Skin Cancers

Skin cancer is a malignant growth on the skin which can have many causes. The most common skin cancers are basal cell cancer, squamous cell cancer, and melanoma. 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. Unlike many other cancers, including those originating in the lung, pancreas, and stomach, only a small minority of those afflicted will actually die of the disease.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. Melanoma is the least common skin cancer but it is potentially the most serious: there are over 8,000 new cases each year in the UK and 1,800 deaths. More people now die of Melanoma in the UK than in Australia. It is the second most common cancer in the young population (20 – 39 age group). It is estimated that approximately 85% of cases are caused by too much sun. Non-melanoma skin cancers are the most common skin cancers. The majority of these are called Basal Cell Carcinomas. These are usually localised growths caused by excessive cumulative exposure to the sun and do not tend to spread.

 

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 DNA damage 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.[citation needed] Since sunbeds cause mostly indirect DNA damage (free radicals) their use is associated with the deadliest form of skin cancer, malignant melanoma.[citation needed]
    1. UVA rays affect the skin at a deeper level than UVB rays, reaching through the epidermis and the dermis to the hypodermis where connective tissues and blood vessels are located. UVA activates the melanin of the epidermis causing changes in pigmentation as well as loss of elasticity of the skin, which contributes to premature wrinkling, sagging and aging of the skin.
    2. UVB rays primarily affect the epidermis causing sunburns, redness, and blistering of the skin. The melanin of the epidermis is activated with UVB just as with UVA; however, the effects are longer lasting with pigmentation continuing over 24 hours.
  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.
  4. Human papilloma virus (HPV) is often associated with squamous cell carcinoma of the genital, anal, oral, pharynx, and fingers. It is believed that the HPV vaccine might help to prevent these cancers as well as cervical cancers.
  5. Skin cancer is one of the potential dangers of ultraviolet germicidal irradiation.

Many believe that skin cancer can be prevented altogether by avoiding sunlight entirely, or wearing protective clothing while outdoors. However, studies show that Melanoma Skin Cancer is more common in those who work indoors. Skin Cancer is most common on areas of the body that are not normally exposed to the sun, and then exposing the skin to UV rays excessively.

Skin cancer generally has a 20- to 30-year latency period. Many instances of skin cancer in older individuals today can be traced to behaviours as young adults in the 1970s and early 1980s. Deep tans at that time were routinely spoken of as "healthy." Sunburns represented an inconvenient rite of spring or an awkward preliminary stage in the process of acquiring a "healthy" tan. Severe burns were commonplace. Today we know the approach to be reckless. The incidence rates of skin cancer today in persons over 50 years of age reflect that day's popular ignorance.

 

Types

The most common types of skin cancers are:

  • Basal Cell Carcinoma
  • Squamous Cell Carcinoma
  • Melanoma

Basal cell carcinomas (BCC) are the most common. They present on sun exposed areas of the skin, especially the face. They rarely metastasize, and rarely causes death. They are easily treated with surgery or radiation. Squamous cell carcinomas(SCC) are common, but much less common than basal cell cancers. They metastasize more frequently than BCC's. Even then, the metastasis rate is quite low, with the exception of SCC's of the lip, ear, and in immunosuppressed patients. Melanomas are the least frequent of the 3 common skin cancers. They frequently metastasize, and are deadly once spread.

Less common skin cancers include: Dermatofibrosarcoma protuberans,Merkel cell carcinoma,Kaposi's sarcoma, keratoacanthoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, merkel cell carcinoma, Pagets's disease of the breast, atypical fibroxanthoma, leimyosarcoma, and angiosarcoma

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.[citation needed] The indirect DNA damage is caused by free radicals and reactive oxygen species. Research indicates that the absorption of three sunscreen ingredients into the skin, combined with a 60-minute exposure to UV, leads to an increase of free radicals in the skin.

 

Skin cancer as a group

Many laymen and even professionals consider the basal cell carcinoma (BCC), the squamous cell carcinoma (SCC) and the malignant melanoma as one group - namely skin cancer. This grouping is problematic for two reasons:

  • the mechanism that generates the first two forms is different from the mechanism that generates the melanoma. The direct DNA damage is responsible for BCC and SCC while the indirect DNA damage causes melanoma.
  • the mortality rate of BCC and SCC is around 0.3 causing 2000 deaths per year in the US. In comparison the mortality rate of melanoma is 15-20% and it causes 6500 deaths per year.[2]:29,31

Even though it is rare, malignant melanoma is responsible for 75% of all skin cancer related death cases.

While sunscreen has been shown to protect against BCC and SCC it may not protect against malignant melanoma. When sunscreen penetrates into the skin it generates reactive chemicals. It has been found that sunscreen use is correlated with malignant melanoma.The lab-experiments and the epidemiological studies suggests that sunscreen use correlates with melanoma incidence. The question that has to be asked is: "Are sunscreen users also the ones with the highest lifetime exposure to ultraviolet lights?" or are sun screens tumor promoters or carcinogens themselves. Logics might suggest that sunscreen users also are the ones most likely to be burned or have been burned by sun light. If it is true that some suncreen induces the formation of skin cancers, the physical sunscreen which are metallic in nature (zinc and titanium) are likely safer and likely to be inert. In the past, most sunscreens were chemical blockers (benzones, etc.).

 

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, discoloration, and changes in existing moles.

  • 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.
  • 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.
  • Most melanomas are brown to black looking lesions. Signs that might indicate a malignant melanoma include change in size, shape, color or elevation of a mole. The appearance of a new mole during adulthood, or new pain, itching, ulceration or bleeding.

 

Diagnosis

Diagnosis is only confirmed with a skin biopsy. Most skin biopsies are done under local anesthetic with an injection. A shave biopsy is good for diagnosing basal cell carcinoma, while not as well for squamous cell carcinoma. A punch biopsy is preferred for diagnosing squamous cell carcinoma and melanoma over the shave biopsy technique. Excisional biopsy (where the entire lesion is removed down to the deep dermis and subcutanous fat) is the method of choice for diagnosing melanomas. However, for cosmetic reason and practical reasons, a punch biopsy is often used to initially diagnose many large melanomas or melanomas of cosmetically important anatomic locations (nose, face, eyelids, nails, fingers and toes).

 

Treatment

Treatment is dependent on type of cancer, location of the cancer, age of the patient, and if the cancer is primary or recurrence. One should look at the specific type of skin cancer (basal cell carcinoma, squamous cell carcinoma, or melanoma) of concern in order to determine the correct treatment required. An example would be a small basal cell cancer on the cheek of a young man, where the treatment with the best cure rate (Mohs surgery) might be indicated. In the case of an elderly frail man with multiple complicating medical problems, a difficult to excise basal cell cancer of the nose might warrant radiation therapy (slightly lower cure rate) or no treatment at all. Topical chemotherapy might be indicated for large superficial basal cell carcinoma for good cosmetic outcome, whereas it might be inadequate for invasive nodular basal cell carcinoma or invasive squamous cell carcinoma.

For low-risk disease, radiation therapy, topical chemotherapy (imiquimod or 5-fluorouracil) and cryotherapy (freezing the cancer off) can provide adequate control of the disease; both, however, may have lower overall cure rates than certain type of surgery. Other modalities of treatment such as photodynamic therapy, topical chemotherapy, electrodessication and curettage can be found in the discussions of basal cell carcinoma and squamous cell carcinoma.

Mohs' micrographic surgery (mohs surgery) is a technique used to remove the cancer with the least amount of surrounding tissue and the edges are checked immediately to see if tumor is found. This provides the opportunity to remove the least amount of tissue and provide the best cosmetically favorable results. This is especially important for areas where excess skin is limited, such as the face. Cure rates are equivalent to wide excision. Special training is required to perform this technique.

In the case of disease that has spread (metastasized), further surgical procedures or chemotherapy may be required.

Scientists have recently been conducting experiments on what they have termed "immune- priming". This therapy is still in its infancy but has been shown to effectively attack foreign threats like viruses and also latch onto and attack skin cancers. More recently researchers have focused their efforts on strengthening the body's own naturally produced "helper T cells" that identify and lock onto cancer cells and help guide the killer cells to the cancer. Researchers infused patients with roughly 5 billion of the helper T cells without any harsh drugs or chemotherapy. This type of treatment if shown to be effective has no side effects and could change the way cancer patients are treated.

 

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 sun exposure during the day, especially from 9 AM to 4 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
  • reapply sun block every 2 hours and after swimming
  • chemoprevention using topical imiquimod or 5-fluorouracil[citation needed]

Although it is generally accepted that UV exposure is the greatest risk factor in melanoma development, some sceptics say no data conclusively proves a link between moderate sun exposure and the likelihood of melanoma.

Australian scientist Ian Frazer who developed a vaccine for cervical cancer, says that a vaccine effective in preventing for certain types of skin cancer has proven effective on animals and could be available within a decade. The vaccine would only be effective against Squamous Cell Carcinoma.

 

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 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.

Oral Cancers

Oral cancer is any cancerous tissue growth located in the mouth. It may arise as a primary lesion originating in any of the oral tissues, by metastasis from a distant site of origin, or by extension from a neighboring anatomic structure, such as the nasal cavity or the maxillary sinus. Oral cancers may originate in any of the tissues of the mouth, and may be of varied histologic types: teratoma, adenocarcinoma derived from a major or minor salivary gland, lymphoma from tonsillar or other lymphoid tissue, or melanoma from the pigment producing cells of the oral mucosa. Far and away the most common oral cancer is squamous cell carcinoma, originating in the tissues that line the mouth and lips. Oral or mouth cancer most commonly involves the tissue of the lips or the tongue. It may also occur on the floor of the mouth, cheek lining, gingiva (gums), or palate (roof of the mouth). Most oral cancers look very similar under the microscope and are called squamous cell carcinoma. These are malignant and tend to spread rapidly.

Known risk factors

In 2008, in the US alone, about 34,000 individuals will be diagnosed with oral cancer. 66% of the time these will be found as late stage three and four disease. Low public awareness of the disease is a significant factor, but these cancers could be found at early highly survivable stages through a simple, painless, 5 minute examination by a trained medical or dental professional.

All cancers are diseases of the DNA in the cancer cells. Oncogenes are activated as a result of mutation of the DNA. The exact cause is often unknown. Risk factors that predispose a person to oral cancer have been identified in epidemiological studies.

Smoking and other tobacco use are associated with about 75 percent of oral cancer cases, caused by irritation of the mucous membranes of the mouth from smoke and heat of cigarettes, cigars, and pipes. Tobacco contains over 19 known carcinogens, and the combustion of it, and by products from this process, is the primary mode of involvement. Use of chewing tobacco or snuff causes irritation from direct contact with the mucous membranes.

In many Asian cultures chewing betel, paan and Areca is known to be a strong risk factor for developing oral cancer. In India where such practices are common, oral cancer represents up to 40% of all cancers, compared to just 4% in the UK.

Alcohol use is another high-risk activity associated with oral cancer. There is known to be a strong synergistic effect on oral cancer risk when a person is both a heavy smoker and drinker. Their risk is greatly increased compared to a heavy smoker, or a heavy drinker alone.

Some oral cancers begin as leukoplakia a white patch (lesion), red patches, (erythroplakia) or non healing sores that have existed for more than 14 days. In the US oral cancer accounts for about 8 percent of all malignant growths. Men are affected twice as often as women, particularly men older than 40/60. In Indian subcontinent Oral Submucous Fibrosis is very common.This condition is characterized by limited opening of mouth and burning sensation on eating of spicy food. This is a progressive lesion in which the opening of the mouth becomes progressively limited, and later on even normal eating becomes difficult. It occurs almost exclusively in India and Indian communities living abroad.

Human Papilloma Virus, (HPV) particularly version 16 (there are over 120 varieties) is a known risk factor and independent causative factor for oral cancer. (Gilsion et.al.Johns Hopkins) A fast growing segment of those diagnosed does not present with the historic stereotypical demographics. Historically that has been people over 50, blacks over whites 2 to 1, males over females 3 to 1, and 75% of the time people who have used tobacco products or are heavy users of alcohol. This new and rapidly growing sub population between 20 and 50 years old is predominantly non smoking, white, and males slightly outnumber females. Recent research from Johns Hopkins indicates that HPV is the primary risk factor in this new population of oral cancer victims. HPV16 (along with HPV18) is the same virus responsible for the vast majority of all cervical cancers and is the most common sexually transmitted infection in the US. Oral cancer in this group tends to favor the tonsil and tonsillar pillars, base of the tongue, and the oropharnyx. Recent data suggest that individuals that come to the disease from this particular etiology have some slight survival advantage.

 

Symptoms

Skin lesion, lump, or ulcer:

  • On the tongue, lip, or other mouth area
  • Usually small
  • Most often pale colored, may be dark or discolored
  • Early sign may be a white patch (leukoplakia) or a red patch (erythroplakia) on the soft tissues of the mouth
  • Usually painless initially
  • May develop a burning sensation or pain when the tumor is advanced

Additional symptoms that may be associated with this disease:

  • Tongue problems
  • Swallowing difficulty
  • Mouth sores that do not resolve in 14 days
  • Pain and paraesthesia are late symptoms.

 

Signs and tests

An examination of the mouth by the health care provider or dentist shows a visible and/or palpable (can be felt) lesion of the lip, tongue, or other mouth area. As the tumor enlarges, it may become an ulcer and bleed. Speech/talking difficulties, chewing problems, or swallowing difficulties may develop, particularly if the cancer is on the tongue.

While a dentist, physician or other medical professional may suspect a particular lesion is malignant, the only definitive method for determining this is through biopsy and microscopic evaluation of the cells in the removed sample. A tissue biopsy, whether of the tongue or other oral tissues, and microscopic examination of the lesion confirm the diagnosis of oral cancer.

Treatment

Surgical excision (removal) of the tumor is usually recommended if the tumor is small enough, and if surgery is likely to result in a functionally satisfactory result. Radiation therapy is often used in conjunction with surgery, or as the definitive radical treatment, especially if the tumour is inoperable.

Owing to the vital nature of the structures in the head and neck area, surgery for larger cancers is technically demanding. Reconstructive surgery may be required to give an acceptable cosmetic and functional result. Bone grafts and surgical flaps such as the radial forearm flap are used to help rebuild the structures removed during excision of the cancer.

Survival rates for oral cancer depend on the precise site, and the stage of the cancer at diagnosis. Overall, survival is around 50% at five years when all stages of initial diagnosis are considered. Survival rates for stage 1 cancers are 90%, hence the emphasis on early detection to increase survival outcome for patients.

Following treatment, rehabilitation may be necessary to improve movement, chewing, swallowing, and speech. Speech therapists may be involved at this stage.

Chemotherapy is useful in oral cancers when used in combination with other treatment modalities such as radiation therapy. It is seldom used alone as a monotherapy. When cure is unlikely it can also be used to extend life and can be considered palliative but not curative care. Biological agents, such as Cetuximab have recently been shown to be effective in the treatment of squamous cell head and neck cancers, and are likely to have an increasing role in the future management of this condition when used in conjunction with other treatments.

Treatment of oral cancer will usually be by a multidisciplinary team, with treatment professionals from the realms of radiation, surgery, chemotherapy, nutrition, dental professionals, and even psychology all possibly involved with diagnosis, treatment, rehabilitation, and patient care.

Complications

  • Postoperative disfigurement of the face, head and neck
  • Complications of radiation therapy, including dry mouth and difficulty swallowing
  • Other metastasis (spread) of the cancer

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