Purpose Early/initiating oncogenic mutations have been identified for many cancers, but such mutations remain unidentified in uveal melanoma (UM). An extensive search for such mutations was undertaken, focusing on the RAF/MEK/ERK pathway, which is often the target of initiating mutations in other types of cancer. Methods DNA samples from primary UMs were analyzed for mutations in 24 potential oncogenes that affect the RAF/MEK/ERK pathway. For GNAQ, a stimulatory αq G-protein subunit which was recently found to be mutated in uveal melanomas, re-sequencing was expanded to include 67 primary UMs and 22 peripheral blood samples. GNAQ status was analyzed for association with clinical, pathologic, chromosomal, immunohistochemical and transcriptional features. Results Activating mutations at codon 209 were identified in GNAQ in 33/67 (49%) primary UMs, including 2/9 (22%) iris melanomas and 31/58 (54%) posterior UMs. No mutations were found in the other 23 potential oncogenes. GNAQ mutations were not found in normal blood DNA samples. Consistent with GNAQ mutation being an early or initiating event, this mutation was not associated with any clinical, pathologic or molecular features associated with late tumor progression. Conclusions GNAQ mutations occur in about half of UMs, representing the most common known oncogenic mutation in this cancer. The presence of this mutation in tumors at all stages of malignant progression suggests that it is an early event in UM. Mutations in this G-protein provide new insights into UM pathogenesis and could lead to new therapeutic possibilities.

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The novel coronavirus (SARS-CoV-2) pandemic has necessitated a dramatic shift in how our dermatology residents and fellows are educated. Distance or online learning has become the norm, and several national and international academic societies have combined resources to assure that continuing medical education occurs during this difficult time. The purpose of this communication is to review select online resources available to dermatology trainees and to encourage our colleagues to continue to advance our specialty through distance learning.

Atopic dermatitis (AD) is a highly prevalent, itchy inflammatory skin disorder that is thought to arise from a combination of skin barrier defect and immune dysregulation. Kallikreins (KLK), a family of serine proteases with a diverse array of homeostatic functions, including skin desquamation and innate immunity, are hypothesized to contribute to AD pathogenesis. However, their precise role in AD has not been clearly defined. In this study, RNA sequencing analyses identified KLK7 as the most abundant and differentially expressed KLK in both human AD and murine AD-like skin. Further, in mice, Klk7 expression was localized to the epidermis in both steady state and inflammation. Unexpectedly, KLK7 was dispensable for the development of ADassociated skin inflammation. Instead, KLK7 was selectively required for AD-associated chronic itch. Even without the alleviation of skin inflammation, KLK7-deficient mice exhibited significantly attenuated scratching, compared with littermate controls, after AD-like disease induction. Collectively, our findings indicate that KLK7 promotes AD-associated itch independently from skin inflammation and reveal a previously unrecognized epidermal-neural mechanism of AD associated itch.

The novel coronavirus disease 2019 (COVID-19) pandemic has disrupted clinical practice everywhere. The aim of this study was to quantify the specific impact of COVID-19 on skin cancer treatment at an academic dermatologic surgery practice. We conducted a retrospective chart review to compare metrics such as patient visits, histological upgrading, and Mohs stages per tumor between 60-day periods immediately before and after COVID-19 was declared a pandemic. Out of 1138 total encounters, decreases of 58% in total in-person visits and 38% in Mohs surgeries performed were observed following declaration of the pandemic. More squamous cell carcinoma and squamous cell carcinoma in situ (SCC/SCCIS) and less basal cell carcinoma (BCC) tumors were treated post-declaration compared to pre-declaration. There was a significantly higher histological upgrade rate for total tumors, as well as for the BCC subgroup, but not the SCC/SCCIS subgroup. While the overall number of dermatologic surgeries decreased after declaration of the pandemic, the higher histological upgrade rate reflects an appropriate triage of higher risk skin cancers. These findings may be useful both to assess the effectiveness of protocols for COVID-19 and to prepare for future resource-limited scenarios.

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