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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.

IMPORTANCE: Early melanoma diagnosis is associated with better health outcomes, but there is insufficient evidence that screening, such as having routine skin checks, reduces mortality. OBJECTIVE: To assess melanoma-specific and all-cause mortality associated with melanomas detected through routine skin checks, incidentally or patient detected. A secondary aim was to examine patient, sociodemographic, and clinicopathologic factors associated with different modes of melanoma detection. DESIGN, SETTING, AND PARTICIPANTS: This prospective, population-based, cohort study included patients in New South Wales, Australia, who were diagnosed with melanoma over 1 year from October 23, 2006, to October 22, 2007, in the Melanoma Patterns of Care Study and followed up until 2018 (mean [SD] length of follow-up, 11.9 [0.3] years) by using linked mortality and cancer registry data. All patients who had invasive melanomas recorded at the cancer registry were eligible for the study, but the number of in situ melanomas was capped. The treating doctors recorded details of melanoma detection and patient and clinical characteristics in a baseline questionnaire. Histopathologic variables were obtained from pathology reports. Of 3932 recorded melanomas, data were available and analyzed for 2452 (62%; 1 per patient) with primary in situ (n = 291) or invasive (n = 2161) cutaneous melanoma. Data were analyzed from March 2020 to January 2021. MAIN OUTCOMES AND MEASURES: Melanoma-specific mortality and all-cause mortality. RESULTS: A total of 2452 patients were included in the analyses. The median age at diagnosis was 65 years (range, 16-98 years), and 1502 patients (61%) were men. A total of 858 patients (35%) had their melanoma detected during a routine skin check, 1148 (47%) self-detected their melanoma, 293 (12%) had their melanoma discovered incidentally when checking another skin lesion, and 153 (6%) reported “other” presentation. Routine skin-check detection of invasive melanomas was associated with 59% lower melanoma-specific mortality (subhazard ratio, 0.41; 95% CI, 0.28-0.60; P < .001) and 36% lower all-cause mortality (hazard ratio, 0.64; 95% CI, 0.54-0.76; P < .001), adjusted for age and sex, compared with patient-detected melanomas. After adjusting for prognostic factors including ulceration and mitotic rate, the associations were 0.68 (95% CI, 0.44-1.03; P = .13), and 0.75 (95% CI, 0.63-0.90; P = .006), respectively. Factors associated with higher odds of routine skin-check melanoma detection included being male (female vs male, odds ratio [OR], 0.73; 95% CI, 0.60-0.89; P = .003), having previous melanoma (vs none, OR, 2.36; 95% CI, 1.77-3.15; P < .001), having many moles (vs not, OR, 1.39; 95% CI, 1.10-1.77; P = .02), being 50 years or older (eg, 50-59 years vs <40 years, OR, 2.89; 95% CI, 1.92-4.34; P < .001), and living in nonremote areas (eg, remote or very remote vs major cities, OR, 0.23; 95% CI, 0.05-1.04; P = .003). CONCLUSIONS AND RELEVANCE: In this cohort study, melanomas diagnosed through routine skin checks were associated with significantly lower all-cause mortality, but not melanoma-specific mortality, after adjustment for patient, sociodemographic, and clinicopathologic factors.

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.

Supplemental Digital Content is available in the text.Little is known ?Query_Start?about?Query_End?the risk of progression of lentigo maligna to lentigo maligna melanoma. We determine the annual risk of progression of lentigo maligna to lentigo maligna melanoma by analysing a prospective population-based survey of recently diagnosed anterior (visible in a mirror) head and neck lentigo malignas and lentigo maligna melanomas. Six hundred eighty-two consecutive patients aged 18–80 years with non-recurrent lentigo maligna or lentigo maligna melanoma, diagnosed between 1 July 2015 and 20 April 2016, were identified from pathology notifications to the New South Wales Cancer Registry (Australia) and sent survey questionnaires soon after diagnosis (median 4.6 months interquartile range: 3.8–5.7). Details of the time the lesion was present and when changes to it were noticed before diagnostic biopsy were ascertained by surveying the patients, of whom 53.5% agreed to participate. There was little difference between the proportions of lentigo maligna melanoma and lentigo maligna in the consenting and non-consenting patients (P= 0.56). Two hundred twenty-eight lentigo maligna (median age 67 years, range: 38–80) and 33 lentigo maligna melanoma (70 years, 43–80) were surveyed. There was no difference between the time lentigo maligna melanoma was present on the skin (median 18 months, range: 0–690) and the time lentigo maligna was (18 months, 0–665) (P= 0.972). The estimated risk of progression of lentigo maligna to lentigo maligna melanoma was 3.5% per year (95% confidence interval: 2.5–5.0). This equates to an average time for lentigo maligna to progress to lentigo maligna melanoma of 28.3 years (95% confidence interval: 20.0–40.5) in this population. Although our data suggests that the annual progression rate of lentigo maligna is more than 25 times greater than previously suggested, the rate is still low.

The evidence‐based national clinical practice guidelines for the management of cutaneous melanoma published in 2008 are currently being updated. This article summarises the findings from multiple chapters of the guidelines on different methods of melanoma detection and of monitoring the skin for patients at high risk of melanoma. Early detection of melanoma is critical, as thinner tumours are associated with enhanced survival; therefore, strategies to improve early detection are important to reduce melanoma‐related mortality. Clinicians who perform skin examinations for the purpose of detecting skin cancer should be trained in and use dermoscopy.The use of short term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual melanocytic lesions of concern.The use of long term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual or multiple melanocytic lesions for routine surveillance of high risk patients.The use of total body photography should be considered in managing patients at increased risk for melanoma, particularly those with high naevus counts and dysplastic naevi.There is insufficient evidence to recommend the routine use of automated instruments for the clinical diagnosis of primary melanoma. Determining the relative indications for each diagnostic method and how each method should be introduced into the surveillance of a patient requires careful consideration and an individualised approach.

IMPORTANCE: The diagnosis of a life-threatening disease like melanoma can affect all aspects of a person’s life, including health-related quality of life (HRQOL) and psychological aspects of melanoma such as fear of cancer recurrence (FCR). Economic evaluations of psychological interventions require preference-based (utility) instruments that are sensitive to changes in well-being and HRQOL; however, very few studies have evaluated the sensitivity of these instruments when used for people with melanoma. OBJECTIVE: To compare utility scores from the multiple-attribute instrument Assessment of Quality of Life—8-Dimension Scale (AQoL-8D) with the mapped utility scores of the Functional Assessment of Cancer Therapy–Melanoma (FACT-M) and to investigate the sensitivity of both instruments in identifying the influence of FCR on HRQOL. DESIGN, SETTING, AND PARTICIPANTS: This assessment of data from a randomized clinical trial of a psychoeducational intervention to reduce FCR, conducted at 3 high-risk melanoma clinics in Australia, evaluated 164 patients with early-stage melanoma and a high risk of developing a second primary melanoma. MAIN OUTCOMES AND MEASURES: The FACT-M and AQoL-8D were used to assess HRQOL and FCR among the study participants. Concurrent validity was assessed by comparing the total and subdomain scores of the 2 instruments, and the strength of associations was assessed using Pearson correlation coefficient. Convergent validity was assessed by comparing participants’ HRQOL, demographic, and clinical characteristics using the χ2 test and F statistic. Both the FACT-M and AQoL-8D utilities were regressed on FCR Inventory (FCRI) severity scores to estimate the effect of elevated FCR on HRQOL. RESULTS: A total of 164 participants completed the baseline questionnaires, but only 163 met all inclusion criteria and underwent the full analysis: 72 were women; 91 were men; and mean (SD) age was 58.2 (12.1) years. Both the AQoL-8D and FACT-M instruments showed good concurrent validity and could differentiate between relevant subgroups including level of FCRI severity. The AQoL-8D and FACT-M utilities were strongly correlated (r2 = 0.57). Respondents had a mean (SD) AQoL-8D utility of 0.77 (0.2), and a mean (SD) FACT-M utility score of 0.76 (0.07). High levels of FCRI severity were associated with a decrease in utility of 0.12 (95% CI, −0.19 to −0.05) as measured by AQoL-8D, and a decrease of 0.03 (95% CI, −0.05 to −0.01) as measured by the FACT-M. CONCLUSIONS AND RELEVANCE: For economic evaluations of psychological interventions in melanoma, the AQoL-8D and FACT-M are valid measures of utility; however, the AQoL-8D demonstrates greater sensitivity to FCRI severity. Our results suggest a significant association between FCR and HRQOL.

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.

IMPORTANCE: The identification of a subgroup at higher risk of melanoma may assist in early diagnosis. OBJECTIVE: To characterize melanoma patients and the clinical features associated with their melanomas according to patient risk factors: many nevi, history of previous melanoma, and family history of melanoma, to assist with improving the identification and treatment of a higher-risk subgroup. DESIGN, SETTING, AND PARTICIPANTS: The Melanoma Patterns of Care study was a population-based observational study of physicians’ reported treatment of 2727 patients diagnosed with an in situ or invasive primary melanoma over a 12-month period from October 2006 to 2007 conducted in New South Wales. Our analysis of these data took place from 2015 to 2016. MAIN OUTCOMES AND MEASURES: Age at diagnosis and body site of melanoma. RESULTS: Of the 2727 patients with melanoma included, 1052 (39%) were defined as higher risk owing to a family history of melanoma, multiple primary melanomas, or many nevi. Compared with patients with melanoma who were at lower risk (ie, without any of these risk factors), the higher-risk group had a younger mean age at diagnosis (62 vs 65 years, P < .001), but this differed by risk factor (56 years for patients with a family history, 59 years for those with many nevi, and 69 years for those with a previous melanoma). These age differences were consistent across all body sites. Among higher-risk patients, those with many nevi were more likely to have melanoma on the trunk (41% vs 29%, P < .001), those with a family history of melanoma were more likely to have melanomas on the limbs (57% vs 42%, P < .001), and those with a personal history were more likely to have melanoma on the head and neck (21% vs 15%, P = .003). CONCLUSIONS AND RELEVANCE: These findings suggest that a person’s risk factor status could be used to tailor surveillance programs and education about skin self-examination.

IMPORTANCE: The comparative diagnostic performance of dermoscopic algorithms and their individual criteria are not well studied. OBJECTIVES: To analyze the discriminatory power and reliability of dermoscopic criteria used in melanoma detection and compare the diagnostic accuracy of existing algorithms. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective, observational study of 477 lesions (119 melanomas [24.9%] and 358 nevi [75.1%]), which were divided into 12 image sets that consisted of 39 or 40 images per set. A link on the International Dermoscopy Society website from January 1, 2011, through December 31, 2011, directed participants to the study website. Data analysis was performed from June 1, 2013, through May 31, 2015. Participants included physicians, residents, and medical students, and there were no specialty-type or experience-level restrictions. Participants were randomly assigned to evaluate 1 of the 12 image sets. MAIN OUTCOMES AND MEASURES: Associations with melanoma and intraclass correlation coefficients (ICCs) were evaluated for the presence of dermoscopic criteria. Diagnostic accuracy measures were estimated for the following algorithms: the ABCD rule, the Menzies method, the 7-point checklist, the 3-point checklist, chaos and clues, and CASH (color, architecture, symmetry, and homogeneity). RESULTS: A total of 240 participants registered, and 103 (42.9%) evaluated all images. The 110 participants (45.8%) who evaluated fewer than 20 lesions were excluded, resulting in data from 130 participants (54.2%), 121 (93.1%) of whom were regular dermoscopy users. Criteria associated with melanoma included marked architectural disorder (odds ratio [OR], 6.6; 95% CI, 5.6-7.8), pattern asymmetry (OR, 4.9; 95% CI, 4.1-5.8), nonorganized pattern (OR, 3.3; 95% CI, 2.9-3.7), border score of 6 (OR, 3.3; 95% CI, 2.5-4.3), and contour asymmetry (OR, 3.2; 95% CI, 2.7-3.7) (P < .001 for all). Most dermoscopic criteria had poor to fair interobserver agreement. Criteria that reached moderate levels of agreement included comma vessels (ICC, 0.44; 95% CI, 0.40-0.49), absence of vessels (ICC, 0.46; 95% CI, 0.42-0.51), dark brown color (ICC, 0.40; 95% CI, 0.35-0.44), and architectural disorder (ICC, 0.43; 95% CI, 0.39-0.48). The Menzies method had the highest sensitivity for melanoma diagnosis (95.1%) but the lowest specificity (24.8%) compared with any other method (P < .001). The ABCD rule had the highest specificity (59.4%). All methods had similar areas under the receiver operating characteristic curves. CONCLUSIONS AND RELEVANCE: Important dermoscopic criteria for melanoma recognition were revalidated by participants with varied experience. Six algorithms tested had similar but modest levels of diagnostic accuracy, and the interobserver agreement of most individual criteria was poor.

IMPORTANCE: Regular surveillance of individuals at high risk for cutaneous melanoma improves early detection and reduces unnecessary excisions; however, a cost analysis of this specialized service has not been undertaken. OBJECTIVE: To determine the mean cost per patient of surveillance in a high-risk clinic from the health service and societal perspectives. DESIGN, SETTING, AND PARTICIPANTS: We used a bottom-up microcosting method to measure resource use in a consecutive sample of 102 patients treated in a high-risk hospital-based clinic in Australia during a 12-month period. EXPOSURE: Surveillance and treatment of melanoma. MAIN OUTCOMES AND MEASURES: All surveillance and treatment procedures were identified through direct observation, review of medical records, and interviews with staff and were valued using scheduled fees from the Australian government. Societal costs included transportation and loss of productivity. RESULTS: The mean number of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95% CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI, US $532-$665]); the cost discounted across 20 years was A $11 546 (95% CI, A $10 263-$12 829) (US $7839 [95% CI, US $6969-$8710]). The mean annual societal cost per patient (excluding health system costs) was A $972 (95% CI, A $899-$1045) (US $660 [95% CI, US $611-$710]); the cost discounted across 20 years was A $12 721 (95% CI, A $12 554-$14 463) (US $8637 [95% CI, US $8523-$9820]). Diagnosis of melanoma or nonmelanoma skin cancer and frequent excisions for benign lesions in a relatively small number of patients was responsible for positively skewed health system costs. CONCLUSIONS AND RELEVANCE: Microcosting techniques provide an accurate cost estimate for the provision of a specialized service. The high societal cost reflects the time that patients are willing to invest to attend the high-risk clinic. This alternative model of care for a high-risk population has relevance for decision making about health policy.

IMPORTANCE: The clinical phenotype and certain predisposing genetic mutations that confer increased melanoma risk are established; however, no consensus exists regarding optimal screening for such individuals. Early identification remains the most important intervention in reducing melanoma mortality. OBJECTIVE: To evaluate the impact of full-body examinations every 6 months supported by dermoscopy and total-body photography (TBP) on all patients and sequential digital dermoscopy imaging (SDDI), when indicated, on detecting primary melanoma in an extreme-risk population. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study from February 2006 to February 2011, with patients recruited from Sydney Melanoma Diagnostic Centre and Melanoma Institute Australia who had a history of invasive melanoma and dysplastic nevus syndrome, history of invasive melanoma and at least 3 first-degree or second-degree relatives with prior melanoma, history of at least 2 primary invasive melanomas, or a CDKN2A or CDK4 gene mutation. EXPOSURES: Six-month full-body examination compared with TBP. For equivocal lesions, SDDI short term (approximately 3 months) or long term (≥6 months), following established criteria, was performed. Atypical lesions were excised. MAIN OUTCOMES AND MEASURES: New primary melanoma numbers, characteristics, and cumulative incidence in each patient subgroup; effect of diagnostic aids on new melanoma identification. RESULTS: In 311 patients with a median (interquartile range [IQR]) follow-up of 3.5 (2.4-4.2) years, 75 primary melanomas were detected, 14 at baseline visit. Median (IQR) Breslow thickness of postbaseline incident melanomas was in situ (in situ to 0.60 mm). Thirty-eight percent were detected using TBP and 39% with SDDI. Five melanomas were greater than 1 mm Breslow thickness, 3 of which were histologically desmoplastic; the other 2 had nodular components. The benign to malignant excision ratio was 1.6:1 for all lesions excised and 4.4:1 for melanocytic lesions. Cumulative risk of developing a novel primary melanoma was 12.7% by year 2, with new primary melanoma incidence during the final 3 years of follow-up half of that observed during the first 2 years (incidence density ratio, 0.43 [95% CI, 0.25-0.74]; P = .002). CONCLUSIONS AND RELEVANCE: Monitoring patients at extreme risk with TBP and SDDI assisted with early diagnosis of primary melanoma. Hypervigilance for difficult-to-detect thick melanoma subtypes is crucial.

IMPORTANCE Lentigo maligna (LM) is a clinical, pathologic, and therapeutic challenge with a higher risk of local recurrence than other types of melanoma correctly treated and also carries the cosmetically sensitive localization of head and neck. OBJECTIVE To determine whether in vivo reflectance confocal microscopy (RCM) mapping of difficult LM cases might alter patient care and management. DESIGN Analysis of LM and LM melanoma (LMM) in a series of patients with large facial lesions requiring complex reconstructive surgery and/or recurrent or poorly delineated lesions at any body sites were investigated. SETTINGS Two tertiary referral melanoma centers in Sydney, Australia. PARTICIPANTS Thirty-seven patients with LM (including 5 with LMM) were mapped with RCM. Fifteen patients had a recurrent LM, including 9 with multiple prior recurrences. The LM was classified amelanotic in 10 patients, lightly pigmented in 9, and partially pigmented in 18. INTERVENTIONS The RCM images were obtained in 4 radial directions (allowing for anatomic barriers) for LM margin delineation using an RCM LM score previously described by our research team. MAIN OUTCOME MEASURES Differences in the margin of LM as determined by RCM vs dermoscopy vs histopathologic analysis. RESULTS Seventeen of 29 patients (59%) with dermoscopically visible lesions had subclinical (RCM-identified) disease evident more than 5 mm beyond the dermoscopy margin (ie, beyond the excision margin recommended in published guidelines). The RCM mapping changed the management in 27 patients (73%): 11 patients had a major change in their surgical procedure, and 16 were offered radiotherapy or imiquimod treatment as a consequence of the RCM findings. Treatment was surgical in 17 of 37 patients. Surgical excision margins (based on the RCM mapping) were histopathologically involved in only 2 patients, each of whom had an LM lesion larger than 6 cm. CONCLUSIONS AND RELEVANCE In vivo RCM can provide valuable information facilitating optimal patient care management.

IMPORTANCE Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. OBJECTIVE To determine the dermoscopy features of NM. DESIGN Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. SETTING Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. RESULTS Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. CONCLUSIONS AND RELEVANCE When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.

OBJECTIVE To describe and analyze the clinical and dermoscopic characteristics of desmoplastic melanoma (DM) as a function of pathologic subtype and phenotypic traits. DESIGN Retrospective case series. SETTING Eight high-risk dermatology clinics. PATIENTS Patients with DM confirmed by histopathologic analysis whose records included a high-quality dermoscopic image. MAIN OUTCOME MEASURES Clinical, dermoscopic, and histopathologic features of DM. RESULTS A total of 37 DM cases were identified. The majority of patients had fair skin, few nevi, and no history of melanoma. Lentigo maligna was the most frequent subtype of melanoma associated with DM. The most frequent clinical presentation of DM was a palpable and/or indurated lesion located on sun-exposed skin. Forty-three percent of cases were classified as pure DM, and 57% as mixed DM. Pure DM lesions were thicker than mixed DM lesions (4.10 vs 2.83 mm) (P = .22) and were less likely to have an associated epidermal non-DM component (63% vs 100%) (P = .004). Dermoscopically, DMs had at least 1 melanoma-specific structure, the most frequent being atypical vascular structures. Peppering was more frequently seen in pure DM (44% in pure DM vs 24% in mixed DM) (P = .29). In contrast, crystalline structures, polymorphous vessels, and vascular blush were more commonly seen in mixed DM. CONCLUSIONS Though DM can be difficult to diagnose based on clinical morphologic characteristics alone, dermoscopy has proved to be a useful aid during the evaluation of clinically equivocal lesions or those lesions with a benign appearance. The most common dermoscopic clues observed in DMs included atypical vascular structures, peppering, and occasionally other melanoma-specific structures.

OBJECTIVES To determine morphologic features of melanophages under in vivo reflectance confocal microscopy (RCM) and to highlight morphologic features that are important in distinguishing melanophages from melanocytes. DESIGN Consecutive retrospective study. SETTING Referral center for pigmented lesions. PATIENTS The study group retrospectively constituted 20 consecutive patients having biopsy-proven lichen planus–like keratoses that dermoscopically and histopathologically showed many melanophages and that had been imaged under RCM before biopsy. MAIN OUTCOME MEASURES The RCM characteristics of isolated dermal bright cells were scored blinded to dermoscopic features and histopathologic diagnosis. RESULTS Under RCM, melanophages were significantly smaller than melanocytes (mean [SD] cell diameter, 13.6 [1.6] vs 18.2 [2.9] μm, P = .006). Nuclei (intracellular low-reflectance round-oval structures) were visible in only 16% (29 of 184) of the cells in melanophages vs 57% (28 of 49) of the cells in melanocytes (P < .001). When identified, nuclei were smaller in melanophages than in melanocytes (mean [SD] diameter, 3.2 [1.2] vs 6.4 [0.7] μm, P < .001). Compared with melanocytes, melanophages were significantly more ill defined (76% [140 of 184] vs 18% [9 of 49], P < .001), less round (23% [42 of 184] vs 69% [34 of 49], P < .001), and less dendritic (1% [2 of 184] vs 12% [6 of 49]) (P = .001). CONCLUSION Observed differences in morphologic features should enable distinction between melanophages and melanocytes under RCM, thereby improving the accuracy of skin lesion diagnosis using this technique.Arch Dermatol. 2010;146(5):492-498 --

OBJECTIVE To test the interobserver and intraobserver reproducibility of the standard terminology for description and diagnosis of melanocytic lesions in in vivo confocal microscopy. DESIGN A dedicated Web platform was developed to train the participants and to allow independent distant evaluations of confocal images via the Internet. SETTING Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. PARTICIPANTS The study population was composed of 15 melanomas, 30 nevi, and 5 Spitz/Reed nevi. Six expert centers were invited to participate at the study. INTERVENTION Evaluation of 36 features in 345 confocal microscopic images from melanocytic lesions. MAIN OUTCOME MEASURE Interobserved and intraobserved agreement, by calculating the Cohen κ statistics measure for each descriptor. RESULTS High overall levels of reproducibility were shown for most of the evaluated features. In both the training and test sets there was a parallel trend of decreasing κ values as deeper anatomic skin levels were evaluated. All of the features, except 1, used for melanoma diagnosis, including roundish pagetoid cells, nonedged papillae, atypical cells in basal layer, cerebriform clusters, and nucleated cells infiltrating dermal papillae, showed high overall levels of reproducibility. However, less-than-ideal reproducibility was obtained for some descriptors, such as grainy appearance of the epidermis, junctional thickening, mild atypia in basal layer, plump bright cells, small bright cells, and reticulated fibers in the dermis. CONCLUSION The standard consensus confocal terminology useful for the evaluation of melanocytic lesions was reproducibly recognized by independent observers.Arch Dermatol. 2009;145(10):1137-1143--

OBJECTIVE To determine the predictive dermoscopic features of amelanotic and hypomelanotic melanoma. DESIGN A total of 105 melanomas (median Breslow thickness, 0.76 mm), 170 benign melanocytic lesions, and 222 nonmelanocytic lesions lacking significant pigment (amelanotic, partially pigmented, and light colored) were imaged using glass-plate dermoscopy devices and scored for 99 dermoscopic features. Diagnostic models were derived from and tested on independent randomly selected lesions. SETTING Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES Sensitivity, specificity, and odds ratios for individual features and models for the diagnosis of melanoma and malignancy. RESULTS The most significant negative predictors of melanoma were having multiple (>3) milialike cysts (odds ratio, 0.09; 95% confidence interval, 0.01-0.64), comma vessels with a regular distribution (0.10; 0.01-0.70), comma vessels as the predominant vessel type (0.16; 0.05-0.52), symmetrical pigmentation pattern (0.18; 0.09-0.39), irregular blue-gray globules (0.20; 0.05-0.87), and multiple blue-gray globules (0.28; 0.10-0.81). The most significant positive predictors were having a blue-white veil (odds ratio,13; 95% confidence interval, 3.9-40.0), scarlike depigmentation (4.4; 2.4-8.0), multiple blue-gray dots (3.5; 1.9-6.4), irregularly shaped depigmentation (3.3; 2.0-5.3), irregular brown dots/globules (3.2; 1.8-5.6), 5 to 6 colors (3.2; 1.6-6.3), and predominant central vessels (3.1; 1.6-6.0). A simple model distinguishing melanomas from all nonmelanomas had a sensitivity of 70% and a specificity of 56% in the test set. A model distinguishing all malignant lesions from benign lesions had a sensitivity of 96% and a specificity of 37%. CONCLUSION Although the diagnostic accuracy of dermoscopy for melanoma lacking significant pigment is inferior to that of more pigmented lesions, features distinguishing the former from benign lesions can be visualized on dermoscopic evaluation.Arch Dermatol. 2008;144(9):1120-1127--

OBJECTIVE To determine whether 6 weeks could replace 3 months for short-term sequential digital dermoscopy imaging (ST-SDDI) of suspicious melanocytic lesions and determine the proportion of melanomas missed. DESIGN Consecutive lesions (n = 2602) undergoing ST-SDDI monitored from 1859 patients were included. Half of the patients underwent 6-week monitoring followed by 3-month monitoring (range, 2.5-4.5 months) if changes were not seen. The remainder underwent 3-month monitoring only. Any change during this time led to excision. Lesions unchanged were then followed up over time. SETTING A tertiary referral institution. MAIN OUTCOME MEASURES The proportion of changed melanomas (sensitivity) and odds ratios (ORs) for melanoma of changed lesions. RESULTS Eighty-one melanomas were detected using ST-SDDI (Breslow thickness: median, in situ; maximum, 0.8 mm). Of 39 melanomas detected using ST-SDDI in the 6-week monitored lesions, 27 (69%) were detected at 6 weeks and 12 (31%) at 3 months. The OR for melanoma for a lesion changing at 6 weeks was 19 (95% confidence interval [CI], 10-35), and the overall OR for melanoma for a lesion changing during the short-term monitoring period (6 weeks to 4.5 months) was 47 (95% CI, 23-94). For lesions remaining unchanged at 3 months, 99.2% (1118 of 1127 lesions) were shown to be benign as defined by an unremarkable further follow-up. Seventy-five percent (15 of 20) of the lentigo maligna melanomas, 93% (40 of 43) of other in situ melanomas, and 96% (26 of 27) of the invasive melanomas were detected using ST-SDDI. CONCLUSION Three months remains the standard interval for ST-SDDI, where the sensitivity for the diagnosis of melanoma for changed (non–lentigo maligna) lesions is high but not 100%.Arch Dermatol. 2008;144(4):502-506--

Dermoscopy (surface microscopy) is a clinical technique which uses a hand-held magnifying instrument, usually with liquid at the skin-instrument interface, to examine pigmented lesions on the skin surface. A magnification of ×10 is usually used. Dermoscopy assists in deciding if the lesion should be excised or biopsied, requires monitoring or can be safely left in situ.The technique provides a bridge between the naked eye appearance of a lesion and the histopathological examination. Multiple dermoscopic features have been described and many of their histological correlates have been determined. Dermoscopic diagnosis usually involves a two-step procedure. The first step is to decide if the lesion is melanocytic or not. If melanocytic, the second step is to decide if the lesion is benign or malignant. Multiple algorithms have been developed to help in this decision. Dermoscopic criteria have been developed for melanoma and naevi. Several non-melanocytic pigmented lesions can be diagnosed with dermoscopy, including pigmented basal cell carcinoma, seborrhoeic keratoses, haemangioma and lichen planus-like keratosis.

Background:There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. Objective:The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. Methods:Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. κ Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. Results:Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean κ value: 0.53). Conclusion:The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions. (J Am Acad Dermatol 2003;48:679-93.)

A prediction of the theory of immunologic surveillance is that tumour antigens can be recognised by cell-mediated immunity during early development of the primary tumour by formation of tumour antigen-specific cytotoxic lymphocytes (CTLs) and that such recognition leads to destruction of those tumour cells (tumour regression) with subsequent appearance of tumour antigen-loss variants. However, this has never been shown in nonviral-induced experimental animal models of primary malignancy or in human primary cancer. We examined 2 groups of human melanoma patients where primary tumour regression was observed. Twenty-three patients with multiple (≥3) primary melanoma showed significant histologic regression of their last tumour (median tumour regression 33%) compared to matched tumours from patients with a single primary melanoma (median 0%) (p = 0.008) or compared to their first primary tumour (median 0%) (p = 0.001). This increased regression is consistent with an “immunisation effect” seen in murine tumour transplantation studies where innoculation with ≥3 asynchronous tumours induces transplantation rejection on subsequent challenge. A significant decrease in MART-1-positive stained tumour area in the last primary tumour from multiple melanoma subjects (median 8%) vs. matched single melanoma patients (median 79%) (p = 0.004) and in the last vs. first tumour (median 76%) in multiple primary subjects was found (p = 0.008). Metastatic tumours from 17 patients whose primary skin melanomas had completely regressed (occult primary melanoma) also showed significant MART-1 tumour-loss variants (median 0% MART-1-positive tumour) compared to matched metastatic tumours from patients with nonregressing primary tumours (median 51%) (p = 0.001). A correlation with the presence of peripheral blood MART-1-specific CTLs (MHC class I-restricted IFN-γ producing T lymphocytes) and MART-1 tumour antigen-loss variants was found (p = 0.001). Thus, in 2 groups of human melanoma subjects, we provide evidence of tumour regression associated with Melan A/MART-1 tumour antigen-loss variants correlating with formation of specific Melan A/MART-1 CTLs. © 2001 Wiley-Liss, Inc.

To examine the acceptability of photography as an aid to skin examinations in men over 50 years of age.

Objective:To examine the acceptability of photography as an aid to skin examinations in men over 50 years of age. Methods:A randomised trial of men selected from the electoral roll. All participants were photographed, but only half received their photographs. Skin examinations by GPs at years one and two. Results:55% of men consented to have photographs taken and 51% did so. 86% of respondents had risk factors for melanoma (compared to 68% of non‐responders) and 47% had two or more risk factors (compared to 23% of non‐responders). At year one, 91% of participants remaining in study regions had been examined. Photographs were lost by only six participants. Conclusions:Men over 50 years of age respond to personalised health messages about melanoma and respondents include a high proportion of males with risk factors for melanoma. Implications:These initial results suggest that photography may be a logistically acceptable approach for assisting in the early detection of melanoma.

BACKGROUND AND DESIGN: In vivo cutaneous surface microscopy (oil epiluminescence, dermatoscopy, and dermoscopy) has been shown to greatly enhance the clinical diagnosis of melanoma. The pseudopod is a morphologic feature seen on surface microscopy that corresponds to the radial growth of tumor in melanoma. While it is one of the most specific surface microscopic features of invasive melanoma, it has remained poorly defined. We studied 239 pigmented lesions, 80 melanomas (62 invasive and 18 in situ) and 159 randomly selected pigmented nonmelanomas. We photographed these lesions in vivo using immersion oil and a Heine Dermaphot camera (Heine Ltd, Herrsching, Germany). We then scored the lesions in a ''blinded'' fashion for the presence of pseudopods based on strictly defined morphologic criteria. RESULTS: We defined the morphologic criteria of the pseudopod. As defined, the pseudopod retained a 97% specificity and 23% sensitivity for invasive melanoma. No difference was seen in the mean Breslow thickness between melanomas with and without pseudopods. None of the in situ melanomas were observed to have pseudopods. CONCLUSION: We suggest morphologic criteria for a highly specific in vivo cutaneous surface microscopic feature of invasive melanoma, the pseudopod.(Arch Dermatol. 1995;131:436-440)

OBJECTIVES: To examine whether older people were less able to distinguish changes of melanoma than younger people, and to test whether an educational brochure illustrating changes of melanoma would increase their ability to detect the changes. DESIGN: Photographic images of pigmented skin lesions were altered using computer graphics software. Images of typical changes of melanoma were shown to groups of volunteers younger than 30 years (n=52) and older than 45 years (n=41). Short intervals (seconds) between viewing of the original and changed lesions were used to test ability to distinguish the changes, and longer intervals (29 and 60 days) were used to test their ability over more realistic intervals. All participants were randomized to receive an educational brochure (designed using the same technology) to evaluate whether this would assist in identifying early changes of melanoma. SETTING: A cross section of volunteers employed in a large semigovernment utility. INTERVENTION: An educational brochure that illustrated typical changes of melanoma. MAIN OUTCOME MEASURE: Score of correct or incorrect detection of changed or unchanged skin lesions. RESULTS: Tests at short intervals showed that both age groups were able to detect early changes of melanoma but had poor ability to detect changes of melanoma at longer intervals. Repeated viewing of the original lesions enabled the participants to once more recognize the changes. Both groups had low ability to detect the appearance of new pigmented lesions. The educational brochure improved the ability of participants to detect change. CONCLUSIONS: The main difficulty people have in self-detection of melanoma is limited ability to recall the appearance of their skin. This ability did not differ between the age groups. Educational material that focused on change was effective in increasing the ability to detect changes over short intervals. Photographic records may be the most effective aid for detection of changes at longer intervals.Arch Dermatol. 1997;133:301-311

OBJECTIVES: To create a simple diagnostic method for invasive melanoma with in vivo cutaneous surface microscopy (epiluminescence microscopy, dermoscopy, dermatoscopy) and to analyze the incidence and characteristics of those invasive melanomas that had no diagnostic features by means of hand-held surface microscopes. DESIGN: Pigmented skin lesions were photographed in vivo with the use of immersion oil. All were excised and reviewed for histological diagnosis. A training set of 62 invasive melanomas and 159 atypical nonmelanomas and a test set of 45 invasive melanomas and 119 atypical nonmelanomas were used. Images from the training set were scored for 72 surface microscopic features. Those features with a low sensitivity (0%) and high specificity (>85%) were used to create a simple diagnostic model for invasive melanoma. SETTING: All patients were recruited from the Sydney (Australia) Melanoma Unit (a primary case and referral center). PATIENTS: A random sample of patients whose lesions were excised, selected from a larger database. MAIN OUTCOME MEASURES: Sensitivity and specificity of the model for diagnosis of invasive melanona. RESULTS: The model gave a sensitivity of 92% (98/107) and specificity of 71%. Of the 9 "featureless" melanomas the model failed to detect, 6 were pigmented and thin and had a pigment network. The other 3 were thicker, hypomelanotic lesions lacking a pigment network, some with prominent telangiectases, and all with only small areas of pigment. All featureless melanomas noted by the patients had a history of change in color, shape, or size. CONCLUSIONS: Surface microscopy does not allow 100% sensitivity in diagnosing invasive melanoma and therefore cannot be used as the sole indicator for excision. Clinical history is an important consideration when featureless lesions are diagnosed.Arch Dermatol. 1996;132:1178-1182

While partial spontaneous histopathological regression is a common finding in invasive primary melanoma, proven complete regression is rarer, with only 33 cases having been documented. None of the patients in these reported cases had a biopsy specimen taken from the original lesion, which would unequivocally prove the diagnosis of complete regressing melanoma. Over 4 years, we saw a 62-year-old white man who refused treatment of a biopsy speciman-proved superficial spreading melanoma (Breslow thickness, 0.7 mm) that eventually regressed completely. A biopsy specimen confirmed complete histopathological regression. There was no clinical evidence of regional or distant metastases throughout the 4 years. To our knowledge, this is the first documented case of a biopsy speciman-proved primary melanoma completely regressing. We present sequential photographic documentation and review the literature about this phenomenon. While the prevalence of such an event is unknown, evidence is presented that it may be more common than previously thought.Arch Surg. 1997;132:553-556