Sections from 95 skin lesions excised at pigmented lesion clinics in England and Scotland were studied by eight histopathologists in order to evaluate consistency in the use of histopathological terms for features of diagnostic and prognostic importance for cutaneous malignant melanoma. The level of agreement (kappa) amongst the panel improved after discussion and re-definement of criteria for several features. These included, architectural and nuclear atypia, pagetoid infiltration and radial and vertical growth phases. A high level of agreement was achieved for an overall benign or malignant diagnosis (kappa = 0.77) but use of more specific terms such as benign naevi with atypia and melanoma < or = 0.76 mm thickness, was associated with only an intermediate level of agreement. Of the original diagnosis of melanoma, 17% were re-classified by the panel as benign with atypia and 2% reported to be benign were judged to be melanoma. This reflected the high proportion of borderline lesions in the study. The use of standardized diagnostic criteria with precise definitions has been shown to improve consistency in diagnosis and it is recommended for general application. From this should emanate more reliable incidence figures for thin melanoma, and improved understanding of the nature of these early lesions, to the benefit of patient and clinician alike. The poor concordance in distinguishing severe dysplasia in the junctional component of melanocyte proliferations from melanoma in situ and superficial dermal invasion improved only modestly despite intensive efforts. Since melanoma in situ and severe dysplasia cannot be distinguished by objective measurements and since their clinical management is the same, the panel suggests that attempts to separate them in diagnostic reports should be discontinued and they could both be referred to as melanocytic intraepidermal neoplasia (MIN). If it becomes accepted that dermal invasion without a vertical growth component can also be managed identically to MIN, then this invasive radial phase may be appropriately referred to as microinvasion and linked to MIN for the purposes of clinical management.

Tumor formation can occur after maternal transmission of SDHD, a finding with important clinical implications for SDHD families. Tumor formation in SDHD mutation requires the loss of both the wild-type SDHD allele and maternal 11p15, leading to the predominant but now not exclusive pattern of disease inheritance after paternal SDHD transmission.

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Background Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta. Methods Twenty patients underwent two hybrid 18F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18F-NaF quantification method was compared to validated cardiovascular risk scores. Results Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease. Conclusions AMA is a simple, rapid and reproducible method of quantifying global 18F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.

Inherited thoracic aortopathies denote a group of congenital conditions that predispose to disease of the thoracic aorta. Aortic wall weakness and abnormal aortic hemodynamic profiles predispose these patients to dilatation of the thoracic aorta, which is generally silent but can precipitate aortic dissection or rupture with devastating and often fatal consequences. Current strategies to assess the future risk of aortic dissection or rupture are based primarily on monitoring aortic diameter. However, diameter alone is a poor predictor of risk, with many patients experiencing dissection or rupture below current intervention thresholds. Developing tools that improve the risk assessment of those with aortopathy is internationally regarded as a research priority. A robust understanding of the molecular pathways that lead to aortic wall weakness is required to identify biomarkers and therapeutic targets that could improve patient management. Here, we summarize the current understanding of the genetically determined mechanisms underlying inherited aortopathies and critically appraise the available blood biomarkers, imaging techniques, and therapeutic targets that have shown promise for improving the management of patients with these important and potentially fatal conditions.

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Atherosclerosis is a chronic immunomodulated disease that affects multiple vascular beds and results in a significant worldwide disease burden. Conventional imaging modalities focus on the morphological features of atherosclerotic disease such as the degree of stenosis caused by a lesion. Modern CT, MR and positron emission tomography scanners have seen significant improvements in the rapidity of image acquisition and spatial resolution. This has increased the scope for the clinical application of these modalities. Multimodality imaging can improve cardiovascular risk prediction by informing on the constituency and metabolic processes within the vessel wall. Specific disease processes can be targeted using novel biological tracers and “smart” contrast agents. These approaches have the potential to inform clinicians of the metabolic state of atherosclerotic plaque. This review will provide an overview of current imaging techniques for the imaging of atherosclerosis and how various modalities can provide information that enhances the depiction of basic morphology.

Background: There remain major uncertainties regarding disease activity within the retained native aortic valve as well as bioprosthetic valve durability following transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison to subjects with bioprosthetic surgical aortic valve replacement (SAVR). Methods: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, CT angiography and 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET). Participants (n=47) were imaged once with 18 F-NaF PET/CT either at one-month (n=9, 19%), 2 years (n=22, 47%) or 5 years (16, 34%) after valve implantation. Subsequently patients underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made to matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. Results: In patients with TAVI, native aortic valves demonstrated 18 F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, p=0.023). 18 F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio 1.3 [1.2-1.7] versus 1.3 [1.2-1.5] respectively, p=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8% respectively, p=0.78), CT (15% versus 14% respectively, p=0.87) and PET (15% versus 29% respectively, p=0.09). Baseline 18 F-NaF uptake was associated with subsequent change in peak aortic velocity for both TAVI (r=0.7, p<0.001) and SAVR (r=0.7, p<0.001). On multivariable analysis, 18 F-NaF uptake was the only predictor of peak velocity progression (p<0.001). Conclusions: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR suggesting comparable mid-term durability. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ Unique Identifier: NCT02304276