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Hypocellular Myelodysplastic Syndrome

Definition

  • Myelodysplastic syndrome with decreased marrow cellularity

Diagnostic Criteria

  • Exclusions
  • Decreased bone marrow cellularity
    • <30% if age 60 or under
    • <20% if over 60
  • Occurs in 5-10% of MDS patients
    • More frequent in women
  • Hypocellular MDS presents special differential diagnostic problems
    • Distinction between various MDS may be compromised by decreased cellularity but should be made, if possible, based on standard criteria:

Myelodysplastic Syndromes

  Circulating Blasts Marrow Blasts Ring Sideroblasts Dysplastic Lineages Cytopenias
RCUD <1% <5% <15% Any 1 lineage 1 or 2
RARS 0 <5% ≥15% Only erythroid 1 or 2
RCMD <1% <5% Variable 2 or more lineages 1, 2 or 3
RAEB-1 <5% 5-9% Variable 1 or more 1, 2 or 3
RAEB-2 5-19% 10-19% or Auer rods Variable 1 or more 1, 2 or 3
del(5q) <1% <5% Variable Frequently hypolobated small megakaryocytes Usually 1 (anemia)
  • RCUD = refractory cytopenia (anemia, neutropenia or thrombocytopenia) with unilineage dysplasia; RARS = refractory anemia with ringed sideroblasts; RCMD = refractory cytopenia with multilineage dysplasia; RAEB = refractory anemia with excess blasts; del(5q) = 5q- syndrome
  • All MDS must not have absolute monocytosis
  • If chemotherapy or radiation therapy related, should be reported as "therapy-related myeloid neoplasm"
  • In children, consider provisional WHO entity "refractory cytopenia of childhood" for low blast count MDS
  • Myelodysplastic syndrome unclassifiable (MDS-U)
    • Must not meet criteria of any specific WHO category
    • Persistent cytopenia(s) with any of the following:
      • Unilineage marrow dysplasia with pancytopenia OR
      • <1% blasts in blood, <5% blasts in marrow and cytogenetic abnormalities but no lineage with ≥10% dysplastic forms OR
      • Findings of RCUD or RCMD but with 1% blasts in peripheral blood
        • (2-4% blasts would be classified as RAEB-1)
    • Nonclonal causes must be excluded

 


Dita Gratzinger MD PhD
Tracy I George MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting: 10/23/11

Supplemental studies

Cytogenetic abnormalities are found in about 50% of hypocellular MDS

Cytogenetic studies should be performed in all cases of myelodysplasia or suspected myelodysplasia

  • FISH for MDS associated abnormalities is not indicated for screening but is helpful if <20 metaphases were examined on karyotyping
  • In the setting of persistent cytopenia in the absence of definitive morphologic features of MDS:
    • The following abnormalities are considered presumptive evidence of MDS
      • Deletions
        • -5, del(5q)
        • -7, del(7q)
        • del(9q)
        • del(11q)
        • del(12p)
        • t(12p)
        • -13, del(13q)
        • i(17q), t(17p)
        • idic(X)(q13)
      • Translocations
        • t(1;3)(p36.3;q21.2)
        • t(2;11)(p21;q23)
        • t(3;21)(q26.2;q22.1)
        • inv(3)(q21q26.2) and t(6;9)(p23;q24)
          • Most frequently present as AML and need to be closely monitored for overt transformation
        • t(11;16)(q23;p13.3)
    • The following are commonly found in MDS but are not by themselves considered definitional for MDS
      • +8
      • -Y
      • del(20q)

Differential Diagnosis

Hairy Cell Leukemia Aplastic Anemia Hypocellular (Hypoplastic) MDS Hypocellular AML
Variable cellularity Low cellularity Low cellularity Low cellularity
No dysplasia Mild erythroid dyspoiesis allowed but no ring sideroblasts Dysplasia present Variable dysplasia
Marrow blasts <5% Marrow blasts ≤1%, no ALIP Marrow blasts <20%, ALIP Marrow blasts ≥20%
Blood blasts rare No blood blasts Blood blastsl <20% Blood blasts ≥20%
Cytogenetics nonspecific May have cytogenetic abnormalities May have defining abnormalities May have defining abnormalities
Clonal B cells No B cell clone No B cell clone No B cell clone
ALIP = abnormal localization of immature precursors

Non-neoplastic disorders may simulate myelodysplasia

  • Vitamin/micronutrient deficiencies
    • B12/folate
    • Copper
      • Ring sideroblasts present
      • Cytoplasmic vacuoles
      • May be due to
        • Zinc excess
        • Gastrectomy
        • Total parenteral nutrition
  • Infections
    • HIV
    • Parvovirus
    • HHV-6 in children
  • Toxins
    • Ethanol
    • Heavy metals
  • Growth factors
    • Granulocyte-macrophage colony-stimulating factor (GMCSF)
    • Erythropoietin
  • Drugs (numerous)
    • Chemotherapeutic agents
      • e.g. megaloblastoid change with folate antagonists
    • Valproic acid, MMF (mycophenolate mofetil), Ganciclovir
      • Pseudo-Pelger-Helger anomaly
  • Autoimmune/rheumatologic
    • e.g. systemic lupus erythematosus
  • Congenital
    • Congenital dyserythropoietic anemias
    • Inherited bone marrow failure syndromoes (Fanconi etc.)
    • Monocytopenia immunodeficiency syndrome

Myelodysplastic Syndromes

  Circulating Blasts Marrow Blasts Ring Sideroblasts Dysplastic Lineages Cytopenias
RCUD <1% <5% <15% Any 1 lineage 1 or 2
RARS 0 <5% ≥15% Only erythroid 1 or 2
RCMD <1% <5% Variable 2 or more lineages 1, 2 or 3
RAEB-1 <5% 5-9% Variable 1 or more 1, 2 or 3
RAEB-2 5-19% 10-19% or Auer rods Variable 1 or more 1, 2 or 3
del(5q) <1% <5% Variable Frequently hypolobated small megakaryocytes Usually 1 (anemia)
  • RCUD = refractory cytopenia (anemia, neutropenia or thrombocytopenia) with unilineage dysplasia; RARS = refractory anemia with ringed sideroblasts; RCMD = refractory cytopenia with multilineage dysplasia; RAEB = refractory anemia with excess blasts; del(5q) = 5q- syndrome
  • All MDS must not have absolute monocytosis
  • If chemotherapy or radiation therapy related, should be reported as "therapy-related myeloid neoplasm"
  • In children, consider provisional WHO entity "refractory cytopenia of childhood" for low blast count MDS
  • Myelodysplastic syndrome unclassifiable (MDS-U)
    • Must not meet criteria of any specific WHO category
    • Persistent cytopenia(s) with any of the following:
      • Unilineage marrow dysplasia with pancytopenia OR
      • <1% blasts in blood, <5% blasts in marrow and cytogenetic abnormalities but no lineage with ≥10% dysplastic forms OR
      • Findings of RCUD or RCMD but with 1% blasts in peripheral blood
        • (2-4% blasts would be classified as RAEB-1)
    • Nonclonal causes must be excluded

 

Clinical

  • Approximately 15% of MDS patients have hypocellular variant
  • May indicate better overall survival, independent of IPSS

International Prognostic Scoring System (IPSS)

Points are assigned based on abnormal findings

Points: 0 0.5 1 1.5 2
BM blast % <5 5-10 - 11-20 21-30
Cytogenetic Group Good Intermediate Poor    
Number of cytopenic lineages 0-1 2-3      
  • Cytogenetic groups
    • Good: Normal, -Y, del(5q), del(20q)
    • Intermediate: All others
    • Poor: Complex, chromosome 7 abnormalities
  • Cytopenias
    • Hemoglobin <10 mg/dl
    • Absolute neutrophil count <1.8 x 103/μL
    • Platelets <100 x 103/μL

Risk groups are determined based on points assigned as above

Risk Group Points Median Survival Evolution to Acute Leukemia
Low 0 5.7 years 9.4 years
Intermediate-1 0.5-1.0 3.5 years 3.3 years
Intermediate-2 1.5-2.0 1.2 years 1.1 years
High >2.5 0.4 years 0.2 years
  • Treatment based on risk group assigned and ability to tolerate therapy including
    • Supportive care
    • Immunosuppressive agents
    • Bone marrow transplantation
    • Intensive cytotoxic treatment
    • Demethylating agents
    • Farnesyl transferase inhibitors

Blood 89:2079, 1997

 

Classification / Lists

WHO 2008 Classification of Myeloid Neoplasms

Myeloproliferative Neoplasms (MPN)

Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1

Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)

Myelodysplastic Syndromes (MDS)

Therapy Related Myeloid Neoplasms

 

Bibliography

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