The diagnostic interface between histology and molecular tests in myeloproliferative disorders

Purpose of review The sighting of the Philadelphia chromosome in 1960, later shown to harbor the BCR-ABL mutation in chronic myeloid leukemia, is arguably the most seminal contribution to molecular oncology. In the decades that followed, other cytogenetic and molecular disease markers have been described and effectively incorporated into routine diagnostic tests. This review discusses how this process is unfolding in myeloproliferative disorders. Recent findings In 2003, a karyotypically-occult FIP1L1-PDGFRA was reported in a subset of patients with blood eosinophilia and, bone marrow mastocytosis; this mutation has since joined several other molecular markers for eosinophilic (e.g. PDGFR beta- and FGFR1-rearrangements) and mast cell (e.g. KITD816V) disorders. In 2005, JAK2V617F was described in polycythemia vera and other BCR-ABL(-) myeloproliferative disorders; the particular discovery has already had a major impact on current diagnostic approaches in polycythemia vera. These remarkable molecular discoveries are both redefining and reinforcing the diagnostic role of bone marrow histopathology. Summary Recent progress in the molecular pathogenesis of myeloproliferative disorders calls for a paradigm shift in traditional diagnostics, which is based on subjective technologies or assignment to a 'consensus'-based ever-changing list of inclusionary and exclusionary criteria. Routine clinical practice might be better served by diagnostic algorithms that incorporate molecular disease markers, which complement histological impression.