Melanoma Is a Potentially Fatal Form of Skin Cancer

Early and accurate diagnosis of melanoma is critical for long-term survival.1 The analysis of biopsied tissue using a microscope (histopathology) has long been the standard of care for melanoma diagnosis. While it is adequate for diagnosis in most cases, evidence suggests that approximately 10-15% of biopsied melanocytic lesions may be histopathologically ambiguous.2-5 In these situations, microscopic examination may reveal a few features that are characteristic of melanoma but others that are more typical of a benign nevus. As a result, even experienced dermatopathologists occasionally disagree as to whether a given melanocytic lesion is benign or malignant.

Using Molecular Diagnostics to Help Guide Melanoma Therapy

Myriad Genetic Laboratories has developed myPath® Melanoma, a clinically validated test to be used as an adjunct to histopathology when the distinction between a benign nevus and a malignant melanoma cannot be made confidently by histopathology alone. The test measures the expression of 23 genes by qRT-PCR methodology and distinguishes melanoma from nevi with a sensitivity of 90% and a specificity of 91%. 6

An algorithm is applied that combines the measurements of gene expression, assigns a weight to each gene component, and establishes a threshold value. The result is a single numerical score that classifies a melanocytic lesion as ‘likely benign’, ‘likely malignant’, or ‘indeterminate’. myPath Melanoma has been clinically validated utilizing rigorous laboratory processes to produce a precise and reproducible result. The myPath Melanoma test has been shown to: • Reduce indeterminate diagnoses • Increase diagnostic confidence • Personalize treatment recommendations

Learn More about myPath Melanoma Testing

Hereditary Melanoma

Increased surveillance is critical to the prevention, early detection and treatment of melanoma, especially among patients who are at increased risk due to genetic factors. Several genes have been associated with hereditary melanoma, including the p16 gene (also known as CDKN2A).7,8,9  Mutations in p16 account for 20-40 percent of hereditary melanoma cases. CDK4 10 gene mutations may account for approximately 2 percent of cases and unknown, or as yet unidentified genes, may account for the remainder of hereditary melanoma cases. In the U.S., p16 mutations are likely responsible for approximately 1400-2800 new melanoma cases each year, making them the most significant known cause of hereditary melanoma.  These mutations are also associated with an increased risk of pancreatic cancer in some families.11

risk of melanoma and pancreatic cancer in patients with p16 mutation

Who Should Be Tested for Hereditary Melanoma

Knowing the potential risk of melanoma can help you and your patient make better, more informed decisions about your patient’s health, before the onset of cancer or before a second cancer has had a chance to develop. Genetic testing for hereditary melanoma should be considered if:*

  • Two or more melanomas are found in an individual or family
  • Melanoma and pancreatic cancer occur in an individual or family
  • The person has a relative with a p16 mutation

Using Hereditary Cancer Testing to Reduce Melanoma Risk and Improve Patient Care

If hereditary cancer testing confirms the presence of a p16 mutation, the development of a patient-specific medical management plan may significantly reduce the risk of cancer. A positive result from p16 testing can result in:**

  • Targeted screening and surveillance for melanoma
  • Improved compliance with tailored screening recommendations and preventive measures
  • Improved outcomes through prevention and earlier diagnosis and treatment of cancer, should it develop
  • Counseling patients and their family members on the underlying cause of the pattern of melanoma and possibly pancreatic cancer
  • Eligibility for clinical trials for pancreatic cancer screening. 12
  • Avoiding unnecessary interventions for family members who do not test positive for the mutation known to be in the family

*Assessment criteria are based on individual medical society guidelines.

**Any discussion of medical management options is for general informational purposes only and does not constitute a recommendation.  While genetic testing and medical society guidelines provide important and useful information, all medical management decisions should be made based on consultation between each patient and his or her healthcare professional.


1. Data is adapted from information found at:

2. Shoo BA, Sagebiel RW, Kashani-Sabet M. Discordance in the histopathologic diagnosis of melanoma at a melanoma referral center. Journal of the American Academy of Dermatology. 2010;62(5):751-6.

3. Veenhuizen KC, De Wit PE, Mooi WJ, et al. Quality assessment by expert opinion in melanoma pathology: experience of the pathology panel of the Dutch Melanoma Working Party. J Pathol. 1997;182(3):266-72.

4. Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol. 1996;27(6):528-31.

5. McGinnis KS, Lessin SR, Elder DE, et al. Pathology review of cases presenting to a multidisciplinary pigmented lesion clinic. Archives of dermatology. 2002;138(5):617-21.

6. Clarke L et al. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma J Cutan Pathol 2015; 42:244-252.

7. Greene MH. The genetics of hereditary melanoma and nevi. 1998 update. Cancer 1999 86:2464-77.

8. Bishop DT, Demenais F, Goldstein AM, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst 2002;94(12):894-903.

9. Kefford RF, et al. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: a consensus statement of the Melanoma Genetics Consortium. J Clin Oncol. 1999;17(10):3245-51.

10. Goldstein AM, et al. Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. J Natl Cancer Inst. 2000 92:1006-10. PMID: 10861313.

11. Vasen HF, Gruis NA, Frants RR, van Der Velden PA, Hille ET, Bergman W. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000;87(6):809-811.

12. Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, Nio Y, Schulick RS, Bassi C, Kluijt I, Levy MJ, Chak A, Fockens P, Goggins M, Bruno M; International Cancer of Pancreas Screening (CAPS) Consortium. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 Mar;62(3):339-47.