3D Whole-body skin imaging for automated melanoma detection.

BACKGROUND: Existing artificial intelligence for melanoma detection has relied on analysing images of lesions of clinical interest, which may lead to missed melanomas. Tools analysing the entire skin surface are lacking. OBJECTIVES: To determine if melanoma can be distinguished from other skin lesions using data from automated analysis of 3D-images. METHODS: Single-centre, retrospective, observational convenience sample of patients diagnosed with melanoma at a tertiary care cancer hospital. Eligible participants were those with a whole-body 3D-image captured within 90 days prior to the diagnostic skin biopsy. 3D-images were obtained as standard of care using VECTRA WB360 Whole Body 3-dimensional Imaging System (Canfield Scientific). Automated data from image processing (i.e. lesion size, colour, border) for all eligible participants were exported from VECTRA DermaGraphix research software for analysis. The main outcome was the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 35 patients contributed 23,538 automatically identified skin lesions >2 mm in largest diameter (102-3021 lesions per participant). All were White patients and 23 (66%) were males. The median (range) age was 64 years (26-89). There were 49 lesions of melanoma and 22,489 lesions that were not melanoma. The AUC for the prediction model was 0.94 (95% CI: 0.92-0.96). Considering all lesions in a patient-level analysis, 14 (28%) melanoma lesions had the highest predicted score or were in the 99th percentile among all lesions for an individual patient. CONCLUSIONS: In this proof-of-concept pilot study, we demonstrated that automated analysis of whole-body 3D-images using simple image processing techniques can discriminate melanoma from other skin lesions with high accuracy. Further studies with larger, higher quality, and more representative 3D-imaging datasets would be needed to improve and validate these results.

The long-term evolution of melanocytic nevi among high-risk adults.

BACKGROUND: There is little understanding regarding the long-term natural history of melanocytic nevi among adults. OBJECTIVE: The objective of the study was to describe the long-term natural history of individual nevi located on the torso of high-risk patients. METHODS: All patients attending Memorial Sloan Kettering Cancer Center (MSKCC) who underwent two total body photography (TBP) sessions 15+ years apart were included ('retrospective' group). To account for a potential selection bias, we also included consecutive patients who had TBP 15+ years ago and consented to undergo follow-up TBP ('prospective' group). We compared baseline and follow-up torso images on the TBPs and evaluated the number of total, new and disappearing nevi; number of seborrheic keratoses and actinic keratoses; each nevus' diameter at both time points; each nevus' colour change; the presence of clinical atypia; and when dermoscopy was available, the dermoscopic features at each time point. RESULTS: One hundred six patients were included in the study. Although the average age of the patients was 40 at baseline TBP, most patients developed new nevi between imaging sessions (median 16.4 years) with an average of 2.6 (SD = 4.8) nevi per participant. The average number of disappearing nevi was 0.3 (SD = 0.6). In addition, 62/106 (58%) patients had an absolute increase, and 9/106 (8%) patients had an absolute decrease in their total nevus count. Roughly half (49%: 1416/2890) of the nevi that could be evaluated at both time points increased in diameter by at least 25%. Only 6% (159/2890) of nevi shrunk in diameter by at least 25%. Patients with a history of melanoma had a higher rate of disappearing nevi, and their nevi were more likely to grow. Most nevi demonstrated no significant dermoscopic changes. CONCLUSIONS: High-risk patients acquire new nevi throughout life with very few nevi disappearing over time. Contrary to prior reports, most nevi in adults increase in diameter, while few nevi shrink.

Skin cancer risk among testicular germ-cell cancer survivors: a systematic review and meta-analysis.

Testicular germ-cell tumours (TGCT) are the most common cancer among young adult men. Previous studies suggested TGCT survivors have an increased risk for skin cancer. The goal of this study was to systematically review the literature and evidence regarding skin cancer risk among TGCT survivors compared with the general population. PubMed, EMBASE, Web of Science, Cochrane Databases and reference lists were included in the search. A systematic review of all comparative studies with more than 10 TGCT survivors reporting on skin cancer incidence was performed. A meta-analysis of the Standardized Incidence Rate (SIR) was calculated by pooling study-specific log-transformed estimates using the random-effects model. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Nineteen studies that reported on 147 935 TGCT survivors were included. Pooled SIR for skin cancer and for melanoma incidence among TGCT survivors were 1.93 (95% CI 1.62-2.29, P < 0.0001) and 1.81 (95% CI 1.57-2.08, P < 0.0001), respectively. In conclusion, compared to the general population, TGCT survivors have an increased risk for developing skin cancer and melanoma. Additional long-term studies that include TGCT survivors, additional risk factors and all subtypes of skin cancer are required.

The differences in clinical and dermoscopic features between in situ and invasive nevus-associated melanomas and de novo melanomas.

BACKGROUND: Nevus-associated melanomas (NAM) account for 30% of all melanomas and are associated with younger age and with thinner Breslow thickness. Previous studies of NAM dermoscopy found conflicting results. OBJECTIVE: To compare the clinical and dermoscopic features of NAM and de novo melanomas (DNM), stratified by melanoma thickness, in a relatively large cohort of patients. METHODS: A cross-sectional study of all melanomas biopsied between 2004 and 2019 at a large cancer centre. Lesions were categorized as in situ and invasive NAM or DNM. Dermoscopic images were reviewed and annotated. Associations between melanoma subtype and dermoscopic features were analysed via logistic regression modelling. Bivariate analyses were conducted using non-parametric bootstrap and chi-squared methods. RESULTS: The study included 160 NAM (86 in situ and 74 invasive) and 218 DNM (109 in situ and 109 invasive). NAM were associated with younger age, greater likelihood of being present on the torso, and thinner Breslow thickness. NAM were 2.5 times more likely to show a negative pigment network than DNM. In situ NAM were 2.1 and two times more likely to display dermoscopic area without definable structures and tan structureless areas than DNM, respectively. In situ melanomas were more likely to present a pigment network, and invasive melanomas more commonly presented scar-like depigmentation and shiny white structures. Streaks, blotches and shiny white structures were associated with deeper Breslow depth. CONCLUSIONS: Even though the nevus component of NAM could not be identified dermoscopically in the current series, negative pigment network, tan structureless areas and areas without definable structures are dermoscopic clues for NAM.

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.

Association between the dermoscopic morphology of peripheral globules and melanocytic lesion diagnosis.

BACKGROUND: The presence of peripheral globules is associated with enlarging melanocytic lesions; however, there are numerous patterns of peripheral globules distribution and it remains unknown whether specific patterns can help differentiate enlarging naevi from melanoma. OBJECTIVE: To investigate whether morphological differences exist between the peripheral globules seen in different subsets of naevi and in melanoma. METHODS: A cross-sectional study of clinical notes that mentioned peripheral globules, in addition to all melanoma images with peripheral globules on the International Skin Imaging Collaboration archive. Dermoscopic images were reviewed and annotated. Associations between diagnosis and categorical features were measured with odds ratios. Non-parametric tests were used for continuous factors. RESULTS: 184 lesions with peripheral globules from our clinic were included in the analysis; only 6 of these proved to be melanoma. 109 melanomas with peripheral globules from the International Skin Imaging Collaboration archive were added to the analysis. Melanomas were more common on the extremities and among older individuals. Melanomas were more likely to display atypical, tiered and/or focal peripheral globules. Only 5% of melanomas lacked dermoscopic melanoma-specific structures compared to 48% of naevi. CONCLUSIONS: Melanocytic lesions with atypical or asymmetrically distributed peripheral globules, especially when located on the extremities, should raise suspicion for malignancy. Melanocytic lesions with typical and symmetrically distributed peripheral globules, and with no other concerning dermoscopic features, are unlikely to be malignant.

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.

Incompletely excised lentigo maligna melanoma is associated with unpredictable residual disease: clinical features and the emerging role of reflectance confocal microscopy.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) poses a treatment and surgical challenge given unpredictable subclinical extension resulting in incomplete excision. OBJECTIVES: To describe the demographic, clinical and pathologic characteristics of incompletely excised LM/LMM. To evaluate the potential role of reflectance confocal microscopy (RCM). PATIENTS AND METHODS: A retrospective review of a melanoma database at a tertiary cancer centre for patients referred with 'incompletely excised LM/LMM' or 'incompletely excised melanoma' between October 2006 and July 2017. We recorded clinical and pathological data and surgical margins needed to clear the residual LM/LMM. The second part consisted of a prospective cohort of patients in which RCM was performed when presenting with incompletely excised LM/LMM. RESULTS: We included a total of 67 patients (retrospective + prospective cohort); mean age was 64.9 (standard deviation: 11.3) years and 52.2% were males. For the retrospective cohort (n = 53), the mean scar size was 3.4 cm. The average initial margins excised prior to presentation were 4.8 mm (range 3-7 mm). The average additional margin needed to clear the residual, incompletely excised LM/LMM was 7.8 mm. For the prospective cohort (n = 14), there were no differences in age, gender or size when compared to the retrospective cohort. RCM had a diagnostic accuracy of 78.6%, a sensitivity of 90.9%, a specificity of 33.3% and a positive predictive value of 83.3% for the detection of incompletely excised LM/LMM. CONCLUSIONS: Incompletely excised LM/LMM is a poorly characterized clinical-pathological scenario that may require considerable extra margins for microscopic clearance. RCM may emerge as a valuable tool for the evaluation of patients with incompletely excised LM/LMM.

Reflectance confocal microscopy and dermoscopy aid in evaluating repigmentation within or adjacent to lentigo maligna melanoma surgical scars.

BACKGROUND: Determining whether repigmentation within or adjacent to lentigo maligna or lentigo maligna melanoma (LM/LMM) scars represents recurrence of melanoma is challenging. The use of reflectance confocal microscopy (RCM) and dermoscopy may aid in differentiating true melanoma recurrence from other causes of repigmentation. OBJECTIVES: To describe the characteristics of repigmentation within or adjacent to LM/LMM scars observable on RCM and dermoscopy. METHODS: We retrospectively analysed patients who presented with new pigmentation within or adjacent to scars from surgically treated LM/LMM between January 2014 and December 2018. Clinical and demographic characteristics and time to recurrence were recorded. RCM was used to evaluate areas of pigmentation before biopsy. If available, dermoscopic images were also evaluated. RESULTS: In total, 30 confocal studies in 29 patients were included in the study cohort. Twenty-one patients had biopsy-confirmed recurrent LM/LMM; the remainder had pigmented actinic keratosis (n = 4) or hyperpigmentation/solar lentigo (n = 5). RCM had sensitivity of 95.24% (95% CI, 76.18-99.88%), specificity of 77.7% (95% CI, 39.99-97.19%), positive predictive value of 90.91% (95% CI, 74.58-97.15%) and negative predictive value of 87.5% (95% CI, 50.04-98.0%). The most common dermoscopic feature observed among patients with recurrent LM/LMM was focal homogeneous or structureless areas of light-brown pigmentation (92.8% vs. 37.5% in patients with other diagnoses; P = 0.009). LM-specific dermoscopic criteria were present in only 28.5% of patients with recurrent LM/LMM. CONCLUSIONS: Reflectance confocal microscopy and dermoscopy are valuable tools for the comprehensive evaluation of repigmentation within or adjacent to LM scars.

Accuracy of tele-consultation on management decisions of lesions suspect for melanoma using reflectance confocal microscopy as a stand-alone diagnostic tool.

BACKGROUND: Diagnostic accuracy of reflectance confocal microscopy (RCM) as a stand-alone diagnostic tool for suspect skin lesions has not been extensively studied. OBJECTIVE: Primary aim was to measure experts' accuracy in RCM-based management decisions. Secondary aim was to identify melanoma-specific RCM features. METHODS: The study enrolled patients ≥18 years that underwent biopsy of skin lesions clinically suspected to be melanoma. One hundred lesions imaged by RCM were randomly selected from 439 lesions prospectively collected at four pigmented lesion clinics. The study data set included 23 melanomas, three basal cell and two squamous cell carcinomas, 11 indeterminate melanocytic lesions and 61 benign lesions including 50 nevi. Three expert RCM evaluators were blinded to clinical or dermoscopic images, and to the final histopathological diagnosis. Evaluators independently issued a binary RCM-based management decision, 'biopsy' vs. 'observation'; these decisions were scored against histopathological diagnosis, with 'biopsy' as the correct management decision for malignant and indeterminate lesions. A subset analysis of 23 melanomas and 50 nevi with unequivocal histopathological diagnosis was performed to identify melanoma-specific RCM features. RESULTS: Sensitivity, specificity and diagnostic accuracy were 74%, 67% and 70% for reader 1, 46%, 84% and 69% for reader 2, and 72%, 46% and 56% for reader 3, respectively. The overall kappa for management decisions was 0.34. Readers had unanimous agreement on management for 50 of the 100 lesions. Non-specific architecture, non-visible papillae, streaming of nuclei, coarse collagen fibres and abnormal vasculature showed a significant association with melanoma in the evaluation of at least two readers. CONCLUSIONS: Reflectance confocal microscopy tele-consultation of especially challenging lesions, based on image review without benefit of clinical or dermoscopy images, may be associated with limited diagnostic accuracy and interobserver agreement. Architectural and stromal criteria may emerge as potentially useful and reproducible criteria for melanoma diagnosis.

A case report of disappearing pigmented skin lesions associated with pembrolizumab treatment for metastatic melanoma.

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death (PD)-1 receptor. Common cutaneous adverse side-effects of PD-1 inhibitors include maculopapular rash, pruritus, vitiligo and lichenoid skin and mucosal reactions. Here we describe a man in his sixties with metastatic melanoma treated with pembrolizumab who subsequently developed fading or disappearance of pigmented skin lesions, lightening of the skin, and poliosis of the eyebrows, eyelashes and scalp and body hair. Compared with baseline high-resolution three-dimensional total-body photography, we observed fading or disappearance of solar lentigines, seborrhoeic keratoses and melanocytic naevi, suggesting that PD-1 inhibitors may affect the evolution of these benign skin lesions. With dermatoscopic follow-up, altered lesions showed either blue-grey peppering/granularity or fading in colour without other identifiable features. No halo lesions or lesions with surrounding inflammation were identified. One changed pigmented lesion that showed blue-grey peppering/granularity on dermoscopy was biopsied and interpreted as a macular seborrhoeic keratosis with melanophages. Further studies are required to elucidate the effects of PD-1 inhibition on benign skin lesions.

Dermoscopic features and patterns of poromas: a multicentre observational case-control study conducted by the International Dermoscopy Society.

BACKGROUND: Poromas are benign cutaneous sweat gland tumours that are challenging to identify. The dermoscopic features of poromas are not well characterized. OBJECTIVE: To determine the clinical-dermoscopic features of poromas. METHODS: Cross-sectional, observational study of 113 poromas and 106 matched control lesions from 16 contributors and eight countries. Blinded reviewers evaluated the clinical and dermoscopic features present in each clinical and dermoscopic image. RESULTS: Poromas were most commonly non-pigmented (85.8%), papules (35.4%) and located on non-acral sites (65.5%). In multivariate analysis, dermoscopic features associated with poroma included white interlacing areas around vessels (OR: 7.9, 95% CI: 1.9-32.5, P = 0.004), yellow structureless areas (OR: 2.5, 95% CI: 1.1-6.0, P = 0.04), milky-red globules (OR: 3.9, 95% CI: 1.4-11.1, P = 0.01) and poorly visualized vessels (OR: 33.3, 95% CI: 1.9-586.5, P = 0.02). The presence of branched vessels with rounded endings was positively associated with poromas but did not reach statistical significance (OR: 2.4, 95% CI: 0.8-6.5, P = 0.10). The presence of any of these five features was associated with a sensitivity and specificity of 62.8% and 82.0%, respectively. CONCLUSION: We identified dermoscopic features that are specific to the diagnosis of poroma. Overall, however, the prevalence of these features was low. Significant clinical and dermoscopic variability is a hallmark of these uncommon tumours, which are most prevalent on non-acral sites.

Dermoscopy and the diagnosis of primary cutaneous B-cell lymphoma.

BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCLs) are frequently misdiagnosed, and a biopsy is needed to attain the correct diagnosis. OBJECTIVE: To characterize the dermoscopic features of PCBCL. METHODS: In this retrospective observational study, we analysed the pathology reports of 172 newly diagnosed PCBCL for the initial clinical differential diagnosis. The dermoscopic images of 58 PCBCL were evaluated for dermoscopic features. Two dermoscopy experts, who were blinded to the diagnosis and the study objective, evaluated images from 17 cases for a dermoscopic differential diagnosis. RESULTS: Of 172 biopsy-proven PCBCL lesions, cutaneous lymphoma was suspected by the clinician in 16.3%; the leading diagnosis was basal cell carcinoma in 17.4%, and other skin neoplasms in 21%. Studying 58 PCBCL dermoscopic images, we most frequently identified salmon-coloured background/area (79.3%) and prominent blood vessels (77.6%), mostly of serpentine (linear-irregular) morphology (67.2%). Dermoscopic features did not differ significantly by subtype or location. Blinded evaluation by dermoscopy experts raised a wide differential diagnosis including PCBCL, arthropod bite, basal cell carcinoma, amelanotic melanoma and scar/keloid. CONCLUSIONS: Two dermoscopic features, salmon-coloured area/background and serpentine vessels, are frequently seen in PCBCL lesions. These characteristic dermoscopic features, although not specific, can suggest a possible diagnosis of PCBCL.

A Clinical Aid for Detecting Skin Cancer: The Triage Amalgamated Dermoscopic Algorithm (TADA).

PURPOSE: Family physicians (FPs) frequently evaluate skin lesions but may not have the necessary training to accurately and confidently identify lesions that require skin biopsy or specialist referral. We evaluated the diagnostic performance of a new, simplified dermoscopy algorithm for skin cancer detection. METHODS: In this cross-sectional, observation study, attendees of a dermoscopy course evaluated 50 polarized dermoscopy images of skin lesions (27 malignant and 23 benign) using the Triage Amalgamated Dermoscopic Algorithm (TADA). The dermoscopic criteria of TADA include architectural disorder (ie, disorganized or asymmetric distribution of colors and/or structures), starburst pattern, blue-black or gray color, white structures, negative network, ulcer, and vessels. The study occurred after 1 day of basic dermoscopy training. Clinical information related to palpation (ie, firm, dimpling) was provided when relevant. RESULTS: Of 200 course attendees, 120 (60%) participated in the study. Participants included 64 (53.3%) dermatologists and 41 (34.2%) primary care physicians, 19 (46.3%) of whom were FPs. Fifty-two (43%) individuals had no previous dermoscopy training. Overall, the sensitivity and specificity of TADA for malignant skin lesions was 94.8% and 72.3%, respectively. Previous dermoscopy training and years of dermoscopy experience were not associated with diagnostic sensitivity (P = .13 and P = .05, respectively) or specificity (P = .36 and P = .21, respectively). Specialty type was not associated with sensitivity (P = .37) but dermatologists had a higher specificity than nondermatologists (79% v. 72%, P = .008). CONCLUSIONS: After basic instruction, TADA may be a useful dermoscopy algorithm for FPs who examine skin lesions as it has a high sensitivity for detecting skin cancer.