MELANOMA

by Gary White, MD

This melanoma has all the features: large, irregular edges, multicolored, with some very dark black areas.

The "ugly duckling sign" of melanoma refers to the fact that a melanoma often looks different from the other moles. This spot on the upper back was a melanoma.

A melanoma is often assymmetry in shape (or color).

An irregular, notched border is a worrisome sign (here a melanoma).

A very dark black or a multi-colored mole is a worrisome sign (here a melanoma).

Diameter 7 mm or greater ("larger than a pencil eraser") is a worrisome sign (here a melanoma).

The dark growth in this "mole" was new (and turned out to be a melanoma).

Melanoma, Key Points

Melanoma is a potentially fatal neoplasm of the skin originating from melanocytes. It is the most deadly of the common skin cancers and its incidence is on the rise. However, in countries with aggressive sunscreen use (e.g., Australia), rates may be leveling off.

• The current lifetime risk of melanoma in the US for a non-Hispanic Caucasian is about 1 in 50.
  
• The incidence of invasive melanoma over the last 30 years has doubled. But, the mortality from melanoma has remain unchanged. This is the classic epidemiologic evidence of overdiagnosis.
• Taking aspirin regularly reduced the risk of melanoma in postmenopausal women in a large observational study from the Women's Health Initiative comprising nearly 60,000 women [SAD Aug 2013]. Acetaminophen and other NSAIDs did not protect.
  
• Another study found 20% increased risk of cutaneous melanoma with regular alcohol consumption [British J Dermatology 2014 May].
  
• Sildenafil (Viagra) increased the risk of melanoma 2.24 fold in a large prospective followup study [JAMA Intern Med 2014;174;964-70]. Exposure to natalizumab, a drug used to treat multiple sclerosis, increases one's risk for melanoma [JAAD 2019;80;820].
• Adults with a history of lithium exposure had a 32% lower risk of melanoma than did those who were not exposed in an unadjusted analysis of data from more than 2 million patients [J Invest Dermatol. 2017;137:2087].
• About 15% of patients with melanoma had a germline pathogenic or potentially pathogenic gene. Patients with melanoma should have all the usual cancer screening and should be questioned about cancers in relatives. Referral for genetic testing should be done when cancers seem abundant in the family tree.
• There is a greater than twofold risk of melanoma in patients with renal cell carcinoma (RCC) and a nearly threefold risk of RCC in patients with melanoma.
• For patients under 50, melanoma is more likely to occur in areas of intermittent sun exposure (e.g., the back) as opposed to chronic sun exposure (e.g., the face, neck, arms) [Int J Cancer. 1998 Oct 29;78(3):276-80].
• Look for the ugly duckling, the mole that stands out as larger and darker than the rest.
• Approximately 70% of melanomas arise from normal skin. (About 30% of melanomas arise from preexisting nevi.)

Risk Factors

The average lifetime risk of a person born in the US today to develop a melanoma is as follows:

The following table tries to quantify the risk for various factors [much of the data from J of Cancer Treatment and Research 2016;4;1]. A relative risk (RR) of 2 means double the risk. An RR of 1.5 means a 50% elevated risk.

Other factors that increase risk include:

• Childhood skin cancer treated with radiation
• Large congenital melanocytic nevus (> 20 cm in adulthood)
• Immunosuppression, e.g., transplant patients, HIV infection
• Drugs, e.g., Viagra, natalizumab.

Body Site

In a study of melanoma in the US from 1975-2006 [Cancer Epidemiol Biomarkers Prev. 2010;19:2401], the specific body site distribution was as follows:

In another study of patients at high risk for melanoma [JAMA Derm 2017;153;23], those with many nevi were more likely to have melanoma on the trunk, those with a family history of melanoma were more likely to have melanoma on the limbs and those with a personal history were more likely to have melanoma on the head and neck.

Clinical

Most melanomas have some darkly pigmented area--black or dark brown. This is not always true however, as some melanomas are amelanotic. Still, the typical dark black, brown, or two-toned nevus, usually flat, and > 6 mm is most suspect. When doing a complete skin exam, look for the lesion that is larger, darker, and more irregularly shaped than all the other moles--the so-called ugly duckling sign. Rarely, a melanoma may develop a halo.

Every health care practitioner should be well-versed in the ABCDE's of melanoma. S/he should be able to recognize a suspicious lesion and either provide appropriate initial care or quickly refer the patient. Any lesion that satisfies two of the following should be biopsied:

ABCDE Criteria

 A      Asymmetric shape        
 B      Border, irregular        
 C      Colors, multiple or dark black        
 D      Diameter, 7 mm. or greater
 E      Evolving

Any lesion with 2 or more should be removed [JAAD 2015;72;717]. See also Mole vs. Melanoma.

ABCDE Criteria--Simplified

A slightly simplified ABCDE criteria has been designed for patients and used in a structured skin self-examination study [JAMA Derm 2016;152;979]:

Patients were told to seek medical attention for any mole that was abnormal in all 3 features or that changed from normal to abnormal in any of the features. Note: in one study, no melanomas with a diameter of less than 5 mm recurred or metastasized [Ann Surg 1970;172;902].

Ugly Duckling Sign

The ugly duckling (UD) sign is very useful in helping identify melanoma. It asks the question, "What mole/Is there a mole that is different from all the others?" This simple idea of "different from all the others" is easily understood, but hard to quantify. Unfortunately, the seborrheic keratoses may be the Achilles' heel of the UD strategy as it is likely to appear very different from the other "moles". Thus, the ugly ducking strategy may be more helpful in younger patients.

One group has proposed combining the ABCDE rule and UD sign into one mnemonic, the ABCDEF rule where F stands for "funny looking" [J Clin Aesthet Dermatol. 2015 Feb; 8: 15].

Treatment, Brief Overview

• All suspicious lesions should be removed preferably in their entirety.
• Treatment should be carried out by a dermatologist and possibly an oncologist depending upon the situation.

RegionalDerm

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