Pathogenic variants in<i>PIK3CA</i>are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly

Pediatric Blood & Cancer · 2023 · 18 citations

• Medicine
• Pathology
• Radiology

Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.

Genomic profiling informs diagnoses and treatment in vascular anomalies

Nature Medicine · 2023 · 60 citations

• Medicine
• Pathology
• Biology

Development and Initial Validation of a Multidimensional Acne Global Grading System Integrating Primary Lesions and Secondary Changes

JAMA Dermatology · 2020 · 44 citations

• Medicine
• Dermatology
• Medical physics

Importance: The qualitative grading of acne is important for routine clinical care and clinical trials, and although many useful systems exist, no single acne global grading system has had universal acceptance. In addition, many current instruments focus primarily on evaluating primary lesions (eg, comedones, papules, and nodules) or exclusively on signs of secondary change (eg, postinflammatory hyperpigmentation, scarring). Objectives: To develop and validate an acne global grading system that provides a comprehensive evaluation of primary lesions and secondary changes due to acne. Design, Setting, and Participants: This diagnostic study created a multidimensional acne severity feature space by analyzing decision patterns of pediatric dermatologists evaluating acne. Modeling acne severity patterns based on visual image features was then performed to reduce dimensionality of the feature space to a novel 2-dimensional grading system, in which severity levels are functions of multidimensional acne cues. The system was validated by 6 clinicians on a new set of images. All images used in this study were taken from a retrospective, longitudinal data set of 150 patients diagnosed with acne, ranging across the entire pediatric population (aged 0-21 years), excluding images with any disagreement on their diagnosis, and selected to adequately span the range of acne types encountered in the clinic. Data were collected from July 1, 2001, through June 30, 2013, and analyzed from March 1, 2015, through December 31, 2016. Main Outcomes and Measures: Prediction performance was evaluated as the mean square error (MSE) with the clinicians' scores. Results: The scale was constructed using acne visual features and treatment decisions of 6 pediatric dermatologists evaluating 145 images of patients with acne ranging in age from 0 to 21 years. Using the proposed scale to predict the severity scores on a new set of 40 images achieved an overall MSE of 0.821, which is smaller than the mean within-clinician differences (MSE of 0.998). Conclusions and Relevance: By integrating primary lesions and secondary changes, this novel acne global grading scale provides a more clinically relevant evaluation of acne that may be used for routine clinical care and clinical trials. Because the severity scores are based on actual clinical practice, this scoring system is also highly correlated with appropriate treatment choices.