Aesthetic, Anti-Aging, and regenerative medicine: skin cancer: the cancer next door.
Subject: Regenerative medicine (Evaluation)
Skin cancer (Care and treatment)
Aging (Health aspects)
Cancer (Care and treatment)
Cancer (Physiological aspects)
Author: McQuillan, Sharon
Pub Date: 08/01/2012
Publication: Name: Townsend Letter Publisher: The Townsend Letter Group Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 The Townsend Letter Group ISSN: 1940-5464
Issue: Date: August-Sept, 2012 Source Issue: 349-350
Product: Product Code: 8000432 Cancer Therapy NAICS Code: 621 Ambulatory Health Care Services
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 303012915
Full Text: The skin is the largest organ of the body, and probably the most overlooked in terms of care and maintenance. The skin has many functions, including temperature control, fluid barrier, sensory input, protection, and site of metabolism, and plays a role in immune function. We expose our skin daily to UV radiation, pollutants, and extremes in temperature and weather with little thought to the effects.

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Skin cancer is the most common form of cancer in the US. (1) Each year there are more new cases of skin cancer than incidence of cancers of the breast, prostate, lung, and colon combined. (2) It is estimated that over 1 million new cases will occur annually. The annual rates of all forms of skin cancer are increasing each year, constituting a growing public concern. It is has also been estimated that nearly half of all Americans who live to age 65 will develop skin cancer at least once. (3)

Cancer occurs when normal cells undergo a transformation wherein they multiply and grow abnormally. The most common warning sign of skin cancer is a change in the appearance of the skin, such as a new growth, a sore that will not heal, or a change in an existing skin growth.

There are many types of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. The most common forms of skin cancer are basal cell carcinoma and squamous cell carcinoma, and are often referred to as nonmelanoma skin cancers. Melanoma is the most serious form of skin cancer due to its ability to mestastasize (or spread) throughout the body.

There are many risk factors contributing to the causes of skin cancer. The most frequent cause of skin cancer is ultraviolet light exposure. The following are also other important risk factors to consider:

* immunosuppression

* exposure to chemicals, such as arsenic, tar hydrocarbons, oils, soot

* having fair skin that freckles or sunburns easily

* having light colored hair and/or light colored eyes

* genetic disorders affecting skin pigment

* people who have experienced a severe sunburn early in life

* family history of skin cancer

* use of tanning beds

Precancerous Skin Conditions

Many skin cancers start as precancerous lesions. These precancerous lesions are changes in the skin that are not cancerous but have the potential of becoming cancerous over time. There are two basic types of precancerous lesions associated with skin cancer: actinic keratoses and dysplastic nevi. Actinic keratoses refers to scaly or crusty growths caused by the sun's damaging ultraviolet rays. Most often, actinic keratoses appear as multiple, discrete, flat or elevated keratotic lesions. They typically are 3 to 10 mm in diameter and possess an erythematous base covered by scale. (7) Actinic keratoses if not treated can become basal cell or squamous cell carcinoma.

Actinic keratoses often appear on bald scalps, face, ears, lips, backs of the hands, forearms, or any other areas exposed to the sun. Actinic keratosis is the second most frequent reason for patients to visit a physician. (4) Actinic keratosis is the most common precancerous lesion, affecting more than 58 million Americans. (5) An actinic keratosis can follow one of the following paths: regression, no change, or progression to squamous or basal cell carcinoma. Criscione et al. examined the progression of actinic keratoses to squamous cell carcinoma and basal cell carcinoma. The study examined 7784 actinic keratoses in high-risk populations and found that nearly 65% of primary squamous cell carcinomas and 36% of basal cell carcinomas arise from clinically diagnosed actinic keratoses. (6)

There are a multitude of treatment options for actinic keratoses. These include topical medications, cryosurgery, chemical peels, carbon dioxide or erbium YAG laser treatment, and photodynamic therapy. Successful topical medications include 5-fluorouracil (5-FU), imiquimod 5% cream, diclofenac, and ingenol mebutate. A highly effective treatment for actinic keratoses on the face and scalp is photodynamic therapy (PDT). During PDT, a photosensitizing agent, 5-aminolevulinic acid (5-ALA), is applied to the affected areas. The medicated area is exposed to blue light, which activates the 5-ALA, selectively destroying the actinic keratoses, causing minimal damage to the surrounding skin.

Dysplastic nevi refer to abnormal or atypical moles. While dysplastic nevi are not cancerous themselves, they should be closely observed for changes, as they can develop into melanoma over time. Dysplastic nevi can be inherited or sporadic. It is suggested that the ultraviolet light is an initiator and promoter in the transformation of melanocytes into atypical moles or melanoma. The International Agency for Research on Cancer raised the classification of UV-emitting tanning devices from "probable carcinogenic to humans" to "carcinogenic to humans." (8) Additionally, it has been determined that the use of UV tanning beds before age 30 increases the risk of melanoma by 75%. (9)

Melanoma can develop from atypical moles. The risk of an atypical mole becoming a melanoma is estimated to be 1 in 200,000. Cutaneous melanomas are associated with precancerous lesions at least 50% of the time in patients younger than 30 years. (10) Patients with many atypical moles (> 50) are at a higher risk of developing melanoma than those with a few atypical moles. The risk increases when there is a family history of melanoma. (11)

Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most common form of skin cancer with an estimated 2.8 million cases diagnosed annually in the US. (12) Basal cell carcinomas are rarely fatal but, if allowed to grow, can be disfiguring. Basal cell carcinoma accounts for 80% of all skin cancers diagnosed; however, it is the least likely of skin cancers to metastasize.

Basal cell carcinoma typically appears on sun-exposed skin, most frequently on the face or scalp (the nose in particular). Basal cell carcinoma usually presents as a raised, smooth, pearly bump on the sun-exposed skin of the head, neck, or shoulders. Small blood vessels may be visible within the lesion, with ulcerations developing frequently. Oftentimes a basal cell carcinoma is mistaken for a sore that will not heal. The average tumor size ranges from a few millimeters to several centimeters in diameter.

Basal cell carcinoma is diagnosed by removing all or a part of the growth by scraping a small piece of the skin under local anesthesia, known as a shave biopsy. The skin sample is then checked for malignant cells. The prognosis for patients with basal cell carcinoma is excellent, with a 100% survival rate for BCCs that have not spread to other locations. Although basal cell carcinoma is considered malignant, it rarely metastasizes.

Basal cell carcinoma is successfully treated using a variety of treatment modalities. The goal of BCC treatment is to remove or destroy the cancerous lesion completely while leaving as small a scar as possible. Treatment options include curettage and dessication, surgical excision, radiation therapy, cryosurgery, Mohs micrographic surgery, and topical medications. Curettage and desiccation involves the removal of the tumor using a spoonlike instrument followed by the application of electric current to control bleeding and destroy the remaining cancer cells. Mohs micrographic surgery refers to a technique wherein the surgeon removes the lesion a small piece at a time, while examining the excised tissue under a microscope. This allows for the removal of as little healthy tissue as possible and enjoys a success rate of 98%. Topical medications used to treat basal cell carcinoma include 5-fluorouracil (5-FU) and imiquimod.

Patients with basal cell carcinoma have a 35% chance of developing another lesion within three years and a 50% chance of developing another BCC within five years. Regular skin screenings are recommended to avoid recurrence. (13), (14) A recurrence of basal cell carcinoma is likely if one of the following conditions exists:

* ulcerations that does not heal

* tissue destruction

* scar that becomes red, scaled, or crusted, or enlarges with large telangiectasia

* scar that enlarges slowly over a period of months

* development of a papule or nodule within a scar

Lesions with any of these symptoms should be biopsied immediately.

Squamous Cell Carcinoma

Squamous cell carcinoma (SCC) is the second most common form of nonmelanoma skin cancer and accounts for 20% of skin cancer malignancies, and 90% of all cancers of the head and neck. (15) Unlike basal cell carcinoma, squamous cell carcinomas are associated with a risk of metastasis. Despite increased public awareness, the incidence of SCC continues to rise. Speculated causes for the increased incidence of skin cancer include an aging population, improved detection methods, increased use of tanning beds, and environmental factors.

Squamous cell carcinoma begins in the squamous cells, which are thin, flat cells that resemble fish scales under a microscope. Squamous cell carcinoma presents as a well-defined, red, scaling, thickened patch of sunexposed skin. Like basal cell carcinoma, squamous cell carcinomas may ulcerate and bleed. The behavior of squamous cell carcinoma depends on its site of origin, with each anatomical site possessing its own spread pattern and prognosis. Other forms of squamous cell carcinoma include keratoacanthoma, actinic chelitis, and Bowen's disease. Keratoacanthama refers to a rapidly growing form of SCC that forms a mound with a central crater. Actinic chelitis is an SCC involving the lower lip that presents with redness and scale and blurs the border of the lip and adjacent skin. Bowen's disease, also known as squamous cell carcinoma in situ, refers to SCC that presents as scaly patches on sun-exposed parts of the trunk and extremities.

Squamous cell carcinoma is characterized by the malignant transformation of epidermal keratinocytes. People with actinic keratoses have atypical squamous cells in one-third to one-half of the epidermis, and those with numerous actinic keratoses are at increased risk for developing SCC. (16) Those patients with Bowen's disease have atypical keratinocytes throughout the entire epidermis. Exposure to cancer-promoting stressors determines the risk of developing squamous cell carcinoma. These risk factors include exposure to ultraviolet radiation, immunosuppression, tobacco and alcohol use, age, family and/or genetic predisposition, nutritional status, and exposure to industrial products, heavy metals, and radiation. (17)

Squamous cell carcinoma is diagnosed by removing a small sample of skin under local anesthesia using a circular punch blade, known as a punch biopsy. The skin sample is then checked for malignant cells. The prognosis for patients with squamous cell carcinoma is generally good when tumors are adequately treated with an overall five-year survival rate at >90%. Various mortality rates have been reported with ranges of 4% to 8%. The outcome of patients with advanced-stage SCC is considerably worse. For patients with lymph node metastasis, the five-year survival rate is lower, estimated at 25% to 45%. (18)

Squamous cell carcinoma is successfully treated using a variety of modalities. The goal of SCC treatment is to remove or destroy the cancerous lesion completely while leaving as small of a scar as possible. Treatment options include curettage and desiccation, surgical excision, radiation therapy, cryosurgery, Mohs micrographic surgery, and topical medications.

Melanoma

Melanoma accounts for less than 5% of skin cancer cases but causes more than 75% of skin cancer deaths. An estimated 123,590 new cases of melanoma were diagnosed in the US in 2011--53,360 noninvasive and 70,230 invasive, with nearly 8790 resulting in death. (19) The incidence of melanoma continues to rise at a rate faster than that of the seven most common cancers connbined. (20)

Most melanomas occur in the face (47%). The remainder are found on the neck (29%), the scalp (14%), and the ears (10%). The majority of malignant melanomas are brown to black pigmented lesions, but they can also present as skin-colored, pink, red, purple, blue, or white. Melanoma originates in the melanocytes in the basal layer of the epidermis. Warning signs of melanoma include a change in size, shape, color, or elevation of a mole. Other warning signs include the appearance of a new mole during adulthood, or a new pain, itching, ulceration, or bleeding experienced with an existing mole. The American Cancer Society has developed the ABCDEs of moles, a basic guideline of early melanoma warning signs. Based on this guideline, melanoma should be suspected in any skin lesion that is (A)symmetrical, has an irregular (B)order, is dark in (C)olor, larger than 6 mm in (D)iameter, or is (E)levated. Another melanoma recognition tool is the "Ugly Duckling Sign." The Ugly Duckling concept refers to the observation that moles in the same patient tend to resemble one another and that malignant melanoma usually deviates from this pattern. (21)

There are three main types of cutaneous malignant melanoma: superficial spreading melanoma, lentigo maligna, and nodular lesions. Superficial spreading melanoma is the most common type, accounting for about 70% of all cases. There are two growth phases associated with superficial spreading melanoma: the initial radial growth phase, where growth is confined to the epidermis; and the vertical phase, where the melanocyte growth invades the papillary and reticular dermis. Lentigo meligna comprise about 2O% of head and neck melanomas. They are typically flat with irregular borders and are commonly found on the face, neck, or extremities. Nodular melanoma are aggressive lesions that are invasive from their development onset.

Melanoma is diagnosed by removing a small sample under local anesthesia known as an excisional biopsy, which focuses on obtaining a full-thickness biopsy. The skin sample is then checked for malignant cells. The prognosis of cutaneous melanoma depends on the thickness of the lesion. The currently accepted treatments for malignant melanoma are excision and Mohs surgery. In general, the margin of excision for successful melanoma treatment should be about 10 times as wide as the deepest penetration of the tumor. (22) In their review of 625 patients who underwent Mohs surgery for malignant melanoma, Bricca et al. showed that the five-year survival and metastatic rates for Mohs surgery were equivalent or better than rates of local excision. (23)

Skin Cancer Prevention

Successful skin cancer treatment directly correlates with early detection as well as prevention measures. While there are some risk factors that are not controllable, there are many that can be limited or eliminated altogether. The two most effective prevention measures are sun avoidance and skin self-examination.

Ultraviolet radiation is the main cause of skin cancer. Sun avoidance techniques include:

* limiting sun exposure

* avoiding the sun's most intense rays between 10 am and 2 pm

* wearing broad-brimmed hats and protective clothing while outdoors

* regularly using a waterproof sunscreen with UVA protection and SPF 30 or higher

* avoiding tanning beds

Skin self-examinations performed monthly improve the chance of finding abnormal skin lesions early, before it has done significant damage. Performing an exam monthly assists in the recognition of new or changing skin conditions. Self-exams should be performed after showering and should be conducted in a well-lit room and include the use of full-length and hand-held mirrors. Use the mirrors to fully look at all parts of the body, including the scalp. Learn where your moles, birthmarks, and blemishes are and what they look like. Every time an exam is performed, these areas should be checked for changes in size, texture, and color, as well as for signs of ulceration and bleeding. Any noticeable change in skin condition should prompt follow-up with a primary care provider.

Although the number of skin cancers in the US continues to rise, early detection has made them easier to treat, resulting in decreased death rates. When treated successfully, the cure rate for basal cell carcinoma and squamous cell carcinoma approaches 95%. In many cases, the outcome of malignant melanoma depends on tumor thickness, with a majority of thin lesions cured by surgery alone. Public awareness is vital to facilitate the early detection and treatment of skin cancer. Primary care physicians should make a point of performing a full-body skin examination for skin cancer and be equipped to biopsy suspicious lesions as well as counsel their patients in the importance of self-examination.

Physicians interested in expanding their practices to include simple dermatological procedures are invited to attend the American Academy of Anti-Aging Medicine's Dermatology for the Anti-Aging Physician course, which is being held December 13-15, 2012, at the Venetian Casino and Resort in Las Vegas, Nevada. For more information, please contact the American Academy of Anti-Aging Medicine (A4M) at www.a4m.com or 888-997-0112.

Notes

(1.) Rogers HW, Weinstock MA, Harris AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States. Arch Dermatol. 2010;146(3):283-287.

(2.) American Cancer Society. Cancer facts and figures 2011. www.cancer.org.

(3.) Sun Protection. Cancer trends progress report--2009/2010 update. National Cancer Institute. Available at www.cancer.gov.

(4.) Feldman SR, Fleischer AB Jr, McConnel RC. Most common dermatologic problems identified by internists, 1990-1994. Arch Intern Med. 1998;158(7): 726-730.

(5.) Lewen Group Inc. The burden of skin diseases 2005. Society for Investigative Dermatology and American Academy of Dermatology Association, 2005.

(6.) Criscione VD, Weinstock MA, Naylor MF, Luque C, Eide MJ, Bingham SF. Actinic keratoses natural history and risk of malignant transformation in the Veteran Affairs Tropical Tretinoin Chemoprevention Trial. Cancer. 2009;115:2523-2530.

(7.) Anwar J, Wrone Da, Kimya-Asadi A, Alam M. The development of actinic keratoses into invasive squamous cell carcinoma: evidence and evolving classification schemes. Clin Dermatol. 2004;22(3):189-196.

(8.) IARC Working Group. Special report: Policy. A review of human carcinogens--Part D: radiation. Lancet. 2008-2009;10:751-752.

(9.) IARC Working Group. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. Int 1 Cancer. 2006;120:1 116-1122.

(10.) NIH Consensus Conference. Diagnosis and treatment of early melanoma. LAMA. 1992;268(10):1314-1319.

(11.) Marinkovic M, Janjic K, Nikolic J. Dysplastic nevus--a risk factor of developing skin melanoma clinical and epidemiological study with retrospective review of I iterature. Med Pregl. 2011;64(5-6):315-318.

(12.) Rogers H. Your new study of nonmelanoma skin cancers. E-mail to Skin Cancer Foundation. April 1,2010.

(13.) Marcil I, Stern RS. Risk of developing s subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and meta-analysis. Arch Dermatol. 2000;136(12):1524-1530.

(14.) McLoore NM, Tolland J, Walsh M, et al. Follow-up of basal cell carcinomas: as audit of current practice. J Ear Acad Dermatol Venereol. 2006;20(6):698-701.

(15.) Johnson TM, Rowe DE, Nelson BR, Swanson NA. Squamous cell carcinoma of the skin. J Am Acad Dermatol. 1992;26(3 Pt. 2):467-484.

(16.) Newman MD, Weinberg JM. Topical therapy in the treatment of actinic keratosis and basal cell carcinoma. Cutis. 2007;79(4 Suppl):18-28.

(17.) Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. May an Proc. 2008;83(4):489-501.

(18.) Clayman CL, Lee JJ, Holsinger FC, et al. Mortality risk from squamous cell skin cancer. J Clin Oncol. 2005;23(4):759-765.

(19.) American Cancer Society. Melanoma skin cancer overview. Available at www.cancer.org.

(20.) Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA. Increasing burden of melanoma in the United States. I Invest Dermatol. 2009;129(7):1 666-1 674.

(21.) Grob JJ, Bonerandi JJ. The "ugly duckling" sign: identification of the common characteristics of nevi in an individual as a basis for melanoma screening. Arch Dermatol. 1998; 134(1):103-104.

(22.) Cohn-Cedermark G, Rutgvist LE, Andersson R, Breivald M, Ingvar C, Johansson H. Long term results of a randomized study by the Swedish Melanoma Study Group on a 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm. Cancer. 2000;89(7):14951501

(23.) Bricca GM et al. Cutaneous head and neck melanoma treated with Mohs micrograph ic surgery. J Am Acad Dermatol. 2005;52(1):92-100.

by Sharon McQuillan, MD

Sharon McQuillan, MD, is a board-certified physician who specializes in aesthetic, anti-aging, and regenerative medicine. She founded the Ageless Aesthetic Institute, a level 4 ACCME-accredited aesthetic training program for medical professionals, in order to standardize and elevate the practice of aesthetic medicine. Dr. McQuillan has educated thousands of medical professionals in the art and science of aesthetic and anti-aging treatments for over a decade. She lectures internationally on aesthetic and regenerative medicine for many organizations and is the medical director of the Aesthetic Fellowship, hosted by the American Academy of Anti-Aging Medicine. Dr. McQuillan owns and operates the Ageless Institute in Aventura, Florida, offering anti-aging, aesthetic, regenerative, and weight loss treatments. In 2009, Dr. McQuillan formed the Ageless Regenerative Institute in conjunction with a team of experts in stem cell therapies. This team has developed an approved method and protocol for the harvesting and isolation of adipose-derived stem cells for autologous transplantation.
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