Administration of the mutant BRAF inhibitor dabrafenib is associated with induction of keratinocytic proliferation, which in some cases develops features of low-grade malignancy. Highly oncogenic HPV infection is unlikely to be a contributor to the formation of SCCs or verrucal keratoses.

The current gold standard for clinical diagnosis of melanoma is excisional biopsy and histopathologic analysis. Approximately 15-30 benign lesions are biopsied to diagnose each melanoma. In addition, biopsies are invasive and result in pain, anxiety, scarring, and disfigurement of patients, which can add additional burden to the health care system. Among several imaging techniques developed to enhance melanoma diagnosis, optical coherence tomography (OCT), with its highresolution and intermediate penetration depth, can potentially provide required diagnostic information noninvasively. Here, we present an image analysis algorithm, "optical properties extraction (OPE)," which improves the specificity and sensitivity of OCT by identifying unique optical radiomic signatures pertinent to melanoma detection. We evaluated the performance of the algorithm using several tissue-mimicking phantoms and then tested the OPE algorithm on 69 human subjects. Our data show that benign nevi and melanoma can be differentiated with 97% sensitivity and 98% specificity. These findings suggest that the adoption of OPE algorithm in the clinic can lead to improvements in melanoma diagnosis and patient experience. Significance: This study describes a noninvasive, safe, simple-to-implement, and accurate method for the detection and differentiation of malignant melanoma versus benign nevi.

Summary B‐RAF inhibitors (BRAFi) have been shown to improve rates of overall and progression‐free survival in patients with stage IV metastatic melanoma positive for the BRAF V600E mutation. However, the main drawback is the development of verrucal keratosis (hyperkeratotic papules with verruca‐like characteristics with benign histological findings) and cutaneous squamous cell carcinomas (cuSCC). We have found upstream mutations in RAS as well as PIK3CA in both verrucal keratosis and cuSCC. This suggests that verrucal keratosis is an early clinical presentation of cuSCC in patients on BRAFi.

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