Age
• FDA Issues Early Communication Regarding Deferasirox Safety in MDS
• Mental Status Changes Precede Hematopoietic Stem Cell Transplantation

• Waxing and Waning Pulmonary Nodules and Myelodysplastic Syndrome
• Disseminated Varicella-Zoster Virus Infection Following Azacitidine in a Patient With Myelodysplastic Syndrome
• Acute Interstitial Nephritis Due to Deferasirox: A Case Report

• Acute Leukemia Resource Center