Mole or Melanoma?

    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.

Why Cancer Happens

    According to Greek mythology, Cancer was the crab that the goddess Juno immortalized in the night sky after the lowly creature sacrificed himself in a fabled battle between Hercules and the nine-headed Hydra.  Since Juno was stingy with the number of stars she allotted to the crab’s constellation, the amateur astronomer often looks in vain for a body with claws. Nevertheless, first century physicians, searching for picturesque language to describe their patients’ ailments, found in the crab constellation a name for hard masses covered with tortuous veins – particularly those that seemed to burrow deeply into the body.  And so we came to know cancer, the disease that inspires today’s most sophisticated research in cell biology, by a name that has no scientific meaning whatsoever.

The biggest risk factor: age

Cancer is a problem of birth, growth and death of cells, and occurs because our bodies are in a constant state of renovation, from development as tiny embryos until death many decades later. At first we grow and change shape. Then shape becomes fixed but body maintenance requires cell replacement on a regular, repetitive timetable. The master plans laying out instructions for regular destruction and reconstruction of cells lie in the DNA coiled into chromosomes.  Just as job-site blueprints get smudged, torn and stained, DNA accumulates damage over time. External agents such solar, cosmic and X- radiation, toxic chemicals, some hormone use, and some viruses add to the innate wear and tear.  In some people DNA code errors are built in from birth, handed down from one generation to the next.  Errors in the blueprint lead to the imperfect cells which give rise to cancer.

Errors in cell reproduction are visible everywhere. We call them signs of aging. Crinkles around the eyes, sagging skin, “liver” spots, bunions and so on – all are external, visible reminders that internally, similar changes are underway. It is no coincidence that tobacco smoking, single-handedly responsible for most cancer deaths, also produces conspicuous, premature aging.  The most remarkable thing about cancer is that it occurs so infrequently despite billions of cycles of error-producing cell reproduction in each person.  Fortunately for us, DNA also contains numerous safeguards for getting rid of error-ridden rogue cells before they get out of control.

What makes a cancer diagnosis

While cancer cells are identified under microscopes by changes in their appearance, looks alone do not make a cancer diagnosis. Until abnormal cells acquire the ability to grow unchecked, and to travel to other parts of the body (to metastasize), they are precancerous.  In many cases, pre-cancerous cells never make the transition to cancer, but we are unable to predict with 100% accuracy which ones will and which ones won’t.  A large number of breast abnormalities detected on mammograms will not go on to run wild, but few women will comfortably forgo treatment without 100% accurate prediction of the growth potential of their abnormal cells.

Difficulties in prediction

In addition to the breast, the prostate gland in men and the colon in both sexes are the sites of cell growth abnormalities that can, but do not always, result in cancer. Prostates enlarge with age and develop nodules of cell growth called adenomas. Colons develop polyps – enlargements of the lining protruding into the colon on flat or narrow stalks, with or without adenomas on their surfaces. Intuitively, it seems as if detecting these abnormalities and removing them before they have a chance to become cancerous is a good idea. This thinking drives the screening studies aimed at early treatment of cancer. But many of these common cancers are very slow and indolent in their growth and epidemiologic studies do not bear out the intuitive bias.  Unless a patient is young at the onset of a slow growing cancer, treatment does not necessarily lengthen life. Routine prostate cancer screening has fallen out of fashion because, while removing a cancerous prostate may prevent death from prostate cancer, treated patients do not outlive untreated ones.  Decisions about treatment have to be weighed carefully, with attention paid to age and the potential for harm and diminished quality of life that can go along with cancer treatment.

While all cancers begin slowly, some escape the body’s control mechanisms more easily and become aggressive and difficult to treat.  Primary brain, liver, pancreatic and ovarian cancer fall in this category. Toxic external factors that alter DNA may render cancer cells more resistant to the body’s methods of keeping slower growing cancers in check. Lung cancer from smoking, blood cancers secondary to radiation and some viruses, ovarian cancers stimulated by hormone use, and asbestos-induced lung tumors  gallop along compared to the slow movers like prostate and colon cancer.


Currently cancer treatment consists of removing cancers surgically and/or intervening with drugs or radiation to kill the abnormal cells. Both approaches leave something to be desired. Surgery removes a tumor already developed, but not the underlying biology that produced the tumor. Chemotherapy that seems effective at first is often followed by a relapse in which the cancer is less responsive – not surprising since the cells surviving the first rounds of treatment are resistant to the drug’s actions. Radiation induces cell damage in all exposed tissues and accounts for cancer development years later in people who have survived the first bout.

The new paradigm for thinking of cancer is as an age and genetics related derangement of cell growth that is also influenced by environmental factors.  Effective, tolerable treatments require understanding of the individual biology of each person’s cancer.  As the interior of living cells give up their secrets to researchers, we are beginning to see some real successes with drugs such as Gleevec (used for chronic myelogenous leukemia) – drugs aimed at specific pathways in the life of microscopic cancer cells – and also with immunotherapy in melanoma.  Perhaps we will eventually  be able to retire the image of the crab to his home in the sky.


Factors in cancer development

Under your control

Not under your control

Avoiding tobacco  Your genetic makeup
Using sunscreen The passage of time
Maintaining normal weight Cosmic radiation
Choosing high quality foods, low in sugar Accidental radiation exposure
Eating and exercising enough to avoid constipation (avoiding slow transit of waste through the colon) Exposure to carcinogenic agents not currently recognized as carcinogenic


Minimizing post menopausal hormone use Bad luck
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