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Original Investigation |

Characteristics and Associations of High-Mitotic-Rate Melanoma ONLINE FIRST

Sarah Shen, MBBS, BMedSci1,2; Rory Wolfe, BSc, PhD2; Catriona A. McLean, FRCPA, MD3; Martin Haskett, FACD1; John W. Kelly, FACD, MD1
[+] Author Affiliations
1Victorian Melanoma Service, Alfred Hospital, Victoria, Australia
2Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
3Department of Anatomical Pathology, Alfred Hospital, Victoria, Australia
JAMA Dermatol. Published online August 20, 2014. doi:10.1001/jamadermatol.2014.635
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Importance  Mitotic rate is now recognized as having independent prognostic significance in melanoma survival. However, its clinicopathologic associations have not been the focus of any previous study.

Objective  To identify a set of patient and tumor characteristics associated with high-mitotic-rate melanoma with the aim of facilitating the earlier detection of aggressive primary invasive melanoma.

Design, Setting, and Participants  Cross-sectional study of patients from a multidisciplinary melanoma clinic based in a public hospital. A total of 2397 cases from January 2006 to December 2011 were reviewed by the Victorian Melanoma Service, and 1441 patients with 1500 primary invasive melanomas were included in the study.

Main Outcomes and Measures  Mitotic rate was measured as number of mitoses per mm2 and analyzed as ordered categories (0, <1, 1 and <2, 2, 3-4, 5-9, and ≥10) according to patient demographics, phenotypic markers, historical data, tumor presentation, and histopathologic features.

Results  Melanomas with higher mitotic rates were more likely to occur in men (odds ratio [OR], 1.5; 95% CI, 1.3-1.8), patients 70 years or older (OR, 2.1; 95% CI, 1.7-2.8), and those with a history of solar keratosis (OR, 1.3; 95% CI, 1.1-1.6). These melanomas occurred more frequently on the head and neck (OR, 1.4; 95% CI, 1.0-1.9) and presented more often as amelanotic (OR, 1.9; 95% CI, 1.4-2.5) and rapidly growing (≥2 mm/mo) lesions (OR, 12.5; 95% CI, 8.4-18.5). An association was seen with the nodular melanoma subtype (vs superficial spreading [reference]) (OR, 2.5; 95% CI, 1.8-3.4), greater tumor thickness (vs ≤1 mm [reference]) (>1-4 mm: OR, 4.5; 95% CI, 3.2-6.1; >4 mm: OR, 12.6; 95% CI, 7.5-21.1), and ulceration (OR, 2.0; 95% CI, 1.5-2.7). These histopathologic features, along with amelanosis and rate of growth, remained as significant associations with high mitotic rate in the overall multivariate analysis.

Conclusions and Relevance  High-mitotic-rate primary cutaneous melanoma is associated with aggressive histologic features and atypical clinical presentation. It has a predilection for the head and neck region and is more likely to be seen in elderly men with a history of cumulative solar damage who present clinically with rapidly developing disease.

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Clinical Photograph of a High-Mitotic-Rate Melanoma Lesion

This man in his 80s presented with a rapidly growing amelanotic nodular melanoma on the scalp. At diagnosis, it had a Breslow thickness of 7.4 mm and a mitotic rate of greater than 90 mitoses/mm2.

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