Faculty Bibliography

Image-based analysis as a method for mutation detection can be advantageous in settings when tumor tissue is limited or unavailable for direct testing. Here, we utilize two distinct and complementary machine learning methods of analyzing whole slide images (WSI) for predicting mutated BRAF. In the first method, WSI of melanomas from 256 patients were used to train a deep convolutional neural network (CNN) in order to develop a fully automated model that first selects for tumor-rich areas (Area Under the Curve AUC=0.96) then predicts for mutated BRAF (AUC=0.71). Saliency mapping was performed and revealed that pixels corresponding to nuclei were the most relevant to network learning. In the second method, WSI were analyzed using a pathomics pipeline that first annotates nuclei and then quantifies nuclear features, demonstrating that mutated BRAF nuclei were significantly larger and rounder nuclei compared to BRAF WT nuclei. Lastly, we developed a model that combines clinical information, deep learning, and pathomics that improves the predictive performance for mutated BRAF to AUC=0.89. Not only does this provide additional insights on how BRAF mutations affect tumor structural characteristics, machine learning-based analysis of WSI has the potential to be integrated into higher order models for understanding tumor biology.

BACKGROUND:As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS:In this IRB-approved retrospective case series, biopsies of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS:Twelve cases were included. Histopathological features from two injection site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsies came from generalized eruptions that demonstrated interface changes consistent with an exanthematous drug reaction. Three biopsies revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS:Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid. This article is protected by copyright. All rights reserved.

OBJECTIVES/OBJECTIVE:Pedunculated lipofibromas are soft, compressible, skin-colored nodules that typically present as an acquired solitary lesion, predominantly located on the buttocks and thighs. We aimed to differentiate between pedunculated lipofibromas and nevus lipomatosus superficialis. Although benign, this may be important as treatment options vary. METHODS:We describe 3 cases of solitary pedunculated lipofibromas occurring in older, obese adults that required clinicopathologic correlation for the correct diagnosis. RESULTS:The histopathologic features of pedunculated lipofibromas include a broad-based lesion with aggregates of mature adipocytes extending upwards into the dermis without an associated inflammatory infiltrate. The primary histopathologic differential diagnoses include fibroepithelial polyps with adipocytes and nevus lipomatosus superficialis, which is more frequently found in children or young adults and is typically characterized clinically by multiple lesions with a cerebriform to verrucoid surface. CONCLUSIONS:While the precise relationship between pedunculated lipofibromas and nevus lipomatosus is still unknown, we propose using pedunculated lipofibroma as a more specific clinical term to refer to solitary pedunculated or broad-based fatty lesions with a smooth surface that occur in older patients and in a wide anatomic distribution.