Table 5.

Summary of a proposed definition of idiopathic cytopenia(s) of undetermined significance (ICUS) (Valent et al40).

*Note that both morphological dysplasia and ring sideroblasts have a differential diagnosis and by themselves are not MDS-defining; other causes of these changes must be ruled out. 
ICUS Definition (3 components)

  1. Meaningful cytopenias (hemoglobin < 11 g/dL, absolute neutrophil count < 1500/mm3, or platelets < 100 × 109/L) lasting more than 6 months

  2. Does not meet minimal diagnostic criteria for MDS (see below)

  3. Other recognized causes of cytopenias have been excluded (see below)

 
Minimal Diagnostic Criteria for MDS—both “prerequisite” criteria, plus at least one “decisive” criterion or preponderance of co-criteria

  • ▪ “Pre-requisite” criteria

    • – Meaningful cytopenias as above

    • – Exclusion of other non-MDS hematopoietic disorders or non-hematopoietic disorders as cause of cytopenias

  • ▪ MDS-related (“decisive”) criteria

    • – Dysplasia in at least 10% of all cells in one or more myeloid lineages or at least 15% ring sideroblasts*

    • – 5% to 19% blast cells in bone marrow smears

    • – Typical chromosomal abnormality (by conventional karyotyping or FISH)

  • ▪ “Co-criteria”

    • – Abnormal marrow flow cytometry phenotype clearly indicative of a monoclonal erythroid or myeloid cell population

    • – Clear molecular signs of a clonal cell population—in HUMARA assay, gene chip profiling, or point mutation analysis (eg, RAS mutations)

    • – Markedly and persistently reduced colony formation (± cluster formation) of bone marrow or/and circulating progenitor cells (CFU-assay)

 
“Required” Investigations to Exclude Other Causes of Cytopenias

  1. Detailed case history (toxins, drugs, mutagenic events, etc)

  2. Thorough clinical investigations, including X-ray or sonography of spleen

  3. Differential blood count (microscopic) and complete serum chemistry

  4. Bone marrow smear, histology and immunohistochemistry

  5. Flow cytometry of bone marrow and peripheral blood cells

  6. Chromosome analysis including FISH

  7. Molecular analysis where appropriate (for example, T-cell receptor rearrangement for neutropenia)

  8. Exclusion of viral infections (HCV, HIV, CMV, EBV, others)

 
*Note that both morphological dysplasia and ring sideroblasts have a differential diagnosis and by themselves are not MDS-defining; other causes of these changes must be ruled out. 
ICUS Definition (3 components)

  1. Meaningful cytopenias (hemoglobin < 11 g/dL, absolute neutrophil count < 1500/mm3, or platelets < 100 × 109/L) lasting more than 6 months

  2. Does not meet minimal diagnostic criteria for MDS (see below)

  3. Other recognized causes of cytopenias have been excluded (see below)

 
Minimal Diagnostic Criteria for MDS—both “prerequisite” criteria, plus at least one “decisive” criterion or preponderance of co-criteria

  • ▪ “Pre-requisite” criteria

    • – Meaningful cytopenias as above

    • – Exclusion of other non-MDS hematopoietic disorders or non-hematopoietic disorders as cause of cytopenias

  • ▪ MDS-related (“decisive”) criteria

    • – Dysplasia in at least 10% of all cells in one or more myeloid lineages or at least 15% ring sideroblasts*

    • – 5% to 19% blast cells in bone marrow smears

    • – Typical chromosomal abnormality (by conventional karyotyping or FISH)

  • ▪ “Co-criteria”

    • – Abnormal marrow flow cytometry phenotype clearly indicative of a monoclonal erythroid or myeloid cell population

    • – Clear molecular signs of a clonal cell population—in HUMARA assay, gene chip profiling, or point mutation analysis (eg, RAS mutations)

    • – Markedly and persistently reduced colony formation (± cluster formation) of bone marrow or/and circulating progenitor cells (CFU-assay)

 
“Required” Investigations to Exclude Other Causes of Cytopenias

  1. Detailed case history (toxins, drugs, mutagenic events, etc)

  2. Thorough clinical investigations, including X-ray or sonography of spleen

  3. Differential blood count (microscopic) and complete serum chemistry

  4. Bone marrow smear, histology and immunohistochemistry

  5. Flow cytometry of bone marrow and peripheral blood cells

  6. Chromosome analysis including FISH

  7. Molecular analysis where appropriate (for example, T-cell receptor rearrangement for neutropenia)

  8. Exclusion of viral infections (HCV, HIV, CMV, EBV, others)

 
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