Benefits of a brief psychological intervention targeting fear of cancer recurrence in people at high risk of developing another melanoma: 12-month follow-up results of a randomized controlled trial.

BACKGROUND: People with melanoma want and need effective interventions for living with fear of cancer recurrence (FCR). OBJECTIVES: This study reports the 12-month outcomes of a brief, psychological intervention designed to reduce FCR in people at high risk of developing another primary melanoma compared with usual care. METHODS: In this two-arm randomized controlled trial, adults previously diagnosed with stage 0, I or II melanoma were randomly allocated to the intervention (n = 80) or control (usual care) arm (n = 84). The trial was registered with the Australian and New Zealand Clinical Trials Registry on 19 March 2013 (registration: ACTRN12613000304730). The intervention comprised a 76-page psychoeducational resource and three individually tailored, telephone-based sessions with a psychologist, scheduled at specific time points around participants' dermatological appointments. The primary outcome was the level of self-reported fear of new or recurrent melanoma assessed at 12 months postintervention using the severity subscale of the Fear of Cancer Recurrence Inventory. RESULTS: Compared with the control arm, the intervention group reported significantly lower FCR at 12 months postintervention; the between-group mean difference was -1·41 for FCR severity [95% confidence interval (CI) -2·6 to -0·2; P = 0·02] and -1·32 for FCR triggers (95% CI -2·6 to -0·02; P = 0·04). The odds ratio for FCR severity scores ≥13 (54% intervention, 63% control) was 0·59 (95% CI 0·30-1·14, P = 0·12). There were no differences between groups in secondary outcomes, such as anxiety, depression or health-related quality of life. CONCLUSIONS: The previously reported 6-month benefits of this brief, patient-centred psychological intervention in reducing FCR were found to continue 12 months postintervention, with no known adverse effects, supporting implementation as part of routine melanoma care.

Analysis of an electrical impedance spectroscopy system in short-term digital dermoscopy imaging of melanocytic lesions.

BACKGROUND: Electrical impedance spectroscopy (EIS) is a noninvasive diagnostic technique that measures tissue impedance. OBJECTIVES: To evaluate the effect of adding an EIS measurement at baseline to suspicious melanocytic lesions undergoing routine short-term sequential digital dermoscopy imaging (SDDI). METHODS: Patients presented with suspicious melanocytic lesions that were eligible for short-term SDDI (with no clear feature of melanoma on dermoscopy). EIS measurement was performed at the first visit following dermoscopic photography. Normally, an EIS score of ≥ 4 is considered positive; however, this protocol investigated a higher cut-off in combination with SDDI. When the EIS score was ≥ 7 the lesion was excised immediately owing to the high risk of melanoma. Lesions with a score < 7 were monitored with standard SDDI over a 3-month period. RESULTS: From a total of 160 lesions analysed, 128 of 154 benign lesions received an EIS score of 0-6, giving a specificity of the EIS method for the diagnosis of melanoma of 83·1% [95% confidence interval (CI) 76·3-88·7]. Five of the six melanomas found in this study had an EIS score ≥ 7, with a sensitivity for melanoma diagnosis of 83·3% (95% CI 35·9-99·6). When EIS 0-6 lesions were subsequently followed up with SDDI, one additional melanoma was detected (EIS = 6) giving a sensitivity for the diagnosis of melanoma overall of 100% (95% CI 54·1-100; six of six malignant melanomas excised) and a specificity of 69·5% (95% CI 61·5-76·6; 107 of 154 benign lesions not excised). CONCLUSIONS: If utilizing a protocol where an EIS score ≤ 3 requires no SDDI and ≥ 7 requires immediate excision, it reduced the need for SDDI by 46·9% (n = 75/160; 95% CI 39·0-54·9).

Protocol for a within-trial economic evaluation of a psychoeducational intervention tailored to people at high risk of developing a second or subsequent melanoma.

INTRODUCTION: Psychological support programmes are not currently funded for people with a history of melanoma. A major barrier to the implementation of effective psychological interventions in routine clinical care is a lack of cost-effectiveness data. This paper describes the planned economic evaluation alongside a randomised controlled trial of a psychoeducational intervention for people with a history of melanoma who are at high risk of developing new primary disease. METHOD AND ANALYSIS: The economic evaluation is a within-trial analysis to evaluate the incremental costs and health outcomes of a psychoeducational intervention compared to usual care from the perspective of the Australian healthcare system. Cost-effectiveness and cost-utility analyses will be conducted, providing estimates of the cost to reduce fear of melanoma recurrence and the cost per quality-adjusted life-year (QALY) gained. Fear of melanoma recurrence will be measured using the Fear of Cancer Recurrence Inventory and preference-based quality of life measured using the Assessment of Quality of Life-8 Dimensions (AQoL-8D) instrument. The AQoL-8D will provide utilities for estimation of QALYs in the cost-utility analysis. Unit costs of health services and medicines will be taken from the Medicare Benefits Schedule and the Pharmaceutical Benefits Scheme national databases. Health outcomes, and health service and medication use will be collected at baseline, 6 and 12 months follow-up. The within-trial analysis will be conducted at 12 months, consistent with the end point of the trial. ETHICS AND DISSEMINATION: Approval to conduct the study was granted by the Sydney Local Health District (RPAH zone) Ethics Review Committee (X13-0065 and HREC/13/RPAH/86), the Department of Health and Ageing Human Research Ethics Committee (21/2013), the University of Sydney Human Research Ethics Committee (2013/595), and the Australian Institute of Health and Welfare Ethics Committee (EO 2013/4/58). TRIAL REGISTRATION NUMBER: ACTRN12613000304730; Pre-results.

Doctors' recognition and management of melanoma patients' risk: An Australian population-based study.

BACKGROUND: Guidelines recommend that health professionals identify and manage individuals at high risk of developing melanoma, but there is limited population-based evidence demonstrating real-world practices. OBJECTIVE: A population-based, observational study was conducted in the state of New South Wales, Australia to determine doctors' knowledge of melanoma patients' risk and to identify factors associated with better identification and clinical management. METHODS: Data were analysed for 1889 patients with invasive, localised melanoma in the Melanoma Patterns of Care study. This study collected data on all melanoma diagnoses notified to the state's cancer registry during a 12-month period from 2006 to 2007, as well as questionnaire data from the doctors involved in their care. RESULTS: Three-quarters (74%) of patients had doctors who were aware of their risk factor status with respect to personal and family history of melanoma and the presence of many moles. Doctors working in general practice, skin cancer clinics and dermatology settings had better knowledge of patients' risk factors than plastic surgeons. Doctors were 15% more likely to know the family history of younger melanoma patients (<40years) than of those ≥80 years (95% confidence interval 4-26%). Early detection-related follow-up advice was more likely to be given to younger patients, by doctors aware of their patients' risk status, by doctors practising in plastic surgery, dermatology and skin cancer clinic settings, and by female doctors. CONCLUSION: Both patient-related and doctor-related factors were associated with doctors' recognition and management of melanoma patients' risk and could be the focus of strategies for improving care.

Dermoscopy and in vivo confocal microscopy are complementary techniques for diagnosis of difficult amelanotic and light-coloured skin lesions.

BACKGROUND: Amelanotic melanomas are often difficult to diagnose. OBJECTIVES: To find and test the best methods of diagnosis using dermoscopy and reflectance confocal microscopy (RCM) tools. METHODS: We selected consecutive, difficult-to-diagnose, light-coloured and amelanotic skin lesions from three centres (in Australia and Italy). Dermoscopy and RCM diagnostic utility were evaluated under blinded conditions utilizing 45 melanomas (16 in situ, 29 invasive), 68 naevi, 48 basal cell carcinomas (BCCs), 10 actinic keratoses, 10 squamous cell carcinomas (SCCs) and 13 other benign lesions. RESULTS: Sensitivity and specificity for melanoma with dermoscopy pattern analysis by two blinded observers and their 'confidence in diagnosis' were low. The amelanotic dermoscopy method had the highest sensitivity (83%) for a diagnosis of malignancy (melanoma, BCC or SCC), but specificity was only 18%. Multivariate analysis confirmed the utility of RCM features previously identified for the diagnosis of BCC and melanoma (highest odds ratio for melanoma: epidermal disarray, dark and/or round pagetoid cells). RCM sensitivity was 67% and 73% for melanoma and BCC diagnosis, respectively, and its specificity for nonmalignant lesion diagnosis was 56%. RCM reader confidence was higher than for dermoscopy; 84% of melanomas would have been biopsied and biopsy avoided in 47% of benign lesions. All melanomas misclassified by either dermoscopy or RCM were detected by the other tool. CONCLUSIONS: Dermoscopy and RCM represent complementary/synergistic methods for diagnosis of amelanotic/light-coloured skin lesions.

Clinical practice guidelines for identification, screening and follow-up of individuals at high risk of primary cutaneous melanoma: a systematic review.

Understanding how individuals at high-risk of primary cutaneous melanoma are best identified, screened and followed up will help optimize melanoma prevention strategies and clinical management. We conducted a systematic review of international clinical practice guidelines and documented the quality of supporting evidence for recommendations for clinical management of individuals at high risk of melanoma. Guidelines published between January 2000 and July 2014 were identified from a systematic search of Medline, Embase and four guideline databases; 34 guidelines from 20 countries were included. High-risk characteristics that were consistently reported included many melanocytic naevi, dysplastic naevi, family history, large congenital naevi, and Fitzpatrick Type I and II skin types. Most guidelines identify risk factors and recommend that individuals at high risk of cutaneous melanoma be monitored, but only half of the guidelines provide recommendations for screening based on level of risk. There is disagreement in screening and follow-up recommendations for those with an increased risk of future melanoma. High-level evidence supports long-term screening of individuals at high risk and monitoring using dermoscopy. Evidence is low for defining screening intervals and duration of follow-up, and for skin self-examination, although education about skin self-examination is widely encouraged. Clinical practice guidelines would benefit from a dedicated section for identification, screening and follow-up of individuals at high risk of melanoma. Guidelines could be improved with clear definitions of multiple naevi, family history and frequency of follow-up. Research examining the benefits and costs of alternative management strategies for groups at high risk will enhance the quality of recommendations.

Surveillance for treatment failure of lentigo maligna with dermoscopy and in vivo confocal microscopy: new descriptors.

BACKGROUND: Nonsurgical treatment (radiotherapy, imiquimod) is increasingly employed for the management of lentigo maligna (LM). While the diagnosis of LM remains difficult, the detection of treatment failure is even more challenging. OBJECTIVES: To describe the sensitivity and specificity for the diagnosis of LM of individual features and methods using dermoscopy and in vivo reflectance confocal microscopy (RCM) to aid in the detection of treatment failure of LM following nonsurgical treatment. METHODS: A retrospective study of dermoscopy and RCM images (blinded to the correlation with pathology) in patients with biopsy-confirmed LM who were undergoing nonsurgical treatment in two referral institutions - one in Sydney, Australia, and the other in Barcelona, Spain. Ninety-eight patients were treated nonsurgically for LM during the period 2006-2012. Thirty-one patients had abnormal dermoscopy or RCM evaluation, and had a biopsy that identified LM recurrence in 15 patients and nonmelanoma diagnoses in 16 patients (one Bowen disease, 15 solar changes). RESULTS: The diagnosis of treatment failure was difficult with dermoscopy, with a sensitivity of 80% and specificity of 56%, even with the interpretation of an expert. The best criterion was asymmetric hyperpigmented follicular openings, but this was present in only 47% of treatment failure LM. Isolated, very fine brown dots ('dust' appearance) correlated highly with the diagnosis of treatment failure LM (73% sensitivity and 88% specificity) and with pagetoid cells seen with RCM. The LM score, comprising six criteria, had a specificity of 94% and sensitivity of 100%. CONCLUSIONS: These methods and descriptors should help to manage the diagnosis of treatment failure.

Melanoma survivors at high risk of developing new primary disease: a qualitative examination of the factors that contribute to patient satisfaction with clinical care.

BACKGROUND: Providing ongoing clinical care that adequately addresses patients' medical, psychosocial and information needs is challenging, particularly for patient groups at increased risk of developing life-threatening disease such as malignant melanoma. This study examined a model of clinical care developed by the High Risk Clinic (HRC) of the Sydney Melanoma Diagnostic Centre in relation to patient satisfaction. METHODS: Semi-structured telephone interviews were conducted and analyzed using the framework of Miles and Huberman, and themes were organized using the qualitative software package, QSR NVivo8. RESULTS: Twenty HRC patients participated in the study (nine men, 11 women; mean age 57.6 years, age range 34-74 years; response rate 91%). Satisfaction with clinical care at the HRC was high. Factors contributing to patient satisfaction included: rapid and regular access to physicians who were perceived by participants as experts, the development of confidence and trust in one's treating doctor, and a sense of being cared about and understood by one's healthcare team. Although one-third of the participants reported some inconveniences in attending the clinic, these were viewed as minor difficulties and not significant barriers to care. Formal psychological support was not sought or expected by participants, although many expressed long-standing melanoma-related fears and concerns. CONCLUSIONS: Accessible, expert medical attention, delivered in a patient-centered manner was integral to melanoma survivors' satisfaction with clinical management. Appropriate referrals to psychological support may further increase satisfaction with clinical care.

Slow-growing melanoma: a dermoscopy follow-up study.

BACKGROUND: Recent evidence suggests that melanoma is a family of different tumours with varying abilities to grow and metastasize. Trends in melanoma epidemiology show a strong increase in the incidence of thin melanoma, with no corresponding increase in mortality or incidence of thick melanoma. We initially evaluated five cases and found that none had baseline features suggestive of melanoma; excision was performed based on slight changes visible only in side-by-side comparisons of dermoscopic images. OBJECTIVES: To assess the clinico-dermoscopic features and the growth patterns of melanomas that were excised after a follow-up of 1 year or more due to their inconspicuous features at the baseline consultation. METHODS: In a multicentre, retrospective study of histopathologically confirmed melanomas excised after follow-up, we analysed dermoscopic images obtained at the initial consultation and compared them with images obtained at the last follow-up consultation. Images were analysed and graded using standard algorithms and scored for changes in size, symmetrical or asymmetrical structural change, and development of new melanoma-specific criteria. An overall score reflecting the amount of change was calculated for each lesion. RESULTS: Our series consisted of 103 melanomas. After a median follow-up of 20 months, most lesions were still in situ or early invasive (median Breslow thickness of 0.48 mm), with only three lesions showing tumour thickness of 1 mm or more. The most frequent baseline characteristics were asymmetrical pigmentation (78.6% of lesions), reticular overall pattern (62.1%), and regression features (35.9%). Most melanomas (58.3%) showed minor to moderate changes over time, with < 2 mm size increase, with asymmetrical structural change, and without development of new melanoma-specific criteria. Major changes were visible only after a mean follow-up of 33 months. CONCLUSIONS: This study provides evidence for the existence of a subgroup of slow-growing melanomas, which may explain the increase in the incidence of thin melanoma, despite stable rates of thick melanoma and melanoma-associated mortality.

Impact of dermoscopy and short-term sequential digital dermoscopy imaging for the management of pigmented lesions in primary care: a sequential intervention trial.

BACKGROUND: Studies have shown the benign to malignant ratio of excised pigmented skin lesions is suboptimal in primary care. OBJECTIVES: To assess the impact of dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) on the management of suspicious pigmented skin lesions by primary care physicians. METHODS: A total of 63 primary care physicians were trained in the use of dermoscopy and SDDI (interventions) and then recruited pigmented lesions requiring biopsy or referral in routine care by naked eye examination. They were then given a dermatoscope and the option of a SDDI instrument, and change of diagnosis and management was assessed. RESULTS: Following the use of the interventions on 374 lesions a total of 163 lesions (43.6%) were excised or referred, representing a reduction of 56.4%. Of the 323 lesions confirmed to be benign, 118 (36.5%) were excised or referred, leading to a reduction of 63.5% (P < 0.0005) in those requiring excision or referral. The baseline naked eye examination benign to melanoma ratio was 9.5 : 1 which decreased to 3.5 : 1 after the diagnostic interventions (P < 0.0005). Of the 42 malignant lesions included in the study (34 melanoma, six pigmented basal cell carcinoma and two Bowen disease) only one in situ melanoma was incorrectly managed (patient to return if changes occur) resulting in the correct management of 97.6% and 97.1% of malignant pigmented lesions and melanoma, respectively. CONCLUSIONS: In a primary care setting the combination of dermoscopy and short-term SDDI reduces the excision or referral of benign pigmented lesions by more than half while nearly doubling the sensitivity for the diagnosis of melanoma.

Dermoscopy compared with naked eye examination for the diagnosis of primary melanoma: a meta-analysis of studies performed in a clinical setting.

BACKGROUND: Dermoscopy is a noninvasive technique that enables the clinician to perform direct microscopic examination of diagnostic features, not seen by the naked eye, in pigmented skin lesions. Diagnostic accuracy of dermoscopy has previously been assessed in meta-analyses including studies performed in experimental and clinical settings. OBJECTIVES: To assess the diagnostic accuracy of dermoscopy for the diagnosis of melanoma compared with naked eye examination by performing a meta-analysis exclusively on studies performed in a clinical setting. METHODS: We searched for publications from 1987 to January 2008 and found nine eligible studies. The selected studies compare diagnostic accuracy of dermoscopy with naked eye examination using a valid reference test on consecutive patients with a defined clinical presentation, performed in a clinical setting. Hierarchical summary receiver operator curve analysis was used to estimate the relative diagnostic accuracy for clinical examination with, and without, the use of dermoscopy. RESULTS: We found the relative diagnostic odds ratio for melanoma, for dermoscopy compared with naked eye examination, to be 15.6 [95% confidence interval (CI) 2.9-83.7, P = 0.016]; removal of two outlier studies changed this to 9.0 (95% CI 1.5-54.6, P = 0.03). CONCLUSIONS: Dermoscopy is more accurate than naked eye examination for the diagnosis of cutaneous melanoma in suspicious skin lesions when performed in the clinical setting.

Melanoma histological Breslow thickness predicted by 75-MHz ultrasonography.

BACKGROUND: Ultrasound at 20 MHz tends to overestimate melanoma Breslow thickness due to lymphocytic infiltration or naevus remnant. Objectives To determine the efficacy of 75-MHz ultrasound for estimating melanoma thickness and to assess its reliability to predict surgical requirement. METHODS: One hundred and twelve suspicious skin lesions were imaged prospectively with the 75-MHz ultrasound in A and B mode. This instrument has a penetration of 3 mm and a lateral resolution of 21 mum. Measurements were performed by two observers and the mean was compared with the histological Breslow thickness. RESULTS: Forty-five of 52 melanomas and 22 of 36 naevi had clear hypoechogenicity boundaries. The median histological Breslow thickness of melanomas was 0.4 mm and 22 were in situ. The median percentage error of the machine was 13% of the histological Breslow thickness, with a high correlation (Pearson's r = 0.908, P < 0.001). Measurement was highly reliable for invasive melanoma, even in the presence of lymphocytic infiltration or naevus. CONCLUSIONS: In this series, 75-MHz measurement was highly reliable for predicting invasive melanoma thickness.

Phase I/II study of treatment with matured dendritic cells with or without low dose IL-2 in patients with disseminated melanoma.

BACKGROUND: In the present study, we have examined whether treatment of patients with metastatic melanoma with matured dendritic cell (DC) vaccines with or without low dose IL-2 may improve treatment outcomes. METHODS: Sixteen patients received DC vaccines (DCs) sensitized with autologous melanoma lysates and 18 patients received DCs sensitized with peptides from gp100, MART-1, tyrosinase, MAGE-3.A2, MAGE-A10 and NA17. IL-2 was given subcutaneously (sc) at 1 MU/m2 on the second day after each injection for 5-14 days in half of each group. DCs were given by intranodal injection. RESULTS: There were 2 partial responses (PR) and 3 with stable disease (SD) in the nine patients receiving DCs + peptides + IL-2, and 1 PR and 1 SD in nine patients treated with DCs + peptides without IL-2. There were only two patients with SD in the group receiving DCs + autologous lysates and no IL-2. Median overall survival for all patients was very good at 18.5 months but this was most probably due to selection of a favourable group of patients for the study. There was no significant difference in survival between the groups by log rank analysis. Treatment was not associated with significant side effects. The quality and yield of the DCs in the preparations were generally good. CONCLUSIONS: We conclude that mature DC preparations may be superior to immature DC preparations for presentation of melanoma peptides and that IL-2 may increase clinical responses to the DCs plus peptides. However, in our view the low response rates do not justify the cost and complexity of this treatment approach.

Three-point checklist of dermoscopy: an open internet study.

BACKGROUND: In a pilot study, the three-point checklist of dermoscopy has been shown to represent a valid and reproducible tool with high sensitivity for the diagnosis of skin cancer in the hands of a small group of nonexperts. OBJECTIVES: To re-evaluate these preliminary results in a large number of observers independently from their profession and expertise in dermoscopy. METHODS: The study was conducted via the internet to provide worldwide access for participants. After a short web-based tutorial, the participants evaluated dermoscopic images of 165 (116 benign and 49 malignant) skin lesions (15 training and 150 test lesions). For each lesion participants scored the presence of the three-point checklist criteria (asymmetry, atypical network and blue-white structures). Kappa values, odds ratios, sensitivity, specificity and likelihood ratios were estimated. RESULTS: Overall, 150 participants joined the study. The three-point checklist showed good interobserver reproducibility (kappa value: 0.53). Sensitivity for skin cancer (melanoma and basal cell carcinoma) was 91.0% and this value remained basically uninfluenced by the observers' professional profile. Only 20 participants lacking any experience in dermoscopy performed significantly more poorly, but the sensitivity was still remarkably high (86.7%) when considering that they were untrained novices in dermoscopy. The specificity was 71.9% and was significantly influenced by the profession, with dermatologists performing best. CONCLUSIONS: Our study confirms that the three-point checklist is a feasible, simple, accurate and reproducible skin cancer screening tool.

A randomised trial of skin photography as an aid to screening skin lesions in older males.

OBJECTIVES: We have previously shown that photographs assist in detection of change in skin lesions and designed the present randomised population based trial to assess the feasibility of photographs as an aid to management of skin cancers in older men. SETTING: 1899 men over fifty, identified from the electoral roll in two regions in New South Wales (NSW), Australia, were invited by mail to participate. METHODS: A total of 973 of 1037 respondents were photographed and randomised into intervention (participants given their photographs) or control groups (photographs withheld by investigators). At one and two years from the time of photography, all participants were advised to see their primary care practitioner for a skin examination. Those in the intervention group were examined with their photographs and those in the control group without their photographs. RESULTS: The results indicated that the practitioners were more likely to leave suspicious lesions in place for follow up observation (37% v 29%) (p=0.006) and less likely to excise benign non pigmented lesions (20 v 32%). There was little difference in excision rates for benign pigmented lesions (21% v 23%). Lesions excised were more likely to be non-melanoma skin cancer (58% v 42%) from patients who had photographs compared to those without photographs (p=0.005). The use of skin photography resulted in a substantial savings due to the reduced excision of benign lesions. CONCLUSIONS: These results suggest that it would be feasible to conduct a large scale randomised trial to evaluate the value of photography in early detection of melanoma and that such a trial could be cost effective due to the reduced excision of benign skin lesions.

Short-term digital surface microscopic monitoring of atypical or changing melanocytic lesions.

OBJECTIVE: To examine the outcome of short-term digital surface microscopic monitoring of suspicious or changing atypical melanocytic lesions. DESIGN: Digital surface microscopic (oil epiluminescence microscopy, and dermoscopy) images of clinically melanocytic lesions were taken with a color calibrated 3 CCD video instrument. In general, lesions were moderately atypical, flat or only slightly raised, without a history of change or surface microscopic evidence of melanoma, or were mildly atypical lesions with a history of change. Lesions were monitored during a 2.5- to 4.5-month period (median, 3.0 months). With the exception of overall change in pigmentation consistent with that seen in surrounding skin (solar exposure changes), any morphologic change after monitoring was considered an indication to excise. SETTING: Sydney Melanoma Unit, Sydney, Australia (a referral center). PATIENTS: A consecutive sample of 318 lesions from 245 patients (aged 4-81 years). MAIN OUTCOME MEASURE: Specificity for the diagnosis of melanoma. RESULTS: Of the 318 lesions, 81% remained unchanged. Of the 61 lesions that showed morphologic changes, 7 (11% of changed and 2% of total lesions) were found to be early melanoma (5 in situ and 2 invasive with a Breslow thickness of 0.25 mm and 0.28 mm, respectively). None of these melanomas developed any classic surface microscopic features of melanoma and therefore could be identified only by morphologic change. The specificity for the diagnosis of melanoma by means of short-term digital monitoring was 83%. CONCLUSION: On the assumption that all melanoma will change during the monitored period, surface microscopy digital monitoring is a useful adjunct for the management of melanocytic lesions.

Primary melanoma tumour regression associated with an immune response to the tumour-associated antigen melan-A/MART-1.

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-gamma 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.

A method for the diagnosis of primary cutaneous melanoma using surface microscopy.

For a melanoma to be diagnosed, it must have neither of two morphological negative features and one or more of nine positive features. The negative features are symmetry of pattern and a single color. The positive features are blue-white veil, multiple brown dots, pseudopods, radial streaming, scar-like pigmentation, peripheral black dots or globules, five or six colors, multiple blue-gray dots, and a broadened network. This method gives a 92% sensitivity and 71% specificity for the diagnosis of melanoma.

Increase in the sensitivity for melanoma diagnosis by primary care physicians using skin surface microscopy.

BACKGROUND: Skin surface microscopy (oil epiluminescence microscopy, dermoscopy, dermatoscopy) has been shown to increase the diagnostic accuracy of melanoma. However, all studies to date have been in an expert setting. OBJECTIVES: To determine whether primary care physicians (PCP) (general practitioners) could improve their melanoma diagnosis using surface microscopy after a short education intervention. METHODS: Seventy-four practising PCP completed a pretest of 50 melanomas and 50 atypical non-melanoma pigmented skin lesions (PSL) containing matched clinical and surface microscopy photographs. PCP were randomized between a surface microscopy education intervention or control group, followed by an identical post-test. RESULTS: Following training there was a significant improvement in the post-test vs. pretest in both clinical melanoma diagnosis (62.7% vs. 54.6%; P = 0.007) and surface microscopy melanoma diagnosis (75.9% vs. 57.8%; P = 0.000007). No difference was found in the control group between the post-test vs. pretest clinical melanoma diagnosis (53.7% vs. 50.6%; P = 0.21) or the surface microscopy melanoma diagnosis (54.8% vs. 52.9%; P = 0.56). Following training there was a significant improvement in the diagnosis of melanoma using surface microscopy vs. clinical diagnosis (75.9% vs. 62.7%; P = 0.000007), which was absent in the control group (54.8% vs. 53.7%; P = 0.59). No significant difference was found in clinical vs. surface microscopy post-test results for non-melanoma PSL in either the intervention group or control group. Improvement in the sensitivity for the diagnosis of melanoma with surface microscopy was seen without a decrease in specificity; this indicated that the effect should occur without increasing the number of needless excisions. CONCLUSIONS: All PCP in countries where melanoma leads to significant mortality should be trained in skin surface microscopy.