Skin cancers

Skin cancers


Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
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much more. Try it free today! 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. 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. 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. 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. 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’. 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. 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 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. 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. 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.

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