Essential thrombocythemia manifesting as livedoid and purpuric skin lesions: Report of two cases and literature review.

Essential thrombocythemia is a chronic myeloproliferative syndrome which usually runs its course as an asymptomatic elevated platelet count. Cutaneous manifestations secondary to microcirculation abnormalities are rare but can represent a helpful diagnostic clue in order to prevent major thromboembolic events. We report two cases of heterogeneous livedoid and "net-like" skin lesions in the context of essential thrombocythemia with identical histopathologic findings (medium-sized blood vessels with luminal obliteration by eosinophilic material, mostly positive for the platelet marker CD61, without vasculitis). In conclusion, we seek to raise awareness of the clinicopathological features of essential thrombocythemia to allow for prompt diagnosis and treatment.

Practical tips for managing FLT3 mutated acute myeloid leukemia with midostaurin.

INTRODUCTION: FLT3 inhibitors have been recently introduced as novel treatment targets in patients with FLT3-mutated acute myeloid leukemia (AML). Midostaurin is an oral multikinase inhibitor that targets multiple receptor tyrosine kinases including FLT3 and has been approved for the treatment of AML with FLT3 mutations in patients candidates for intensive chemotherapy. This article presents an updated overall overview of the use of midostaurin in clinical practice. AREAS COVERED: Tests and examinations to be performed before the use of midostaurin, antifungal and antimicrobial treatment, as well as antifungal and antimicrobial prophylaxis are discussed. Practical tips for the treatment of QTc interval prolongation and heart failure are also presented. EXPERT OPINION: Midostaurin is the first agent showing significant survival benefit when combined with chemotherapy in FLT3-mutated AML patients. Optimal use of midostaurin should be a priority, being essential to know the interactions with other drugs like strong CYP3A4 inhibitors or inducers, which are particularly used in the concomitant treatment of AML patients and may increase toxicity or decrease therapeutic benefit. The active role of hematologists and nursing teams is crucial to ensure patient adherence to midostaurin treatment and to minimize adverse effects by administrating the optimal dose for each situation.

Strategy for identification of a potential inherited leukemia predisposition in a 299 patient's cohort with tumor-only sequencing data.

Myeloid neoplasms (MN) are usually sporadic late-onset cancers; nevertheless, growing evidence suggests that ∼5% of the cases could emerge as a consequence of inherited predisposition. Distinguishing somatic from germline variants is of vital importance, in order to establish an appropriate individualized management and counsel the patients and their relatives. Since many of the genes associated with myeloid neoplasm germline predisposition (MNGP) are also affected in sporadic MN, we intended to design a strategy to identify potentially inherited variants in a tumor only NGS panel in a cohort of 299 patients with a variety of MN. We considered as indicative of potential inherited origin, variants detected in BM sample at a ∼50% VAF classified as pathogenic, likely pathogenic or of unknown significance detected in MNGP-related genes. A total of 104 suspicious variants from 90 patients were filtered-in in tumor samples. Mutational patterns, follow-up data, and sequencing of a range of non-myeloid tissues were used for narrowing down the list of suspicious variants, and ultimately discriminate their nature. Our data supports the importance of considering variants found upon tumor-only sequencing as potentially of germline origin, and we offer a pipeline to define the nature of the variants.