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Non-Melanoma

1. Predisposing Factors / Prevention

​Most skin cancers are preventable. As they are commonly induced by ultraviolet light, avoidance of excessive sun exposure combined with the use of appropriate clothing and a good sunscreen lotion (SPF 15 or higher in a substantive base that does not easily wash off by sweat or swimming) is recommended.

Risk Factors 

Skin cancer is the most common tumour in white populations around the world. The three major types are basal cell carcinoma, squamous cell carcinoma, and cutaneous malignant melanoma. All 3 types of skin cancers are at least twice as common in subjects with light skin hair and eye color compared to those with dark features (Elwood et al 1984). Other host factors which increase risk of skin cancer, are freckling, presence of large numbers of acquired melanocytic nevi (skin moles), and propensity to burn rather than tan in the sun. (Gallagher et al 1995 a,b)

The most important environmental risk factor for all 3 types of skin cancer is solar ultraviolet radiation (UVR). Solar UVR is thought to account for about 93% of CMM incidence in Canada (Armstrong & Kricker 1994) and, the figure is likely to be similar for non-melanocytic skin cancer.

Childhood sun exposure is thought to be very important in accounting for adult risk of CMM (Khlat et al 1995) as is strong intermittent recreational sun exposure particularly among indoor workers with un-acclimatized skin (Elwood et al 1985). Recently evidence is accumulating that childhood and intermittent recreational exposure are also important in accounting for basal cell carcinoma (Gallagher et al 1995a, Kricker et al 1995).

Squamous cell carcinoma appears to be related more to constant chronic occupational sunlight exposure (Gallagher et al 1995b) than to intermittent exposure.

Studies of exposure to artificial UVR mainly from sun lamps and sun beds, have shown modest increased relative risks for CMM, in the order of 1.1 to 1.2. These results need confirmation in more detailed studies which control for concurrent sun exposure.

Prevention 

Use of protective clothing in the summer sun and use of sunscreens are likely to reduce risk of non-melanocytic skin cancers. Not enough evidence is available to indicate whether use of sunscreens will reduce risk of melanoma.

General population screening for cutaneous malignant melanoma is not recommended as no trials have demonstrated that such screening decreases mortality. Subjects with a strong family history of melanoma (2 or more first degree relatives with the disease) may carry a p16 germline mutation predisposing to the disease. These individuals and individuals with atypical nevus syndrome (formerly Dysplastic Nevus Syndrome) should be under regular surveillance by a dermatologist.


References: 

  1. Armstrong BK, Kricker A. How much melanoma is caused by sun? Melanoma Res. 1993;3:395-401.  

  2. Elwood JM, Gallagher RP, Hill GB, et al. Pigmentation and skin reaction to sun as risk factors for cutaneous melanoma: Western Canada Melanom Study. BMJ 1984;288:99-102.  

  3. Elwood JM, Gallagher RP, Hill GB, Pearson JCG. Cutaneous melanoma in relation to intermittent and constant sun exposure-The Western Canada Melanoma Study. Int J Cancer 1985;35:427-433.  

  4. Khlat M, Vail A, Parkin M, Green A. Mortality from melanoma in migrants to Australia: variation by age at arrival and duration of stay. Am J Epidemiol. 1992;135:1103-1113.  

  5. Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentation factors, and risk of non-melanocytic skin cancer I. Basal cell carcinoma. Arch Dermatol 1995;131:157-163.  

  6. Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentation factors, and risk of non-melanocytic skin cancer II. Squamous cell carcinoma. Arch Dermatol 1995;131:164-169.

Sun Protection 

Sun protection is important for people of all ages.

The relationship between skin cancer and sun exposure is well accepted. However, the exact path between sun exposure and skin cancer is still not completely known. Recently the incidence of basal cell carcinoma has been associated with sun exposure during early childhood. Actinic keratosis and squamous cell carcinoma increase with cumulative sun exposure. The rate of malignant melanoma appears greater in people with intense intermittent sun exposure and increases as one approaches the equator.

UVB (280-320 nanometers) is responsible for most sunburns and the carcinogenic effects of sunlight and UVA (320-400 mm) is responsible mainly for tanning, although in high doses it can burn. UVB penetration is limited to the epidermis whereas UVA, a co-carcinogen also penetrates deeper into the dermis and is likely the major cause of photo-aging.

Sunscreens are very effective at preventing sunburn (UVB protection) and most also contain UVA screens. Those that contain Parsol 1789 protect best for UVA. Sunscreens absorb into the skin and vanish once applied unlike sunblocks which are opaque. Sunblocks contain micronized zinc oxide or titanium dioxide. These physical agents prevent light from reaching the skin thus they will leave a white or tinted film after application. Sunscreens are effective immediately upon application and many are waterproof.

SPF (sun protective factor) is a laboratory derived value of UVB protection. At present there is no similar rating of UVA protection. A SPF of 15 means someone will require 15 times the usual amount of UVB to cause a sunburn, that is if one usually burns in 15 minutes, with a sunscreen SPF 15 they would need 15 x 15 minutes or 225 minutes to burn. SPF 30 is the minimum recommended. Most people do not apply enough sunscreen. Those products with lower SPFs do not protect adequately.

It is generally accepted that sunscreen use lowers the risk of skin cancer, however, there is no epidemiologic confirmation yet.

Perhaps more important than sunscreens is an effort to reduce excessive exposure. Clothing helps, the tighter the weave and more opaque the fabric, the better the sun protection. Hats with broad brims are much more effective than peaked caps. Shade also helps, but alone may only diminish UV exposure by 30%. Since UV is most intense between the hours of 10.00 a.m. and 4.00 p.m., plan outdoor activities outside these hours when possible.

Effective sun protection encompasses behavior change and includes all the options outlined.

2. Staging

Updated September 21, 2016

Please refer ​to the UICC TNM-7th Ed 2011 staging system for carcinomas and Merkel cell cancer. See pages 32-25 of this pdf: http://www.uicc.org/sites/main/files/private/TNM_Classification_of_Malignant_Tumours_Website_15%20MAy2011.pdf​

1. Basal Cell Carcinoma

Revised 11 January 2013

Small Lesions Less than 0.5 cm in Diameter

Small basal cell carcinomas are best treated by surgical excision with a minimum 4 mm margin in all directions, or by curettage and electro-fulguration. It is important to assess and mark the margins under good light, prior to the infiltration of local anesthetic. Lesions with ill-defined edges, particularly on the face, may be best treated by radiation therapy or by Mohs micrographic surgery and this can be arranged by referral to the Skin Management Clinic. The inner canthus, nasolabial groove, paranasal skin, and postauricular skin have a high incidence of local recurrence and should not be treated with electro-fulguration and curettage except in certain cases. Recurrent tumours at these sites can be assessed by the Skin Management Clinic. The more common small nodular lesions that have been completely excised, as verified by a pathologist, do not require referral to the Agency.

Lesions 0.5 to 2.0 cm in Diameter (minimum 5 mm margin)

Most patients with these lesions will be referred to a dermatologist, a surgeon or to the Skin Management Clinic of the BCCA. Depending upon the clinical circumstances of each patient, treatment may be curettage and electro-fulguration, excision with primary closure, including Mohs micrographic surgery, or radiation therapy; or if on the face and ill-defined, Mohs micrographic surgery. If excision will cause significant cosmetic deformity, or in older patients, radiation therapy may be the preferred treatment. No referral to the Skin Management Clinic is necessary, if there has been a complete excision verified by a pathologist.

Large Lesions by Virtue of Area or Degree of Infiltration (minimum 5 mm margin)

Patients with these lesions are often best referred for specialist opinion or to the Skin Management Clinic. Treatment may be by radiation therapy, standard surgery, including a wide excision and flap repair or skin graft, or micrographic surgery. Great care must be taken to determine the extent of the lesion prior to undertaking surgery. If excision will cause significant cosmetic deformity, radiation therapy may be the preferred treatment. A surgeon may find it advisable to obtain a pathologist's opinion during surgery with regard to completeness of removal. Tumours that are ill-defined or recurrent after surgery are often best treated with radiation therapy or Mohs micrographic surgery (see 6.4.9). Micrographic surgery may also be considered for lesions recurrent after radiation therapy.

Superficial Basal Cell Carcinoma on the Trunk and Limbs

Below the knee radiation therapy is avoided when possible. Due to the high dose of radiation required and the usually poor blood supply in elderly patients, post treatment ulceration can take many months to heal. The tumour can be treated by surgical excision or curettage and electrofulguration.

Recurrent Basal Cell Carcinomas

If the cancer is recurrent, consider changing therapeutic modality to treat the recurrence e.g., if recurrence after surgery, consider radiation therapy and vice versa.

Incompletely Excised Basal Cell Carcinomas

While histologically incompletely excised basal cell carcinomas are sometimes observed, those with a morpheic, spindling pattern should always be treated to histologic cure. These lesions have a very high recurrence rate unless aggressively treated by micrographic surgery, radiation therapy or wide simple surgery.

Morpheic Basal Cell Carcinoma

(Synonym: Sclerosing, Spindling, Infiltrating)

Morpheic basal cell carcinomas require excision with wider margins up to a centimeter. Consideration should be given to micrographic surgery.

Topical 5-fluorouracil Therapy

Topical 5-fluorouracil therapy, while appropriate for actinic keratosis, is not appropriate therapy for basal cell carcinomas because of a very low cure rate, and the possibility of subclinical spread.

Interferon

Interferon is an alternate form of treatment for selected types of Basal Cell and Squamous Cell Carcinomas in patients where surgery and radiation therapy are contraindicated.​

2. Squamous Cell Carcinoma

Revised 4 March 2005

Premalignant Lesions 

Actinic keratosis

Actinic keratosis do not require referral to the Agency and are normally managed by the primary care physician or by a dermatologist. Actinic keratosis are premalignant lesions and may develop into in situ or invasive squamous carcinomas. Appropriate treatment modalities include topical 5-fluorouracil therapy, liquid nitrogen cryotherapy, light electro-fulguration, and infrequently, surgical excision. If 5-fluorouracil therapy is used, the treatment course can be repeated at intervals of a few months until all dysplastic tissue has been removed. See sunscreen use (2).

Carcinoma In Situ (Including Bowen's Disease)​

After a biopsy, these lesions are usually treated by surgical excision. In difficult cases, referral for specialist opinions or to the Skin Management Clinic is recommended. For the management of gynecologic cases see the section on Gynecology in this Manual.

Invasive Squamous Cell Carcinoma

Squamous cell carcinoma can be either a slowly evolving lesion arising from a long standing actinic keratosis or a rapidly growing lesion with a high metastatic potential. Immuno-suppressed patients are particularly at risk for rapidly growing and potentially metastatic SCC. Review more frequently. All squamous carcinomas should be treated promptly by surgical excision with an adequate margin or by radiation therapy. A pathology report including the words "anaplastic," "poorly differentiated," or "neurotropism" suggests a lesion at increased risk for recurrence or metastasis. In small circumscribed lesions, a margin of 5 mm is usually adequate. Referral to a surgeon, dermatologist, or to the Skin Management Clinic is recommended. If surgery will result in significant disfigurement, the Skin Management Clinic would be pleased to review the patient since radiation therapy may be preferable.

It is recommended that invasive squamous cell carcinoma not be treated with curettage and electro-fulguration, cryotherapy or topical 5-fluorouracil, as it is not possible to be sure of adequacy of removal of the squamous cell carcinoma with these modalities. In those instances where a lesion thought to be a basal cell carcinoma is treated with electro-fulguration and curettage and later is found to be a well differentiated squamous cell carcinoma, the dermatologist may elect to follow the lesion closely and treat with surgical excision or radiation therapy only if necessary. If the histology is other than well differentiated or it was a very rapidly enlarging "acute" lesion, further surgery or radiation therapy should be arranged for the patient. Rapidly enlarging squamous carcinomas even with a well differentiated histology should be treated aggressively and require close follow-up.

Squamous cell carcinomas of the skin may metastasize to regional lymph nodes. 

Patients with squamous cell carcinoma of the skin should have their regional lymph nodes assessed by their physician at their initial presentation and at each follow-up visit.

Basosquamous growth patterns are normally consistent with basal cell carcinomas with squamous metaplasia (i.e. they usually behave like basal cell carcinomas). However, these lesions should be reviewed and clarified by a pathologist.

Squamous cell carcinoma of the lip is discussed under the Head and Neck section.

3. Keratoacanthomas

A true keratoacanthoma is considered to be a benign self-limited tumour. However, there may be difficulty separating keratoacanthoma from squamous cell carcinoma, clinically and histologically. It is suggested that, in general, this lesion is best treated as if it were a low risk invasive squamous cell carcinoma, that is, by complete excision or by radiation therapy.

​ 

4. Merkel Cell Tumour

This rare small cell malignancy of the skin is characterized by its potentially aggressive behavior. Locally it is capable of producing satellite metastases whilst regional nodes are commonly involved. Conversely the appearance of systemic metastases is often delayed, thus opening a window for the possibility of curative therapy.

Staging

Liver function tests and a CT scan of the regional nodes should be obtained. Metastatic small cell carcinoma of the bronchus must be excluded; chest X-ray and CT scan of the chest should be performed. If either is abnormal the patient should be referred for bronchoscopy.

Treatment

  • Primary tumour. Either a biopsy followed by radiation therapy with a wide margin (3 cm.) or wide excision with a similar margin. The choice will depend on the potential morbidity and cosmetic result of either treatment.
  • Regional lymph nodes. Prophylactic or, in the case of those with established metastases, therapeutic irradiation of the regional nodes is recommended. This is considered preferable to surgical node dissection.
  • Systemic therapy. Adjuvant chemotherapy is not recommended. There may be a role for palliative chemotherapy for systemic metastases.​
  •  

5. Kaposi's Sarcoma Classical

Patients with localized disease are treated effectively with wide field irradiation. Those patients with more extensive disease can nevertheless have a prolonged survival with the disease confined to the skin for many years. Progressive or symptomatic disease can be effectively treated with palliative irradiation. Rarely, patients with symptomatic systemic disease may require palliative chemotherapy.

AIDS-Related

These tumours are commonly seen in patients with AIDS. Small lesions (less than 2.0 cm in diameter) respond well to liquid nitrogen cryotherapy or intralesional interferon. Larger symptomatic lesions can be treated with radiotherapy. Radiation therapy is not recommended as a cosmetic treatment for flat asymptomatic lesions since the resulting post irradiation presentation is often larger and now more obvious than the initial lesion. Wide field irradiation is usually not indicated due to possible bone marrow suppression with a resulting impairment of the patient's immune status. Symptomatic systemic disease may require chemotherapy.

See also under Lymphoma, Chronic Leukemia, Myeloma​

6. Other Skin Cancers

A variety of other skin tumours occur and the physicians at the Skin Management Clinic are always willing to see or discuss patients and make recommendations on management or undertake special therapy.​

7. Extramammary Paget's Disease

This relatively rare disease is most frequently reported in the skin of the perineum (peri-anal, vulvar, scrotal and upper thigh regions), but has been reported in the axilla, on the abdominal wall, and even on the tongue. It is diagnosed by biopsy. It may be associated with an underlying invasive malignancy, which should be excluded by investigation before treatment of the Paget's Disease is undertaken. Extra-mammary Paget's Disease has a significant propensity for recurring locally after surgery or radiation therapy, and has occasionally been reported to recur in grafted tissues used to replace surgical excision defects.

Wide local excision has been the main treatment recommendation for many years, with micrographic surgery (Mohs Technique) being reserved for larger lesions. Radiation therapy is certainly an acceptable alternative in situations where surgery might be functionally destructive, (e.g. in the perianal area), or when the disease has recurred after excision. Topical therapy is not recommended.​

Chemotherapy

Updated 15 November 2014

Fluorouracil (flure oh yoor' a sill) cream is a drug that is used to treat actinic keratoses. This is a pre-cancerous skin growth caused by chronic sun exposure. Fluorouracil reacts against the pre-cancerous sun-damaged skin cells but does not usually affect normal cells of the skin. It is a drug which is applied to the skin.

Fluorouracil is not a suitable therapy for invasive skin cancers.

Please see detailed information on this page: Fluorouracil Topical therapy​

Cryotherapy

​​Reviewed 15 November 2014 

Cryotherapy is a form of treatment using extreme cold. It is typically achieved using liquid nitrogen. It is primarily used for treatment of a single, or a small number of, precancerous skin growths, such as actinic keratosis. It is most efficiently delivered using a specially designed apparatus, called Cry-AC, instead of cotton tip applicators. 

Cryotherapy is not usually effective enough against invasive skin cancers, which require surgery. Should liquid nitrogen therapy for invasive skin malignancy be necessary, it can be arranged by referral to the Skin Management Clinic.

Surgery

Updated 15 November 2014​​ 

Surgery is indicated for the removal of many cutaneous malignancies. If the surgical excision of any skin malignancy is expected to produce a significant cosmetic deformity (especially of the face), or if the patient is medically unfit for surgery, radiation therapy is usually considered to be the treatment of choice. Similarly, if a skin malignancy should recur locally after apparent adequate surgery, radiation therapy or microscopically controlled surgery (Mohs technique) may be the treatment of choice. In these instances, patients can be referred to the Skin Management Clinic.
 
Micrographic Surgery  

This surgery consists of the removal and immediate examination of serial slices of the edges and base of a malignant tumour site. Slices are examined microscopically for presence of tumour and if tumour is present, a further slice is taken from the surrounding skin. This is continued until the histology indicates that all tumour is removed. This technique is far more comprehensive than a standard frozen section examination of a rush specimen.

Mohs micrographic surgery is particularly indicated for the treatment of recurrent tumours, especially those recurrent after radiation therapy. In addition, large tumours, tumours with ill-defined margins and those close to important anatomic structures such as the eyelids and nasal alar rim will have a higher cure rate if treated by Mohs micrographic surgery, compared to conventional surgery.

Referral should be made to a dermatologist trained in this technique.

In cases where surgery, including Mohs sugery, is expected to result in complex wound repair, significant cosmetic or functional defect of the tumor site, or cancers recurring after surgery, consideration should be made to explore radiation therapy as an alternative, especially for elderly patients. Similarly, when patients are medically unfit to go for surgery, radiation therapy should be considered.  

Imiquimod

Published November 2006
Updated: August 20, 2014 

Treatment of Actinic Keratoses and Basal Cell Carcinomas with Topical Imiquimod

Topical imiquimod (Aldara®) has been granted approval by Health Canada for treating actinic keratoses and basal cell carcinomas (BCC). Imiquimod is formulated as a cream that is applied topically to skin lesions, and is believed to induce the local production of cytokines in the skin such as interferon, which in turn have an antineoplastic effect on certain tumor cells.

For actinic keratoses, topical imiquimod is used two to three times weekly for 16 weeks. As with all treatments for actinic keratoses, accurate clinical diagnosis is important prior to initiating therapy. Lesions that are atypical or that do not respond adequately to standard therapy should be biopsied to rule out invasive carcinoma. 

If topical imiquimod is being considered for BCC, it is critically important to be aware that this treatment is recommended ONLY for low risk, superficial BCCs located on the trunk, neck, or extremities (excluding the hands and feet). It is also important to note that the Health Canada approved labeling for topical imiquimod is restricted to uncomplicated BCCs that would be amenable to simple surgical excision, but where patients have chosen not to have such surgery AND are willing to return for regular follow up. Superficial BCCs occur more commonly on the trunk and extremities and usually appear as well circumscribed, scaly red plaques that are barely elevated. In clinical studies topical imiquimod cleared 82% of treated tumors of BCC.(1) The recommended treatment course for a given tumor is 5 times weekly topical application for a total of six weeks. Prior to treatment, the diagnosis of superficial BCC should be confirmed by biopsy. Following treatment with topical imiquimod, any areas that appear suspicious for residual BCC on clinical examination should undergo repeat biopsy and definitive treatment with an alternative therapy if necessary. 

Topical imiquimod is NOT considered appropriate treatment for:

  • nodular basal cell carcinoma
  • sclerosing or morpheaform basal cell carcinoma
  • recurrent basal cell carcinoma
  • squamous cell carcinoma
  • may be considered for lentigo maligna after consultation with a dermatologist

References
Geisse et.al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: Results from two phase III, randomized, vehicle-controlled studies. J. Amer. Acad. Dermatol. May 2004: 722-733

Bath-Hextall, F., et al., Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial. Lancet Oncol, 2014. 15(1): p. 96-105.

Radiation Therapy

Radiation therapy is a preferred treatment modality in tumours whose excision would produce significant cosmetic deformity especially on the ear, eyelid margin or nasal alar rim. Radiation may also be preferable in older patients or others in whom surgery might be contra-indicated for reasons of general health, debility, etc.

If a skin cancer has recurred after radiation therapy, further radiation therapy is usually not possible. Excision of such a recurrence would be the treatment of choice, and consideration should be given to Mohs micrographic surgery.

Because of long-term damage to the skin, radiation therapy usually is not given to persons under the age of forty and is uncommonly given to patients under fifty. Surgery, including Mohs micrographic surgery, is usually performed in the younger patient.

Expected Reaction

Under normal circumstances patients receive a one-week course of irradiation for small lesions (<4.0 cm) and a two-week course or longer for larger lesions.

One week after the treatment brisk erythema will develop in the irradiated area. If the original lesion is ulcerated, there will be a period of exudation after which a large and unsightly crust will form. This process takes about six weeks to resolve. The development of secondary infection, of course, would require the appropriate treatment, although such infection does not normally occur.​

Follow-up

​ 1. Basal Cell Carcinoma

The patient is usually seen 6 to 8 weeks after radiation treatment or curettage and electro-fulguration. Patients are then advised to see their physician at six-month intervals for the first year and yearly thereafter, for examination of the treatment site and other sun-exposed skin. Many patients will develop a second basal cell carcinoma. Many patients who continue to develop new lesions require follow-up examinations quarterly.

2. Squamous Cell Carcinoma - Low Risk

Criteria: Well differentiated on histology and slowly growing by history.

The minimum intervals suggested for follow-up examination of the treatment site and regional lymph nodes is one year. Each patient should have their sun-exposed skin examined at each visit. Even after five years, they should be inspected, at least annually, for new actinic keratosis or skin cancers.

3. Squamous Cell Carcinoma - High Risk

Criteria: Poorly differentiated or infiltrating on histology or rapidly growing lesion by history. More frequent follow-up for immuno-suppressed individuals is required.

Examination of the treatment site and the regional lymph nodes every two to three months for the first year, decreasing in stages to annually after 5 years.

Each patient should have their sun-exposed skin examined at each follow-up visit and even after five years, examined at least yearly for new actinic keratosis or skin cancers.

4. Recurrences

All patients registered at BCCA will be seen at the request of the referring physician.

Referral Info for the New Patient Visit

Updated 22 February 2006 

The following suggestions are intended to assist the practitioner in providing the best possible management for his or her patient with skin cancer.

We are concerned about the number of patients who, after surgery with a curative intent, are referred with incompletely excised skin cancers; these patients present a difficult problem and often require radiation therapy that might have been avoided by alternative initial management. We prefer that patients with difficult tumours be jointly assessed so that the best possible treatment is advised. A multidisciplinary Skin Management Clinic assesses all patients with skin cancer who are referred to the Vancouver Cancer Centre. This management clinic is available for the assessment of any patient with a skin cancer. In addition to providing treatment services when appropriate, we would be pleased to see any patient for a consultation only. Please designate your preference in the referral letter that should accompany the patient to the Agency.

Appointments for referral of patients can be made by telephoning the Admitting Department at the Vancouver Centre: 

Tel: 604.877.6098 
Toll free tel: 1-800-663-3333 (in BC)
Fax: 604.708.2005

SOURCE: Non-Melanoma ( )
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