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A number of morphological classifications are in place to classify patients with MDS. The current term, MDS, was adopted by the French, American, and British (FAB) Cooperative Group in 1976 in their classification scheme of these disorders. The WHO classification was proposed as a modification of the FAB system⁵⁶ and was revised in 2016⁵⁷ from the previous version (2008)⁵⁸ (Table 26.2).

Table 26.2 Classification scheme of myelodysplastic syndromes (MDS) in the 2016 revision of the World Health Organization (WHO) classification, and corresponding terminology in the 2008 WHO classification.

Source: Adapted from Sanz‐De Pedro et al.⁴⁶

2016 WHO classification	2008 WHO classification
MDS with single‐lineage dysplasia	Refractory cytopenia with unilineage dysplasia
MDS with ring sideroblasts (MDS‐RS) MDS‐RS and single‐lineage dysplasia MDS‐RS and multilineage dysplasia	Refractory anaemia with ring sideroblasts
MDS with multilineage dysplasia	Refractory cytopenia with multilineage dysplasia
MDS with excess blasts‐1	Refractory anaemia with excess blasts‐1
MDS with excess blasts‐2	Refractory anaemia with excess blasts‐2
MDS, unclassifiable (MDS‐U) MDS‐U with 1% blood blasts MDS‐U with single‐lineage dysplasia and pancytopenia MDS‐U based on defining cytogenetic abnormality	MDS, unclassifiable (MDS‐U)
RCC (refractory cytopenia of childhood (provisional)	Childhood myelodysplastic syndrome (provisional)

The 2016 WHO classification identifies six entities of MDS: MDS with single‐lineage dysplasia (MDS‐SLD), MDS with ring sideroblasts (MDS‐RS), MDS with multilineage dysplasia (MSD‐MLD), MDS with excess blasts (MDS‐EB), MDS with isolated del(5q), and MDS unclassifiable (MDS‐U). There is an additional provisional entity, ‘refractory cytopenia of childhood’ (RCC) (Table 26.3).

Table 26.3 WHO 2016 classification.

Source: Adapted from Hong et al.⁴⁴

Type	Dysplastic lineages	Cytopeniaa	Ring sideroblasts in erythroid elements of BM	Blasts	Cytogenetics
MDS‐SLD	1	1 or 2	RS <15% (or <5%b)	PB <1% BM <5% No Auer rods	Any, unless fulfils criteria for isolated del(5q)
MDS‐MLD	2 or 3	1–3	RS <15% (or <5%b)	PB <1% BM <5% No Auer rods	Any, unless fulfils criteria for isolated del(5q)
MDS‐RS‐SLD:	1	1 or 2	RS ≱15% (or ≱5%b)	PB <1% BM <5% No Auer rods	Any, unless fulfils criteria for isolated del(5q
MDS‐RS‐MLD	2 or 3	1–3	RS ≱15% (or ≱5%b)	PB <1% BM <5% No Auer rods	Any, unless fulfils criteria for isolated del(5q
MDS with isolated del(5q)	1–3	1–2	None or any	PB <1% BM <5% No Auer rods	del(5q) alone or with one additional abnormality except ‐7 or del(7q)
MDS‐EB‐1	0–3	1–3	None or any	PB 2~4% or BM 5~9%, No Auer rods	Any
MDS‐EB‐2	0–3	1–3	None or any	PB 5~19% or BM 10%~19% or Auer	Any
MDS‐U with 1% peripheral blood blast	1–3	1‐3	None or any	PB=1%c BM<5% Auer rods	Any
MDS‐U with single‐lineage dysplasia and pancytopenia	1	3	None or any	PB <1% BM <5% No Auer rods	Any
Defining cytogenetic abnormality	0	1–3	<15%d	PB <1% BM <5% No Auer rods	MDS defining abnormality
RCC Refractory cytopenia of childhood	1–3	1–3	None	PB <2% BM <5% No Auer rods	Any

WHO, World Health Organization; MDS, myelodysplastic syndromes; PB, peripheral blood; BM, bone marrow; RS, ring sideroblasts

^a Cytopenias MDS‐defining: Hb<100g/L, PLT<100×109/L, ANC<1.8×109/L; absolute monocytes count<1.0×109/L;

^b with SF3B1 mutation;

^c 1% PB blasts must be recorded on at least two separate observations;

^d If with ≥15% ring sideroblasts and significant erythroid dysplasia, and are classified as MDS‐RS‐SLD.

Table 26.4 Differential diagnosis of clonal or idiopathic cytopenias and myelodysplastic syndromes.

Source: Adapted from Montalban‐Bravo et al.⁶⁰

Features	CHIP	ICUS	CCUS	MDS
Cytopenias	No	Yes (1 or more)	Yes (1 or more)	Yes (1 or more)
Dysplasia	No	None or minimal (non‐diagnostic for MDS)	None or minimal (non‐diagnostic for MDS)	Yes (>10% of elements per lineage in at least one
Somatic mutations	Yes, at a variant allele frequency ≥2%. Most commonly: DNMT3A, TET2, ASXL1, SRSF2, TP53	No	Up to 36% overall with similar mutation VAF compared to MDS17% of ICUS without dysplasia45% of ICUS with some dysplasia	Up to 85% of patients
Risk of progression	Very low (0.5–1% per year) outside of therapy‐related setting	Up to 10% at five years	Up to 80% at five years but determined by mutational patterns

CHIP, clonal hematopoiesis of indeterminate potential; ICUS, idiopathic cytopenia of undetermined significance; CCUS, clonal cytopenia of undetermined significance; MDS, myelodysplastic syndromes.

For MDS with ring sideroblasts, since the presence of the SF3B1 mutation is associated with the presence of RS, the updated WHO classification of MDS‐RS includes patients who have the SF3B1 mutation but lack excess blasts or an isolated del(5q) abnormality.

MDS with excess blasts is separated into patients with <10% marrow blasts (MDS‐EB‐1) and those with 10–19% marrow blasts (MDS‐EB‐2). It should also be noted that the denominator used for determining blast percentage in all myeloid neoplasms was redefined to include all nucleated bone marrow cells as opposed to only nonerythroid cells. This modification shifted a select group of patients previously categorized as AML to MDS‐EB.

MDS‐U (unclassifiable) is defined as the presence of 1% blasts in the peripheral blood, recorded on at least two separate occasions, with <5% BM blasts. MDS‐U also includes cases with single‐lineage dysplasia or isolated del(5q) and pancytopenia, or defining cytogenetic abnormality and one to three lineages cytopenia.