Australian Researchers Investigate Patient, Tumor Characteristic Associations For High-Mitotic Rate Melanoma

Australian Researchers Investigate Patient, Tumor Characteristic Associations For High-Mitotic Rate Melanoma

melanoma researchA study by a team of Australian researchers has investigated patient and tumor characteristics for high-mitotic rate melanoma (high-mitonic is a marker of tumor cell growth) with the objective of increasing earlier detection of this aggressive and often fatal cancer in patients. A tumor characteristic known as mitotic rate (measure of cell division) has been connected with prognosis and survival in melanoma patients. However, the literature is scarce regarding the clinical presentation of high-mitotic rate melanoma, which could help in identifying those patients at risk for poor prognosis.

A new original investigation report published this week in the journal JAMA Dermatology entitled Characteristics and Associations of High-Mitotic-Rate Melanoma,” (JAMA Dermatol. Published online August 20, 2014. doi:10.1001/jamadermatol.2014.635) is coauthored by Sarah Shen, MBBS, BMedSci, Rory Wolfe, BSc, PhD, Catriona A. McLean, FRCPA, MD, Martin Haskett, FACD, and John W. Kelly, FACD, MD, variously of the Victorian Melanoma Service, Alfred Hospital at Victoria; Monash University’s Department of Epidemiology and Preventive Medicine at Melbourne, and the Department of Anatomical Pathology at Alfred Hospital, Victoria, Australia.

The researchers note that Mitotic rate is now recognized as having independent prognostic significance in melanoma survival, but that its clinicopathologic associations have not been the focus of any previous study.

Consequently, the investigation’s objective was 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, with a cross-sectional study of patients from a multidisciplinary melanoma clinic based in a public hospital. A total of 2397 cases were reviewed by the Victorian Melanoma Service from January 2006 to December 2011, and 1441 patients with 1500 primary invasive melanomas were included in the study. Of the 1,500 melanomas, 813 (54 percent) occurred in men and 687 presented in women.

Mitotic rate was measured as number of mitoses per mm2 and analyzed as ordered categories according to patient demographics, phenotypic markers, historical data, tumor presentation, and histopathologic features.

The researchers found that melanomas with higher mitotic rates were more likely to occur in the head and neck of men 70 years or older, and those with a history of solar keratosis caused by sun damage. These melanomas occurred more frequently on the head and neck and presented more often as amelanotic and be rapidly growing lesions (greater than or equal to 2 mm/per month). An association was observed with the nodular melanoma subtype (vs superficial spreading [reference]), greater tumor thickness, and ulceration . These histopathologic features, along with amelanosis and rate of growth, remained as significant associations with high mitotic rate in the overall multivariate analysis. A history of blistering sunburns and family history of melanoma were associated with lower mitotic rate activity.

The coauthors cite previous studies of aggressive melanoma that have focused on characteristics and associations of thick melanomas, which have been shown to have a strong association with the nodular subtype,12- 17 to grow rapidly, and to occur more frequently in elderly men and in individuals with fewer nevi and fewer freckles. However, they observe that existing literature has scarce data regarding the clinical presentation and associations of high-mitotic-rate melanoma to assist in identifying those at risk for poor prognosis. The aim of this study was to delineate the clinical, phenotypic, and histologic associations of high-mitotic-rate melanoma.

They say that to their knowledge, this is the first formal description of the clinicopathologic associations of high-mitotic-rate melanoma, and that high-mitotic-rate primary cutaneous melanoma is associated with aggressive histologic features and atypical clinical presentation. This cancer 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.

The researchers conclude that “The results from this single-center study merit replication elsewhere to confirm generalizability and to further explore the potential implications for detection and treatment of at-risk patients, who in this study were found to have a distinct phenotypic and historical profile,” observing that that “such atypical clinical features may pose a challenge to timely detection; thus a high index of suspicion is warranted when the patient reports a history of morphologic change and rapid growth.”

In a related editorial, Samuel J. Balin, M.D., Ph.D., of the University of California, Los Angeles, and Raymond L. Barnhill, M.D., M.Sc., of the University of California, Los Angeles Medical Center, write: “Clinicians have no guidelines by which to estimate clinically which suspect lesions might have a high mitotic rate, and therefore pose more of a threat, and which might have a low mitotic rate and ultimately behave less aggressively. The study by Shen et al in this issue of JAMA Dermatology addresses this deficiency in knowledge and elucidates the clinical characteristics of rapidly growing tumors. Although this study was conducted in a scientifically sound fashion, certain aspects concerning the analysis and significance of mitotic rate in melanoma have not yet been resolved.”

“Shen et al provide clinicians with more data and ultimately another tool to factor into their clinical decision-making process. By understanding the clinical characteristics of more rapidly growing tumors, clinicians can better guide their own screening and treatment decisions and better counsel patients, from diagnosis through treatment, and ultimately to prognosis,” Drs. Balin and Barnhill conclude.

More information on this topic can be found in:

JAMA Dermatology. Published online August 20, 2014.

DOI: 10.1001/jamadermatol.2014.635


JAMA Dermatology. Published online August 20, 2014.

DOI: 10.1001/jamadermatol.2014.924

The JAMA Network Journals
JAMA Dermatology

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