Abstract
This review highlights the main changes in the revised 2016 WHO Classification of Myeloid Neoplasms (published in 2017) that impact the diagnosis and management of patients with myelodysplastic syndrome (MDS). The revision was based on data accumulated since the 2008 WHO classification of MDS, much of which relates to new molecular genetic information about these neoplasms. The new information has led to some reorganization of the MDS disease categories, including a broadening of the subset of cases classified as MDS with ring sideroblasts, many of which have mutations in the spliceosome gene SF3B1. Other revisions have refined the definitions of some disease categories to improve disease risk stratification. The revised categories in the new classification ensure that MDS patients receive risk-adapted therapies based on the most recently available data.
References
1.
Arber DA, et al: The 2016 revision to the World Health Organization Classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391–2405.
2.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileria SA, Stein H, Thiele J, Arber D, Hasserjian RP, LeBeau MM, Orazi A, Siebert R (eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition. Lyon, International Agency for Research on Cancer, 2017.
3.
Busque L, et al: Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet 2012; 44: 1179–1181.
4.
Laurie CC, et al: Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nat Genet 2012; 44: 642–650.
5.
Malcovati L, et al: Clinical significance of somatic mutation in unexplained blood cytopenia. Blood 2017; 129: 3371–3378.
6.
Greenberg P, et al: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.
7.
Della Porta MG, et al: Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes. Leukemia 2014; 29: 66–75.
8.
Senent L, et al: Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes. Haematologica 2013; 98: 568–575.
9.
Brunning RD, et al: Myelodysplastic syndromes/neoplasms; in Swerdlow SH, et al. (eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, International Agency for Research on Cancer, 2008, pp 88–93.
10.
Bain BJ: The bone marrow aspirate of healthy subjects. Br J Haematol 1996; 94: 206–209.
11.
Parmentier S, et al: Assessment of dysplastic hematopoiesis: lessons from healthy bone marrow donors. Haematologica 2012; 97: 723–730.
12.
Steensma DP: Dysplasia has a differential diagnosis: distinguishing genuine myelodysplastic syndromes (MDS) from mimics, imitators, copycats and impostors. Curr Hematol Malig Rep 2012; 7: 310–320.
13.
Germing U, et al: Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the Düsseldorf Registry on myelodysplastic syndromes. Leuk Res 2012; 36: 727–734.
14.
Maassen A, et al: Validation and proposals for a refinement of the WHO 2008 classification of myelodysplastic syndromes without excess of blasts. Leuk Res 2013; 37: 64–70.
15.
Verburgh E, et al: A new disease categorization of low-grade myelodysplastic syndromes based on the expression of cytopenia and dysplasia in one versus more than one lineage improves on the WHO classification. Leukemia 2007; 21: 668–677.
16.
Wang SA, et al: Acute erythroid leukemia with < 20% bone marrow blasts is clinically and biologically similar to myelodysplastic syndrome with excess blasts. Mod Pathol 2016; 29: 1221–1231.
17.
Zhou Y, et al: Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Mod Pathol 2012; 25: 237–245.
18.
Gupta V, et al: Clinical relevance of cytogenetic abnormalities at diagnosis of acquired aplastic anaemia in adults. Br J Haematol 2006; 134: 95–99.
19.
Jacobs KB, et al: Detectable clonal mosaicism and its relationship to aging and cancer. Nat Genet 2012; 44: 651–658.
20.
Soupir CP, et al: Identification of del(20q) in a subset of patients diagnosed with idiopathic thrombocytopenic purpura. Br J Haematol 2009; 144: 800–802.
21.
Yoshida K, et al: Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011; 478: 64–69.
22.
Malcovati L, et al: Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood 2011; 118: 6239–6246.
23.
Patnaik MM, et al: Prognostic irrelevance of ring sideroblast percentage in World Health Organization-defined myelodysplastic syndromes without excess blasts. Blood 2012; 119: 5674–5677.
24.
Cazzola M, Rossi M, Malcovati L: Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms. Blood 2013; 121: 260–269.
25.
Pellagatti A, et al: Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype. Blood 2006; 108: 337–345.
26.
Germing U, et al: Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica 2006; 91: 1596–1604.
27.
Malcovati L, et al: Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005; 23: 7594–7603.
28.
Malcovati L, et al: SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood 2015; 126: 233–241.
29.
Margolskee E, et al: Myelodysplastic syndrome, unclassifiable (MDS-U) with 1% blasts is a distinct subgroup of MDS-U with a poor prognosis. Am J Clin Pathol 2017; 148: 49–57.
30.
Woll PS, et al: Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell 2014; 25: 794–808.
31.
Germing U, et al: Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study. Leukemia 2012; 26: 1286–1292.
32.
Schanz J, et al: New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol 2012; 30: 820–829.
33.
Baumann I, et al: Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria. Histopathology 2012; 61: 10–17.
34.
Yoshimi A, et al: High incidence of Fanconi anaemia in patients with a morphological picture consistent with refractory cytopenia of childhood. Br J Haematol 2013; 160: 109–111.
35.
Greenberg PL, et al: Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012; 120: 2454–2465.
36.
Malcovati L, et al: Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood 2013; 122: 2943–2964.
37.
Jadersten M, et al: TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 2011; 29: 1971–1979.
38.
Cleven AH, et al: High p53 protein expression in therapy-related myeloid neoplasms is associated with adverse karyotype and poor outcome. Mod Pathol 2015; 28: 552–563.
© 2018 S. Karger AG, Basel
2018
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