Dermoscopy and reflectance confocal microscopy of solitary flat pink lesions: A new combined score to diagnose amelanotic melanoma.

BACKGROUND: Differential diagnosis of amelanotic/hypomelanotic melanoma among solitary flat pink lesions is challenging, due to limited clinical and dermoscopic clues. Dermoscopy and reflectance confocal microscopy assessments improve diagnostic accuracy, but their combined capacity among solitary flat pink lesions is yet to be defined. OBJECTIVES: To determine (i) whether diagnostic accuracy is improved with combined dermoscopy and reflectance confocal microscopy, (ii) a model to estimate probability of flat amelanotic/hypomelanotic melanoma among solitary flat pink lesions. METHODS: A retrospective single-centre study of solitary flat pink lesions, excised for suspected malignancy between 2011 and 2022 was performed. Images were independently evaluated by two dermatologists, blinded to histopathological diagnosis. Diagnostic performance was evaluated on the receiver operating characteristic curve and the area under the curve. Predictive features were identified by univariate and multivariate logistic regression analyses. A final predictive nomogram of independent risk factors was calculated by backward likelihood ratio. Hypothesis being tested was formulated before data collection. RESULTS: A total of 184 patients (87 females, 47.3%) were included; mean age was 57.6 years (19-95). Combined dermoscopy and reflectance confocal microscopy was more sensitive (83%, CI 69.2-92.4 and 91.5%, CI 79.6-97.6) than dermoscopy alone (76.6%, CI 62.0-87.7 and 85.1%, CI 71.7-93.8). Predictive features defined the new model, including linear irregular vessels (4.26-folds, CI 1.5-12.1), peripheral pigment network (6.07-folds, CI 1.83-20.15), remnants of pigmentation (4.3-folds, CI 1.27-14.55) at dermoscopy and atypical honeycomb (9.98-folds, CI 1.91-51.96), disarranged epidermal pattern (15.22-folds, CI 2.18-106.23), dendritic pagetoid cells in the epidermis (3.77-folds, CI 1.25-11.26), hypopigmented pagetoid cells (27.05-folds, CI 1.57-465.5), and dense and sparse nests (3.68-folds, CI 1.24-10.96) in reflectance confocal microscopy. Diagnostic accuracy of the model was high (AUC 0.91). CONCLUSIONS: Adjunctive reflectance confocal microscopy increases diagnostic sensitivity of flat amelanotic/hypomelanotic melanoma differential diagnosis. The proposed model requires validation.

Dynamic optical coherence tomography evaluation in locally advanced basal cell carcinoma during sonidegib treatment.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the Caucasian population. It has a multifactorial pathogenesis, in which constitutive activation of the Sonic Hedgehog signalling (SHH) pathway (via mutations in PTCH1 or SMO genes) represents by far the most common genetic aberration. The introduction of vismodegib and sonidegib, two SHH pathway inhibitors, changed the therapeutic approach of locally advanced and metastatic BCCs. EADO's (European Association of Dermato-Oncology) new staging system refers to these as 'difficult-to-treat' BCCs. OBJECTIVE: The aim was to evaluate sonidegib's effectiveness in patients affected by difficult-to-treat BCCs by using non-invasive diagnostic techniques. METHODS: We retrospectively evaluated 14 patients (4 females, 10 males; mean age 77 ± 11 years) affected by difficult-to-treat BCCs treated with oral sonidegib 200 mg/day that were followed with total body videodermoscopy (V-Track, Vidix 4.0) and dynamic optical coherence tomography (D-OCT, VivoSight Dx) since May 2022. Considering the risk of rhabdomyolysis routine blood tests, especially for creatine kinase concentrations, were performed. All treated patients were inserted in the BasoCare database, which aims to offer support to patients taking sonidegib. Complete and partial responses were evaluated by the overall reduction of the number of lesions and their individual sizes. Safety was evaluated by assessing the occurrence and severity of adverse reactions. RESULTS: Eighty per cent achieved complete clearance and 75% reduction of diameter. D-OCT scans performed at every follow-up showed concordance with clinical appearance and demonstrated reduction of hyporeflective structures, that is, islets of tumour cells and overall improvement of morphology. CONCLUSION: Sonidegib can be considered an effective treatment option in cases where surgery or radiotherapy would be unfeasible or has previously failed, although pigmented lesions did not show complete clearance, suggesting that there are factors other than the SHH pathway involved in tumour growth. Videodermoscopy and D-OCT were useful in the quick and seamless follow-up of lesions and added valuable information in assessing efficacy.

Online prediction tools for melanoma survival: A comparison.

BACKGROUND: Breslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that accurately considers these and other predictors could be valuable for clinicians managing melanoma patients. OBJECTIVE: To compare online melanoma survival prediction tools that request user input on clinical and pathological features. METHODS: Search engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared. RESULTS: Three tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival. LIMITATIONS: The authors did not have access to the base data used to compile various prediction tools. CONCLUSION: The LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects.

Plants and Small Molecules: An Up-and-Coming Synergy.

The emergence of Arabidopsis thaliana as a model system has led to a rapid and wide improvement in molecular genetics techniques for studying gene function and regulation. However, there are still several drawbacks that cannot be easily solved with molecular genetic approaches, such as the study of unfriendly species, which are of increasing agronomic interest but are not easily transformed, thus are not prone to many molecular techniques. Chemical genetics represents a methodology able to fill this gap. Chemical genetics lies between chemistry and biology and relies on small molecules to phenocopy genetic mutations addressing specific targets. Advances in recent decades have greatly improved both target specificity and activity, expanding the application of this approach to any biological process. As for classical genetics, chemical genetics also proceeds with a forward or reverse approach depending on the nature of the study. In this review, we addressed this topic in the study of plant photomorphogenesis, stress responses and epigenetic processes. We have dealt with some cases of repurposing compounds whose activity has been previously proven in human cells and, conversely, studies where plants have been a tool for the characterization of small molecules. In addition, we delved into the chemical synthesis and improvement of some of the compounds described.

The role of case studies in recent paleopathological literature: An argument for continuing relevance.

OBJECTIVE: To critically examine the role that case studies play in recent paleopathological literature, by evaluating their frequency of publication, academic impact, and the public engagement they generate. MATERIALS: Articles published in International Journal of Paleopathology between 2011 and 2018 (N = 377). METHODS: Articles were coded as case studies, population studies, methodological studies, or reviews. Case studies were coded as cultural practices, differential diagnosis, historical, or methodological/theoretical. We utilized bibliometric analysis to assess academic impact and altmetric analysis to evaluate public engagement. RESULTS: Case studies continue to be the most frequently published, but least frequently cited, article type. There are no significant differences in public engagement data between article types. Methodological/theoretical case studies have the most academic impact. Differential diagnosis case studies have the least academic impact and generate the least public engagement. CONCLUSIONS: The case study genre includes a variety of approaches, some of which hold significant potential for contributing to the discipline of paleopathology and beyond. SIGNIFICANCE: This study updates Mays' (2012b) citation analysis, pioneers the use of altmetric data to analyze public engagement with paleopathological publications, and identifies less productive approaches and areas of heightened relevance in the case study genre. LIMITATIONS: Publications in only one journal were analyzed. Only one source was utilized for citation data (Google Scholar) and one source for altmetric data (PlumX). SUGGESTIONS FOR FUTURE RESEARCH: Expanding the granular analysis of case studies piloted here to additional journals and/or citation indexes to enlarge the sample size and provide keener insights.

Dermoscopy of cutaneous adnexal tumours: a systematic review of the literature.

Cutaneous adnexal tumours (ATs) encompass a variegated group of hamartomas and benign or malignant tumours, originating from the hair follicle, sebaceous, eccrine or apocrine glands that may simulate other cutaneous neoplasms. This study aims to provide a comprehensive overview of the spectrum of clinical and dermoscopic features of ATs, to better define these lesions and assist in the differential diagnosis. We performed a two-step systematic search of the literature in PubMed, Embase and Cochrane Library databases from inception until 4 September 2020. In the first step, we aimed to define histological variants of ATs with descriptions of dermoscopic criteria. The second step included a search for the name of each previously identified AT variants in the same databases adding 'AND (epilum* or dermosc* or dermatosc*)'. All study types in English language reporting dermoscopic images of ATs were included. Collisions between ATs and other inflammatory or neoplastic skin lesions were excluded, with the exception of collisions with a sebaceous nevus. The protocol of this study was prospectively registered in PROSPERO (CRD42021244677). In total, 206 articles met our inclusion criteria, encompassing 372 ATs in 365 patients. Most ATs were apocrine-eccrine (n = 217, 58.3%, n = 173 benign) with a prevalence of poromas (n = 82), followed by follicular ATs (n = 88, 23.7%, n = 83 benign) and sebaceous ATs (n = 67, 18.0%, n = 49 benign). Most patients had a single AT lesion (320, 86.0%), while 42 (11.3%) had multiple ATs. A syndrome causing multiple ATs was identified in 15 patients. Histopathological analysis revealed 82% benign (n = 305) and 18.0% malignant (n = 67). ATs were classified according to their ability to mimic four groups of more common skin tumours: basal cell carcinoma, squamous cell carcinoma, melanocytic lesions and benign cutaneous lesions. Moreover, we have highlighted the ability of malignant variants of ATs to simulate benign skin lesions. This systematic review offers a comprehensive overview of the common clinical and dermoscopic features of follicular, sebaceous and apocrine-eccrine ATs and details possible differential dermoscopic features.

Dermoscopic spectrum of mycosis fungoides: a retrospective observational study by the International Dermoscopy Society.

BACKGROUND: The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited. OBJECTIVE: To evaluate dermoscopic morphology and dermoscopic-pathological correlations of classic MF stages and investigate dermoscopic features of MF variants. METHODS: Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic-pathological correlation assessment of different stages of classic MF were performed. RESULTS: A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF and 8 poikilodermatous MF). Linear/linear-curved vessels and white scales in the skin furrows were significantly associated with patch-stage MF, while clustered dotted vessels were related to plaque-stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumour-stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumours, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumours), bright white lines/structureless areas to dermal fibrosis and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines. CONCLUSION: Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants.

Clinical and dermatoscopic predictors of squamous cell carcinoma of the lips: a case-control, multicentric study.

BACKGROUND: Squamous cell carcinoma of the lip accounts for 20% of all oral carcinomas. Its diagnosis may be challenging because it clinically resembles actinic cheilitis and inflammatory lesions of the lips. OBJECTIVES: To determine clinical and dermatoscopic predictors of squamous cell carcinoma of the lip vs. other lip lesions. METHODS: Multicentre retrospective morphological study, including histologically confirmed cases of squamous cell carcinoma of the lip and controls consisting of actinic cheilitis and inflammatory lesions of the lips. Clinical and dermatoscopic images were evaluated for the presence of predefined criteria. Crude and adjusted odds ratios and corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression respectively. RESULTS: A total of 177 lip lesions were evaluated, 107 (60.5%) were squamous cell carcinomas and 70 (39.5%) were controls. The most frequent dermatoscopic criteria of lip squamous cell carcinoma were scales (100%), white halos (87.3%) and ulceration (79.4%). The majority of squamous cell carcinomas displayed polymorphic vessels (60.8%), with linear (68.6%) and hairpin (67.6%) being the most frequent types. Multivariate logistic regression analysis showed that clinical predictors of lip squamous cell carcinoma were exophytic appearance and clinical hyperkeratosis, with 43-fold and 6-fold higher probability respectively. White clods and ulceration in dermoscopy presented a 6-fold and 4-fold increased risk for squamous cell carcinoma respectively. CONCLUSIONS: A scaly lesion with exophytic growth, dermatoscopically displaying white clods, ulceration and linear and hairpin vessels is very likely a squamous cell carcinoma of the lip.

Flat scalp melanoma dermoscopic and reflectance confocal microscopy features correspond to histopathologic type and lesion location.

BACKGROUND: Dermoscopy and Reflectance Confocal Microscopy (RCM) features of scalp melanoma according to lesion location and histopathology have not been fully investigated. OBJECTIVES: To reveal dermoscopic and RCM features of scalp melanoma according to lesion location and histopathology. METHODS: We retrospectively retrieved images of suspicious, atypical excised, flat melanocytic lesions of the scalp, assessed on dermoscopy and RCM at five centres, from June 2007 to April 2020. Lesions were classified according to histopathological diagnoses of nevi, lentigo maligna melanoma (LM/LMM) or superficial spreading melanoma (SSM). Clinical, dermoscopic and RCM images were evaluated; LM/LMM and SSM subtypes were compared through multivariate analysis. RESULTS: Two hundred forty-seven lesions were included. In situ melanomas were mostly LM (81.3%), while invasive melanomas were mostly SSM (75.8%). Male sex, baldness and chronic sun-damaged skin were associated with all types of melanomas and in particular with LM/LMM. LMs were mostly located in the vertex area and SSM in the frontal (OR: 8.8; P < 0.05, CI 95%) and temporal (OR: 16.7; P < 0.005, CI 95%) areas. The dermoscopy presence of pseudo-network, pigmented rhomboidal structures, obliterated hair follicles and annular-granular pattern were associated with LM diagnoses, whereas bluish-white veil was more typical of SSM. Observations on RCM of atypical roundish and dendritic cells in the epidermis were associated with SSM (42.4%) and dendritic cells with LM (62.5%) diagnoses. Folliculotropism on RCM was confirmed as a typical sign of LM. CONCLUSIONS: Flat scalp melanomas reveal specific dermoscopic and RCM features according to histopathologic type and scalp location.

Dermoscopy comparative approach for early diagnosis in familial melanoma: influence of MC1R genotype.

BACKGROUND: MC1R polymorphisms interact with CDKN2A mutations modulating melanoma risk and contribute to a less suspicious clinical and dermoscopic appearance of melanomas. Different strategies, including dermoscopic comparative approach and digital monitoring, are used for the melanoma diagnosis in this context. OBJECTIVE: To analyse the diagnostic accuracy of the morphologic approach and comparative approach in dermoscopy, and to detect melanoma in familial melanoma (FamMM) patients according to different genetic backgrounds. METHODS: Two independent readers evaluated 415 lesions belonging to 25 FamMM: 26 melanomas (62% in situ, 36% early invasive) and 389 naevi, blinded for dermoscopic and histopathologic diagnosis, following two different steps. First step-Randomized: all lesions were randomly located in one single folder. Second step-Comparative approach: the lesions were clustered by patient. Sensitivity, specificity and number needed to excise (NNE) for melanoma diagnosis were calculated for both diagnostic strategies. Sensitivity and specificity were also assessed regarding the genetic background. RESULTS: The comparative approach showed lower sensitivity compared to the morphologic approach (69.2 and 73.1 vs. 76.9 both readers) but better specificity (95.9 and 95.1 vs. 84.3 and 90.2, respectively). NNE was better in the comparative approach. The readers had more difficulties diagnosing lesions from CDKN2A mutation carriers with red hair colour (RHC) MC1R variants. CONCLUSION: The comparative approach can be useful in high-risk patients to decrease the NNE. Early melanomas in CDKN2A carriers with RHC polymorphisms are more difficult to diagnose even with the comparative approach and benefit from the detection of changes during digital dermoscopy monitoring for early diagnosis.

Dermatoscopy of combined blue nevi: a multicentre study of the International Dermoscopy Society.

BACKGROUND: Combined blue nevi (CBN) may mimic melanoma and are relatively often biopsied for diagnostic reasons. OBJECTIVE: To better characterize CBN and to compare it with melanoma. METHODS: We collected clinical and dermatoscopic images of 111 histologically confirmed CBN and contrasted their dermatoscopic characteristics with 132 partly blue coloured melanomas. Furthermore, we compared the accuracy of human experts using pattern analysis with a computer algorithm based on deep learning. RESULTS: Combined blue nevi are usually flat or slightly elevated and, in comparison with melanoma, more frequent on the head and neck. Dermatoscopically, they are typified by a blue structureless part in combination with either brown clods (n = 52, 46.8%), lines (n = 28, 25.2%) or skin-coloured or brown structureless areas (n = 31, 27.9%). In contrast with melanoma, the blue part of CBN is more often well defined (18.9% vs. 4.5%, P < 0.001) and more often located in the centre (22.5% vs. 5.3%, P < 0.001). Melanomas are more often chaotic (OR: 28.7, 95% CI: 14.8-55.7, P < 0.001), have at least one melanoma clue (OR: 10.8, 95% CI: 5.2-22.2 P < 0.001) in particular white lines (OR: 37.1, 95% CI: 13.4-102.9, P < 0.001). Using simplified pattern analysis (chaos and clues), two raters reached sensitivities of 93.9% (95% CI: 88.4-97.3%) and 92.4% (95% CI: 86.5-96.3%) at corresponding specificities of 59.5% (95% CI: 49.7-68.7%) and 65.8% (95% CI: 56.2-74.5%). The human accuracy with pattern analysis was on par with a state-of-the-art computer algorithm based on deep learning that achieved an area under the curve of (0.92, 95% CI: 0.87-0.96) and a specificity of 85.3% (95% CI: 76.5-91.7%) at a given sensitivity of 83.6% (95% CI: 72.5-91.5%). CONCLUSION: CBN usually lack melanoma clues, in particular white lines. The accuracy of pattern analysis for combined nevi is acceptable, and histopathologic confirmation may not be necessary in exemplary cases.

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.