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A 65-year-old woman comes to the dermatology clinic because of concern about an unusual mole on her left arm. She is frightened because several of her family members have been diagnosed and treated for skin cancer. Her medical history is otherwise noncontributory. A skin biopsy is performed and shows proliferation of abnormal melanocytes. Which of the following mutations is the patient most likely to have?
Content Reviewers:Rishi Desai, MD, MPH
Skin cancer is an uncontrolled growth of cells within the skin.
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.
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.
Now, a tumor develops if there’s a DNA mutation in any of these cell types that leads to uncontrolled 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.
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.
The second most common type of skin cancer is squamous cell carcinoma which involves squamous keratinocytes.
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