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Blood, 1 January 2008, Vol. 111, No. 1, pp. 1-2. This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Peterson, L. Search for Related Content PubMed Articles by Peterson, L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Next Article  CLINICAL TRIALS AND OBSERVATIONS Comment on Wilkins et al, page 60 Prefibrotic myelofibrosis: is this diagnosis valid? LoAnn Peterson FEINBERG SCHOOL OF MEDICINE, NORTHWESTERN UNIVERSITY Wilkins and colleagues evaluate the utility of the World Health Organization (WHO) diagnostic criteria intended to separate cases previously classified as essential thrombocythemia (ET) into 2 groups: "true ET" and "prefibrotic myelofibrosis." Focusing on bone marrow histology, the authors found substantial variation in classification of cases. Primary myelofibrosis (PMF) is a clonal myeloproliferative disorder (MPD) characterized by a proliferation of abnormal megakaryocytes, reactive bone marrow fibrosis, and extramedullary hematopoiesis (see figure). In 2001, the World Health Organization (WHO) published criteria for diagnosing MPDs and included the concept of "prefibrotic myelofibrosis," which is meant to represent the early stage of PMF.1 The diagnostic criteria in the WHO classification emphasize bone marrow histology and are based largely on multiple publications from a group that has studied trephine biopsy specimens from patients with MPDs.2 This group suggested that many patients diagnosed with ET using the Polycythemia Vera Study Group (PVSG) criteria actually have prefibrotic myelofibrosis, and further suggested that bone marrow biopsies from patients with thrombocythemia can be reliably subdivided into prefibrotic MF and ET and that there is an apparent reduction in life expectancy in the patients with prefibrotic MF compared with true ET.3 View larger version (76K): [in this window] [in a new window]   Bone marrow biopsy from patient with early primary myelofibrosis. (Left) The marrow is hypercellular with clusters of abnormal megakaryocytes. (Right) Reticulin stain highlights reticulin fibrosis with reticulin surrounding megakaryocytes.   The findings from Wilkins and colleagues are important because diagnosis of prefibrotic myelofibrosis has been controversial and has generated much discussion among those interested in MPDs. Prefibrotic MF is also included in the revised WHO criteria,4 but there is little prospective data available to validate the diagnostic criteria for distinguishing prefibrotic MF from ET. The current study by Wilkins and colleagues is large and well done. Three experienced hematopathologists independently reviewed bone marrow trephine biopsies from 370 patients with ET that was diagnosed using the PVSG criteria. Biopsies were evaluated for 16 morphologic features reported to be of value in distinguishing prefibrotic MF from ET. Cases were categorized into ET or prefibrotic MF according to the WHO classification. The researchers found substantial interobserver variability in the classification of these cases, even though there was reasonable agreement about several of the histological features. No difference was found in clinical outcome between those cases classified as ET versus those classified as prefibrotic MF. The findings of this report suggest that the published histological criteria for distinguishing ET from prefibrotic MF are difficult to apply reproducibly. This does not mean that the criteria are invalid, however. The study could be criticized on the grounds that the investigators were relying on biopsy morphology with limited clinical information (age and sex only), with no laboratory data or blood films to examine. It is possible that evaluating other clinical and laboratory features along with histopathology would have increased the reproducibility of the classification. It is interesting that the rate of transformation to myelofibrosis in the patient population studied was extremely low even though the median follow-up was 68 months. This low rate of progression raises the possibility that the population had a very small number of prefibrotic MF patients, making the detection of the subgroup difficult. As the authors indicate, even experienced hematopathologists may need specialized training to identify prefibrotic MF, but the study addressed the utility of the criteria in a real practice setting. This paper will undoubtedly stimulate additional discussion regarding the classification of the MPDs. It provides further insight into our understanding of the classification MPDs at a time when our knowledge is being enhanced and diagnostic criteria revised by the recent and ongoing discoveries of JAK2 and other mutations5,6 in these neoplasms. Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. REFERENCES Thiele J, Pierre R, Imbert M, et al. Chronic idiopathic myelofibrosis. In Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds.). World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues2001;Lyon, France IARC Press pp. 35–38. Thiele J, Kvasnicka HM, Boeltken B, et al. Initial (prefibrotic) stages of idiopathic (primary) myelofibrosis (IMF)—a clinicopathological study. Leukemia 1999; 13:1741–1748.[CrossRef][Medline] [Order article via Infotrieve] Thiele J, Kvasnicka HM, Orazi A. Bone marrow histopathology in myeloproliferative disorders—current diagnostic approach. Semin Hematol 2005; 42:184–195.[CrossRef][Medline] [Order article via Infotrieve] Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 2007; 110:1092–1097.[Abstract/Free Full Text] Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365:1054–1061.[Medline] [Order article via Infotrieve] Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders N Engl J Med 2005; 352:1779–1790.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Bone marrow pathology in essential thrombocythemia: interobserver 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 Blood 2008 111: 60-70. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Peterson, L. Search for Related Content PubMed Articles by Peterson, L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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