• Current WHO criteria are inadequate for diagnosing "early-stage" PV.• Hemoglobin and hematocrit values are inadequate surrogate markers for erythrocytosis.We prospectively evaluated the accuracy of the 2007 World Health Organization (WHO) criteria for diagnosing polycythemia vera (PV), especially in "early-stage" patients.A total of 28 of 30 patients were diagnosed as PV owing to an elevated Cr-51 red cell mass (RCM), JAK2 positivity, and at least 1 minor criterion. A total of 18 PV patients did not meet the WHO criterion for an increased hemoglobin value and 8 did not meet the WHO criterion for an increased hematocrit value. Bone marrow morphology was very valuable for diagnosis. Low serum erythropoietin (EPO) values were specific for PV, but normal EPO values were found at presentation (20%). We recommend revision of the WHO criteria, especially to distinguish early-stage PV from essential thrombocythemia. Major criteria remain JAK2 positivity and increased red cell volume, but Cr-51 RCM is mandatory for patients who do not meet the defined elevated hemoglobin or hematocrit value (>18.5 g/dL and 60% in men and >16.5 g/dL and 56% in women, respectively). Minor criteria remain bone marrow histology or a low serum EPO value. For patients with a normal EPO value, marrow examination is mandatory for diagnostic confirmation. Because the therapies for myeloproliferative disorders differ, our data have major clinical implications. (Blood. 2013;122(11):1881-1886 IntroductionIn 2007, the World Health Organization (WHO) published consensus criteria for the diagnosis of Philadelphia-negative myeloproliferative neoplasms (MPNs), of which the most common are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).1 However, these criteria have never been objectively evaluated prospectively. 2 The importance of distinguishing these diseases in their early phase rests upon differences in treatment and prognosis.3,4 A recent study, 5 for example, showed that patients with PV should have a target hematocrit of less than 45% which significantly lowers the risk of cardiovascular death and major thrombosis.The 2007 WHO criteria for the diagnosis of PV include 2 major criteria and 3 minor criteria. Major criteria include (1) hemoglobin .18.5 g/dL in men, 16.5 g/dL in women, or other evidence of increased red cell volume (RCV); and (2) presence of JAK2V617F or other functionally similar mutation such as JAK2 exon 12 mutation. Minor criteria include (1) bone marrow biopsy specimen showing hypercellularity for age with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation; (2) serum erythropoietin (EPO) level below the reference range for normal; and (3) endogenous erythroid colony formation in vitro. Diagnosis requires the presence of both major criteria and 1 minor criteria or the presence of the first major criterion together with 2 minor criteria.It is generally accepted that the JAK2 V617F mutation or other JAK2 mutations (exon 12) is present in...

urrent treatment for angiosarcomas of the scalp, face, and neck typically involves surgery, radiotherapy, and neoadjuvant and/or adjuvant chemotherapy with doxorubicin hydrochloride or taxanes; yet, even following aggressive therapy, patient survival is abysmal. 1-4 Use of β-blockers, such as propranolol hydrochloride, has shown remarkable efficacy against benign vascular tumors, 5 and the use of β-blockers has been reported in a retrospective analysis to increase patient survival and reduce tumor metastasis and/or recurrence in several major cancer types. 6 We report that monotherapy with the β-blocker propranolol is capable of reducing the proliferative index of a cutaneous angiosarcoma. In addition, the combination of propranolol, paclitaxel, and radiotherapy led to substantial regression of a cutaneous facial angiosarcoma. Institutional review board approval for working with tissue samples donated by the patient was granted by Texas Tech University Health Sciences Center. Patient and family consent was verbal and documented.

Patients with metastatic angiosarcoma undergoing chemotherapy, radiation, and/or surgery experience a median progression free survival of less than 6 months and a median overall survival of less than 12 months. Given the aggressive nature of this cancer, angiosarcoma clinical responses to chemotherapy or targeted therapeutics are generally very poor. Inhibition of beta adrenergic receptor (β-AR) signaling has recently been shown to decrease angiosarcoma tumor cell viability, abrogate tumor growth in mouse models, and decrease proliferation rates in preclinical and clinical settings. In the current study we used cell and animal tumor models to show that β-AR antagonism abrogates mitogenic signaling and reduces angiosarcoma tumor cell viability, and these molecular alterations translated into patient tumors. We demonstrated that non-selective β-AR antagonists are superior to selective β-AR antagonists at inhibiting angiosarcoma cell viability. A prospective analysis of non- selective β-AR antagonists in a single arm clinical study of metastatic angiosarcoma patients revealed that incorporation of either propranolol or carvedilol into patients' treatment regimens leads to a median progression free and overall survival of 9 and 36 months, respectively. These data suggest that incorporation of non-selective β-AR antagonists into existing therapies against metastatic angiosarcoma can enhance clinical outcomes.

No abstract