Evaluation of dynamic dermoscopic features of melanoma and benign naevi by sequential digital dermoscopic imaging and total body photography in a high-risk Australian cohort.

BACKGROUND/OBJECTIVES: Sequential digital dermoscopic imaging (SDDI) and total body photography (TBP) are recommended as a two-step surveillance method for individuals at high-risk of developing cutaneous melanoma. Dermoscopic features specific to melanoma have been well described, however, dynamic changes on serial imaging are less understood. This study aims to identify and compare dermoscopic features in developing melanomas and benign naevi that underwent SDDI and TBP to understand which dermoscopic features may be associated with a malignant change. METHOD: Histopathology reports from a private specialist dermatology clinic from January 2007 to December 2019 were reviewed. Histopathologically confirmed melanoma and benign naevi that underwent SDDI and TBP with a minimum follow-up interval of 3 months were included. RESULTS: Eighty-nine melanomas (38.2% invasive, median Breslow thickness 0.35 mm, range: 0.2-1.45 mm) and 48 benign naevi were evaluated by three experienced dermatologists for dermoscopic changes. Features most strongly associated with melanoma included the development of neovascularisation, asymmetry and growth in pigment network, additional colours, shiny white structures, regression, structureless areas and change to a multi-component pattern. The presence of atypical vessels (p = 0.02) and shiny white structures (p = 0.02) were significantly associated with invasive melanoma. CONCLUSION: Evaluation for certain evolving dermoscopic features in melanocytic lesions monitored by SDDI and TBP is efficient in assisting clinical decision making. SDDI with TBP is an effective tool for early detection of melanoma.

Improving Skin cancer Management with ARTificial Intelligence (SMARTI): protocol for a preintervention/postintervention trial of an artificial intelligence system used as a diagnostic aid for skin cancer management in a specialist dermatology setting.

INTRODUCTION: Convolutional neural networks (CNNs) can diagnose skin cancers with impressive accuracy in experimental settings, however, their performance in the real-world clinical setting, including comparison to teledermatology services, has not been validated in prospective clinical studies. METHODS AND ANALYSIS: Participants will be recruited from dermatology clinics at the Alfred Hospital and Skin Health Institute, Melbourne. Skin lesions will be imaged using a proprietary dermoscopic camera. The artificial intelligence (AI) algorithm, a CNN developed by MoleMap Ltd and Monash eResearch, classifies lesions as benign, malignant or uncertain. This is a preintervention/postintervention study. In the preintervention period, treating doctors are blinded to AI lesion assessment. In the postintervention period, treating doctors review the AI lesion assessment in real time, and have the opportunity to then change their diagnosis and management. Any skin lesions of concern and at least two benign lesions will be selected for imaging. Each participant's lesions will be examined by a registrar, the treating consultant dermatologist and later by a teledermatologist. At the conclusion of the preintervention period, the safety of the AI algorithm will be evaluated in a primary analysis by measuring its sensitivity, specificity and agreement with histopathology where available, or the treating consultant dermatologists' classification. At trial completion, AI classifications will be compared with those of the teledermatologist, registrar, treating dermatologist and histopathology. The impact of the AI algorithm on diagnostic and management decisions will be evaluated by: (1) comparing the initial management decision of the registrar with their AI-assisted decision and (2) comparing the benign to malignant ratio (for lesions biopsied) between the preintervention and postintervention periods. ETHICS AND DISSEMINATION: Human Research Ethics Committee (HREC) approval received from the Alfred Hospital Ethics Committee on 14 February 2019 (HREC/48865/Alfred-2018). Findings from this study will be disseminated through peer-reviewed publications, non-peer reviewed media and conferences. TRIAL REGISTRATION NUMBER: NCT04040114.

A Distinct Pretreatment Immune Gene Signature in Lentigo Maligna Is Associated with Imiquimod Response.

Lentigo maligna (LM) is a common subtype of in situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Although surgery is the standard treatment, there is associated morbidity, and options such as imiquimod cream or radiotherapy may be used if surgery is refused or inappropriate. Complete response rates following imiquimod treatment are variable in the literature. The aim of this study was to evaluate the host immune response both before and following treatment with imiquimod to better identify likely responders. Paired pre- and post-imiquimod treatment specimens were available for 27 patients. Patients were treated with imiquimod 5 days per week for 12 weeks; at 16 weeks, lesions were excised for histological assessment. Of the 27 patients, 16 were responders and 11 failed to clear the disease. PDL1 protein expression was increased, accompanied by a unique gene signature in lesions from patients that subsequently histologically cleared LM by 16 weeks. This comprised 57 upregulated immune genes in signaling networks for antigen presentation, type I interferon signaling, and T-cell activation. This may represent an early responder group to imiquimod, and this unique gene signature potentially can be used as a biomarker of LM response to imiquimod.

Dermatoscopy aids in the diagnosis of the solitary red scaly patch or plaque-features distinguishing superficial basal cell carcinoma, intraepidermal carcinoma, and psoriasis.

BACKGROUND: Intraepidermal carcinoma (IEC), superficial basal cell carcinoma (sBCC), and psoriasis are common entities that may all present as well-defined, brightly erythematous plaques. Currently, there are limited data on the dermatoscopic features that differentiate these diagnoses. OBJECTIVE: We sought to describe the most significant morphologic findings seen on dermatoscopy of IEC, sBCC, and psoriasis, and formulate a diagnostic model based on these features. METHOD: We conducted a retrospective observational study using macrophotography and dermatoscopy to evaluate the presence or absence of dermatoscopic features and formulated diagnostic models for each diagnosis. A convenient sample of 300 lesions was collected from 255 patients from two hospital dermatology clinics and 4 private dermatology practices. These comprised 150 cases of sBCC, 100 cases of psoriasis, and 50 cases of IEC. RESULTS: The most significant dermatoscopic features of IEC were a clustered vascular pattern, glomerular vessels, and hyperkeratosis. When all 3 features were observed together, the diagnostic probability for IEC was 98%. sBCCs were characterized by a scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots/globules; the diagnostic probability was 99% if 4 of these 6 features were identified. For psoriasis, the significant features identified were a homogenous vascular pattern, red dots, and light-red background, yielding a diagnostic probability of 99% if all 3 features were present. LIMITATIONS: Lack of evaluation of interobserver/intraobserver reproducibility is a limitation. CONCLUSION: Dermatoscopy is valuable in the diagnosis and differentiation of IEC, sBCC, and psoriasis because of consistent dermatoscopic morphology.

Implementing novel models of posttreatment care for cancer survivors: Enablers, challenges and recommendations.

AIM: The American Society of Clinical Oncology and US Institute of Medicine emphasize the need to trial novel models of posttreatment care, and disseminate findings. In 2011, the Victorian State Government (Australia) established the Victorian Cancer Survivorship Program (VCSP), funding six 2-year demonstration projects, targeting end of initial cancer treatment. Projects considered various models, enrolling people of differing cancer types, age and residential areas. We sought to determine common enablers of success, as well as challenges/barriers. METHODS: Throughout the duration of the projects, a formal "community of practice" met regularly to share experiences. Projects provided regular formal progress reports. An analysis framework was developed to synthesize key themes and identify critical enablers and challenges. Two external reviewers examined final project reports. Discussion with project teams clarified content. RESULTS: Survivors reported interventions to be acceptable, appropriate and effective. Strong clinical leadership was identified as a critical success factor. Workforce education was recognized as important. Partnerships with consumers, primary care and community organizations; risk stratified pathways with rapid re-access to specialist care; and early preparation for survivorship, self-management and shared care models supported positive project outcomes. Tailoring care to individual needs and predicted risks was supported. Challenges included: lack of valid assessment and prediction tools; limited evidence to support novel care models; workforce redesign; and effective engagement with community-based care and issues around survivorship terminology. CONCLUSION: The VCSP project outcomes have added to growing evidence around posttreatment care. Future projects should consider the identified enablers and challenges when designing and implementing survivorship care.

Characteristics and associations of high-mitotic-rate melanoma.

IMPORTANCE: Mitotic rate is now recognized as having independent prognostic significance in melanoma survival. However, its clinicopathologic associations have not been the focus of any previous study. OBJECTIVE: To identify a set of patient and tumor characteristics associated with high-mitotic-rate melanoma with the aim of facilitating the earlier detection of aggressive primary invasive melanoma. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of patients from a multidisciplinary melanoma clinic based in a public hospital. A total of 2397 cases from January 2006 to December 2011 were reviewed by the Victorian Melanoma Service, and 1441 patients with 1500 primary invasive melanomas were included in the study. MAIN OUTCOMES AND MEASURES: Mitotic rate was measured as number of mitoses per mm2 and analyzed as ordered categories (0, <1, 1 and <2, 2, 3-4, 5-9, and ≥10) according to patient demographics, phenotypic markers, historical data, tumor presentation, and histopathologic features. RESULTS: Melanomas with higher mitotic rates were more likely to occur in men (odds ratio [OR], 1.5; 95% CI, 1.3-1.8), patients 70 years or older (OR, 2.1; 95% CI, 1.7-2.8), and those with a history of solar keratosis (OR, 1.3; 95% CI, 1.1-1.6). These melanomas occurred more frequently on the head and neck (OR, 1.4; 95% CI, 1.0-1.9) and presented more often as amelanotic (OR, 1.9; 95% CI, 1.4-2.5) and rapidly growing (≥2 mm/mo) lesions (OR, 12.5; 95% CI, 8.4-18.5). An association was seen with the nodular melanoma subtype (vs superficial spreading [reference]) (OR, 2.5; 95% CI, 1.8-3.4), greater tumor thickness (vs ≤1 mm [reference]) (>1-4 mm: OR, 4.5; 95% CI, 3.2-6.1; >4 mm: OR, 12.6; 95% CI, 7.5-21.1), and ulceration (OR, 2.0; 95% CI, 1.5-2.7). These histopathologic features, along with amelanosis and rate of growth, remained as significant associations with high mitotic rate in the overall multivariate analysis. CONCLUSIONS AND RELEVANCE: High-mitotic-rate primary cutaneous melanoma is associated with aggressive histologic features and atypical clinical presentation. It has a predilection for the head and neck region and is more likely to be seen in elderly men with a history of cumulative solar damage who present clinically with rapidly developing disease.

Efficacy of imiquimod cream, 5%, for lentigo maligna after complete excision: a study of 43 patients.

OBJECTIVE: To determine the efficacy of imiquimod cream, 5%, in the treatment of lentigo maligna (LM). DESIGN: Open-label before-and-after interventional study. SETTING: A multidisciplinary melanoma clinic at a major tertiary hospital. PATIENTS: Forty-three patients with biopsy-proven LM of greater than 5 mm in diameter completed this study. INTERVENTIONS: Imiquimod cream, 5%, was applied to the lesion 5 days a week for 12 weeks. The original lesion was excised with a 5-mm margin. MAIN OUTCOME MEASURES: The primary outcome was histopathologic evidence of LM in the excision specimen assessed independently by 2 of 3 dermatopathologists. Visible inflammation during treatment and macroscopic clearance were recorded. RESULTS: When 5 of the 43 patients with discordant histopathologic assessment of the excision specimen were excluded, 20 of 38 patients (53% [95% confidence interval, 36%-69%]) demonstrated histopathologic clearance of LM after imiquimod treatment. Visible inflammation was significantly associated with histopathologic clearance (P = .04), but the positive predictive value was low (62%). Macroscopic clearance showed some association with histopathologic clearance (P = .11). Dermatopathologist concordance for all 43 specimens was substantial (κ = 0.77; 95% confidence interval, 0.57-0.96). CONCLUSIONS: Imiquimod cream, 5%, has limited efficacy in the treatment of LM when determined by histopathologic assessment of the entire treated area. The clinical signs of visible inflammation during treatment and apparent lesion clearance cannot be relied on to assess efficacy.