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Background: MYH9-related disease (MYH9-RD) is a rare autosomal dominant genetic syndrome characterized by congenital thrombocytopenia associated with the risk of developing progressive nephropathy, sensorineural deafness, and presenile cataract. During the collection of a large case-series of patients with MYH9-RD we noticed several cases with unexplained elevation of liver enzymes. Our aim was to evaluate if the alteration of liver tests is a feature of the MYH9-RD and to define its clinical significance. Methods and Findings: Data concerning liver tests, prospectively recorded in the Italian Registry for MYH9-RD, were collected and compared with those of three control populations: patients with autoimmune thrombocytopenia, patients with inherited thrombocytopenias other than MYH9-RD, and the participants to a large epidemiologic survey in an Italian geographic isolate. Thirty-eight of 75 evaluable MYH9-RD patients (50.7%) showed an elevation of ALT and/or AST, and 17 of 63 (27.0%) an increase of GGT. The increases ranged from 1.9±0.7 to 2.7±1.6 fold the upper normal limit. The prevalence of liver test alterations was significantly higher in MYH9-RD patients than in each of the control populations, with odds ratios ranging from 8.2 (95% CIs 2.2-44.8) to 24.7 (14.8-40.8). Clinical follow-up and more detailed liver studies of a subset of patients, including ultrasound liver scan, liver elastography and liver biopsy in one case, did not show any significant structural damage or evolution towards liver insufficiency. Conclusions: Elevation of liver enzymes is a frequent and previously unrecognized feature of the MYH9-RD syndrome; however, this defect does not appear to have poor prognostic value. [ABSTRACT FROM AUTHOR]

Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54-17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8x109/L or lower, and platelet count of 4006109/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45-13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment. [ABSTRACT FROM AUTHOR]

Background: The marginal zone is an anatomically distinct B-cell compartment of lymphoid tissue with an abundant antigenic influx. Among marginal zone-derived lymphomas the WHO classification listed, in addition to extranodal marginal zone B-cell lymphoma of MALT type, two other marginal zone B-cell neoplasms: splenic marginal zone B-cell lymphoma (+/- villous lymphocytes) and nodal marginal zone B-cell lymphoma (+/- monocytoid B cells). These two entities are well characterized histologically, but specific biological markers are lacking. Treatment options are heterogeneous, including a watch-and-wait policy, surgery with or without chemotherapy, purine analogs, and interferon. No prospective studies have been conducted so far., Information Sources: Clinical and pathologic data were reviewed by searches of the published medical literature, including searches in PubMed , important printed publications, and abstracts presented at recent hematology and pathology meetings., State of the Art: Splenic and nodal marginal zone lymphomas are typical low-grade lymphomas with an indolent course. A subset of patients, however, presents with more aggressive disease and have a shorter survival. Clinical and biological prognostic factors identified in reported series are heterogeneous. The role played by hepatitis C virus (HCV) in marginal zone lymphomas is not fully elucidated, but there is demonstration that eradication of HCV infection in splenic lymphoma with villous lymphocytes causes regression of the lymphoma. The optimal treatment has not yet been identified. Retrospective series, however, show that splenectomy is a good option if symptoms from the presence of spleen enlargement or cytopenias need to be treated. The utility of purine analogs and of anti-CD20 immunotherapy needs to be clarified in prospective trials., Perspectives: Clinicians and pathologists should co-operate to define stringent diagnostic criteria for these indolent disorders. The optimal therapeutic approach and the role of new treatments need to be assessed in prospective clinical trials.