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Overdiagnosis of early melanoma is a significant problem. Due to subtle unique and overlapping clinical and histological criteria between pigmented lesions and the risk of mortality from melanoma, some benign pigmented lesions are diagnosed as melanoma. Although histopathology is the gold standard to diagnose melanoma, there is a demand to find alternatives that are more accurate and cost-effective. In the current "omics" era, there is gaining interest in biomarkers to help diagnose melanoma early and to further understand the mechanisms driving tumor progression. Genomic investigations have attempted to differentiate malignant melanoma from benign pigmented lesions. However, genetic biomarkers of early melanoma diagnosis have not yet proven their value in the clinical setting. Protein biomarkers may be more promising since they directly influence tissue phenotype, a result of by-products of genomic mutations, posttranslational modifications and environmental factors. Uncovering relevant protein biomarkers could increase confidence in their use as diagnostic signatures. Currently, proteomic investigations of melanoma progression from pigmented lesions are limited. Studies have previously characterised the melanoma proteome from cultured cell lines and clinical samples such as serum and tissue. This has been useful in understanding how melanoma progresses into metastasis and development of resistance to adjuvant therapies. Currently, most studies focus on metastatic melanoma to find potential drug therapy targets, prognostic factors and markers of resistance. This paper reviews recent advancements in the genomics and proteomic fields and reports potential avenues, which could help identify and differentiate melanoma from benign pigmented lesions and prevent the progression of melanoma., (© 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Systemic melanoma therapies have the potential to affect basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cuSCC) development. In this study, we aim to compare the incidence of BCC and cuSCC in patients with metastatic melanoma treated with antiprogrammed cell death-1 (anti-PD1), BRAF inhibitor (BRAFi) monotherapy or dabrafenib and trametinib combination therapy (CombiDT) with a group of control patients having similar risk factors. We reviewed the records of melanoma patients on anti-PD1, BRAFi, or CombiDT, and patients from the High-Risk Melanoma Clinic, Westmead Hospital. We also performed an immunohistochemical analysis of BCCs under anti-PD1 compared with controls using PD1, PD-L1, CD3, CD8, and CD20 stains. For the results, in all, 340 patients were included; 82 on anti-PD1, 134 on BRAFi, 69 on CombiDT, and 55 controls. BRAFi had the highest incidence of BCC (12.7%), followed by CombiDT (10.1%) and anti-PD1 (2.4%). The incidence of BCC was significantly lower in patients on anti-PD1 (2.4% vs. 19.4%; P<0.001) compared with controls. Patients on anti-PD1 were 8.54 times less likely to develop BCC than the controls [hazard ratio, 0.117 (95% confidence interval, 0.026-0.526), P=0.005]. BRAFi and CombiDT showed no significant differences in BCC incidence compared with controls. BRAFi had the highest cuSCC incidence (23.9%), followed by anti-PD1 (7.3%) and CombiDT (2.9%). The incidence of cuSCC was significantly higher in patients on BRAFi (23.9% vs. 3.5%; P<0.001) compared with controls, but anti-PD1 and CombiDT showed no differences in cuSCC incidence compared with controls. Immunohistochemistry analysis of 10 BCC from under anti-PD1 and 8 BCC from controls patients showed that while all BCC had negative PD-L1 staining, the percentage of PD1 staining in anti-PD1 group is significantly lower than that of the control group (independent t test, 8% vs. 26%; P<0.001). In conclusion, our study suggests that anti-PD1 therapy decreases the incidence of BCC, as a result of the PD1/PD-L1 blockade. Future studies investigating the role of anti-PD1 in suppressing or treating BCC may be warranted.

Atypical fibroxanthoma (AFX) is a rare spindle cell neoplasm predominantly found on the head and neck of elderly individuals with sun-damaged skin, with no evidence-based guidelines for their management. A systematic retrospective review of the literature focusing on treatment modality found a recurrence and metastasis rate of 8.0% (5.6% when adjusted for incomplete excisions) and 0.5% for local excision and 4.6% and 3.2% for Mohs micrographic surgery, respectively. Our results suggest that with clear surgical margins, AFX is unlikely to recur and metastases are rare, with significantly higher rates in the immunosuppressed population., (© 2017 The Australasian College of Dermatologists.)

With increasing use of immunotherapies such as anti-cytotoxic T cell lymphocyte antigen-4 and anti-programmed cell death 1 antibodies, various skin toxicities have emerged. Severity of skin toxicities varies from mild lichenoid reaction to severe toxic epidermal necrolysis. Appropriate diagnosis and management of these skin toxicities are essential for optimal patient care and to avoid unnecessary cessation of anti-cancer therapies. This review summarises a wide range of cutaneous manifestations associated with immunotherapy usage in patients with metastatic melanoma., (© 2018 S. Karger AG, Basel.)

The introduction of anti-programmed cell death-1 (anti-PD1) monoclonal antibodies has revolutionized the treatment of various advanced malignancies. Despite its efficacy, anti-PD1 therapy is accompanied by a variety of cutaneous adverse events. A 79-year-old man developed erythematous scaly plaques and pustules of the forehead, legs and arms after four cycles of nivolumab infusions every 2 weeks. Histology showed intracorneal pustules with dermal neutrophils and eosinophils. He was treated successfully with topical corticosteroids without discontinuation of nivolumab. We report subcorneal pustular eruption as a novel cutaneous adverse event in patients on anti-PD1 therapy. Other neutrophilic eruptions (psoriasis, Sweet's syndrome, acute generalized pustulosis) have been reported in patients on anti-PD1 treatments, suggesting the neutrophil as another cell type modulated by anti-PD1 antibodies.

Background/objectives: Various cutaneous side-effects have been reported with anti-melanoma systemic therapies. This study investigated the changes in melanocytic lesion pigmentation in patients on four different therapies., Methods: We analysed the serial dermatoscopic photographs of atypical melanocytic lesions taken from patients with advanced metastatic melanoma on four different systemic therapies (selective BRAF-inhibitor monotherapy, dabrafenib combined with trametinib [D&T], anti-programmed cell death protein 1 [anti-PD1] therapies, and anti-PD1 combined with ipilimumab) seen from February 2013 to May 2016. We compared these changes with the melanocytic lesions of 10 control patients., Results: In the control group, 19% of naevi lightened, 64% did not change and 17% darkened. Only the BRAF inhibitor group showed more darkened lesions than controls (37%, P < 0.001). Meanwhile, there were more lightened naevi in the D&T therapy group (86%, P < 0.001) as well as the anti-PD1 and ipilimumab groups (59%, P < 0.001) than controls. Patients on anti-PD1 monotherapy had more lightened (49%) and fewer darkened naevi (9%) than controls, but differences were not significant., Conclusions: Our study showed that different anti-melanoma systemic therapies have different effects on the pigmentation of melanocytic lesions. BRAF inhibitor may have the propensity to cause darkening while D&T therapy and anti-PD1 caused lightening compared with controls. The findings emphasise the importance of regular dermatological monitoring in specialised clinics for patients on anti-melanoma systemic therapy. Clinicians should expect changes in the global pigmentation of melanocytic lesions but be suspicious of lesions with structural changes., (© 2017 The Australasian College of Dermatologists.)

Background: The literature provides mixed results regarding cost comparisons of Mohs micrographic surgery (MMS) and traditional excision (TE)., Objective: To complete a prospective cohort study comparing true costs of MMS with projected costs of TE for head and neck basal cell carcinoma (BCC)., Methods: Patients referred for MMS of biopsy-proven BCC were eligible for inclusion. For each case, surgery with TE was planned before the patient proceeded to MMS. The true costs of MMS were compared with projected costs of TE. All TE patients with inadequate excision were assumed to have subsequent TE, and the cost of the subsequent procedure was assumed to be equal to the first., Results: The mean cost of MMS was $628.47 (95% CI: $617.73-$639.21) compared with $587.51 (95% CI: $558.42-$616.59) for TE. This difference of $40.96 to initial margin clearance was significant (z = 4.48, p < .001)., Conclusion: On average, MMS was found to be $40.96 more expensive than TE in treating BCC-a small but appreciable difference. This being the case, any fiscal comparison must also be tempered with a consideration of effectiveness. Accordingly, further work in the form of a cost-utility study is required to truly define the cost-effectiveness of MMS compared with TE in this setting.

Background: Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses., Methods: In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide., Results: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001). No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued., Conclusions: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials Registry number, ACTRN12612000625875.).

Diffuse melanosis cutis (DMC) is a rare presentation of metastatic melanoma associated with a particularly guarded prognosis. We report a case of a 35-year-old man with BRAF(V600E) metastatic melanoma treated with dabrafenib (as well as ipilimumab and whole brain radiotherapy), who is alive, 25 months after the onset of his DMC. This is significantly longer than the reported mean survival of 4 months, highlighting the importance of BRAF mutation testing and the promising survival advantage of using targeted therapies compared with conventional chemotherapeutic regimens., (© 2014 The Australasian College of Dermatologists.)

Basal cell carcinoma and squamous cell carcinoma are the most common malignancies and are classified under the umbrella of non-melanoma skin cancer (NMSC). NMSC exerts a small but appreciable decrement in quality of life (QOL). The impact posed may arise from the tumour itself or as a result of treatment, and through symptoms, functional limitations, cosmetic burden and auxiliary considerations such as cost and disturbance to the activities of daily living. Researchers have evaluated this burden using a variety of outcome measures including generic, dermatology-specific and disease-specific instruments. The skin cancer index represents a promising disease-specific patient-reported outcome measure in this setting. To overcome some of the constraints inherent to disease-specific instruments, and to allow comparisons with other diseases, utility weightings have been developed. Utility weightings represent a cardinal measure for a specific health status and are established through methods such as the standard gamble, willingness-to-pay and time trade-off, and have also been employed to generate utility weightings for NMSC. Utilities are becoming increasingly important as a means of comparing health states across medicine and are of particular importance from a health-care policy perspective as they are used for resource allocation. The small but definite impact on the individual's QOL posed by NMSC should be a clinical consideration for physicians and it should be recognised by researchers as a potential outcome measure., (© 2014 The Australasian College of Dermatologists.)

Panniculitis is a rare complication of BRAF inhibitor therapy that is used to treat patients with BRAF-mutated metastatic melanoma. We present a clinicopathologic review of 9 patients who developed panniculitis while on BRAF inhibitor therapy. In 13% of patients on vemurafenib, 3% of patients on dabrafenib and 10% on combination of dabrafenib + trametinib, tender erythematous nodular lesions of panniculitis appeared on legs, arms and trunk. Histological evaluation of 8 biopsies from 7 patients showed predominantly neutrophilic infiltrate in 4, lymphocytic in 1, and mixed in 3. Lesions with neutrophilic infiltrate appeared in earlier stages of treatment than those with mixed or lymphocytic infiltrate. All biopsies showed lobular involvement and 5 also had a septal component. In addition, 1 biopsy had lichenoid inflammation in the epidermis and the other had evidence of vasculitis. Most patients responded to conservative medical management without the need to reduce or to stop BRAF inhibitor therapy. Panniculitis seems to be a rare class effect of BRAF inhibitors that is predominantly lobular and neutrophilic, although other patterns can be seen.