Performance of Gene Expression Profile Tests for Prognosis in Patients With Localized Cutaneous Melanoma: A Systematic Review and Meta-analysis.

Importance: The performance of prognostic gene expression profile (GEP) tests for cutaneous melanoma is poorly characterized. Objective: To systematically assess the performance of commercially available GEP tests in patients with American Joint Committee on Cancer (AJCC) stage I or stage II disease. Data Sources: For this systematic review and meta-analysis, comprehensive searches of PubMed/MEDLINE, Embase, and Web of Science were conducted on December 12, 2019, for English-language studies of humans without date restrictions. Study Selection: Two reviewers identified GEP external validation studies of patients with localized melanoma. After exclusion criteria were applied, 7 studies (8%; 5 assessing DecisionDx-Melanoma and 2 assessing MelaGenix) were included. Data Extraction and Synthesis: Data were extracted using an adaptation of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS-PF). When feasible, meta-analysis using random-effects models was performed. Risk of bias and level of evidence were assessed with the Quality in Prognosis Studies tool and an adaptation of Grading of Recommendations Assessment, Development, and Evaluation. Main Outcomes and Measures: Proportion of patients with or without melanoma recurrence correctly classified by the GEP test as being at high or low risk. Results: In the 7 included studies, a total of 1450 study participants contributed data (age and sex unknown). The performance of both GEP tests varied by AJCC stage. Of patients tested with DecisionDx-Melanoma, 623 had stage I disease (6 true-positive [TP], 15 false-negative, 61 false-positive, and 541 true-negative [TN] results) and 212 had stage II disease (59 TP, 13 FN, 78 FP, and 62 TN results). Among patients with recurrence, DecisionDx-Melanoma correctly classified 29% with stage I disease and 82% with stage II disease. Among patients without recurrence, the test correctly classified 90% with stage I disease and 44% with stage II disease. Of patients tested with MelaGenix, 88 had stage I disease (7 TP, 15 FN, 15 FP, and 51 TN results) and 245 had stage II disease (59 TP, 19 FN, 95 FP, and 72 TN results). Among patients with recurrence, MelaGenix correctly classified 32% with stage I disease and 76% with stage II disease. Among patients without recurrence, the test correctly classified 77% with stage I disease and 43% with stage II disease. Conclusions and Relevance: The prognostic ability of GEP tests among patients with localized melanoma varied by AJCC stage and appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients.

Reflectance confocal microscopy features of mycosis fungoides and Sézary syndrome: correlation with histopathologic and T-cell receptor rearrangement studies.

BACKGROUND: Mycosis fungoides/Sézary syndrome (MF/SS) often requires multiple skin biopsies for definitive diagnosis. In vivo reflectance confocal microscopy (RCM) visualizes high-resolution cellular detail of the skin. The objective of this study is to evaluate the morphologic features of MF/SS using RCM and to correlate RCM features with histopathology and T-cell receptor (TCR) gene rearrangement studies. METHODS: A cohort of patients with active/recurrent or suspicious MF/SS disease was prospectively recruited for RCM imaging and histopathologic/RCM images were evaluated. Statistical analyses were performed to identify unique RCM features and to correlate RCM features with histopathologic findings and TCR rearrangement studies. RESULTS: Eighty-three lesions were evaluated. Correlation between RCM and histopathology was moderate for all relatable features (κ = 0.41, p<0.001), almost perfect for intraepidermal atypical lymphocytes [prevalence and bias-adjusted kappa (PABAK) = 0.90], and fair for Pautrier collections (κ = 0.32, p = 0.03). Lesions with Pautrier collections identified by RCM were significantly more likely to show TCR clonality (p = 0.04) and diagnostic features of MF/SS on histopathology (p = 0.03). CONCLUSIONS: Our study captures morphologic RCM criteria for a variety of skin lesions. Pautrier collections visualized by RCM are associated with improved histopathologic diagnosis and detection of TCR gene clonality. Although further studies are needed to validate the diagnostic implications of RCM for MF/SS, our study highlights the potential utility of RCM.

Melanoma in situ colonizing basal cell carcinoma: a case report and review of the literature.

Colonization of basal cell carcinoma (BCC) by melanoma cells is a unique and uncommonly reported cutaneous entity. We describe a bluish nodule on the left forearm found during routine skin cancer surveillance examination with suspicious dermatoscopic findings including central-blue-white veil, sparse atypical dots, and a surrounding pink vascular blush with focal irregular tan-brown pigmentation at the periphery. Histopathology demonstrated a pigmented BCC with an overlying and adjacent melanoma in situ (MIS), as well as colonization of the BCC nodule by melanoma cells. We performed a review of the literature on the topic and discuss other presentations of cutaneous neoplasms composed of both BCC and melanoma, including collision, combined, and biphenotypic tumors. The prognostic and management challenges inherent to this distinctive neoplasm are summarized.

Skin cancer: role of ultraviolet radiation in carcinogenesis.

UV radiation is a carcinogen known to play a role in the development of non-melanoma and melanoma skin cancers. Acute and chronic exposure to UV radiation causes clinical and biological effects that promote the unregulated proliferation of skin cells. In recent decades, changes in climate and increased air pollution have led to environmental changes that increase UV light transmission. In this chapter, we discuss sources of UV radiation that are relevant to human health, as well as the acute and chronic effects that result from UV radiation exposure.

Sunscreens: a review of health benefits, regulations, and controversies.

Ultraviolet radiation plays a major role in the development of nonmelanoma and melanoma skin cancers. Photoprotection by sunscreens has been shown to prevent the development of actinic keratosis, squamous cell carcinoma, melanoma, and photoaging. However, these benefits are only derived if the users apply sunscreen appropriately and practice other sun protection measures. This review discusses the health benefits provided by sunscreen use, updates the latest regulatory landscape on sunscreen, and addresses the controversies and limitations associated with sunscreen use.

Early exposure to methylphenidate increases fear responses in an aversive context in adult rats.

The effects of methylphenidate hydrochloride (MPH) administration during development on fear acquisition and retention in adulthood were examined using classical fear conditioning. Male Sprague-Dawley rats were administered MPH (2 mg/kg) or saline twice daily from postnatal day (PD) 25 to 39, and were trained and tested on PD 81 and 82. During training, shock unconditioned stimulus (US) presentations were explicitly paired with an auditory conditioned stimulus (CS) or occurred unsignaled in the training context. No effect of MPH treatment was found during fear acquisition when shock was signaled or unsignaled during training, but 24 h retention tests in the training context revealed enhanced fear responses in MPH-treated animals that received unsignaled training. These results support recent reports of enhanced anxiety-like behaviors in adult rats caused by early developmental MPH treatment and highlight the need for further research into the long-term effects of developmental exposure to stimulants aimed at pediatric populations.