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Skin cancer
Skin cancer is a malignant growth on the skin which can have many causes. Skin cancer
generally develops in the epidermis (the outermost layer of skin), so a tumor is usually
clearly visible. This makes most skin cancers detectable in the early stages. There are three
common types of skin cancer, each of which is named after the type of skin cell from which
it arises. Cancers caused by UV exposure may be prevented by avoiding exposure to sunlight
or other UV sources, and wearing sun-protective clothes. The use of sunscreen had been
recommended in the past, but there is an increasing body of evidence that sunscreen is not
entirely safe. Skin cancer is an increasingly common condition. This is in part attributed to
increased exposure to ultraviolet radiation, which in turn is thought to be caused by the
increased popularity of sun tanning (sun bathing). Lighter-skinned individuals are more
vulnerable. In the United States, about one out of every three new cancers arises from the
skin.
Skin cancers are the fastest growing type of cancer in the United States. Skin cancer
represents the most commonly diagnosed malignancy, surpassing lung, breast, colorectal and
prostate cancer. More than 1 million Americans will be diagnosed with skin cancer in 2007.
Causes
Our skin consists of three layers — the epidermis, dermis and subcutis. The epidermis, the
topmost layer, is as thin as a pencil line. It provides a protective layer of skin cells that our
body continually sheds. Squamous cells lie just below the outer surface. Basal cells, which
produce new skin cells, are at the bottom of the epidermis. The epidermis also contains cells
called melanocytes, which produce melanin — the pigment that gives skin its normal color.
When you're in the sun, these cells produce more melanin, which helps protect the deeper
layers of skin. The extra melanin is what produces the darker color of tanned skin.
Normally, skin cells within the epidermis develop in a controlled and orderly way. In
general, healthy new cells push older cells toward the skin's surface, where they die and
eventually are sloughed off. This process is controlled by DNA — the genetic material that
contains the instructions for every chemical process in our body. But when DNA is
damaged, changes occur in these instructions. One result is that new cells may begin to grow
out of control and eventually form a mass of cancer cells.
The role of UV light
Much of the damage to DNA in skin cells results from ultraviolet (UV) radiation found in
sunlight and in commercial tanning lamps and tanning beds. UV light is divided into three
wavelength bands: ultraviolet A (UVA), ultraviolet B (UVB) and ultraviolet C (UVC). Only
UVA and UVB rays reach the earth. UVC radiation is completely absorbed by atmospheric
ozone.
At one time scientists believed that only UVB rays played a role in the formation of skin
cancer. And UVB light does cause harmful changes in skin cell DNA, including the
development of oncogenes — a type of gene that can turn a normal cell into a malignant one.
UVB rays are responsible for sunburn and for many basal cell and squamous cell cancers.
But UVA also contributes to skin cancer. It penetrates the skin more deeply than UVB does,
weakens the skin's immune system and increases the risk of cancer, especially melanoma.
Tanning beds deliver high doses of UVA, which makes them especially dangerous. What's
more, occasional exposure to intense UVA puts you at greater risk of skin cancer than
spending long hours in the sun does. An initial high dose of UV radiation will severely
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damage melanocytes, but not destroy them. When these damaged cells are subjected to
further intense bouts of UVA light, they have little capacity to repair their DNA. This makes
them more likely to become malignant.
The BCC and the SCC often carry a UV-signature mutation indicating that these cancers are
caused by UV-B radiation via the direct DNA damage. However the malignant melanoma is
predominantly caused by UV-A radiation via the indirect DNA damage. [2] The indirect
DNA damage is caused by free radicals and reactive oxygen species. It has been shown, that
the absorption of sunscreen into the skin leads to an increase of free radicals in the skin. [3]
Other factors that may contribute to skin cancer
Sun exposure doesn't explain melanomas or other skin cancers that develop on skin not
ordinarily exposed to sunlight. Heredity may play a role. Skin cancer can also develop from
exposure to toxic chemicals or as a result of radiation treatments.
Risk factors
Skin cancer is most closely associated with chronic inflammation of the skin. This includes:
1. Overexposure to UV-radiation can cause skin cancer either via the direct− or via the
indirect DNA damage mechanism. UVA & UVB have both been implicated in causing
DNA damage resulting in cancer. Sun exposure between 10AM and 4PM is most
intense and therefore most harmful. Natural (sun) & artificial UV exposure (tanning
salons) are associated with skin cancer. Since sunbeds cause mostly indirect DNA
damage (free radicals) their use is associated with the deadliest form of skin cancer the malignant melanom.
2. Chronic non-healing wounds, especially burns. These are called Marjolin's ulcers
based on their appearance and can develop into squamous cell carcinoma.
3. Genetic predisposition, including "Congenital Melanocytic Nevi Syndrome". CMNS
is characterized by the presence of "nevi" or moles of varying size that either appear at
or within 6 months of birth. Nevi larger than 20 mm (3/4") in size are at higher risk for
becoming cancerous.
Skin can be protected by avoiding sunlight entirely, or wearing protective clothing while
outdoors. Skin cancer is usually caused by exposing skin to UV rays excessively.
Reduction of risk
Although it is impossible to completely eliminate the possibility of skin cancer, the risk of
developing such a cancer can be reduced significantly with the following steps:
 reducing exposure to ultraviolet (UV) radiation, especially in early years
 avoiding sunburns ( It was shown that sunscreen - while preventing the sunburn - does
not protect from melanoma. [5])
 avoiding sun exposure during the day (usually from 10 AM to 3 PM), when the sun is
highest in the sky
 wearing protective clothing (long sleeves and hats) when outdoors
 using a broad-spectrum sunscreen that blocks both UVA and UVB radiation.
Pathology
Squamous cell carcinoma is a malignant epithelial tumor which originates in epidermis,
squamous mucosa or areas of squamous metaplasia.
Macroscopically, the tumor is often elevated, fungating, or may be ulcerated with irregular
borders. Microscopically, tumor cells destroy the basement membrane and form sheets or
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compact masses which invade the subjacent connective tissue (dermis). In well differentiated
carcinomas, tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from
prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central
nucleus). Their disposal tends to be similar to that of normal epidermis: immature/basal cells
at the periphery, becoming more mature to the centre of the tumor masses. Tumor cells
transform into keratinized squamous cells and form round nodules with concentric,
laminated layers, called "cell nests" or "epithelial/keratinous pearls". The surrounding stroma
is reduced and contains inflammatory infiltrate (lymphocytes). Poorly differentiated
squamous carcinomas contain more pleomorphic cells and no keratinization.[6]
Types
The most common types of skin cancer are basal cell carcinoma (BCC) and squamous cell
carcinoma (SCC) which may be locally disfiguring but are unlikely to metastasize (spread to
other parts of the body).
The others, less common types of skin cancer include:
 Kaposi's sarcoma. This rare form of skin cancer develops in the skin's blood vessels
and causes red or purple patches on the skin or mucous membranes. Like melanoma,
it's a serious form of skin cancer. It's mainly seen in people with weakened immune
systems, such as people with AIDS and people taking medications that suppress their
natural immunity, such as people who've undergone organ transplants.
 Merkel cell carcinoma. In this rare cancer, firm, shiny nodules occur on or just
beneath the skin and in hair follicles. The nodules may be red, pink or blue and can
vary in size from a quarter of an inch to more than 2 inches. Merkel cell carcinoma is
usually found on sun-exposed areas on the head, neck, arms and legs. Unlike basal and
squamous cell carcinomas, Merkel cell carcinoma grows rapidly and often spreads to
other parts of the body.
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Sebaceous gland carcinoma. This uncommon and aggressive cancer originates in the
oil glands in the skin. Sebaceous gland carcinomas — which usually appear as hard,
painless nodules — can develop anywhere, but most occur on the eyelid, where they're
frequently mistaken for benign conditions.
Precancerous skin lesions. Having less pigment (melanin) in your skin provides less
protection from damaging UV radiation. If you have blond or red hair, light-colored
eyes, and you freckle or sunburn easily, you're much more likely to develop skin
cancer than a person with darker features is. If you developed skin cancer once, you're
at risk of developing it again. Even basal cell and squamous cell carcinomas that have
been successfully removed can recur in the same spot, often within two to three years.
. The risk of developing skin cancer increases with age, primarily because many skin
cancers develop slowly. The damage that occurs during childhood or adolescence may
not become apparent until middle age. Still, skin cancer isn't limited to older people.
Basal cell and squamous cell carcinomas are increasing fastest among women younger
than 40.
Having skin lesions known as actinic keratoses can increase your risk of developing
skin cancer. These precancerous skin growths typically appear as rough, scaly patches
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that range in color from brown to dark pink. They're most common on the face, lower
arms and hands of fair-skinned people whose skin has been damaged by the sun.
People with weakened immune systems are at greater risk of developing skin cancer. This
includes people living with HIV/AIDS or leukemia and those taking immunosuppressant
drugs after an organ transplant.
Fragile skin. Skin that has been burned, injured or weakened by treatments for other skin
conditions is more susceptible to sun damage and skin cancer. Certain psoriasis
treatments and eczema creams might increase your risk of skin cancer.
Exposure to environmental hazards. Exposure to environmental chemicals, including
some herbicides, increases your risk of skin cancer.
Signs and symptoms
There are a variety of different skin cancer symptoms. These include crabs or changes in the
skin that do not heal , ulcers in the skin.
Skin cancer develops primarily on areas of sun-exposed skin, including the scalp, face, lips,
ears, neck, chest, arms and hands, and on the legs in women. But it also can form on areas
that rarely see the light of day — the palms, spaces between the toes and the genital area.
A cancerous skin lesion can appear suddenly or develop slowly. Its appearance depends on
the type of cancer.
Basal cell carcinoma usually looks like a raised, smooth, pearly bump on the sun-exposed
skin of the head, neck or shoulders. Sometimes small blood vessels can be seen within the
tumor. Crusting and bleeding in the center of the tumor frequently develops. It is often
mistaken for a sore that does not heal. This is the most common skin cancer, accounting for
nearly 90 percent of all cases. It's also the most easily treated and the least likely to spread.
Basal cell carcinoma usually appears as one of the following:
 A pearly or waxy bump on your face, ears or neck
 A flat, flesh-colored or brown scar-like lesion on your chest or back.
Squamous cell carcinoma is commonly a red, scaling, thickened patch on sun-exposed skin.
Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large
mass. Squamous cell carcinoma is easily treated if detected early, but it's slightly more apt to
spread than is basal cell carcinoma. Most often, squamous cell carcinoma appears as one of
the following:
 A firm, red nodule on your face, lips, ears, neck, hands or arms
 A flat lesion with a scaly, crusted surface on your face, ears, neck, hands or arms.
Skin cancer is generally divided into two stages:
 Local. In this stage, cancer affects only the skin.
 Metastatic. At this point, cancer has spread beyond the skin.
Lab Studies:
 No laboratory studies for skin cancer are available.
Imaging Studies:
 No imaging studies are available for early diagnosis of skin cancer.
 Current imaging techniques (eg, ultrasound, CT scan, MRI, scintigraphy) may help to
detect the rare metastases.
Procedures:
 To diagnose skin cancer, perform a skin biopsy of the affected area and the
surrounding healthy tissue. This procedure often is curative.
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Staging: BCC rarely metastasizes and usually is not staged, unless the cancer is very large
and is suspected of spreading to other parts of the body. BCC staging may be similar to the
staging of squamous cell carcinoma, according to the following scheme:
 Stage 0: Cancer involves only the epidermis and has not spread to the dermis.
 Stage I: Cancer is not large (ie, <2 cm) and has not spread to the lymph nodes or other
organs.
 Stage II: The cancer is large (ie, >2 cm) but has not spread to lymph nodes or other
organs.
 Stage III: The cancer has spread to tissues beneath the skin (eg, muscle, bone,
cartilage), and/or has spread to regional lymph nodes, but has not spread to other
organs.
 Stage IV: The cancer can be any size and has spread to other organs.
Treatment
Most skin cancers can be treated by removal of the lesion, making sure that the edges
(margins) are free of the tumor cells. These excisions provide the best cure for both early and
high-risk disease.
For low-risk disease, radiation therapy and cryotherapy (freezing the cancer off) can provide
adequate control of the disease; both, however, have lower overall cure rates than surgery.
Treatment for skin cancer and the precancerous skin lesions known as actinic keratoses
varies, depending on the size, type, depth and location of the lesions. Often the abnormal
cells are surgically removed or destroyed with topical medications. Most treatments require
only a local anesthetic and can be done in an outpatient setting. Sometimes no treatment is
necessary beyond an initial biopsy that removes the entire growth.
If additional treatment is needed, options may include:
 Freezing. Your doctor may destroy actinic keratoses and some small, early skin
cancers by freezing them with liquid nitrogen (cryosurgery). The dead tissue sloughs
off when it thaws. The treatment may leave a small, white scar. You may also need a
repeat treatment to remove the growth completely.
 Excisional surgery. This type of treatment may be appropriate for any type of skin
cancer. Your doctor cuts out (excises) the cancerous tissue and a surrounding margin
of healthy skin. A wide excision — removing extra normal skin around the tumor —
may be recommended in some cases. To minimize or avoid scarring, especially on
your face, you may need to consult a doctor skilled in skin reconstruction.
 Laser therapy. A precise, intense beam of light vaporizes growths, generally with
little damage to surrounding tissue and with minimal bleeding, swelling and scarring.
A doctor may use this therapy to treat superficial skin cancers or precancerous growths
on lips.
 Mohs' surgery. This procedure is for larger, recurring or difficult-to-treat skin
cancers, which may include both basal and squamous cell carcinomas. Your doctor
removes the skin growth layer by layer, examining each layer under the microscope,
until no abnormal cells remain. This procedure allows cancerous cells to be removed
without taking an excessive amount of surrounding healthy skin. Because it requires
special skill, the surgery should be done only by specially trained doctors.
 Curettage and electrodesiccation. After removing most of a growth, your doctor
scrapes away layers of cancer cells using a circular blade (curet). An electric needle
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destroys any remaining cancer cells. This simple, quick procedure is common in
treating small or thin basal cell cancers. It leaves a small, flat, white scar.
 Radiation therapy. Radiation may destroy basal and squamous cell carcinomas if
surgery isn't an option.
 Chemotherapy. In chemotherapy, drugs are used to kill cancer cells. For cancers
limited to the top layer of skin, creams or lotions containing anti-cancer agents may be
applied directly to the skin. Topical drugs can cause severe inflammation and leave
scars. Other types of chemotherapy can be used to treat skin cancers that have spread
to other parts of the body.
Treatments for skin cancer under study include:
 Photodynamic therapy. This treatment destroys skin cancer cells with a combination
of laser light and drugs that makes cancer cells sensitive to light. Photodynamic
therapy for precancerous skin lesions is currently available by prescription.
 Biological therapy (also called immunotherapy). Interferon and interleukin-2 are
under study to treat melanoma and nonmelanoma skin cancers. These immunotherapy
drugs stimulate your immune system to fight the cancer. Other medications applied to
your skin, such as imiquimod (Aldara), enhance your immune reaction to the presence
of skin cancer.
In the case of disease that has spread (metastasized) further surgical or chemotherapy may be
required.
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A basal cell carcinoma, one of the most common types of skin cancer.