Fergal J Moloney1, Pascale Guitera1, Elliot Coates1, Nikolas K Haass1, Kenneth Ho1, Ritta Khoury2, Rachel L O'Connell3, Leo Raudonikis4, Helen Schmid5, Graham J Mann5, Scott W Menzies1. 1. Discipline of Dermatology, University of Sydney at the Sydney Cancer Centre, Sydney, New South Wales, Australia2Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia3Sydney Melanoma Diagnostic Centre, Sydney Cancer Centre, Sydney, New South. 2. Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia3Sydney Melanoma Diagnostic Centre, Sydney Cancer Centre, Sydney, New South Wales, Australia. 3. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia. 4. Raudonikis Database Services, Mount Colah, New South Wales, Australia. 5. University of Sydney at the Westmead Millennium Institute, Westmead, New South Wales, Australia9Melanoma Institute Australia, Westmead, New South Wales, Australia.
Abstract
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: 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.
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