Myelodysplastic Syndrome: Approach to Diagnosis in the Era of Personalized Medicine

Myelodysplastic syndrome (MDS) is best understood as a gradual replacement of the healthy bone marrow cells by a neoplastic clone that, despite having an advantage over the healthy cells in terms of proliferation, is incapable of full maturation into a functional hematopoietic product. The chief initial clinical consequence of MDS is, therefore, cytopenia of one or more myeloid lineages, as well as the symptoms that would accompany those cytopenias, such as fatigue, bleeding, or infection. Although this definition broadly applies to MDS, not all cases are the same. The disease course may be indolent or aggressive. It may progress as ever worsening cytopenia with increasing transfusion dependence, or may transform into acute myeloid leukemia (AML). It is therefore necessary to tailor a patient's treatment to their expected disease course. Predicting this disease course requires incorporation of many factors, including patient demographics, clinical history, laboratory parameters, morphology, cytogenetics, and molecular analysis. Knowledge of all these data points is necessary to categorize MDS into any of its many subcategories.1 They can not only inform the aggressiveness of the treatment plan, but in some cases even suggest a specific therapeutic strategy, maximizing benefit and minimizing harm to the patient. It is critical for the pathologist to understand how the data generated in the work up of MDS are useful for treatment of the patient, as this will determine what is highlighted in the pathologic report, what aspects of the workup require the most careful scrutiny, and what avenues of research might be most fruitful for improving the management of MDS patients in the future.

In addition to identifying which factors contribute to prognostication in MDS, one must also integrate the various data points to produce a coherent, overall estimate of the expected prognosis. The International Prognostic Scoring System (IPSS)2 was developed for this purpose in 1997, while the more recent Revised International Prognostic Scoring System (IPSS-R)3 was published in 2012; the IPSS-R is shown in Table 1. How each stage of the workup of MDS factors both into the WHO classification and into the IPSS-R will be discussed throughout this review. However, the review will also describe numerous findings that, though too recently established to have been included in the IPSS-R, are nonetheless of prognostic significance. It will also describe the IPSS-M, a proposed successor to the IPSS-R that incorporates molecular data to improve the prognostic capabilities of the traditional scoring system.

This review will also discuss significant differences between the Revised 4th Edition of the WHO Classification and the forthcoming 5th Edition (WHO-HAEM5)4, as well as the recommendations of the International Consensus Classification (ICC)5. For example, the WHO-HAEM5 has replaced the term “myelodysplastic syndrome” with “myelodysplastic neoplasm”; however, it retains the abbreviation “MDS” regardless.

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