Benignity

Abstract: Recommendations from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) for interpreting sequence variants specify the use of computational predictors as "supporting" level of evidence for pathogenicity or benignity using criteria PP3 and BP4, respectively. However, score intervals defined by tool developers, and ACMG/AMP recommendations that require the consensus of multiple predictors, lack quantitative support. Previously, we described a probabilistic framework that quantified the strengths of evidence (supporting, moderate, strong, very strong) within ACMG/AMP recommendations. We have extended this framework to computational predictors and introduce a new standard that converts a tool's scores to PP3 and BP4 evidence strengths. Our approach is based on estimating the local positive predictive value and can calibrate any computational tool or other continuous-scale evidence on any variant type. We estimate thresholds (score intervals) corresponding to each strength of evidence for pathogenicity and benignity for thirteen missense variant interpretation tools, using carefully assembled independent data sets. Most tools achieved supporting evidence level for both pathogenic and benign classification using newly established thresholds. Multiple tools reached score thresholds justifying moderate and several reached strong evidence levels. One tool reached very strong evidence level for benign classification on some variants. Based on these findings, we provide recommendations for evidence-based revisions of the PP3 and BP4 ACMG/AMP criteria using individual tools and future assessment of computational methods for clinical interpretation.

Abstract: The purpose of this study was to prospectively assess the contribution of diffusion-weighted MR imaging (DWI) for characterizing complex adnexal masses. Seventy-seven women (22–87 years old) with complex adnexal masses (30 benign and 47 malignant) underwent MR imaging including DWI before surgery. Conventional morphological MR imaging criteria were recorded in addition to b 1,000 signal intensity and apparent diffusion coefficient (ADC) measurements of cystic and solid components. Positive likelihood ratios (PLR) were calculated for predicting benignity and malignancy. The most significant criteria for predicting benignity were low b 1,000 signal intensity within the solid component (PLR = 10.9), low T2 signal intensity within the solid component (PLR = 5.7), absence of solid portion (PLR = 3.1), absence of ascites or peritoneal implants (PLR = 2.3) and absence of papillary projections (PLR = 2.3). ADC measurements did not contribute to differentiating benign from malignant adnexal masses. All masses that displayed simultaneously low signal intensity within the solid component on T2-weighted and on b 1,000 diffusion-weighted images were benign. Alternatively, the presence of a solid component with intermediate T2 signal and high b 1,000 signal intensity was associated with a PLR of 4.5 for a malignant adnexal tumour. DWI signal intensity is an accurate tool for predicting benignity of complex adnexal masses.

Abstract: OBJECTIVE. We assessed thin-section CT features specific to benignity in solitary pulmonary nodules of 1 cm or smaller that were detected at population-based CT screening for lung cancer.MATERIALS AND METHODS. Two reviewers independently made qualitative (presence or absence of lobulation, spiculation, air bronchogram, cavity, satellite lesions, pleural tag, concave margins, polygonal shape, and peripheral subpleural lesion) and quantitative (lesion size, percentage of ground-glass opacity areas, and two- and three-dimensional ratios of lesion) assessments in CT images of 72 nodules (25 lung cancers, seven atypical adenomatous hyperplasias, and 40 benign lesions). Optimal criteria specific to benignity were studied.RESULTS. The prevalence of polygonal shape (p = 0.005 and p = 0.019, reviewer 1 and reviewer 2), peripheral subpleural lesion (p = 0.011 and p = 0.033), a predominantly solid lesion (p < 0.001 and p < 0.001), and three-dimensional ratios (p < 0.001 and p < 0.001) were greater in benign lesions ...