Dermoscopy of Lentiginous Melanomas and Equivocal Benign Pigmented Macules of the Scalp: A Case-Control Multicentric Study.

INTRODUCTION: Although the dermoscopic features of facial lentiginous melanomas (LM), including lentigo maligna and lentigo maligna melanoma, have been extensively studied, the literature about those located on the scalp is scarce. This study aims to describe the dermoscopic features of scalp LM and assess the diagnostic accuracy of dermoscopy to discriminate them from equivocal benign pigmented macules. METHODS: Consecutive cases of scalp LM and histopathology-proven benign but clinically equivocal pigmented macules (actinic keratoses, solar lentigos, seborrhoeic keratoses, and lichen planus-like keratoses) from four referral centres were included. Dermoscopic features were analysed by two blinded experts. The diagnostic performance of a predictive model was assessed. RESULTS: 56 LM and 44 controls were included. Multiple features previously described for facial and extrafacial LM were frequently identified in both groups. Expert's sensitivity to diagnose scalp LM was 76.8% (63.6-87.0) and 78.6% (65.6-88.4), with specificity of 54.5% (38.9-69.6) and 56.8% (41.0-71.7), and fair agreement (kappa coefficient 0.248). The strongest independent predictors of malignancy were (OR, 95% CI) chaos of colour (15.43, 1.48-160.3), pigmented reticular lines (14.96, 1.68-132.9), increased density of vascular network (3.45, 1.09-10.92), and perifollicular grey circles (2.89, 0.96-8.67). The predictive model achieved 85.7% (73.8-93.6) sensitivity, 61.4% (45.5-75.6) specificity, and 81.5 (73.0-90.0) area under curve to discriminate benign and malignant lesions. A diagnostic flowchart was proposed, which should improve the diagnostic performance of dermoscopy. CONCLUSION: Both facial and extrafacial dermoscopic patterns can be identified in scalp LM, with considerable overlap with benign pigmented macules, leading to low specificity and interobserver agreement on dermoscopy.

Comparison of humans versus mobile phone-powered artificial intelligence for the diagnosis and management of pigmented skin cancer in secondary care: a multicentre, prospective, diagnostic, clinical trial.

BACKGROUND: Diagnosis of skin cancer requires medical expertise, which is scarce. Mobile phone-powered artificial intelligence (AI) could aid diagnosis, but it is unclear how this technology performs in a clinical scenario. Our primary aim was to test in the clinic whether there was equivalence between AI algorithms and clinicians for the diagnosis and management of pigmented skin lesions. METHODS: In this multicentre, prospective, diagnostic, clinical trial, we included specialist and novice clinicians and patients from two tertiary referral centres in Australia and Austria. Specialists had a specialist medical qualification related to diagnosing and managing pigmented skin lesions, whereas novices were dermatology junior doctors or registrars in trainee positions who had experience in examining and managing these lesions. Eligible patients were aged 18-99 years and had a modified Fitzpatrick I-III skin type; those in the diagnostic trial were undergoing routine excision or biopsy of one or more suspicious pigmented skin lesions bigger than 3 mm in the longest diameter, and those in the management trial had baseline total-body photographs taken within 1-4 years. We used two mobile phone-powered AI instruments incorporating a simple optical attachment: a new 7-class AI algorithm and the International Skin Imaging Collaboration (ISIC) AI algorithm, which was previously tested in a large online reader study. The reference standard for excised lesions in the diagnostic trial was histopathological examination; in the management trial, the reference standard was a descending hierarchy based on histopathological examination, comparison of baseline total-body photographs, digital monitoring, and telediagnosis. The main outcome of this study was to compare the accuracy of expert and novice diagnostic and management decisions with the two AI instruments. Possible decisions in the management trial were dismissal, biopsy, or 3-month monitoring. Decisions to monitor were considered equivalent to dismissal (scenario A) or biopsy of malignant lesions (scenario B). The trial was registered at the Australian New Zealand Clinical Trials Registry ACTRN12620000695909 (Universal trial number U1111-1251-8995). FINDINGS: The diagnostic study included 172 suspicious pigmented lesions (84 malignant) from 124 patients and the management study included 5696 pigmented lesions (18 malignant) from the whole body of 66 high-risk patients. The diagnoses of the 7-class AI algorithm were equivalent to the specialists' diagnoses (absolute accuracy difference 1·2% [95% CI -6·9 to 9·2]) and significantly superior to the novices' ones (21·5% [13·1 to 30·0]). The diagnoses of the ISIC AI algorithm were significantly inferior to the specialists' diagnoses (-11·6% [-20·3 to -3·0]) but significantly superior to the novices' ones (8·7% [-0·5 to 18·0]). The best 7-class management AI was significantly inferior to specialists' management (absolute accuracy difference in correct management decision -0·5% [95% CI -0·7 to -0·2] in scenario A and -0·4% [-0·8 to -0·05] in scenario B). Compared with the novices' management, the 7-class management AI was significantly inferior (-0·4% [-0·6 to -0·2]) in scenario A but significantly superior (0·4% [0·0 to 0·9]) in scenario B. INTERPRETATION: The mobile phone-powered AI technology is simple, practical, and accurate for the diagnosis of suspicious pigmented skin cancer in patients presenting to a specialist setting, although its usage for management decisions requires more careful execution. An AI algorithm that was superior in experimental studies was significantly inferior to specialists in a real-world scenario, suggesting that caution is needed when extrapolating results of experimental studies to clinical practice. FUNDING: MetaOptima Technology.

Dermoscopic features and screening strategies for the detection of small-diameter melanomas.

BACKGROUND: Around 70% of cutaneous malignant melanomas (MMs) develop de novo, and small-diameter or 'tiny' lesions are expected to represent the earliest manifestation of most MMs. AIM: To describe the clinical, histopathological and dermoscopic features of tiny MMs, and to investigate the impact of imaging tools, including total body photography (TBP) and sequential digital dermoscopy imaging (SDDI) in their detection. METHODS: Consecutive MMs diagnosed over 2 years in a referral centre were retrospectively included. Tiny MMs were defined as MMs with a diameter of ≤ 5 mm on dermoscopy. Dermoscopic features and the performance of four imaging methods were evaluated. RESULTS: Of the 312 MMs included, 86 (27.6%) measured ≤ 5 mm, and 44.2% of these were invasive. Tiny MMs were more frequently excised for being new and/or changing compared with nontiny MMs (77.9% vs. 50.9%; P < 0.001). Half of the tiny MMs would have been missed by the dermoscopic seven-point checklist (48.2%) or the three-point checklist (49.4%), while Menzies' method and the revised pattern analysis correctly identified respectively 65.9% and 63.5% of the tiny MMs. The most frequent positive features for tiny MMs were asymmetry in structure or colour (77.6%), brown dots (65.9%), irregular dots and globules (76.5%) and atypical pigment network (44.7%). Dermoscopic features predictive of invasion in tiny MMs were atypical vascular pattern (OR = 26.5, 95% CI 1.5-475.5, P < 0.01), shiny white lines (OR = 12.4, 95% CI 0.7-237.8, P = 0.04) and grey/blue structures (OR = 3.7, 95% CI 1.3-10.5, P = 0.01). CONCLUSION: Tiny MMs are frequently invasive and represent a clinical, dermoscopic and histopathological challenge. Dermoscopy alone has suboptimal diagnostic accuracy. Early diagnosis relies on the detection of new or changing lesions aided by TBP and SDDI.

Perspectives and Experiences of Patient-Led Melanoma Surveillance Using Digital Technologies From Clinicians Involved in the MEL-SELF Pilot Randomized Controlled Trial: Qualitative Interview Study.

BACKGROUND: The growing number of melanoma patients who need long-term surveillance increasingly exceeds the capacity of the dermatology workforce, particularly outside of metropolitan areas. Digital technologies that enable patients to perform skin self-examination and send dermoscopic images of lesions of concern to a dermatologist (mobile teledermoscopy) are a potential solution. If these technologies and the remote delivery of melanoma surveillance are to be incorporated into routine clinical practice, they need to be accepted by clinicians providing melanoma care, such as dermatologists and general practitioners (GPs). OBJECTIVE: This study aimed to explore perceptions of potential benefits and harms of mobile teledermoscopy, as well as experiences with this technology, among clinicians participating in a pilot randomized controlled trial (RCT) of patient-led melanoma surveillance. METHODS: This qualitative study was nested within a pilot RCT conducted at dermatologist and skin specialist GP-led melanoma clinics in New South Wales, Australia. We conducted semistructured interviews with 8 of the total 11 clinicians who were involved in the trial, including 4 dermatologists (3 provided teledermatology, 2 were treating clinicians), 1 surgical oncologist, and 3 GPs with qualifications in skin cancer screening (the remaining 3 GPs declined an interview). Thematic analysis was used to analyze the data with reference to the concepts of "medical overuse" and "high-value care." RESULTS: Clinicians identified several potential benefits, including increased access to dermatology services, earlier detection of melanomas, reassurance for patients between scheduled visits, and a reduction in unnecessary clinic visits. However, they also identified some potential concerns regarding the use of the technology and remote monitoring that could result in diagnostic uncertainty. These included poor image quality, difficulty making assessments from a 2D digital image (even if good quality), insufficient clinical history provided, and concern that suspicious lesions may have been missed by the patient. Clinicians thought that uncertainty arising from these concerns, together with perceived potential medicolegal consequences from missing a diagnosis, might lead to increases in unnecessary clinic visits and procedures. Strategies suggested for achieving high-value care included managing clinical uncertainty to decrease the potential for medical overuse and ensuring optimal placement of patient-led teledermoscopy within existing clinical care pathways to increase the potential for benefits. CONCLUSIONS: Clinicians were enthusiastic about the potential and experienced benefits of mobile teledermoscopy; however, managing clinical uncertainty will be necessary to achieve these benefits in clinical care outside of trial contexts and minimize potential harms from medical overuse. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12616001716459; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371865.

Efficiency of Detecting New Primary Melanoma Among Individuals Treated in a High-risk Clinic for Skin Surveillance.

Importance: A previous single-center study observed fewer excisions, lower health care costs, thinner melanomas, and better quality of life when surveillance of high-risk patients was conducted in a melanoma dermatology clinic with a structured surveillance protocol involving full-body examinations every 6 months aided by total-body photography (TBP) and sequential digital dermoscopy imaging (SDDI). Objective: To examine longer-term sustainability and expansion of the surveillance program to numerous practices, including a primary care skin cancer clinic setting. Design, Setting, and Participants: This prospective cohort study recruited 593 participants assessed from 2012 to 2018 as having very high risk of melanoma, with a median of 2.9 years of follow-up (interquartile range, 1.9-3.3 years), from 4 melanoma high-risk clinics (3 dermatology clinics and 1 primary care skin cancer clinic) in New South Wales, Australia. Data analyses were conducted from February to September 2020. Exposures: Six-month full-body examination with the aid of TBP and SDDI. For equivocal lesions, the clinician performed SDDI at 3 or 6 months. Main Outcomes and Measures: All suspect monitored or excised lesions were recorded, and pathology reports obtained. Outcomes included the incidence and characteristics of new lesions and the association of diagnostic aids with rates of new melanoma detection. Results: Among 593 participants, 340 (57.3%) were men, and the median age at baseline was 58 years (interquartile range, 47-66 years). There were 1513 lesions excised during follow-up, including 171 primary melanomas. The overall benign to malignant excision ratio, including keratinocyte carcinomas, was 0.8:1.0; the benign melanocytic to melanoma excision ratio was 2.4:1.0; and the melanoma in situ to invasive melanoma ratio was 2.2:1.0. The excision ratios were similar across the 4 centers. The risk of developing a new melanoma was 9.0% annually in the first 2 years and increased with time, particularly for those with multiple primary melanomas. The thicker melanomas (>1-mm Breslow thickness; 7 of 171 melanomas [4.1%]) were mostly desmoplastic or nodular (4 of 7), self-detected (2 of 7), or clinician detected without the aid of TBP (3 of 7). Overall, new melanomas were most likely to be detected by a clinician with the aid of TBP (54 of 171 [31.6%]) followed by digital dermoscopy monitoring (50 of 171 [29.2%]). Conclusions and Relevance: The structured surveillance program for high-risk patients may be implemented at a larger scale given the present cohort study findings suggesting the sustainability and replication of results in numerous settings, including a primary care skin cancer clinic.

Reflectance confocal microscopy role in mycosis fungoides follow-up.

BACKGROUND: Reflectance confocal microscopy (RCM) is a useful tool for many skin cancers, allowing non-invasive evaluation over time and identifying areas of active disease. Its role to follow-up mycosis fungoides (MF) patients has not yet been evaluated. OBJECTIVE: To assess the level of agreement between RCM and histopathology and to develop a RCM checklist that could help monitoring MF patients. METHOD: Prospective study in a cutaneous lymphoma clinic of a tertiary hospital in Australia. RCM and biopsies were performed on the same area at baseline, before commencing or changing treatment, and at 6 months after starting treatment. Normal skin sites were also analysed and acted as controls. RCM features and histopathological findings were blindly evaluated by the confocalist and pathologist. Correlation between RCM and histology was measured by overall per cent of agreement (OPA), kappa and ROC curves. Additionally, RCM images before and after treatment were assessed blinded from clinical information and correlated to clinical assessment. RESULTS: Thirty-eight MF lesions were included. Nineteen of these 38 were re-assessed by RCM 6 months later. Fifty biopsies were performed (38 at baseline and 12 after 6 months). The combination of four RCM features corresponding to Pautrier's microabscess, epidermal and junctional lymphocytes and interface dermatitis formed the RCM checklist for MF that predicted the severity of disease with AUC of 0.95 (P = .003). CONCLUSION: Reflectance confocal microscopy can assess activity within a lesion and over time and assist in the clinical management of patients with MF.

Diagnostic accuracy of pigmented labial macules by in vivo reflectance confocal microscopy and correlation among techniques.

BACKGROUND: Pigmented labial macules (PLMs) are clinical, dermoscopic, and histopathologic challenges. OBJECTIVE: To describe and evaluate the utility of reflectance confocal microscopy (RCM) in PLMs and to establish a correlation between dermoscopy, RCM, histopathology, and immunohistochemistry. METHODS: Prospective study of PLMs from 4 tertiary referral dermatology centers. The study included 51 biopsy specimen-proven PLMs. Dermoscopic, RCM images, and histopathologic preparations were evaluated for malignant criteria. Diagnostic accuracy of RCM for melanoma diagnosis, RCM Lip Score previously reported, and κ values between techniques were calculated. RESULTS: Included were 5 melanomas and 46 benign PLMs. Dermoscopically, melanomas exhibited more frequently ≥3 colors and ≥3 structures. With RCM, pagetoid spreading, epithelial disarray, continuous proliferation of atypical cells around papillae, nonhomogeneously distributed papillae, marked cellular atypia, and a higher number of dendritic cells per papillae were more frequent in melanomas. The RCM Lip Score was significantly higher in malignant lesions. Good κ values were observed in most of the evaluated features. A perfect sensitivity and specificity was obtained combining dermoscopy and RCM. LIMITATIONS: A low number of melanomas were obtained. CONCLUSIONS: RCM improves lip melanoma diagnosis, and the RCM Lip Score represents a useful tool for the evaluation of a PLM.

Melanomas of the scalp: is hair coverage preventing early diagnosis?

BACKGROUND: Scalp melanomas are usually thicker and show worse prognosis than other sites and other head and neck melanomas. One hypothesis to explain this aggressive behavior could be diagnosis delay attributed to hair concealment of lesions. METHODS: Primary melanomas of the scalp diagnosed over two decades at four reference centers in Australia and Italy were included. Hair coverage and visibility of the lesions were assessed on preoperative photographic documentation by two investigators and correlated with some prognostic factors (Breslow thickness, mitotic rate, and ulceration). Patients records and pathology reports provided clinical and histological data. RESULTS: The majority of 113 melanomas included were located on easily visible areas of the scalp - hairless scalp (49%) or hairline (15%). The remaining ones (36%), considered to be hair-covered, showed more frequently thinning of hair (63%) than a dense hair coverage (37%). Melanomas of "hairy scalps" were more frequently invasive (81%) and had higher median Breslow (0.8 ± 1.3 mm) than those arising on bald scalps or areas with thinning of hair (43%; 0 ± 0.6 mm), P = 0.004. However, when considering only the invasive cases (n = 55), Breslow thickness and mitotic rate were not statistically different between concealed and easily visible areas. Melanomas detected by a doctor were thinner than those first noticed by the patient, relatives, or a hairdresser (P < 0.001). CONCLUSIONS: Most scalp melanomas arose on easily visible areas, which are more prone to ultraviolet damage. Hair-covered ones, despite rare, could be overlooked during examination. Proactive screening of the scalp area should be encouraged.

The steadily growing problem of lentigo maligna and lentigo maligna melanoma in Australia: Population-based data on diagnosis and management.

BACKGROUND/OBJECTIVES: There are limited population-based data documenting the incidence and management of lentigo maligna (LM) and invasive lentigo maligna melanoma (LMM). We report the data on occurrence and management of LM and LMM in an Australian population. METHODS: Prospective collection of incidence and clinician-reported management of melanoma in situ (MIS; n = 450, capped) and localised invasive melanoma (n = 3251) notified to the New South Wales Cancer Registry over 12-months in 2006-2007. RESULTS: The estimated annual incidence of all MIS was 27.0 per 100 000 (LM 12.2, non-LM MIS 5.9 and unclassified MIS 9.0). Patients with LM or LMM were on average approximately 10 years older than those with other melanoma subtypes (P < 0.001). The head and neck was the location of 59% of LM, 44% of LMM and <20% of other melanoma subtypes (P < 0.001). The majority of LM and LMM were treated only by specialists. Diagnostic partial biopsies were more frequent for LM and LMM than for other melanoma subtypes, and primary care physicians were more likely than specialists to do a punch partial biopsy than a shave biopsy. The reported median definitive excision margin for LM was 5.0 mm compared with 7.2 mm for non-LM MIS (P = 0.001). CONCLUSIONS: In this Australian population, LM was twice as frequent as other types of MIS. Improved strategies for diagnosis and management are required.

In Vivo Reflectance Confocal Microscopy for the Diagnosis of Melanoma and Melanotic Macules of the Lip.

Importance: Benign melanotic macules (MAC) are the most frequent cause of lip pigmentation and sometimes difficult to differentiate from lip melanoma (MEL). Objectives: To report in vivo reflectance confocal microscopy (RCM) features of normal lips of different phototypes and to identify features that assist in distinguishing MEL from MAC using dermoscopy and RCM. Design, Setting, and Participants: For this retrospective observational study, 2 groups of patients from 2 tertiary referral centers for melanoma (Sydney Melanoma Diagnostic Centre and Melanoma Institute Australia) were recruited between June 2007 and January 2015. Group 1 included patients with normal lips and different phototypes, and Group 2 consisted of patients with MAC and MEL; RCM and dermoscopy were used for lips analysis. Main Outcomes and Measures: Overall, 92 RCM features were correlated with clinical history, dermoscopic images, and histopathology in all patients with MEL and 5 patients with MAC. Results: Images from the vermillion and/or mucosal part of the lip were recorded from 10 patients with clinically normal lips (mean [SD] age, 34.5 [6.1] years), 16 patients with MAC (mean [SD] age, 49.6 [17.9] years), and 5 patients with 6 cases of MEL (1 patient had a recurrent lesion; mean [SD] age, 56.2 [15.5] years). In normal lips, the draped pattern-a previously described MAC RCM feature-was identified in all cases. In MEL, the following findings were frequent and significantly different from MAC: epidermal disarray; pagetoid infiltration of dendritic and/or round cells; a nonspecific architectural pattern at the dermoepidermal junction (DEJ); nonhomogenously distributed papillae; continuous (lentiginous) proliferation of cells with marked atypia at the DEJ, especially in interpapillary spaces; a higher number of dendritic cells (especially roundish); and atypical round cells at the DEJ. The cellular body area of dendritic cells was about the double in MEL compared with MAC. An RCM lip algorithm was developed that provided 100% sensitivity and 88% specificity for the diagnosis of MEL of the vermillion and mucosal part of the lip. With dermoscopy, MAC were correctly classified as benign in 13 of 16 cases (81%) and MEL were classified as equivocal or malignant in 5 of 6 cases (83%). Conclusions and Relevance: Reflectance confocal microscopy can assist in the differential diagnosis of lip MEL and MAC. An RCM Lip Score that we developed based on study results is proposed and needs to be validated on an independent data set.

Nódulos asépticos y alopécicos del cuero cabelludo / Aseptic and Alopecic Nodules of the Scalp

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