Highlights of 2008 in bone marrow biopsy pathology

The fiftieth anniversary of Blood saw the publication of a series of excellent review articles. The myeloproliferative disorders [1] were first characterised by Gustav Heuck who described myelofibrosis (MF) in 1879. Louis Henri Vaquez described polycythemia vera (PV) in 1892. Essential thrombocythemia (ET) followed somewhat later in 1934 when Emil Epstein and Alfred Goedel recognised it as a distinct clinical syndrome. William Dameshek, however, noted the overlapping clinical features of the three disorders and preferred to consider them ‘closely interrelated’. This clinical observation has considerable relevance to later developments, in particular the identification of JAK2 in all three myeloproliferative neoplasms (MPNs). Currently, JAK2 gene dosage is thought to distinguish PV from JAK2-positive ET. Familial studies have given support to the idea that additional inherited alleles are implicated in the pathogenesis of MPNs and that these remain unidentified. It is also possible that there are inherited modifiers that, whilst not predisposing to the development of MPN, may contribute to the clinical phenotype of JAK2-positive MPN. In addition, data suggest that there may be ‘pre-JAK2’ alleles responsible for clonal haemopoiesis that does not manifest as a clinical MPN. The progression of JAK2positive MPN to JAK2-negative acute leukaemia supports the existence of a JAK2-negative progenitor. Studies of JAK2-negative MPNs have identified variant MPLW515L in JAK2-negative ET associated with marked thrombocytosis and myelofibrosis. A second excellent review on the history of myeloproliferative disorders before and after Dameshek gives further insight into the history of the haematology of the MPNs [2]. The revised 2008 World Health Organisation (WHO) classification included significant revisions to the classification of MPN, including their designation as ‘neoplasms’ and the introduction of ‘primary myelofibrosis’ as a replacement term for ‘chronic idiopathic myelofibrosis’ [3]. Clinical guidance and a useful series of diagnostic algorithms were published by Tefferi and Vardiman [4]. The importance of both the bone marrow biopsy and molecular characterisation is emphasised. The authors remind us that not all cases can be classified and these should be placed into the ‘MPN, unclassifiable’ category when this is the case and closely followed to monitor any changes that might warrant revision of the diagnosis. Spivak and Silver [5] emphasised the variability of the phenotype of the MPNs and the changes that may take place over time as the disease progresses. The ongoing controversy over the reliability of histology of the bone marrow in distinguishing the categories of MPN and the ability to recognise a ‘pre-fibrotic’ phase of primary myelofibrosis is discussed and an alternative proposal based on clinical parameters is proposed. The biologically unsatisfactory adoption of ‘primary’ myelofibrosis was noted. It is clear that J Hematopathol (2009) 2:42–44 DOI 10.1007/s12308-009-0025-0