I am going to confess that I am not quite sure who the Kardashians are or why they are famous, but in researching this article I discovered that one of them, 39-year-old Khloe Kardashian, recently announced that for almost a year, she thought a “tiny spec” on her cheek was a “zit.” When it was finally biopsied, it proved to be a melanoma and she underwent surgery, which resulted in a successful removal—the stage was not announced. I did understand however that she also had a melanoma removed from her back at the age of 19, an incredibly young age, so why she was oblivious to a skin lesion on her face for so long I’m just not sure.

Melanoma occurs annually in about 80,000 Americans; it has doubled over the past 30 years. Melanoma is the most serious type of skin cancer; it arises in melanocytes, the skin cells that produce melanin, the pigment that gives skin its color. Melanocytes can occur in other parts of the body as well, such as the uvea of the eye or along the gastrointestinal tract, and so melanomas may arise in those sites as well. But the vast majority do develop in the skin.

Moles (or nevi) are a common type of benign skin growth. Most are harmless but they may change and become malignant. Most moles are colored tan, brown, black, red or some other color. Again, since as health care professionals we like acronyms, I offer you the ABCDE for detecting suspicious moles:

A—Asymmetry in the mole.

B—Borders that are irregular or notched.

C—Color changes or many colors or uneven colors.

D—Diameter: Most moles are less than 6 mm, so look for growth beyond this size.

E—Evolving: Changing in shape, color, size or any other way should arouse suspicion.

One or more of these signs in a mole should make you wary and prompt an appointment to a dermatologist for evaluation.

Once a melanoma has been diagnosed, as with other solid tumors, the focus of the dermatologist or oncologist is on staging. The primary issue in staging is how superficial or deep the tumor is, and for this I describe the usual system that is used for staging—the TNM system (Tumor, Nodes, Metastases). A stage I tumor is up to 2 mm thick and with negative lymph nodes. Other stages are formed on the basis of the melanoma’s thickness, whether the melanoma is ulcerated, and whether any local lymph nodes are involved. Of course, increasing stage presages a worse prognosis. A stage I tumor has an excellent chance of cure with surgery alone.

There are several subtypes of melanoma based on appearance and shape (e.g., superficial spreading, acral, nodular, lentigo), but a discussion of their characteristics is beyond the scope of our discussion. Once lymph nodes are involved, the patient is stage III and there is a worsening prognosis with an increasing number of lymph nodes that are involved.

In the past, stage IV or metastatic melanoma was uniformly fatal with little benefit to be derived from conventional systemic therapy. The advent of immunotherapy, in particular the checkpoint inhibitors, such as pembrolizumab (Keytruda), ipilimumab (Yervoy) and nivolumab (Opdivo), have completely revolutionized the outcomes for patients with advanced melanoma, providing them with potentially years of good quality survival. In addition, 50% of melanoma patients have a tumor marker known as a BRAF V600E mutation. Patients with this particular marker can be treated with a drug combination that consists of a BRAF inhibitor, and typically includes drugs such as encorafenib plus binimetinib. Such combinations can prolong survival in 40% of patients for several years.

As a consequence, these new systemic therapies have completely altered the outcomes for patients with advanced melanoma. This was formerly a disease with a uniformly dismal outcome with no realistic therapies available. However, now these patients are likely to survive for years with modern modalities of treatment. Prior to immunotherapy, the median survival of a patient with stage IV or advanced melanoma was approximately six months. Recent clinical trials are describing median survivals on the order of six years or better.

The success of immunotherapy in patients with advanced melanoma has increasingly brought this therapy into consideration in the setting of adjuvant therapy for resected stage II and stage III disease. Randomized trials are suggesting that pembrolizumab or other immunotherapeutic agents may be of value following resection of stage II or III melanoma, but these questions currently remain under investigation. Their use in the neoadjuvant setting is also being explored.

As with the non-melanotic skin cancers, the diagnosis and treatment of one melanoma skin cancer increases the risk of diagnosis of a second tumor. Therefore, vigilance for such new tumors is required. Why melanomas are particularly susceptible to immunologic approaches to treatment is unclear. In the past, they were also sensitive to treatment with interferon and IL2, other immunologic treatments that were significantly less effective and more toxic, but were nonetheless the best available treatments for these tumors.

Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.