Chronic myeloid neoplasms
Myelodysplastic syndromes
MDS - WHO classification

Author: Nikhil Sangle, M.D.
Editorial Board Member Review: Genevieve M. Crane, M.D., Ph.D.

Revised: 12 October 2018, last major update August 2011

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: MDS WHO classification

Cite this page: Sangle, N. MDS - WHO classification. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/myeloproliferativemdsclasswho.html. Accessed October 22nd, 2018.
WHO 2016 classification
WHO 2016 classification (Blood 2016;127:2391, Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017):
  • MDS with ring sideroblasts (MDS-RS): associated with mutations in the spliceosome gene SF3B1, overall favorable prognosis, must not meet criteria for isolated del(5q), blasts < 5% BM, < 1% PB, no Auer rods
    • MDS-RS and single lineage dysplasia (former RARS): 1 dysplastic lineage, 1 - 2 cytopenias
    • MDS-RS and multilineage dysplasia: 2 - 3 dysplastic lineages, 1 - 3 cytopenias
  • MDS with single lineage dysplasia:
    • 1 dysplastic lineage, 1 - 2 cytopenias
    • Blasts < 5% BM, < 1% PB, no Auer rods
    • Does not meet criteria for MDS-RS or MDS with isolated del(5q)
  • MDS with multilineage dysplasia:
    • 2 - 3 dysplastic lineages, 1 - 3 cytopenias
    • Blasts < 5% BM, < 1% PB, no Auer rods
    • Does not meet criteria for MDS-RS or MDS with isolated del(5q)
  • MDS with isolated del(5q): the only cytogenetic abnormality that defines a subtype
    • Okay if 1 additional cytogenetic abnormality as long as NOT monosomy 7 or del(7q)
    • None or any ring sideroblasts, 1 - 3 dysplastic lineages, 1 - 2 cytopenias
    • Blasts < 5% BM, < 1% PB, no Auer rods
    • Generally good prognosis unless TP53 mutated
  • MDS with excess blasts: 1 - 3 dysplastic lineages, 1 - 3 cytopenias, none or any ring sideroblasts
    • MDS-EB-1: blasts 5 - 9% BM or 2 - 4% PB, no Auer rods
    • MDS-EB-2: blasts 10 - 19% BM or 5 - 19% PB or Auer rods
  • MDS, unclassifiable: 3 different ways to arrive at this diagnosis
    • MDS-U with 1% blood blasts: 1 - 3 dysplastic lineages, 1 - 3 cytopenias, none or any ring sideroblasts, < 5% BM blasts
    • MDS-U with SLD and pancytopenia: 1 dysplastic lineage, pancytopenia, none or any ring sideroblasts, blasts < 5% BM, < 1% PB, no Auer rods
    • MDS-U based on defining cytogenetic abnormality: 0 dysplastic lineages, 1 - 3 cytopenias, < 15% ring sideroblasts, blasts < 5% BM, < 1% PB, no Auer rods; MDS defining cytogenetic abnormality (see below)
  • Refractory cytopenia of childhood: provisional entity
  • Myeloid neoplasms with germline predisposition: specific underlying genetic defect or syndrome should be listed as part of the diagnosis

Major changes as compared to WHO 2008 classification for MDS (Blood 2016;127:2391):
  • More emphasis on the degree of dysplasia and blast percentage for classification than specific types of cytopenias (e.g. removed "refractory anemia" and "refractory cytopenia" from terminology, start with "myelodysplastic syndrome" followed by appropriate modifier)
  • Myeloid neoplasms with an erythroid predominance (erythroid precursors ≥ 50% of all BM cells):
    • Calculate blast percentage using all nucleated BM cells in the denominator - prior included only nonerythroid
    • Many cases of erythroid / myeloid subtype of acute erythroid leukemia will now be classified as MDS with excess blasts
  • MDS with ring sideroblasts: if an SF3B1 mutation is identified, only need 5% ring sideroblasts for diagnosis; if not identified, still need 15%
  • RARS (refractory anemia with ring sideroblasts) is now MDS-RS with single lineage dysplasia
  • New section recognizing germline predisposition to MDS, MDS / MPN and AML

Clarifications for the 2016 WHO MDS diagnoses:
  • What counts as cytopenia? hemoglobin, < 10 g/dL; platelets, < 100 × 109/L; absolute neutrophil count, < 1.8 × 109/L
  • Diagnosis of MDS may be made with milder levels of cytopenia (rarely); at least 1 cytopenia must be present
  • Threshold for dysplasia remains at 10% dysplastic cells but may still be at that level in nonneoplastic causes of cytopenias; caution advised
  • Same cytogenetic abnormalities remain MDS - defining as in the 2008 WHO in a patient with cytopenia (i.e. even without dysplasia) but must be shown by conventional karyotype (not just by FISH) - see below
    • Loss of chromosome 7 or del(7q)
    • del(5q)
    • Isochromosome 17q or t(17p)
    • Loss of chromosome 13 or del(13q)
    • del(11q)
    • del(12p) or t(12p)
    • del(9q)
    • idic(X)(q13)
    • t(11;16)(q23.3;p13.3)
    • t(3;21)(q26.2;q22.1)
    • t(1;3)(p36.3;q21.2)
    • t(2;11)(p21;q23.3)
    • inv(3)(q21.3;q26.2)/ t(3;3)(21.3;q26.2)
    • t(6;9)(p23;q34.1)
  • Cytogenetic abnormalities not sufficient (also remain from 2008 criteria):
    • Gain of chromosome 8
    • del(20q)
    • Loss of Y
WHO 2008 classification
  • Refractory anemia (RA): < 5% blasts, > 15% ringed sideroblasts; variable marrow cellularity, unicytopenia or bicytopenia, unilineage dysplasia > 10% in one myeloid lineage
  • RA with Ringed Sideroblasts (RARS): 15% or more sideroblasts, less than 5% blasts, erythroid dysplasia only
  • Refractory cytopenia with multilineage dysplasia (RCMD): cytopenia, < 5% blasts, dysplasia in > 10% of cells in two or more lineages, no Auer rods
  • RA with Excess Blasts (RAEB): type 1 has 5 - 9% blasts in blood / marrow, peripheral cytopenia, unilineage or multilineage dysplasia, no Auer rods; type 2 has 10 - 19% blasts in blood / marrow, unilineage or multilineage dysplasia, Auer rods may be present, peripheral cytopenia
  • MDS with isolated 5q- syndrome: anemia, < 5% blasts, del(5q), no Auer rods, normal / increased hypolobated megakarycoytes
  • MDS, unclassified: cytopenia(s), dysplasia in < 10% of cells in one or more myeloid cell lines, accompanied by cytogenetic abnormalities with presumptive evidence of MDS, < 5% blasts
  • Therapy related MDS
Changes of WHO 2001 from FAB
French American British (FAB) classification system for myelodysplasia (used prior to WHO)
  • Refractory anemia (RA): < 5% blasts, < 15% ringed sideroblasts; variable marrow cellularity
  • RA with Ringed Sideroblasts (RARS): 15% or more sideroblasts, less than 30% erythroblasts
  • RA with Excess Blasts (RAEB): 5 - 30% blasts in marrow, < 5% in peripheral blood
  • RA with Excess Blasts in Transformation (RAEB-T): 20 - 30% blasts in marrow, > 5% in peripheral blood (now AML in WHO classification)
  • Chronic myelomonocytic leukemia (CMML): elevated WBC, monocytosis > 1 billion/liter; trilinear dysplasia; 5 - 20% blasts in marrow, > 5% in peripheral blood
  • MDS, unclassified