In ancient mythology, moles were dark spots sent by jealous gods to spoil the faces of beautiful people. Later, moles became signs that the soul had fled the body, a notion that shows up today in Halloween witch masks with hairy warts sprouting from noses. In the 1800s, imitation moles made of leather, velvet and mouse fur covered pox scars in the aristocracy and led to their rebranding as beauty marks. Modernity continued this tradition with some famous stars like Marilyn Monroe enhancing their moles cosmetically. However, modernity also gave rise to the fear of moles because of worry about the most serious form of skin cancer, the melanoma. Most people have moles somewhere on their body. How do you know which ones to worry about?

Melanocytes: the origin of dark spots

    Before you begin worrying, you need to know what you are worrying about. The problem with moles is that, though the vast majority are quite benign, they come from the same type of cells that give rise to the dreaded melanoma. These cells are called melanocytes, one of three types of skin cells.  They make the pigment melanin that gives skin its color and protects it against ultraviolet light, the kind that produces sunburn. Melanocytes store melanin in little capsules inside themselves, ramping up production when the skin is exposed to sunlight, and distributing it to the outer skin layer where cells called keratinocytes absorb it.  Moles, which are technically known as melanocytic nevi, are clumps of melanocytes which appear as dark, often raised spots anywhere on the skin. They are regular shaped with smooth edges, evenly colored, and generally less than a quarter of an inch in diameter. Moles are not freckles, which are discrete spots of reddish-brown keratinocytes that appear mainly in very fair-skinned people because the melanin distribution process in their skin is uneven.

Moles: the cloning of well behaved rogue cells

    Babies are rarely born with any moles. Melanocytic nevi begin to appear in childhood and continue for several decades, peaking in the thirties. Most people have between 10 and 40 moles by adulthood.  Sometimes they begin to reverse and disappear. Recent research suggests that a mole appears when a rogue melanocyte begins to clone itself. This sounds like the same process that begins cancer, and, indeed, initial melanocyte growth involves genetic changes similar to those seen in cancer cells. But in the case of the mole, there appear to be controlling processes at work that prevent continued growth and organize the cells into well-defined architecture characteristic of non-cancerous growths. But will it turn into a melanoma – a cancer which may spread both locally and distantly?

Melanomas: Rogues without controls

    Most moles are and remain benign throughout life. Melanomas, though, are increasing in frequency in recent decades. Projected numbers of new melanoma diagnoses in the US in 2019 estimate over 96,000 cases, more in men than in women.  Deaths from melanoma will exceed 7,200.  Melanomas are twenty times more common in white skinned people than in dark skinned. About 25-30% of these melanomas will arise in previously stable, benign moles, but it is not at all clear that the mole is the source. They may be just as random in their appearance there as they are in any other part of the body. Melanomas also begin with rogue melanocytes, but they lack the control mechanisms of the offspring of the melanocyte that gives rise to a mole. They are biologically different from the cells in moles.

Markers for melanoma risk

    What increases the risk for melanoma development? Fair skin and freckling, a family history of melanoma, chronic unprotected sun exposure, large numbers of nevi, and biopsies showing irregular (dysplastic) features under a microscope. Large number of moles – in the range of 100, also increase the risk that a melanoma will appear in a previously benign spot.  Some melanomas appear in unexposed areas of the body, inside the mouth and in the eye, suggesting that they are different biologically from melanomas that occur in sun-damaged skin.  

Early recognition helps

    Early recognition of a melanoma improves the outcome. Five-year survival rates when the tumor is localized in the skin is 98%. With spread to regional lymph nodes, survival falls to 68% and down to 23% with spread to distant lymph nodes and other organs. Overall five-year survival is 92% and improving with the advent of newer forms of treatment based on immune attack of the tumors.

    Early recognition of melanoma depends on two things – knowing your own moles and examining them and the rest of your skin for any changes on a regular basis. Self-examination means using a mirror or asking a partner to help with scrutiny of your head and backside. What are you looking for?

1. New spots with irregular color or borders. But every new spot, especially in older people, is not cause for worry. Many are so called age spots – flat, brown, over-pigmented areas. Others are overgrowths of keratinocytes called senile or seborrheic keratoses.
2.  Change in old moles, especially irregularities in color or shape. Some melanomas may be pale, not dark. Some may have multiple shades. Some are relatively smooth but others may be bumpy.
3. Growth in size happens to moles at times, particularly with hormonal change, or with sun exposure, and growth alone is a poor predictor of whether or not a mole has transformed to a melanoma. Growth with change in color or border irregularity is more worrisome.
4. A bleeding mole, or failure to heal if the surface is disturbed. 

A biopsy is the only way to know for certain that what a change in a mole, or a suspicious new spot represents, and regular examination by a dermatologist eases worry, especially if you have a family history of melanoma or an unusually large number of moles. And it is never too late to protect your skin from the sun, by avoiding exposure during the height of the day, by covering skin with clothing, and using sunscreen in unavoidably exposed areas.