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The risk of melanoma in adults with giant pigmented nevi

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By Warren R. Heymann, MD
May 27, 2016

Giant pigmented nevi (GPN, defined in reference 1 as > 20 cm in an adult) are among the most challenging lesions from so many perspectives. When diagnosed in childhood, questions from parents regarding the risk of melanoma, approach to monitoring, managing, and addressing the psychologic aspects of the lesion require patience, thoughtfulness, and understanding.

The article by Turtkeltaub et al, exploring the nature of melanoma developing in adult patients with giant pigmented nevi, offers new information about this difficult problem. It also provokes many questions. Briefly, they were able to identify 976 melanomas in adults (> 18 years old) arising in GPN out of 541,250 melanomas derived from the National Cancer Data Base, for an incidence of 0.2% of all melanomas. They compared the tumor characteristics, treatment, and survival of these melanomas to 111,870 cases of superficial spreading melanoma (SSM) and 35,962 of patients with nodular melanoma (NM). Despite the fact that melanomas arising within GPN having a thicker Breslow depth, more positive lymph nodes, and more frequent distant metastases, at all stages having MM in GPN has a similar overall survival compared with SSM. The authors conclude by recommending that dermatologists be aware of the continuing risk of developing melanoma in adults with GPN, and maintain a low threshold for performing a biopsy on any lesions in question (1).

It is completely understandable why the intense conversations about GPN occur early in life. Parents need guidance, despite our inadequate answers. By the time patients with GPN reach adulthood, most have come to grips with how they approach these lesions medically and emotionally (without the presence of parents in the examination room). The key aspect of this article is to remind ourselves, and our patients, that ongoing vigilance in monitoring these lesions is a lifetime affair. Although the value of the incidence rate of malignancies in GPN has been disputed, it is estimated that for these individuals the lifetime-risk for developing melanoma is between 5 and 10% (2). Although rare, one is never free from the burden of risk for developing a melanoma within a GPN as an adult.

With the spectacular advances we have seen in melanoma treatment the last few years, what is the current status of molecular studies in GPN? NRAS mutations are noted exclusively in the largest malformations and some BRAF mutations are observed in medium sized lesions. Size alone does not predict genotype, as some BRAF-mutated medium sized congenital nevi can be as large as or larger than some NRAS mutated lesions. Other genes such as GNAQ, or others yet to be identified, may play a role in the pathogenesis of GPN (3).

Although one would not prescribe BRAF or MEK inhibitors for these patients unless a melanoma with the concordant mutations was present, it is no longer within the realm of science fiction that prophylactic modification of such genes could obviate the development of melanoma within a GPN. Until such breakthroughs occur, keep a vigilant eye on these lesions – throughout life.

1. Turkeltaub AE, et al. Characteristics, treatment, and survival of invasive malignant melanoma (MM) in giant pigmented nevi (PN) in adults: 976 cases from the National Cancer Data Base (NCDB). J Am Acad Dermtol 2016; 74: 1128-34.
2. Viana AC, et al. Congenital melanocytic nevus. An Bras Dermatol 2013; 88: 863-78.
3. Etchevers HC. Hiding in plain sight: molecular genetics applied to giant congenital melanocytic nevi. J Invest Dermatol 2014; 134: 879-82.

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