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Original Investigation |

Association of Patient Risk Factors and Frequency of Nevus-Associated Cutaneous Melanomas

Holger A. Haenssle, MD1,2; Nerjes Mograby, MD1; Anni Ngassa, MD1; Timo Buhl, MD1; Steffen Emmert, MD1,3; Michael P. Schön, MD1; Albert Rosenberger, MD4; Hans Peter Bertsch, MD1
[+] Author Affiliations
1Department of Dermatology, Venereology, and Allergology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
2Department of Dermatology, Venereology, and Allergology, University Medical Center, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany
3Clinic for Dermatology and Venereology, University Medical Center Rostock, Rostock, Germany
4Institute of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
JAMA Dermatol. 2016;152(3):291-298. doi:10.1001/jamadermatol.2015.3775.
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Importance  The reported frequencies of associations between primary cutaneous melanomas and melanocytic nevi vary widely between 4% and 72%. However, earlier histopathologic studies were limited by their retrospective design and did not assess the influence of important patient-related risk factors.

Objectives  To identify the frequency of nevus-associated melanomas and correlate patient- and melanoma-related factors.

Design, Setting, and Participants  A prospective, single-center, observational study with systematic documentation of melanoma risk factors, clinical and dermoscopic criteria of excised lesions, and results of histopathologic examination was conducted at a university-based dermatology clinic. Participants included 832patients at high risk for developing melanoma. Evaluation was performed at regular intervals between April 1, 1997, and May 31, 2012, and data analysis was conducted between September 1, 2012, and December 31, 2013.

Main Outcomes and Measures  Assessment of the frequency of nevus-associated melanoma and the influence of patient- and melanoma-related factors on their manifestation.

Results  During the study, 190 melanomas (81 [42.6%] in situ and 109 [57.4%] invasive) were diagnosed in 113 of the 832 patients (13.6%); there were 42 women (37.2%) and 71 men (62.8%). The median (SD) Breslow thickness of invasive melanomas was 0.42 (0.43) mm. Histopathologic examination revealed remnants of melanocytic nevi in 103 melanomas (54.2%). Most nevus-associated melanomas were found on the trunk (67 [65.1%]); however, statistical significance for the localization was not present (P = .06). In univariate analyses, reported as odds ratios (95% CIs), nevus-associated melanomas were found significantly more frequently in patients of lower melanoma risk (risk group 1 [>50 common and/or ≤3 atypical nevi], 2.75 [1.14-6.64]; P = .02), with more than 100 nevi (1.63 [1.02-3.60]; P = .04), or with the diagnosis of in situ melanoma (14.01 [6.14-31.96]; P < .001). In contrast, nevus-associated melanomas were found significantly less frequently in patients with 1 or more previous melanomas (0.28 [0.21-0.83]; P = .005). All other factors (eg, age, skin type, hair color, and melanoma thickness) showed no significant influence on the manifestation of nevus-associated melanomas. These observations were confirmed in a separate analysis including all 109 invasive melanomas. Multivariate regression analysis identified 3 independent patient-related factors (high nevus count, low risk for melanoma, and female sex) and 1 melanoma-related factor (in situ melanoma) to be indicative of a significantly increased probability of nevus-associated melanomas.

Conclusions and Relevance  In this prospective study of a high-risk patient cohort, 54.2% of primary melanomas were associated with melanocytic nevi. Patients with many nevi and without previous melanomas or traits of familial atypical mole and multiple melanoma syndrome had a higher frequency of nevus-associated melanomas. These patients could thus benefit from sequential digital dermoscopy in addition to total-body photography.

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