2016 World Health Organization (WHO) Classification

The WHO recognizes 6 main types of myelodysplastic syndromes (MDS) and distinguishes subtypes on the basis of blood and bone marrow findings.1

The 5 criteria for classification include dysplastic lineages, cytopenias, ring sideroblasts as a percentage of marrow erythroid elements, bone marrow (BM) and peripheral blood (PB) blasts, and cytogenetics.

WHO classification (2016)1

Criteria for Classification Main Types of MDS
  • Dysplastic lineages
  • Cytopenias
  • Ring sideroblasts as % of bone marrow erythroid elements
  • BM and PB blasts
  • Cytogenetics
  • MDS with single lineage dysplasia (MDS-SLD)
  • MDS with multilineage dysplasia (MDS-MLD)
  • MDS with isolated del(5q)
  • MDS with ring sideroblasts (MDS-RS)
  • MDS with excess blasts (MDS-EB)
  • MDS, unclassified (MDS-U)

BM, bone marrow; PB, peripheral blood; WHO, World Health Organization.

MDS subtypes: descriptions based on blood and bone marrow findings

Name2 Dysplastic Lineages Cytopeniasa Ring Sideroblastsb BM and PB Blasts Cytogeneticsc
MDS with single lineage dysplasia (MDS-SLD) 1 1 or 2 <15%/<5%d BM <5%, PB <1%, no Auer rods Any, unless fulfills all criteria for MDS with isolated del(5q)
MDS with multilineage dysplasia (MDS-MLD) 2 or 3 1-3 <15%/<5%d BM <5%, PB <1%, no Auer rods Any, unless fulfills all criteria for MDS with isolated del(5q)
MDS with ring sideroblasts (MDS-RS)
MDS-RS with single lineage dysplasia (MDS-RS-SLD) 1 1 or 2 ≥15%/≥5%d BM <5%, PB <1%, no Auer rods Any, unless fulfills all criteria for MDS with isolated del(5q)
MDS-RS with multilineage dysplasia (MDS-RS-MLD) 2 or 3 1-3 ≥15%/≥5%d BM <5%, PB <1%, no Auer rods Any, unless fulfills all criteria for MDS with isolated del(5q)
MDS with isolated del(5q) 1-3 1-2 None or any BM <5%, PB <1%, no Auer rods del(5q) alone or with 1 additional abnormality except -7 or del(7q)
MDS with excess blasts (MDS-EB)
MDS-EB-1 0-3 1-3 None or any BM 5%-9%, or PB 2%-4%, no Auer rods Any
MDS-EB-2 0-3 1-3 None or any BM 10%-19%, or PB 5%-19%, no Auer rods Any
MDS, unclassified (MDS-U)
With 1% blood blasts 1-3 1-3 None or any BM <5%, or PB=1%e, Auer rods Any
With single lineage dysplasia and pancytopenia 1 3 None or any BM <5%, or PB <1%, no Auer rods Any
Based on defining cytogenetic abnormality 0 1-3 <15%f BM <5%, or PB <1%, no Auer rods MDS-defining abnormality
Refractory cytopenia of childhood 1-3 1-3 None BM <5%, or PB <2%, no Auer rods Any

aCytopenias defined as: hemoglobin <10 g/dL; platelet count <100 x 109/L; and absolute neutrophil count <1.8 x 109/L. Rarely, MDS may present with mild anemia or thrombocytopenia above these levels. PB monocytes must be <1 x 109/L.

bAs a % of marrow erythroid elements.

cBy conventional karyotype analysis.

dIf SF3B1 mutation is present.

eOne percent PB blasts must be recorded on at least 2 separate occasions.

fCases with ≥15% ring sideroblasts by definition have significant erythroid dysplasia, and are classified as MDS-RS-SLD.

BM, bone marrow; PB, peripheral blood; SF3B1, splicing factor 3B subunit 1.

The basic diagnostic principles of the WHO classification remain consistent; however, updates in 2016 include1:

  • No longer using “refractory anemia” and “refractory cytopenia” and replacing them with MDS followed by the appropriate modifiers: single vs multilineage dysplasia, ring sideroblasts, excess blasts, or del(5q)
  • MDS with isolated del(5q) may be diagnosed if there is 1 additional cytogenetic abnormality besides del(5q), unless the abnormality is monosomy 7 or del(7q)
  • Ring sideroblasts ≥5% and presence of splicing factor 3B subunit 1 (SF3B1) mutation will be classified as MDS with ring sideroblasts (MDS-RS). At least 15% ring sideroblasts are required for an MDS-RS diagnosis in cases lacking a demonstrable SF3B1 mutation
  • MDS-RS cases will be subdivided into cases with single lineage dysplasia (previously classified as refractory anemia with ring sideroblasts) and cases with multilineage dysplasia (previously classified as refractory cytopenia with multilineage dysplasia)
  • In the updated classification, the denominator used for calculating blast percentage in all myeloid neoplasms is all nucleated bone marrow cells, not just the “nonerythroid cells.” This will result in the majority of cases previously diagnosed as the erythroid/myeloid subtype of acute erythroid leukemia now being classified as MDS with excess blasts

References: 1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. 2. Hong M, He G. The 2016 revision to the World Health Organization classification of myelodysplastic syndromes. J Transl Int Med. 2017;5(3):139-143.