Proportion of thick versus thin melanomas as a benchmarking tool

Background: The ratio of benign moles excised for each malignant melanoma diagnosed (number-needed-to-excise (NNE)) is a metric used to express the efficiency of diagnostic accuracy of melanoma. The literature suggests a progressive effort to reduce the NNE, thus raising concerns about missing early melanoma because the NNE does not capture the most significant outcome for melanoma prognosis, which is linked to the Breslow thickness. A lower NNE could reduce health costs related to melanoma diagnosis only if doing so does not increase the proportion of thicker melanomas. Objectives: The diagnostic performance by two tertiary referral centres using the NNE and proportion of thick (Breslow thickness > 1 mm) versus thin (Breslow thickness ≤ 1 mm) excised melanoma (thick/thin ratio: TTR) was compared to determine if a lower NNE is associated with a greater proportion of thicker melanoma. Combining TTR with NNE allows a better estimate of the effectiveness in melanoma diagnosis, assessing both the overall cost for a given pool of excised melanomas and costs due to unnecessary nevi excision at a particular dermatology centre. Methods: Demographic data and Breslow thickness of excised melanoma were extracted from patient histologic records at two referral centres for melanoma (Parma Dermatology Unit and Ravenna and Meldola Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori. IRCCS (IRST)) on all skin tumours excised between 2002 and 2011 and diagnosed as melanoma or melanocytic nevus. NNE and TTR were calculated and compared among the considered variables. Logistic regression was used to assess the contribution of each variable in predicting a higher TTR. Results: Data from 16,738 excised lesions were analysed. The IRST Unit reported a mean NNE of 4.6, whereas the Parma Unit excised 10.6 nevi for each melanoma. No statistically significant differences existed in the mean (IRST Unit, 0.56 ± 0.89 mm; Parma Unit, 1.07 ± 2.2 mm) and median (range) Breslow thickness (IRST Unit, 0.4 (9) mm; Parma Unit 0.4 (30) mm). The TTR between centres was significantly different (Parma Unit, 24%; IRST Unit, 12%; p < 0.001). Based on logistic regression, the diagnosing centre was the most powerful factor in determining a thickness of >1 mm among diagnosed melanomas (OR = 1.8; 95% CI, 1.2–2.7; p < 0.01), with all other factors being equal. The NNE decreased at both centres from younger-to-older patients, whereas the TTR increased simultaneously; however, the increase in TTR was non-significantly related to NNE reduction after adjusting for confounders (age, gender, and localization). Conclusions: A better diagnostic performance is capable of reducing the NNE and TTR, i.e., unnecessary excisions of melanocytic nevi can be reduced without increasing the risk of overlooking melanomas. The TTR, in addition to the NNE, allows stakeholders to better estimate the effectiveness in melanoma diagnosis because both overall costs for a given pool of excised melanomas and costs due for unnecessary nevi excision at a particular dermatology centre can be compared

sex differences in axial and limb distribution of melanocytic naevi

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A New Approach for a Safe and Reproducible Seeds Positioning for Diffusing Alpha-Emitters Radiation Therapy of Squamous Cell Skin Cancer: A Feasibility Study

The purpose of this study is to discuss how to use an external radio-opaque template in the Diffusing Alpha-emitters Radiation Therapy (DaRT) technique’s pre-planning and treatment stages. This device would help to determine the proper number of sources for tumour coverage, accounting for subcutaneous invasion and augmenting DaRT safety. The procedure will be carried out in a first phase on a phantom and then applied to a clinical case. A typical DaRT procedure workflow comprises steps like tumour measurements and delineation, source number assessment, and therapy administration. As a first step, an adhesive fiberglass mesh (spaced by 2 mm) tape was applied on the skin of the patient and employed as frame of reference. A physician contoured the lesion and marked the entrance points for the needles with a radio opaque ink marker. According to the radio opaque marks and metabolic uptake the clinical target volume was defined, and with a commercial brachytherapy treatment planning system (TPS) it was possible to simulate and adjust the spatial seeds distribution. After the implant procedure a CT was again performed to check the agreement between simulations and seeds positions. With the procedure described above it was possible to simulate a DaRT procedure on a phantom in order to train physicians and subsequently apply the novel approach on patients, outlining the major issues involved in the technique. The present work innovates and supports DaRT technique for the treatment of cutaneous cancers, improving its efficacy and safety

Vitamin d and the risk of non-melanoma skin cancer: A systematic literature review and meta-analysis on behalf of the italian melanoma intergroup

We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February 2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61–4.56), although with large heterogeneity across studies (I2 = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the VDR and VDBP genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation

Exogenous sex hormones, menstrual and reproductive history, and risk of non-melanoma skin cancer among women: a systematic literature review and meta-analysis

Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged < 40 years) have experienced steeper growth in their incidence rates in recent years. Hormonal factors were hypothesized to be playing a role in modulating NMSC risk, but the studies published to date provided conflicting results. We systematically reviewed and meta-analysed the studies focusing on the association between hormone-related characteristics (use of exogenous sex hormones, and aspects of menstrual and reproductive history) and the risk of NMSC among women. We included observational and experimental studies published in PubMed and EMBASE until February 2020. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) by applying random effects models with maximum likelihood estimation, and used the I2 statistics to quantify the degree of heterogeneity of risk estimates across studies. Eleven independent studies encompassing a total of over 30,000 NMSC cases were included in quantitative analyses. No evidence of an increased NMSC risk emerged among ever vs. never users of oral contraceptives (SRR 1.13, 95% CI 0.88–1.45) or hormones for menopause (SRR 1.09, 95% CI 0.87–1.37). Likewise, age at menarche or at menopause and parity were not associated with NMSC risk. Heterogeneity across studies was low, and pooled results were comparable between NMSC subtypes. We found no evidence that hormonal factors play a role in the pathogenesis of NMSC among women

Melanoma management during the covid-19 pandemic emergency: A literature review and single-center experience

Background: The current COVID-19 pandemic has influenced the modus operandi of all fields of medicine, significantly impacting patients with oncological diseases and multiple comorbidi-ties. Thus, in recent months, the establishment of melanoma management during the emergency has become a major area of interest. In addition to original articles, case reports and specific guidelines for the period have been developed. Purpose: This article aims to evaluate whether melanoma management has been changed by the outbreak of COVID-19, and if so, what the consequences are. We summarized the main issues concerning the screening of suspicious lesions, the diagnosis of primary melanoma, and the management of early-stage and advanced melanomas during the pandemic. Additionally, we report on the experience of our dermatological clinic in northern Italy. Methods: We performed a literature review evaluating articles on melanomas and COVID-19 published in the last two years on PubMed, as well as considering publications by major healthcare organizations. Concerning oncological practice in our center, we collected data on surgical and therapeutic procedures in patients with a melanoma performed during the first months of the pandemic. Conclusions: During the emergency period, the evaluation of suspicious skin lesions was ensured as much as possible. However, the reduced level of access to medical care led to a documented delay in the diagnosis of new melanomas. When detected, the management of early-stage and advanced melanomas was fully guaranteed, whereas the follow-up visits of disease-free patients have been postponed or replaced with a teleconsultation when possible

The combination of dermoscopy and reflectance confocal microscopy increases the diagnostic confidence of amelanotic/hypomelanotic lentigo maligna

The dermoscopic diagnosis of amelanotic/hypomelanotic lentigo maligna/lentigo maligna melanoma (AHLM/LMM) may be very difficult in its early stages because of lack of pigment. Reflectance confocal microscopy (RCM) is an imaging technique that is especially helpful for the diagnosis of lentigo maligna. To determine the diagnostic performances of dermoscopy and RCM in the diagnosis of AHLM/LMMs we evaluated dermoscopic and RCM images of consecutive cases of histopathologically confirmed AHLM/LMMs, amelanotic/hypomelanotic basal cell carcinoma and squamous cell carcinoma (AHBCCs/AHSCCs), amelanotic/hypomelanotic benign lesions (AHBLs), and actinic keratoses (AKs) from five participating centers. Sensitivity, specificity, accuracy, predictive values, and level of diagnosis confidence were calculated for both diagnostic procedures. Both dermoscopy and RCM showed diagnostic performance >97% in the diagnosis of AHLM/LMMs versus AHBCC/AHSCCs and their combination slightly improved diagnostic performance, with accuracy increasing from 98.0% to 99.1%. Similarly, RCM in combination with dermoscopy showed a tiny increase in the diagnostic performance in the diagnosis of AHLM/LMMs versus AHBLs (accuracy increased from 87.2% to 88.8%) and versus AKs (accuracy increased from 91.4% to 93.4%). Although the increase in diagnostic performance due to RCM was modest, the combination of dermoscopy and RCM greatly increased the level of confidence; high confidence in the diagnosis of AHLM/LMMs versus AHBLs increased from 36.2% with dermoscopy alone to 76.6% with dermoscopy plus RMC. Based on our results, dermoscopy and RCM should be complementary to improve not only diagnostic accuracy but also the level of diagnostic certainty in the diagnosis of AHLM/LMMs

Reliability and inter-observer agreement of dermoscopic diagnosis of melanoma and melanocytic naevi

The aim of this study was to analyse the reliability and the inter- observer agreement of dermoscopy in the diagnosis of melanocytic skin lesions. Nine dermatologists, with a different training experience and who routinely used dermoscopy in different hospitals in Italy, evaluated clinical and dermoscopy photographs of 15 melanocytic lesions (four invasive melanomas, four histologically common naevi, and seven naevi with histological atypia). A further series of dermoscopic photographs of 40 melanocytic lesions was evaluated to quantify inter-observer concordance in recognizing dermoscopic criteria. Compared to the true (histological) diagnosis, clinical diagnosis (categories: melanoma, common naevus, atypical naevus) was correct in 40% of cases (range, 27-53%). The percentage raised to 55% (40-73%) by the use of dermoscopy, with an average improvement of 15.6%. Concerning melanoma, clinical diagnosis resulted in a sensitivity of 41.9%, specificity of 77.8%, positive predictive value (PPV) of 36.1%, negative predictive value (NPV) of 81.8%. By using dermoscopy, an improvement of diagnostic performance was found (sensitivity 75%, specificity 88.8%, VPP 71.0%, VPN 90.7%). The inter-observer agreement in melanoma diagnosis, by using dermoscopy, was similar to that obtained by clinical examination (k statistics = 0.54 and 0.52, respectively). Concerning dermoscopic criteria, the best agreement among observers was found for pseudopods, a dermoscopic parameter related to the radial growth phase of melanoma. We conclude that dermoscopy is an useful tool for a non-invasive diagnosis of melanocytic skin lesions, improving the diagnostic performance compared to clinical examination

More than one shade of pink as a marker of early amelanotic/hypomelanotic melanoma

Amelanotic/hypomelanotic melanoma (AHM) may be difficult to diagnose because of a lack of pigmentation. To evaluate whether dermoscopy can be useful for the diagnosis of early AHM, 133 digital dermoscopic images of lesions histopathologically diagnosed as amelanotic/hypomelanotic superficial spreading melanoma with ≤1 mm thickness (AHSSMs) (n = 27), amelanotic/hypomelanotic non-melanocytic lesions (AHNMLs) (e.g., seborrhoeic keratosis and basal cell carcinoma) (n = 79), and amelanotic/hypomelanotic benign melanocytic lesions (AHBMLs) (e.g., compound and dermal nevi) (n = 27), were dermoscopically assessed by three blinded dermatologists. Using multivariate analysis, we found a significantly increased risk of diagnosing AHSSM versus AHNML and AHBML when the lesion was characterized by the presence of more than one shade of pink (odds ratio [OR] 37.11), irregular dots/globules (OR 23.73), asymmetric pigmentation (OR 8.85), and structureless pattern (OR 7.33). In conclusion, dermoscopy may improve early AHM detection, discriminating AHSSM from amelanotic/hypomelanotic non melanoma lesion