Antiphospholipid-negative Sneddon's syndrome: A comprehensive overview of a rare entity.

The term Sneddon's syndrome (SS) has been used since 1965 to describe a vasculopathy characterized by a combination of cerebrovascular disease with livedo racemosa. SS may be classified as antiphospholipid+ (aPL+) or antiphospholipid- (aPL-). Little is known about aPL- SS; in this review we describe the epidemiology and pathogenesis of aPL- SS, as well as the clinical and histologic features. We discuss recent findings in terms of neurologic and cardiac involvement. Moreover, differential diagnoses of conditions that may present with both livedo racemosa and stroke are discussed. Finally, we discuss real-life practical issues such as the initial investigations to be performed, long-term follow-up, and therapeutic management of aPL- SS patients.

Characterization of small (<4cm) solid renal masses by computed tomography and magnetic resonance imaging: Current evidence and further development.

Diagnosis of renal cell carcinomas (RCC) subtypes on computed tomography (CT) and magnetic resonance imaging (MRI) is clinically important. There is increased evidence that confident imaging diagnosis is now possible while standardization of the protocols is still required. Fat-poor angiomyolipoma show homogeneously increased unenhanced attenuation, homogeneously low signal on T2-weighted MRI and apparent diffusion coefficient (ADC) map, may contain microscopic fat and are classically avidly enhancing. Papillary RCC are also typically hyperattenuating and of low signal on T2-weighted MRI and ADC map; however, their gradual progressive enhancement after intravenous administration of contrast material is a differentiating feature. Clear cell RCC are avidly enhancing and may show intracellular lipid; however, these tumors are heterogeneous and are of characteristically increased signal on T2-weighted MRI. Oncocytomas and chromophobe tumors (collectively oncocytic neoplasms) show intermediate imaging findings on CT and MRI and are the most difficult subtype to characterize accurately; however, both show intermediately increased signal on T2-weighted with more gradual enhancement compared to clear cell RCC. Chromophobe tumors tend to be more homogeneous compared to oncocytomas, which can be heterogeneous, but other described features (e.g. scar, segmental enhancement inversion) overlap considerably between tumors. Tumor grade is another important consideration in small solid renal masses with emerging studies on both CT and MRI suggesting that high grade tumors may be separated from lower grade disease based upon imaging features.

Transition zone and anterior stromal prostate cancers: Evaluation of discriminant location criteria using multiparametric fusion-guided biopsy.

PURPOSE: The purpose of this study was to evaluate precise location criteria on magnetic resonance imaging (MRI) to improve detection of transition zone (TZ) and anterior stroma (AS) prostate cancers using targeted MRI/transrectal ultrasound fusion biopsies as a reference standard. MATERIAL AND METHODS: Ninety-six men (mean age: 65 years±7.7 [SD] [range: 46-83 years]) with an elevated prostate-specific antigen (PSA) (PSA≥4ng/mL) who underwent standard and targeted biopsies on a TZ/AS suspicious lesion were included. The database was reviewed to assess topographical and morphological features of each suspicious lesion on MR images (T2-weighted anatomical images on 1.5T MRI or 3T) including PI-RADS score assessed by a senior radiologist. Histopathological examination of MRI-transrectal ultrasound fusion biopsy specimens was used as the reference standard. RESULTS: Ninety patients had a positive targeted biopsy with a median [IQR] lesion size of 16mm [13-20mm]. Homogeneous hypointensity on T2-weighted mages, lenticular shape, lack of capsule and indistinct margins were present in 77/90 (85%) patients. All TZ/AS prostate cancers were located in the anterior half of the prostate: 3% at the base, 69% in the mid gland and 28% at the apex. Lesions were mainly located close to or within the AS (74%) and more rarely laterally compressed close to the peripheral anterior horn. CONCLUSION: Our results suggest that specific topographic criteria of TZ and AS prostate cancers could add independent information to the usual diagnostic criteria in prostate MRI. Transrectal ultrasound fusion-targeted biopsies based on these specific criteria improve volume estimation of prostate cancers with substantial impact for prognosis and treatment planning.

Genetic landscape of ultra-stable chronic lymphocytic leukemia patients.

Background: Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Beside patients requiring immediate treatment, others show an initial indolent phase followed by progression and others do not progress for decades. The latter two subgroups usually display mutated IGHV genes and a favorable FISH profile. Patients and methods: Patients with absence of disease progression for over 10 years (10-34) from diagnosis were defined as ultra-stable CLL (US-CLL). Forty US-CLL underwent extensive characterization including whole exome sequencing (WES), ultra-deep sequencing and copy number aberration (CNA) analysis to define their unexplored genetic landscape. Microarray analysis, comparing US-CLL with non-US-CLL with similar immunogenetic features (mutated IGHV/favorable FISH), was also carried out to recognize US-CLL at diagnosis. Results: WES was carried out in 20 US-CLL and 84 non-silent somatic mutations in 78 genes were found. When re-tested in a validation cohort of 20 further US-CLL, no recurrent lesion was identified. No clonal mutations of NOTCH1, BIRC3, SF3B1 and TP53 were found, including ATM and other potential progression driving mutations. CNA analysis identified 31 lesions, none with known poor prognostic impact. No novel recurrent lesion was identified: most cases showed no lesions (38%) or an isolated del(13q) (31%). The expression of 6 genes, selected from a gene expression profile analysis by microarray and quantified by droplet digital PCR on a cohort of 79 CLL (58 US-CLL and 21 non-US-CLL), allowed to build a decision-tree capable of recognizing at diagnosis US-CLL patients. Conclusions: The genetic landscape of US-CLL is characterized by the absence of known unfavorable driver mutations/CNA and of novel recurrent genetic lesions. Among CLL patients with favorable immunogenetics, a decision-tree based on the expression of 6 genes may identify at diagnosis patients who are likely to maintain an indolent disease for decades.

Thr 446 phosphorylation of PKR by HCV core protein deregulates G2/M phase in HCC cells.

Hepatitis C virus (HCV) is the major causative viral agent of cirrhosis and hepatocarcinoma (HCC). HCV core protein affects cell homeostasis, playing an important role in viral pathogenesis of HCC. We investigate the effects of HCV core protein expression on cell growth in HCC cell lines. Cell cycle distribution analysis of HepG2 polyclonal core positive cells reveals a peculiar accumulation of cells in G2/M phase. Different pathways mediate G2/M arrest: such as p53 and double strand RNA protein kinase (PKR). Flow cytometry in p53-null cells demonstrates that p53 plays only a marginal role in inducing HCV core-dependent G2/M phase accumulation that seems to be significantly affected by the functional inactivation of PKR. HCC core positive cells are characterized by a significant PKR phosphorylation in Thr 446 residue, which leads deregulation of mitosis. Moreover, we observe that the overexpression of the viral protein induces an upregulation of PKR activity, which does not correlate with an increased eIF-2 phosphorylation. This uncommon behavior of PKR suggests that its activation by HCV core protein could involve alternative PKR-dependent pathways, implicated in core-dependent G2/M accumulation. The described biological effects of HCV core protein on cell cycle could be an additional viral mechanism for both HCV resistance to interferon (IFN) and HCC HCV-related pathogenesis.