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On the Horizon |

Use of Genetic Tools to Control Tumor Margins in Melanoma

Molly Hinshaw, MD
Arch Dermatol. 2009;145(4):475-477. doi:10.1001/archdermatol.2009.7.
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Distribution and Significance of Occult Intraepidermal Tumor Cells Surrounding Primary Melanoma

NorthJP, Kageshita T, Pinkel D, LeBoit PE, Bastian BC J Invest Dermatol. 2008;128(8):2024-2030

Primary melanoma can recur at the excision site if not excised with a safety margin of surrounding uninvolved skin. To characterize the nature of residual melanoma in the skin surrounding primary tumors targeted by safety margins, we used array comparative genomic hybridization and fluorescent in situ hybridization to detect and spatially map aberrations in the skin adjacent to acral melanomas. Melanocytic cells with genetic amplifications in histopathologically normal skin (field cells) were detected exclusively in the epidermis in 84% of 19 cases, with a mean extension of 6.1 mm (in situ melanomas) and 4.5 mm (invasive melanomas) beyond the histopathological margin. Genetic profiling of these field cells indicated that they represent an early phase of disease preceding melanoma in situ. The extent of field cells did not correlate with tumor depth or diameter, indicating that tumor depth is not suited to predict the extent of field cells. These results demonstrate that, on acral sites, melanoma field cells extend significantly into seemingly normal skin. These field cells provide a plausible explanation for the tendency of certain melanoma types to recur locally despite apparently having undergone complete excision.

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Bottom panel: 1 shows melanoma in situ; 2, clinically, dermoscopically, and microscopically normal skin; 3, invasive melanoma of 3.0-mm thickness. Black line: surgical margin; white line: field cell margin identified by amplification of 11q13. Top panel: array comparative genomic hybridization profile of area 3. A log 2 ratio of 0 indicates normal copy number; narrow spikes of increased copy number, regions of amplification that include 11q13. Middle panel: H&E and FISH for areas 1-3. The FISH images represent 1 plane, so not all signals are visible. A green immunofluorescent stain to Melan-A was used to aid in identifying basal melanocytes. Cells with amplification of 11q13 are highlighted by arrowheads for areas 1 and 2. Bar indicates (H&E) 60 μm. Reprinted by permission from Macmillan Publishers Ltd: Journal of Investigative Dermatology (North JP, Kageshita T, Pinkel D, LeBoit PE, Bastian BC. Distribution and significance of occult intraepidermal tumor cells surrounding primary melanoma. J Invest Dermatol. 2008;128[8]:2024-2030). Copyright 2008.

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