|
|
|
Overview |
|
|
Definition |
|
Skin cancers are the most common form of cancer. They are generally
associated with sun exposure; other causes include X-ray or radium burns and
arsenic ingestion. Most skin cancers are curable, but some progress rapidly and
are quite deadly. In the U.S., 700,000 people develop skin cancer each year.
Types of skin cancer include the following:
- Basal cell carcinoma: The most common form of skin cancer. A
superficial eroding ulcer, deriving from and resembling epidermal basal cells.
About 75% of all skin cancers are basal cell carcinoma.
- Squamous cell carcinoma: Second most common type. Arise from
keratinocytes of the epithelium. May develop in normal tissue or preexisting
actinic keratosis, leukoplakia, or burn scar. About 20% of all skin cancers are
squamous cell carcinoma.
- Malignant melanoma: A neoplasm developing from pigmented moles or
melanocytes in normal skin. May spread rapidly; dangerous if not promptly
detected and treated. More than 45,000 new cases occur every year in the U.S.,
causing more than 7,000 deaths, and incidence is rapidly increasing.
- Paget's disease: A rare type. Generally appears as unilateral
dermatitis of the nipple, representing extension of underlying mammary duct
carcinoma. May also appear in groin or perianal area, where it is thought to
arise from apocrine glands.
- Kaposi's sarcoma (KS): Multicentric vascular neoplasm caused by human
herpesvirus type 8 (HHV-8). Aggressive AIDS-related form now endemic, seen in
about one-third of AIDS cases. Previous to the AIDS epidemic, KS was most
commonly seen in its indolent form in elderly men of Italian or Jewish
ancestry.
|

|
|
Etiology |
|
The primary cause of skin cancer is cumulative ultraviolet (UV) radiation
from the sun. UV exposure is thought to induce a mutation in the tumor
suppressor gene p53. KS, as mentioned, is associated with
HHV-8. |

|
|
Risk Factors |
|
- Skin pigmentation: Light-skinned people are most
susceptible
- Outdoor activities: Skin cancer is more common in outdoor workers,
outdoor recreational enthusiasts, sunbathers, etc.
- History of acute sunburn
- Family history
- Large congenital melanocytic nevus
- Actinic keratosis
- HIV – for KS
specifically
|

|
|
Signs and Symptoms |
|
One or more lesions manifesting:
- Failure to resolve
- Enlargement
- Irregular or notched borders
- Shiny or crusted surface
- Change in color or variegated colors
- Bleeding
|

|
|
Differential
Diagnosis |
|
Care must be taken to distinguish the various forms of skin cancer from one
another. Other conditions to rule out include the following:
- Dermatitis
- Benign nevus
- Hematoma
- Venous lake
- Pyogenic granuloma
- Keratoacanthoma
- Actinic keratosis
- Verruca vulgaris
- Seborrheic keratosis
- Dermatofibroma
|

|
|
Diagnosis |
|
|
Physical Examination |
|
- Basal cell carcinoma: Usually occurs in sun-exposed areas. Often
begins as a shiny papule that slowly enlarges. After months or years, the lesion
may have a pearly border, prominent engorged surface vessels, and a central
ulcer. Crusting or bleeding may be apparent.
- Squamous cell carcinoma: Most common in sun-exposed areas. Often
begins as red papule or scaly plaque. May become nodular. In some patients, the
bulk of the lesion is below the level of the surrounding skin.
- Malignant melanoma: May occur anywhere on the body; particularly
common on women's legs and men's torsos. Appearance variable. Signs of malignant
transformation include change in size, color, surface characteristics,
consistency or shape, spread of red, white, or blue pigmentation to surrounding
normal skin, signs of inflammation (bleeding, ulceration, itching, pain) in
surrounding skin.
- Paget's disease: Resembles dermatitis of nipple, groin, or perianal
area, but lesion is sharply marginated, unilateral, and unresponsive to topical
therapy.
- KS: Multiple barely elevated purple, pink, or red papules, or round or
oval brown or purple plaques. In AIDS-related form, appears first on upper body
or mucosa, and may bleed. In indolent form, usually appears on toes or legs.
|

|
|
Pathology/Pathophysiology |
|
Biopsy (excisional for small lesions, incisional for larger ones) with
histological examination is essential. May be done in step sections to determine
thickness. |

|
|
Other Diagnostic
Procedures |
|
The dermatoscope, a modified ophthalmoscope used with immersion oil, is
helpful for close examination of pigmented
lesions. |

|
|
Treatment Options |
|
|
Treatment Strategy |
|
Skin cancer may be treated by curettage and electrodesiccation, surgical
excision, cryotherapy, or occasionally X-ray therapy. The appropriate choice is
based on the type, size, and histologic findings. |

|
|
Drug Therapies |
|
Thick malignant melanoma as well as metastasized melanoma may be treated with
chemotherapy. Dacarbazine is typically used, often in combination with
nitrosoureas such as lomustine and carmustine. Immunotherapy for melanoma is
investigational.
Single-agent or combination chemotherapy (e.g., with vincristine,
vinblastine, doxorubicin, bleomycin, and etoposide) is used in cases of
AIDS-related KS. Intralesional injection of vinblastine has also been reported
effective in some cases of AIDS-related KS. Treatment with interferon-alpha may
slow progression of early lesions or cure others. However, treatment of KS does
not generally prolong life among HIV+ patients because mortality is primarily
determined by opportunistic infections. |

|
|
Surgical Procedures |
|
- Large cancers, recurrences, and lesions with poorly defined borders
are excised under microscopic control (Mohs' surgery). Small, superficial
lesions may be removed by surgical excision. Other treatments such as
cryotherapy may be suitable for patients for whom surgery is contraindicated.
- For melanoma, excision requires a 1-cm lateral tumor-free margin for
lesions less than 1 mm thick. Thicker lesions may require more extensive surgery
along with sentinel node biopsy.
- Mastectomy is generally indicated for Paget's disease of the nipple.
- For indolent, superficial lesions of KS without AIDS, cryosurgery,
electrocoagulation, or electron beam radiation is sufficient to flatten or fade
most lesions.
|

|
|
Complementary and Alternative
Therapies |
|
Certain nutritional approaches and therapeutic diets may positively affect
the prevention and treatment of skin cancer. In a study of 215 patients with
melanoma, 9.6% of patients with stage I disease (primary tumor only) reported
the use of CAM therapies, while 61.1% of patients with locoregional or distant
metastasis were currently using CAM therapies or had used them in the past. CAM
therapy for the purpose of this trial was defined as homeopathy,
immune-enhancing therapies (e.g., mistletoe or thymus extracts), spiritual
therapies, mind-body techniques (e.g., imagery and hypnosis), and botanical
therapies (e.g., herbs and Bach flowers, the latter being a type of homeopathic
preparation of herbs). The purpose of the study was to investigate attitudes of
patients with melanoma toward alternative treatments, their compliance with
conventional treatments, their social support networks, and their methods of
coping.
One of the conclusions of the study was that patients using alternative
therapies do so, in part, to be proactive and to cope with feelings of
helplessness and anxiety. According to the researchers, two-thirds of patients
interested in CAM were desirous of more counseling and emotional support from
their dermatologists. Half of the patients were also interested in receiving
psychotherapy (Sollner et al. 1997). While many CAM treatments have not been
subjected to rigorous scientific investigation, studies suggest that these
treatments may be useful adjuncts for various dermatologic conditions; again,
this needs further investigation (Sollner et al. 1997; Eisenberg
1997). |

|
|
Nutrition |
|
Epidemiologic studies evaluating diet and skin cancer risk often have
conflicting results and do not always make a distinction between closely related
nutrients (e.g., vitamin A and beta-carotene) or between the macronutrient and
micronutrient component (e.g., total fats and specific fatty acids). In
addition, making a definitive conclusion regarding the influence of nutrition on
skin cancer is complicated by the prolonged latent period between UV exposure
and the development of skin cancer. Although randomized, controlled trials may
help clarify nutritional benefits, factors such as the trial period, dosage,
nutrient preparation, and dietary intake of test nutrient by controls may
confound results (Greenberg et al. 1990; Manson et al. 1991; Morrill 1991;
Prince 1991).
A prospective study of 43,217 male participants of the Health Professionals
Follow-Up Study assessed the role of specific nutrients in the prevention of
basal cell carcinoma (BCC) over an 8-year time period. Participants completed a
131-item semi-quantitative food-frequency questionnaire. Follow-up took place
every 2 years, in 1988, 1990, 1992, and 1994, at which time men were asked to
report diagnosis of BCC during the previous 2 years. An inverse association was
found between monounsaturated fat intake and BCC risk. Unexpectedly, low folic
acid intake was associated with a lower risk of BCC. There was no protective
effect for retinol, carotene, or vitamins C, D, or E (van Dam et al. 2000).
Similarly, a randomized, double-blind, placebo-controlled primary prevention
trial showed no benefit of beta-carotene on the development of a nonmelanoma
skin cancer (NMSC), including BCC and squamous cell carcinoma (SCC). Healthy
male physicians (N = 22,071) ages 40 to 84 years were enrolled in this 12-year
study and were assigned to beta-carotene treatment (N = 11,036) or placebo (N =
11,035). At the end of the study, no benefit or harm was discerned from
beta-carotene supplementation (Frieling et al. 2000).
Earlier, smaller scale studies have drawn different conclusions from the two
trials described above; the question has been raised, therefore, whether smaller
studies are easier to control in terms of confounding factors and potential
biases including the diet of control subjects, which can be influenced by
cultural norms. Societal dietary habits have changed from the early and
mid-1990s. A randomized, double-blind, placebo-controlled trial of 2,297
subjects with moderate risk of developing NMSC revealed a protective effect for
SCC when retinol was given p.o. at 25,000 IU per day for up to 5 years (median
time of study, 3.8 years) (Moon et al. 1997). In addition, a case-control study
of 88 males with NMSC demonstrated an inverse relationship between a high intake
of fish, beans, lentils, peas, carrots, Swiss chard, pumpkin, cruciferous
vegetables, and beta-carotene and vitamin C-containing vegetables and the
development of both BCC and SCC. In this study, the mean level of serum
beta-carotene and vitamin A was significantly lower in both BCC and SCC cases
compared with those without skin cancer (Kune et al. 1992). A case-control study
of 46 BCC patients with 46 controls matched for age, gender, and skin type were
assessed for lifestyle and other risk factors. Investigators found that BCC
patients consumed significantly less protein and more fat than did controls. BCC
patients also tended to have a lower intake of beta-carotene, vitamin C,
selenium, and fiber as compared with controls (Sahl et al. 1995). Lignans, a
substance present in dietary sources such as soybeans and flaxseed, may possess
anticancer properties. A mouse model demonstrated the efficacy of flaxseed in
reducing pulmonary metastasis of melanoma cells intravenously injected into the
mice as well as inhibiting the growth of the tumors (Yan et al. 1998).
A randomized, double-blind, placebo-controlled test of selenium
supplementation (200 mcg high-selenium yeast) compared 653 high-risk patients
with prior history of NMSC to a placebo group (659 patients) receiving
low-selenium yeast supplementation. The study showed no differences in the
development of new BCC/SCC in the two groups. However, selenium was found to
reduce total cancer incidence and mortality, and to be protective against three
leading non-skin cancers, namely, lung, prostate, and colon cancers (Combs et
al. 1997). An animal model has shown selenomethionine to reduce experimental
metastasis of melanoma cells in mice and to inhibit the growth of metastatic
tumors in the lungs. The authors suggest that selenomethionine is an active form
of selenium; it may prove appropriate for use in melanoma (Yan et al. 1999).
Experimental animal studies suggest potential innovative applications of
nutrients. Topical nicotinamide, for example, has been shown to prevent systemic
immunosuppression and skin tumorigenesis induced by UVB irradiation in mice
(Gensler 1997).
Therapeutic diets may also be of benefit in the treatment of skin cancer. A
retrospective investigation of 5-year melanoma survival rates in patients
treated with Gerson's diet therapy revealed significantly better outcomes than
for patients reported by other centers (e.g., American Cancer Society). While
the Gerson diet is individualized for each patient, common components are
low-salt and low-fat intakes, with highly concentrated nutrients given through
13 hourly feedings of raw fruit and vegetable juices. About half of the patients
in the study had also received 24 ounces of raw veal liver and carrot juice
daily; raw veal liver was subsequently discontinued in 1987 because of repeated
instances of bacterial contamination. Calories are restricted in the Gerson diet
and metabolism is accelerated by supplemental iodine or exercise. Niacin,
potassium salts, and crude liver extract with injectable vitamin B12
are given to enhance cellular energy production. Protein is initially reduced,
then restored after at least 6 weeks in the form of nonfat cultured dairy
products. Castor oil is administered every other day for weeks, and coffee
enemas given as frequently as every 4 hours over a 24-hour period; these methods
are believed to relieve pain and improve nutritional outcome. The psychosocial
influence of the Gerson treatment has not yet been evaluated but may well be a
factor, as family/community involvement is strongly encouraged and supported,
even during hospitalization (Hildenbrand et al. 1995). |

|
|
Herbs |
|
Many herbs and herbal combinations have been recommended clinically by
naturopathic doctors and botanists for cancer treatment and prevention.
Commercial herbal mixes in the form of teas or formulas containing herbs such as
sheep sorrel (Rumex acetosella), burdock root (Arctium lappa),
slippery elm inner bark (Ulmus fulva), turkey rhubarb (Rheum
palmatum), red clover (Trifolium pratense), and watercress
(Nasturtium officinale) may be helpful. A usual dose is one cup tea bid,
or 2 tbs formula bid for six months. Evaluation and appropriate prescription
should be performed by a trained and licensed herbalist for supportive care of
cancer in general and skin cancer specifically.
Green tea (Camellia sinensis) contains polyphenol constituents,
primarily epigallocatechin gallate (EGCG), with potent antioxidant activity.
Review of the literature reveals that EGCG and green tea polyphenols (GTP) have
demonstrated inhibition of skin tumor initiation, promotion, and progression.
Mechanisms of action include inhibition of DNA binding by carcinogens,
scavenging of initiators, inhibition of cytochrome P-450 enzymes, inhibition of
ornithine decarboxylase activity, maintenance of intercellular communication,
and inhibition of arachidonic acid metabolism (Picard 1996). A more recent
review of green tea confirms that the polyphenol constituents have
anti-inflammatory and anticarcinogenic properties that may significantly improve
various skin disorders (Katiyar et al. 2000).
For KS, some naturopaths recommend a paste made from lemon balm (Melissa
officinalis) cream, several drops of Hoxsey-like formula, and powdered
tumeric applied to lesions bid; can substitute licorice root cream if lemon balm
is unavailable.
In a Chinese study examining in vivo and in vitro natural killer cells (NK)
activities in mice, an ethanol extract of Cordyceps sinensis, an herbal
tonic, was shown to be effective against melanoma by promoting NK activity and
inhibiting pulmonary tumor formation in mice (Xu et al. 1992).
|

|
|
Homeopathy |
|
Homeopathy is a popular CAM therapy sought by patients with melanoma and
warrants further scientific investigation to determine efficacy (Sollner et al.
1997). |

|
|
Acupuncture |
|
No clinical studies are known to have been reported in the literature on the
use of acupuncture for patients specifically with skin
cancer. |

|
|
Massage |
|
Massage is thought to be contraindicated in the case of skin
cancer. |

|
|
Patient Monitoring |
|
Periodic dermatologic monitoring is useful to check for
recurrence. |

|
|
Other
Considerations |
|
|
Prevention |
|
- Skin cancer screening: periodic 2- to 3-minute visual inspection of
entire skin surface including the scalp, hands, and feet by a healthcare
practitioner on at least an annual basis
- Sun avoidance
- Sun-protective measures: clothing, hats, sunscreens
|

|
|
Complications/Sequelae |
|
- Basal cell carcinoma: Rarely metastasizes, but may invade surrounding
tissue. About 5% recur.
- Squamous cell carcinoma: Lesions on sun-exposed skin do not often
metastasize; however, one-third of lingual and mucosal lesions have metastasized
prior to diagnosis.
- Malignant melanoma: May spread rapidly via lymphatics and blood
vessels.
- Paget's disease: Underlying carcinoma should be sought.
- KS: Disseminated lymph node and visceral involvement occurs in 5% to
10% of patients with the indolent form and is more common in AIDS-related KS.
|

|
|
Prognosis |
|
- Basal cell carcinoma: Generally excellent; metastasis is unlikely.
About 5% recurrence rate. Rare fatalities occur due to invasion of carcinoma
into underlying vital structures or orifices.
- Squamous cell carcinoma: Prognosis for small lesions removed early and
completely is excellent. Mucosal lesions more problematic. Closely monitor
treatment and follow-up since metastasis is more likely than with basal cell
carcinoma.
- Malignant melanoma: Survival related to thickness of lesion at time of
diagnosis and treatment. Five-year cure rate is almost 100% for very superficial
lesions removed early. However, such patients may be at higher risk for
subsequent primary melanomas. Mucosal or thick lesions have a poor prognosis, as
does metastatic disease.
- Paget's disease: Prognosis depends on underlying
carcinoma.
- KS: Prognosis is good for indolent superficial lesions. Course of
AIDS-related KS depends on level of immunosuppression.
|

|
|
References |
|
Abdaimi KE, Papavasiliou V, Rabbani SA, Rhim JS, Goltzman D, Kremer R.
Reversal of hypercalcemia with the vitamin D analogue EB1089 in a human model of
squamous cancer. Cancer Res. 1999;59:3325-3328.
Bain C, Green A, Siskind V, Alexander J, Harvey P. Diet and melanoma: an
exploratory case-control study. Ann Epidemiol. 1993;3:235-238.
Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy.
Whitehouse Station, NJ: Merck & Co.; 1999:842-849.
Birt DF, Pelling JC, Nair S, Lepley D. Diet intervention for modifying cancer
risk. Prog Clin Bio Res. 1996;395:223-234.
Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic
Guide to Herbal Medicines. Boston, Mass: Integrative Medicine
Communications; 1998:107,169-170,491.
Boik J. Cancer & Natural Medicine: A Texbook of Basic Science and
Clinical Research. Princeton, Minn: Oregon Medical Press; 1996:64,
66,67,76.
Brinker F. The Hoxsey treatment: cancer quackery or effective physiological
adjuvant? J Naturopathic Med. 1996;6(1):9-23.
Combs GF Jr, Clark LC, Turnbull BW. Reduction of cancer risk with an oral
supplement of selenium. Biomed Environ Sci. 1997;10(2-3):227-234.
Eisenberg D. Alternative therapies for cutaneous disorders. Arch
Dermatol. 1997;133(3):379-380.
Ferrini RL, Hill LM. American College of Preventive Medicine practice policy
statement: screening for skin cancer. Am J Prev Med. 1998;14:80-86.
Frieling UM, Schaumberg DA, Kupper TS, Muntwyler J, Hennekens CH. A
randomized, 12-year primary-prevention trial of beta carotene supplementation
for nonmelanoma skin cancer in the Physicians' Health Study. Arch
Dermatol. 2000;136(2):179-184.
Gensler HL. Prevention of photoimmunosuppression and photocarcinogenesis by
topical nicotinamide. Nutr Cancer. 1997;29(2):157-162.
Greenberg ER, Baron JA, Stukel TA, et al. A clinical trial of beta carotene
to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer
Prevention Study Group. N Engl J Med. 1990;323(12):825-827,789-795.
Hildenbrand GLG, Hildenbrand LC, Bradford K, Cavin SW. Five-year survival
rates of melanoma patients treated by diet therapy after the manner of Gerson: a
retrospective review. Altern Ther Health Med. 1995;1(4):29-37.
Katiyar SK, Ahmad N, Mukhtar H. Green tea and skin. Arch Dermatol.
2000;136(8):989-94.
Kirkpatrick CS, White E, Lee JA. Case-control study of malignant melanoma in
Washington State. II. Diet, alcohol, and obesity. Am J Epidemiol.
1994;139:869-880.
Kune GA, Bannerman S, Field B, et al. Diet, alcohol, smoking, serum
beta-carotene, and vitamin A in male nonmelanocytic skin cancer patients and
controls. Nutr Cancer. 1992;18:237-244.
Leber K, et al. Common skin cancers in the United States: a practical guide
for diagnosis and treatment. Nurse Pract Forum. 1999;10:106-112.
Lefell DJ. The scientific basis of skin cancer. J Am Acad Dermatol.
2000;42(1Pt 2):18-22.
Manson JE, Hunter DJ, Buring JE, Hennekens CH. Letter to the editor. N
Engl J Med. 1991;324(13):924.
Monique RTM, et al. A systematic review of treatment modalities for primary
basal cell carcinoma. Arch Derm. 1999;135:1177-1183.
Moon TE, Levine N, Cartmel B, et al. Effect of retinol in preventing squamous
cell skin cancer in moderate-risk subjects: a randomized, double-blind,
controlled trial. Cancer Epidemiol Biomarkers Prev.
1997;6(11):949-956.
Morrill JS. Letter to the editor. N Engl J Med.
1991;324(13):923-924.
Moss RW. Alternative pharmacological and biological treatments for cancer:
ten promising approaches. J Naturopathic Med. 1996;6:23-32.
National Institutes of Health. Diagnosis and treatment of early melanoma.
NIH Consensus Statement. 1992 January 27-29;10(1):1-26.
Picard D. The biochemistry of green tea polyphenols and their potential
application in human skin cancer. Altern Med Rev. 1996;1(1):31-42.
Prince MR. Letter to the editor. N Engl J Med. 1991;324(13):924.
Sahl WJ, Glore S, Garrison P, Oakleaf K, Johnson SD. Basal cell carcinoma and
lifestyle characteristics. Int J Dermatol. 1995;34(6):398-402.
Scalzo R. Naturopathic Handbook of Herbal Formulas. 2nd ed. Durango,
Colo: Kivaki Press; 1994:37-38.
Sollner W, Zingg-Schir M, Rumpold G, Fritsch P. Attitude toward alternative
therapy, compliance with standard treatment, and need for emotional support in
patients with melanoma. Arch Dermatol. 1997;133(3):316-321.
van Dam RM, Huang Z, Giovannucci E, et al. Diet and basal cell carcinoma of
the skin in a prospective cohort of men. Am J Clin Nutr.
2000;71(1):135-141.
Willard T. Textbook of Advanced Herbology. Calgary, Alberta: Wild Rose
College of Natural Healing, Ltd.; 1992:90, 135-136.
Xu RH, Peng XE, Chen GZ, Chen GL. Effects of Cordyceps sinensis on
natural killer activity and colony formation of B16 melanoma. Chin Med J
(Engl). 1992;105(2):97-101.
Yan L, Yee JA, Li D, McGuire MH, Graef GL. Dietary supplementation of
selenomethionine reduces metastasis of melanoma cells in mice. Anticancer
Res. 1999;19(2A):1337-1342.
Yan L, Yee JA, Li D, McGuire MH, Thompson LU. Dietary flaxseed
supplementation and experimental metastasis of melanoma cells in mice. Cancer
Lett. 1998;124(2):181-186. |

|
Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
responsibility for the accuracy of the information or the consequences arising
from the application, use, or misuse of any of the information contained herein,
including any injury and/or damage to any person or property as a matter of
product liability, negligence, or otherwise. No warranty, expressed or implied,
is made in regard to the contents of this material. No claims or endorsements
are made for any drugs or compounds currently marketed or in investigative use.
The reader is advised to check product information (including package inserts)
for changes and new information regarding dosage, precautions, warnings,
interactions, and contraindications before administering any drug, herb, or
supplement discussed herein. | |