Gynecologic tract melanoma in the contemporary therapeutic era: High rates of local and distant disease progression.

BACKGROUND: Gynecologic tract melanoma (GTM) is a rare malignancy with historically poor outcomes. The current study examines patterns of care and oncologic outcomes in a large single-institution cohort from the contemporary therapeutic era. METHODS: Patterns of care and predictors of outcomes were evaluated for all GTM patients without metastatic disease at diagnosis who were treated at our institution between 2009 and 2020 with >6 months of follow-up. RESULTS: Of the 124 patients included, anatomic subsites were vulvar (n = 82, 66%), vaginal (n = 34, 27%), or cervical (n = 8, 6%). Primary tumor was resected for 85% (n = 106) with surgical nodal evaluation for 60% (n = 75). Systemic therapy, most commonly immune checkpoint inhibitors (ICI, 58% systemic therapy), was used to treat all except one unresectable patient (17/18) and 33% (35/106) of resectable patients. Seven patients received neoadjuvant ICI. Fourteen patients received adjuvant radiation therapy to the pelvis (RT, 13% of those undergoing resection). With a median follow-up of 45 months, 100 patients (81%) recurred. Four-year actuarial outcomes were: 46% local control, 53% nodal control, 36% distant metastasis-free survival, 17% disease-free survival, 49% melanoma-specific survival and 48% overall survival. Mitotic rate > 10/mm2, nodal involvement and non-vulvar anatomic subsite were associated with poor outcomes. Patients treated after 2016 did not have significantly better outcomes than those treated earlier. CONCLUSIONS: Patients with GTM continue to have poor outcomes in the contemporary therapeutic era with particularly notable poor local disease control relative to other mucosal melanoma subtypes. More effective oncologic therapy is needed.

Biologic Therapies for the Management of Cutaneous Findings in Genodermatoses: A Review.

Genodermatoses are genetically inherited dermatologic conditions. The management of cutaneous findings in genodermatoses is challenging, and first-line therapies, such as steroids and/or retinoids, are often inadequate. In recent years, research on the molecular basis of genodermatoses has led to the use of biologic therapies for intractable disease. Here, we review the evidence regarding the use of available biologic therapies for the management of dermatologic findings in genodermatoses. Biologic therapies appear to be promising therapeutic options for several recalcitrant genodermatoses, especially those with underlying immune dysregulation. However, not all genodermatoses are amenable to biologic therapies, and some have been shown to paradoxically worsen under treatment. Biologic therapies offer a novel avenue to target refractory genodermatoses. However, evidence supporting the use of biologic therapies in the management of genodermatoses is mostly limited to case reports and case series. Further studies are warranted to determine the safety and efficacy of biologic therapies for the management of cutaneous findings in genodermatoses.

Resiquimod: a new topical immune-response modifier for the treatment of actinic keratosis.

Resiquimod is a Toll-like receptor (TLR)-7 and TLR-8 agonist that, like imiquimod, belongs to the class of imidazoquinolines, small organic molecules with potent antiviral and anticancer activity. Resiquimod activates myeloid and plasmacytoid dendritic cells while also promoting release of cytokines as interleukin-6, tumor necrosis factor-α and interferon-γ more effectively than imiquimod. Given these immunologic effects, resiquimod is emerging as a new topical pharmacotherapy for actinic keratosis (AK). In the pivotal trial by Stockfleth et al. complete clinical clearance in all the resiquimod-treated arms was more significant than placebo varying from 56% to 74%. Partial clinical clearance, or disappearance of >75% of AKs, was also significantly higher in the resiquimod arms varying from 75% to 87%. Overall, resiquimod is a new molecule that remains a promising therapy for AK, although additional studies are needed to further evaluate its efficacy.

Epigenetic regulatory mechanisms of histone acetylation in the treatment of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy; as such, novel systemic therapies are important for the treatment of locally advanced or metastatic disease. Histone deacetylase (HDAC) inhibitors have been increasingly studied in recent years as epigenome-targeted therapy for cSCC. HDACs inhibitors reduce tumorigenesis by blocking HDAC activity and creating a more relaxed chromatin structure, thus inducing gene expression by inhibiting deacetylation of transcription factors. In vitro experiments and in vivo mice studies have shown that HDAC inhibition halts cSCC pathogenesis. Ginsenoside 20(R)-Rg3 has been successfully employed to inhibit HDAC3 and thereby inhibit cSCC epithelial mesenchymal transition. Similarly, vorinostat has been found to blunt growth of human xenograft epidermoid cSCCs in highly immunosuppressed mice. Additionally, trichostatin A induces irreversible growth arrest in SCC cells, and MS-275 significantly reduces cSCC tumor burden in mice. These recent studies indicate that HDAC inhibitors represent a promising emerging therapy for cSCC.

Teledermatology During COVID-19: An Updated Review.

The coronavirus disease 2019 (COVID-19) pandemic has fundamentally transformed the landscape of providing dermatologic care. In an age of lockdowns and social distancing, teledermatology (TD) has emerged as a powerful tool to deliver remote care. Here, we review literature on TD use during the pandemic to evaluate the positives and negatives of TD implementation. We especially consider the reception of TD in underserved communities and the developing world as well as the ethico-legal challenges wrought by the burgeoning utilization of this new paradigm of care. The potential of TD to occupy a more prominent role in dermatologic care in a post-COVID-19 world is also discussed.