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Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification

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Abstract

Morphology is the basis of the diagnosis of myelodysplastic syndromes (MDS). The WHO classification offers prognostic information and helps with the treatment decisions. However, morphological changes are subject to potential inter-observer variance. The aim of our study was to explore the reliability of the 2008 WHO classification of MDS, reviewing 100 samples previously diagnosed with MDS using the 2001 WHO criteria. Specimens were collected from 10 hospitals and were evaluated by 10 morphologists, working in five pairs. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. The second observer was blinded to the clinical and laboratory data, except for the peripheral blood (PB) counts. Nineteen cases were considered as unclassified MDS (MDS-U) by the 2001 WHO classification, but only three remained as MDS-U by the 2008 WHO proposal. Discordance was observed in 26 of the 95 samples considered suitable (27 %). Although there were a high number of observers taking part, the rate of discordance was quite similar among the five pairs. The inter-observer concordance was very good regarding refractory anemia with excess blasts type 1 (RAEB-1) (10 of 12 cases, 84 %), RAEB-2 (nine of 10 cases, 90 %), and also good regarding refractory cytopenia with multilineage dysplasia (37 of 50 cases, 74 %). However, the categories with unilineage dysplasia were not reproducible in most of the cases. The rate of concordance with refractory cytopenia with unilineage dysplasia was 40 % (two of five cases) and 25 % with RA with ring sideroblasts (two of eight). Our results show that the 2008 WHO classification gives a more accurate stratification of MDS but also illustrates the difficulty in diagnosing MDS with unilineage dysplasia.

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References

  1. Tefferi A, Vardiman JW (2009) Myelodysplastic syndromes. N Engl J Med 361:1872–1885

    Article  PubMed  CAS  Google Scholar 

  2. Brunning RD, Orazi A, Germing U, Le Beau MM, Porwit A, Baumann I, Vardiman JW, Hellstrom-Lindberg E (2008) Myelodysplastic syndromes/neoplasms, overview. In: Swerdlow SH, Campo E, Harris NL et al (eds) World Health Organization classification of tumours of haematopoietic and lymphoid tissues, 4th edn. IARC, Lyon, pp 88–93

    Google Scholar 

  3. Brunning RD, Bennett JM, Flandrin G, Matutes E, Head D, Vardiman JW, Harris NL (2001) Myelodysplastic syndromes. Introduction. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, pp 63–67

    Google Scholar 

  4. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951

    Article  PubMed  CAS  Google Scholar 

  5. Howe RB, Porwit-MacDonald A, Wanat R, Tehranchi R, Hellström-Lindberg E (2004) The WHO classification of MDS does make a difference. Blood 103:3265–3270

    Article  PubMed  CAS  Google Scholar 

  6. Naqvi K, Jabbour E, Bueso-Ramos C, Pierce S, Borthakur G, Estrov Z et al (2011) Implications of discrepancy in morphologic diagnosis of myelodysplastic syndrome between referral and tertiary care centers. Blood 118:4690–4693

    Article  PubMed  CAS  Google Scholar 

  7. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088

    PubMed  CAS  Google Scholar 

  8. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C (1982) French–American–British (FAB) Cooperative Group. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51:189–199

    PubMed  CAS  Google Scholar 

  9. Verburgh E, Achten R, Louw VJ, Brusselmans C, Delforge M, Boogaerts M et al (2007) 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 21:668–677

    PubMed  CAS  Google Scholar 

  10. Mufti GJ, Bennett JM, Goasguen J, Bain BJ, Baumann I, Brunning R et al (2008) Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of Myelodysplastic Syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica 93:1712–1717

    Article  PubMed  Google Scholar 

  11. Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R et al (2007) Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 25:3503–3510

    Article  PubMed  Google Scholar 

  12. Matsuda A, Germing U, Jinnai I, Iwanaga M, Misumi M, Kuendgen A et al (2007) Improvement of criteria for refractory cytopenia with multilineage dysplasia according to the WHO classification based on prognostic significance of morphological features in patients with refractory anemia according to the FAB classification. Leukemia 21:678–686

    PubMed  CAS  Google Scholar 

  13. Germing U, Gattermann N, Strupp C, Aivado M, Aul C (2000) Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 24:983–992

    Article  PubMed  CAS  Google Scholar 

  14. Germing U, Strupp C, Kuendgen A, Isa S, Knipp S, Hildebrandt B et al (2006) Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica 91:1596–1604

    PubMed  Google Scholar 

  15. Patnaik MM, Hanson CA, Sulai NH, Hodnefield JM, Knudson RA, Ketterling RP et al (2012) Prognostic irrelevance of ring sideroblast percentage in World Health Organization defined myelodysplastic syndromes without excess blasts. Blood 119:5674–5677

    Article  PubMed  CAS  Google Scholar 

  16. Kantarjian H, O’Brien S, Ravandi F, Cortes J, Shan J, Bennett JM et al (2008) Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 113:1351–1361

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Celgene provided a grant to the Asociación Madrileña de Hematología y Hemoterapia (AMHH) for the courier service. The authors would like to thank Angel Cedillo (AMHH) for his help in the exchange of samples among the hospitals and Jose María Bellón for the statistical analysis. We thank Lawrence JC Baron for providing language support and Dolores Subirá for her useful comments.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology, Hospital General Universitario Gregorio Marañon, Madrid, Spain

    P. Font & P. Balsalobre

  2. Department of Hematology, Hospital Universitario de La Princesa, Madrid, Spain

    J. Loscertales

  3. Department of Hematology, Hospital Clinico San Carlos, Madrid, Spain

    C. Benavente & A. Villegas

  4. Department of Hematology, Hospital Universitario de Fuenlabrada, Madrid, Spain

    A. Bermejo

  5. Department of Hematology, Hospital Universitario Principe de Asturias, Madrid, Spain

    M. Callejas & M. Lopez-Rubio

  6. Department of Hematology, Hospital Universitario de Getafe, Madrid, Spain

    L. Garcia-Alonso

  7. Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain

    A. Garcia-Marcilla & E. Martin

  8. Department of Hematology, Hospital Universitario Puerta de Hierro, Madrid, Spain

    S. Gil

  9. Department of Hematology, Hospital Universitario Infanta Leonor, Madrid, Spain

    C. Muñoz

  10. Department of Hematology, Hospital Universitario Fundacion Alcorcon, Madrid, Spain

    P. Ricard

  11. Department of Hematology, Fundación Jiménez Díaz, Madrid, Spain

    C. Soto

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  1. P. Font
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  2. J. Loscertales
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  3. C. Benavente
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  5. M. Callejas
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  6. L. Garcia-Alonso
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  7. A. Garcia-Marcilla
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  8. S. Gil
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  9. M. Lopez-Rubio
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  10. E. Martin
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  11. C. Muñoz
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  12. P. Ricard
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  13. C. Soto
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  14. P. Balsalobre
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  15. A. Villegas
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Correspondence to P. Font.

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Font, P., Loscertales, J., Benavente, C. et al. Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification. Ann Hematol 92, 19–24 (2013). https://doi.org/10.1007/s00277-012-1565-4

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  • DOI: https://doi.org/10.1007/s00277-012-1565-4

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