How Do Damaged Skin Cells Turn Into Stage 4 Melanoma?

by Barbara O'Dair Health Writer

Melanoma is the rarest form of skin cancer—and the deadliest. Its main cause is ultraviolet (UV) rays, but that’s not the whole picture. Genetics, fair coloring, indoor tanning, compromised immune systems, and other factors can also play a part. While melanoma mostly occurs on the trunk or limbs, it can appear anywhere, including the scalp, face, nails, and where the sun doesn’t shine. To track melanoma’s spread, doctors use a system of five stages (0 to 4). Here, we’ll walk you through how this skin cancer develops and progresses to help you better understand a melanoma diagnosis.


How Does Sunlight Cause Melanoma?

UV exposure, whether it’s from the sun or a tanning bed, strongly correlates to melanoma, says Rachel Maiman, M.D., a clinical instructor at The Mount Sinai Hospital department of dermatology in New York City. UV light damages the DNA in melanocytes, which are specialized skin cells that produce melanin (the pigment that colors our skin); these cells are also active in the skin’s immune system. The damaged DNA can be repaired only partially, says Dr. Maiman. “Over time, the remaining DNA damage can lead to mutations [in the melanocytes] that produce melanoma.”

mole inspection

How Does Early Melanoma Get Discovered?

Most melanomas show up as a new skin growth. They occur in existing moles just 20% to 30% of the time. “The cancer may be evident as a flat or barely raised lesion with irregular borders and a diameter about the size of a pencil (eraser),” says Omar Hamid, M.D., director of the melanoma program at Cedars-Sinai The Angeles Clinic and Research Institute in Los Angeles. If the melanocytes are still producing pigment, the spot will be brown, tan or black; if not, it can manifest as pink or even white.

derma and mole

Stage 0 Melanoma

Mutated melanocytes can replicate quickly and start to form a tumor in the top layer of skin known as the basal layer of the epidermis. When the cells show abnormal horizontal growth within this superficial layer, doctors diagnose as melanoma in situ, or stage 0 melanoma. (Melanoma diagnoses are based on the depth/thickness of the tumor and how much it has spread.) “If you’re going to have a melanoma, this is where you want to catch it,” says Ramin Fathi, M.D., a board-certified dermatologist and Mohs surgeon at Phoenix Surgical Dermatology Group in Phoenix. “The survival rate is 98-plus percent.”

mole surgery

Stage 1 Melanoma

Tumors that have penetrated the next layer of skin (called the dermis) are classified as stage 1 melanoma. At that point, it usually measures no more than 2 mm and is still local, but it’s now called “invasive.” As with stage 0, stage 1 melanoma is treated with minor surgery and considered curable. Also good news: The risk of recurrence or metastasis is still considered low, according to the Melanoma Research Alliance.

checking lymph nodes

Stage 2 Melanoma

As melanoma progresses, the tumor will grow and change. At stage 2, it’s still local, meaning that while there is cancer in the epidermis and dermis, there is no evidence that it has spread to the lymph nodes. Stage 2 is defined by tumor thickness and extent of ulceration (microscopic breaks in the skin)— ulceration makes for a worse prognosis. Stage 2 tumors can still be treated with surgery, called a wide local excision. But without early detection and treatment, however, the melanoma will likely spread to the lymph nodes and, eventually, beyond.

targeted therapy

Stage 3 Melanoma

This more advanced stage means the melanoma cells have either grown deeper into the dermis and/or traveled from the skin and into nearby lymph nodes. Tell-tale signs that you might have stage 3 melanoma could be finding hardened lumps under your skin, swollen or painful lymph nodes, general fatigue, loss of appetite, and other worrisome issues. Treatment options include immunotherapy and targeted drug therapies. “Those are physicians’ preferred treatments,” says Dr. Fathi.


Stage 4 Melanoma

The last stage of melanoma is called metastatic, or stage 4. “That means it’s gone much further than it should have,” says Dr. Hamid. The tumor cells have now spread to distant lymph nodes and/or distant organs such as the brain, lungs, liver, bones, or gastrointestinal tract. Depending on where it’s landed, you may have trouble breathing, crushing bone pain, or even seizures. Immunotherapy or targeted therapies, sometimes in combinations with other treatments such as chemotherapy, are the usual course of action.

sunscreen and hat

How Can People Protect Themselves From Melanoma, and Detect Melanoma Early?

The good news is that most cases of melanoma are curable when they are detected at an early stage. The main ways to stay safe is to limit your time in the sun, wear sunscreen and a hat, and generally cover up. Dr. Fathi also recommends a regular, full-body skin check in a dermatology office. Dr. Maiman adds, “[Melanoma] is much more likely to spread if not caught and treated early. You should know what to look out for.” To that end, the American Cancer Society offers a comprehensive self-exam that you can perform at any time.

Barbara O'Dair
Meet Our Writer
Barbara O'Dair

Barbara O'Dair is the former editor in chief of Prevention. She has edited or written for the New York Times, Time, Rolling Stone, Health, AARP, and many other digital and print publications.