Skin cancer

Definitions & Key takeaways

Skin cancer is a type of cancer that develops in the cells of the skin. Three main types of skin cancer are basal cell carcinoma (the most common), squamous cell carcinoma (the second most common), and the least common but most deadly, melanoma. Risk factors for skin cancer include exposure to UV radiation, a history of sunburns, fair skin, and a weakened immune system. Diagnosis is made with a tissue biopsy and treatments can include physically removing cells with a high risk of developing into skin cancer. Tumor cells are also commonly removed and treated with radiation, chemotherapy, or immunotherapy.

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Introduction0:00–0:24

Skin cancer is an uncontrolled growth of cells within the skin. There are three main types: basal cell carcinoma, squamous cell carcinoma, and melanoma.
Some skin cancers can spread to other locations in the body and can be fatal, as seen with singer-songwriter Bob Marley, who died shortly after being diagnosed with melanoma.

Skin0:24–2:29

The skin is divided into three layers--the epidermis, dermis, and hypodermis. The hypodermis is made of fat and connective tissue that anchors the skin to the underlying muscle.
Just above is the dermis, which contains hair follicles, nerves and blood vessels. And just above that, the outermost layer of skin, is the epidermis.
The epidermis itself has multiple cell layers that are mostly keratinocytes - which are named for the keratin protein that they’re filled with.
Keratin is a strong, fibrous protein that allows keratinocytes to protect themselves from getting destroyed, when you rub your hands through the sand at the beach.
Keratinocytes start their life at the deepest layer of the epidermis called the stratum basale, or basal layer, which is made of a single layer of small, cuboidal to low columnar stem cells that continually divide and produce new keratinocytes that continue to mature as they migrate up through the epidermal layers, flattening out to a pancake-like squamous shape as they ascend.
But the stratum basale also contains another group of cells - melanocytes, which secrete a protein pigment, or coloring substance, called melanin.
Melanin is actually a broad term that constitutes several types of melanin found in people of differing skin color. These subtypes of melanin range in color from black to reddish yellow and their relative quantity and rate at which they are metabolized define a person’s skin color.
When keratinocytes are exposed to the sun, they send a chemical signal to the melanocytes, which stimulates them into making more melanin.
The melanocytes move the melanin into small sacs called melanosomes, and these get taken up by newly formed keratinocytes, which will later metabolize the melanin as they migrate into higher layers of the epidermis.
Melanin then acts as a natural sunscreen, because its protein structure dissipates, or scatters, UVB light--which if left unchecked can damage the DNA in the skin cells and lead to skin cancer.
Melanocytes can also be found in the dermis, at the base of the hair follicle, where they transfer melanin to the keratinized cells that make up hair.

Pathophysiology2:29–3:29

Now, a tumor develops if there’s a DNA mutation in any of these cell types that leads to uncontrolled cell division. Typically these are mutations in proto-oncogenes which result in a promotion of cell division, or mutations in tumor suppressor genes which result in a loss of inhibition of cell division.
You can think of proto-oncogenes as the accelerator or gas pedal and tumor suppressor genes as the brakes. Too much acceleration or an inability to brake can lead to runaway cell division.
As a result, the mutated cells can start piling up on each other and can become a tumor mass. Some of these tumors are benign and stay well contained or localized.
But some become malignant tumors or cancers, and these are the ones that break through their basement membrane and invade nearby tissues.
Malignant tumor cells can get into nearby blood or lymph vessels, and travel from the primary site to establish a secondary site of tumor growth somewhere else in the body - and that’s called metastasis.

Basal cell carcinoma3:29–4:13

Skin cancer is differentiated based upon the type of skin cell that’s involved in the tumor mass. The most common is basal cell carcinoma, which involves cells in the stratum basale.
These tend to be slow growing tumors that can be locally invasive, but rarely metastasize to distant regions of the body.
Nearby blood vessels in the dermis can become dilated to deliver more nutrients as the tumor grows. Basal cell carcinomas can grow superficially, spreading over several centimeters of the epidermis.
And they can break through the basement membrane and invade the dermis, forming islands or cords of tumor cells. Tumor cells on the periphery of islands typically arrange themselves in a line, like fence-posts, forming a palisading pattern.

Squamous cell carcinoma4:13–5:18

The second most common type of skin cancer is squamous cell carcinoma which involves squamous keratinocytes. Now, a precancerous lesion that can turn into squamous cell carcinoma is called actinic keratosis.
In an actinic keratosis, keratinocytes are damaged by radiation and begin to over-produce keratin. Over time, these damaged keratinocytes can develop into squamous cell carcinoma.
An early stage of squamous cell carcinoma is also called Bowen’s disease or squamous cell carcinoma in situ. At this point, the tumor can be found in the epidermis, but it has not broken through the basement membrane.
Tumor cells are atypical – enlarged and over pigmented. As squamous cell carcinoma becomes more invasive, it can break through the basement membrane and extend into the dermis.
It may even reach the hypodermis, at which point it is more likely to metastasize. Tumor cells at these more advanced stages typically vary in their degree of maturity, have abnormal shapes, and over-produce keratin forming ‘pearls’.

Melanoma5:18–6:08

Finally, the most aggressive form of skin cancer is melanoma which involves melanocytes. Now, melanocytic nevus, more commonly known as a mole, results from a type of melanocyte that over-produces melanin.
These moles can be considered precancerous because they carry an increased risk of becoming a melanoma. Melanomas grow horizontally within the epidermis and superficial dermis; and they grow vertically - invading the dermis.
Metastasis is most associated with the depth of invasion, and in fact, melanoma is the most deadly form of skin cancer because of its tendency to metastasize quickly.
Typically, the tumor cells have a large nuclei with irregular contours, and produce melanin in a variety of colors: brown, red, dark blue, and gray.

Causes6:08–6:33

The causes of skin cancer can be both genetic and environmental. By far, the leading environmental factor is UV exposure from the sun or tanning booths.
Often, the risk of developing skin cancer increases as sun exposure over a lifetime accumulates. Some viral infections, like human papillomavirus; immunosuppression; and having light skin also tend to increase risk.

Skin manifestations6:33–7:51

Skin cancer typically appears on skin that’s exposed to the sun. Basal cell carcinomas can appear as well-circumscribed, pearly, waxy, or shiny solid elevation of skin.
They can also be ulcerated and red or pigmented. Actinic keratosis can appear as dry, rough, almost sandpaper-like patches that are surrounded by tan, brown, red or flesh colored skin.
They tend to commonly form on the lips, face, scalp, arm, ears, and the back of the hands. Squamous cell carcinoma can appear as small, well-circumscribed, red elevations of the skin with scaly plaques on top, which can sometimes ulcerate.
Moles can appear as small; oval; tan, pink, black, or brown spots that can be flat or elevated. Finally, the worrisome signs of melanoma can be remembered using the mnemonic ABCDE where lesions are asymmetrically shaped, borders are irregular or notched, coloration varies within the same lesion, the diameter is larger than the size of a pencil eraser, and the lesion rapidly evolves over time and can cause skin elevation.
These lesions may also be itchy or painful. A tissue biopsy is needed to make a definitive diagnosis of skin cancer, and treatment options include removal with surgery or with cryotherapy, where the tumor is frozen off.

Diagnosis and treatment7:51–8:24

Radiation, chemotherapy or immunotherapy may also be options. And precancerous cells, like in actinic keratosis or melanocytic nevus, are typically removed to prevent their progression to skin cancer with cryotherapy or photodynamic therapy, which is where light is used to induce cellular death.
So, to recap: there are three main types of skin cancer: the most common, basal cell carcinoma; the second most common, squamous cell carcinoma; and the most deadly, melanoma – and they all form from uncontrolled growth of cells within the epidermal layer of the skin.

Review8:24–9:16

Tumors can remain relatively contained, or invade other layers of the skin. The deeper the tumor invades, the greater the risk of metastasis.
UV exposure is a risk factor, so areas of the face and body exposed to the sun are particularly affected, like the scalp; lips; ears; arms; and the backs of the hands.
Diagnosis is made with a tissue biopsy and treatments can include physically removing cells with a high risk of developing into skin cancer.
Tumor cells are also commonly removed and treated with radiation, chemotherapy, or immunotherapy.