The role of histopathology in the diagnosis of essential thrombocythemia (ET) is controversial, and there has been little attempt to quantitate interobserver variability. Diagnostic bone marrow trephine biopsy specimens from 370 patients with ET by Polycythemia Vera Study Group (PVSG) criteria were assessed by 3 experienced hematopathologists for 16 different morphologic features and overall diagnosis according to the World Health Organization (WHO) classification. Our results show substantial interobserver 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 3 hematopathologists. Factor analysis identified 3 independent factors likely to reflect underlying biologic processes. One factor related to overall and lineage-specific cellularity and was significantly associated with JAK2 V617F status (P < .001), a second factor related to megakaryocyte clustering, and a third was associated with the fibrotic process. No differences could be discerned between patients labeled 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 show that histologic 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 morphologic criteria. This study was registered at http:// isrctn.org as #72251782 and at http:// eudract.emea.europa.eu/ as #2004-000245-38. (Blood. 2008;111:60-70)

Material and methods Thirty seven consecutive outpatients who had received warfarin for not less than three months were studied. There were 20 women aged 28-73 years (mean 60 years) and 17 men aged 28-78 years (mean 59 years). Eleven had been receiving warfarin for less than one year, while eight had been treated for longer than 10 years.

The efficacy and tolerability of rIFN-alpha has been evaluated in 17 selected patients with symptomatic polycythaemia vera, diagnosed according to the PRV Study Group criteria. Complete disease control (CR) was achieved, after 1-12 months, in nine patients, with partial control in a further five cases. Three patients failed to respond. Pruritus significantly improved in 83% (10/12) of cases, following 1-28 weeks of treatment. Six patients (35%), however, were unable to tolerate rIFN-alpha, on account of weight loss, myalgia and mental changes. Overall, alpha-interferon therapy significantly improved venesection requirements, MCV and PCV values, platelet counts, pruritus scores and the degree of splenomegaly. Analysis of pooled published data (100 evaluable patients, including the present study) revealed an overall CR of 60%, a PR of 27%, and a failure rate of 13%. Significant pruritus control (> 50% improvement) occurred in 77% of cases. rIFN-alpha appears to be an effective therapy for PV-associated myeloproliferation and/or pruritus, although side-effects remain a concern. Long-term studies are now indicated to determine if the natural history of the disease is altered, in particular whether the incidence of myelofibrosis and/or leukaemic transformation is reduced.

Deletions of the long arm of chromosome 20 are associated with several myeloid malignancies and, in particular, with myeloproliferative disorders and myelodysplastic syndromes (MDS). Together with deletions of chromosome 5q and chromosome 7q, chromosome 20q deletions have previously been thought to be restricted to myeloid cells in patients with MDS. We report here that deletion of chromosome 20q in MDS can arise in a multipotent precursor of both myeloid cells and B cells. Clonal Epstein-Barr virus (EBV)-transformed cell lines, both with and without a 20q deletion, have been isolated from a patient with MDS. Moreover, these cell lines have been shown to provide a useful physical mapping tool and have been used to confirm the interstitial nature of the 20q deletion. Microsatellite polymerase chain reaction (PCR) and PCR analysis of PGK gene methylation have been used to study highly purified populations of peripheral blood cells. The 20q deletion was detectable by microsatellite PCR in peripheral blood granulocytes and monocytes but not in B cells or T cells. Clonality of the different lineages followed the same pattern as the 20q deletion. This represents the first report in which a chromosome abnormality associated with MDS has been immortalized in an EBV-transformed lymphoblastoid cell line. Furthermore, our data show that patients with apparent myeloid restriction of a chromosome deletion may in fact have a disease arising in a multipotent cell with both myeloid and lymphoid potential.

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