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Blood, 1 January 2008, Vol. 111, No. 1, pp. 60-70. Prepublished online as a Blood First Edition Paper on September 20, 2007; DOI 10.1182/blood-2007-05-091850. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-091850v1 111/1/60    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wilkins, B. S Articles by Campbell, P. J Search for Related Content PubMed PubMed Citation Articles by Wilkins, B. S Articles by Campbell, P. J Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 23, 2007 Accepted August 8, 2007 Bone marrow pathology in essential thrombocythemia: inter-observer reliability and utility for identifying disease subtypes Bridget S Wilkins*, Wendy N Erber, David Bareford, Georgina Buck, Keith Wheatley, Clare L East, Beverley Paul, Claire N Harrison, Anthony R Green, and Peter J Campbell Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust & Newcastle University, Newcastle upon Tyne, United Kingdom Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom Department of Haematology, Russels Hall Hospital, Dudley, United Kingdom Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom Oncology Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom Department of Haematology, Bassetlaw Hospital, Worksop, United Kingdom Department of Haematology, St Thomas's Hospital, London, United Kingdom Department of Haematology, University of Cambridge, Cambridge, United Kingdom * Corresponding author; email: bridget.wilkins{at}ncl.ac.uk. The role of histopathology in the diagnosis of essential thrombocythemia (ET) is controversial and there has been little attempt to quantitate inter-observer variability. Diagnostic bone marrow trephine biopsy specimens from 370 patients with ET by PVSG criteria were assessed by three experienced hematopathologists for 16 different morphological features and overall diagnosis according to the WHO classification. Our results demonstrate substantial inter-observer variability particularly for overall diagnosis and individual cellular characteristics such as megakaryocyte morphology. Reticulin grade was the dominant independent predictor of WHO diagnostic category for all three hematopathologists. Factor analysis identified three independent factors likely to reflect underlying biological processes. One related to overall and lineage-specific cellularity, and was significantly associated with JAK2 V617F status (p=0.0002), a second factor related to megakaryocyte clustering and a third was associated with the fibrotic process. No differences could be discerned between patients labelled as having 'prefibrotic myelofibrosis' or 'true ET' in clinical and laboratory features at presentation, JAK2 status, survival, thrombosis, major hemorrhage or myelofibrotic transformation. These results demonstrate that histological criteria described in the WHO classification are difficult to apply reproducibly and question the validity of distinguishing 'true ET' from 'prefibrotic myelofibrosis' on the basis of subjective morphological criteria. This study is registered at http://isrctn.org as #72251782 and at http://eudract.emea.europa.eu/ as #2004-000245-38. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Prefibrotic myelofibrosis: is this diagnosis valid? LoAnn Peterson Blood 2008 111: 1-2. [Full Text] [PDF] This article has been cited by other articles: J. Thiele, H. M. Kvasnicka, J. W. Vardiman, A. Orazi, V. Franco, H. Gisslinger, G. Birgegard, M. Griesshammer, and A. Tefferi Bone Marrow Fibrosis and Diagnosis of Essential Thrombocythemia J. Clin. Oncol., December 1, 2009; 27(34): e220 - e221. [Full Text] [PDF] P. J. Campbell, D. Bareford, W. N. Erber, B. S. Wilkins, P. A. Wright, G. Buck, K. Wheatley, C. N. Harrison, and A. R. Green Reply to J. Thiele et al J. Clin. Oncol., December 1, 2009; 27(34): e222 - e223. [Full Text] [PDF] K. N. Naresh Classification of Philadelphia Translocation-Negative Myeloproliferative Neoplasms: Its Impact on Data From Clinical Trials J. Clin. Oncol., November 1, 2009; 27(31): e175 - e176. [Full Text] [PDF] P. J. Campbell, D. Bareford, W. N. Erber, B. S. Wilkins, P. Wright, G. Buck, K. Wheatley, C. N. Harrison, and A. 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T. Reilly, E. Morra, A. M. Vannucchi, R. A. Mesa, J.-L. Demory, G. Barosi, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment Blood, March 26, 2009; 113(13): 2895 - 2901. [Abstract] [Full Text] [PDF] J. L. Spivak and R. T. Silver The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal Blood, July 15, 2008; 112(2): 231 - 239. [Full Text] [PDF] P. A. Beer, P. J. Campbell, L. M. Scott, A. J. Bench, W. N. Erber, D. Bareford, B. S. Wilkins, J. T. Reilly, H. C. Hasselbalch, R. Bowman, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort Blood, July 1, 2008; 112(1): 141 - 149. [Abstract] [Full Text] [PDF] G. M. Bergamaschi, M. Primignani, G. Barosi, F. M. Fabris, L. Villani, R. Reati, A. Dell'Era, and P. M. 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