A comprehensive approach to the diagnosis of MDS after triage by morphology towards cytogenetics and other techniques

The myelodysplastic syndromes (MDS) are heterogeneous disorders ranging from rather stable conditions such as 5q- to advanced stages close to acute leukaemia. The variability of the clinical course, of cytomorphological phenotypes, and of genetic aberrations outlines MDS classification as a major challenge. However, therapeutic options became more differentiated e.g. due to lenalidomide or reduced intensity conditioning in allogeneic transplantation and require a more detailed risk stratification. Established classification systems as the FAB were mainly based on cytomorphological criteria implicating some problems e.g. of interobserver variability. The WHO proposal of 2001 which subdivided MDS into 10 subtypes focused as well mainly on cytomorphology, but took in addition cytogenetics with respect to the 5q- syndrome into account. Another important classification system is represented by the International Prognostic Scoring System (IPSS) of 1997 which offers an accurate biologically based classification and prognostication. Multiparameter flow cytometry (MFC) and molecular techniques may contribute increasingly by detection of aberrant antigen expression patterns and by the finding that some mutations e.g. the FLT3-LM/ITD or NRAS are associated with leukaemic transformation. In conclusion, a multimodal approach including cytomorphology, cytogenetics, fluorescence in situ hybridization (FISH), PCR, and MFC is possible to achieve a comprehensive characterization of MDS. Diagnostic algorithms providing a hierarchy of methods to guarantee an efficient work-flow, to provide all parameters necessary for classification and for minimal-residual-disease (MRD) strategies, and to guide new treatment strategies are needed.