All about Non-Melanoma Skin Cancers

J. Taylor Whaley, MD
Last Modified: March 9, 2017

What is the skin? 

Skin, which is a thin layer of tissue and the largest organ in the body, serves numerous functions. The most obvious function of skin is serving as a barrier between the outside world and internal organs. It is made up of three layers, the epidermis, the dermis and the hypodermis. The epidermis is the outermost layer. The dermis, which is the layer underneath the epidermis, contains connective tissue, hair follicles and sweat glands. The hypodermis is made up of fat and connective tissue. Over the course of years of exposure, skin is exposed to numerous potential carcinogens, or cancer causing agents, most importantly the sun and its damaging ultraviolet rays.  

What is non-melanoma skin cancer? 

Non-melanoma skin cancer is any type of cancer affecting the skin that is not melanoma. Cancer cells are abnormal cells that grow and can affect other organs in the body. There are numerous types of non-melanoma skin cancers including: basal cell, squamous cell, angiosarcoma, cutaneous B and T cell lymphomas, dermatofibrosarcoma protuberans, Merkel cell carcinoma, and sebaceous gland carcinoma. There are two primary types of non-melanoma skin cancers - basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) and these are the two discussed in this article. These cancers derive their name from the cells in which they originate. Both types of cells, basal and squamous, are located within the epidermis, or the outer layer of our skin. Pre-malignant lesions generally precede the development of non-melanoma skin cancers.  

What causes non-melanoma skin cancer and am I at risk? 

Skin cancer is the most common type of cancer diagnosed each year. The incidence of skin cancers exceeds that of all other cancers, and it is estimated that nearly half of cancers diagnosed every year will be skin cancers. Over the past decade, the incidence of skin cancers has increased dramatically. About 5.4 million basal and squamous cell skin cancers are diagnosed each year, with 8 out of 10 being basal cell and 2 out of 10 being squamous cell. About 2,000 people in the US die each year from non-melanoma skin cancer but frequently these are people with a compromised immune system. Although these cancers can be locally progressive, they rarely metastasize or spread to other parts of the body. Because of early detection and the decreased metastatic potential, non-melanoma skin cancer is often effectively treated and cured with only local treatment.  

Risk factors for developing non-melanoma skin cancers are numerous, including fair complexion, occupational exposures to radium and arsenic, personal history of atypical moles, history of skin cancers, family history of skin cancers, smoking tobacco, immunosuppression from medications and HIV, chronic non-healing wounds and previous burns, genetic syndromes such as basal cell nevus syndrome and xeroderma pigmentosum, and HPV; however, the most common risk factor for development of skin cancer is exposure to ultraviolet radiation from the sun. The vast majority (90%) of skin cancers will occur in individuals with no risk factors other than excess sun exposure.  

Ultraviolet radiation from both sun exposure and tanning salons damage the epidermis and the DNA in the cells found throughout the skin. This damage continues to occur with repeated exposure, eventually leading to mutations that accumulate to cause cancerous cells. It has been shown that severe sunburns are particularly damaging when they occur in children. Childhood sun exposure is the strongest correlate with the development of basal cell carcinomas, while sun damage in the decade preceding diagnosis is closely correlated with the development of squamous cell carcinomas.  

Can skin cancers be prevented?  

The most effective treatment for skin cancers is prevention. The easiest approach to preventing skin cancer is the avoidance of exposure to ultraviolet rays from the sun and tanning salons. General recommendations from the American Cancer Society include avoiding prolonged, unprotected exposure to the sun between 10 A.M. and 4 P.M, as damaging UV exposure is greatest between these times. Further recommendations include wearing a long-sleeve shirt and hat when outside, wearing sunscreen and re-applying often, and limiting swimming activities to mornings and evenings when the sun is not at its hottest. Wearing sunscreen is crucial in prevention of skin cancers. Sunscreen with a sun protection factor (SPF) of 15 or greater should be worn everyday, even in the winter, on any uncovered surface, including our lips. Consistent use of sunscreen has even shown the ability to reduce further skin damage in people with a history of extensive sun exposure. These recommendations, while important for all people, are particularly vital for those with fair skin, light eyes, and red hair. Finally, and most importantly, teaching children the proper ways of avoiding sunburns is crucial for protecting their skin and promoting healthy skin habits in the future.  

What screening tests are available? 

As we age, our years of sun exposure increase, and therefore the risk of skin cancer increases. Because of this increasing risk of cancer with age, it is crucial to examine our own skin regularly and to notice changes early. Be aware of the shapes and coloring of any freckles and moles you have. Skin cancer often develops from an existing lesion, causing its appearance to change. Examine your skin routinely in a mirror, including your back, face, lips, hands, forearms, and scalp. Furthermore, it is recommended that you follow up with your physician regularly. Early diagnosis is crucial in achieving the most appropriate treatment. Because skin cancers are related to exposures, people who have previously developed skin cancers are at much higher risk for future skin cancers, either in the primary (original) site or somewhere else on the body. Because of this, a complete skin exam should be performed by a healthcare provider at regularly scheduled visits.  

What are the signs of non-melanoma skin cancer? 

BCC typically presents as a small pearly or crusty patch that fails to heal. Because they are painless and typically develop slowly, they are often present for months to years before they are brought to the attention of the healthcare provider. Often, BCC can be identified by blood vessels that are prominent within the bump. As the lesions grow, crusting and bleeding ulcers that will not heal are frequently the reason individuals present to their provider. The lesions are most often identified on the face, with more than 70% of BCC diagnosed on the lips, cheeks, ears, nose, and scalp. Other regions of the body commonly diagnosed with BCC include the back of the neck, the shoulders, the forearms and hands, the back, and lower legs.  

Although the lesions are slow-growing and rarely develop the ability to spread to lymphatics or other parts of the body, the lesions can progress locally, leading to destruction of nearby structures which can be disfiguring. Lesions are frequently neglected because of their slow growth. As the BCC grows, it may invade adjacent areas, including blood vessels, cartilage, and bone. Risk factors for recurrence after treatment of basal cell carcinomas include depth of invasion, pathologic sub-type, and perineural invasion.  

The appearance of squamous cell carcinoma is typically a small, painless, elevated and crusty lump. As the lesions grow, they can become an ulceration and may bleed. SCCs tend to develop more rapidly than BCCs, and unlike BCC, SCC can spread to the local lymphatic system. Risk factors for lymph node involvement include tumors > 3 cm, poorly differentiated pathology, recurrent tumors, and tumors with > 4 mm depth of invasion. They can also be rather aggressive locally, causing significant damage and disfiguration to local structures. Risk factors for recurrence after treatment of squamous cell carcinomas include perineural invasion, tumor thickness, and poorly differentiated histology. The most common location of squamous cell carcinomas is the face. Other areas at high risk include the back, shoulders, forearms and hands, and lower legs. 

Actinic keratosis, which is a precancerous dry, scaly lesion, and carcinoma in situ (Bowen’s disease) are typically located in areas of significant sun damage and often possess the potential to become malignant basal cell or squamous cell carcinomas. These lesions initially develop into dysplasia, or atypical cells. Approximately 10% of actinic keratoses will develop into invasive cancer.  

How is non-melanoma cancer diagnosed? 

When non-melanoma skin cancer is suspected, a biopsy is frequently performed to establish the diagnosis. This biopsy removes either the entire lesion or part of it and the layers beneath it, allowing the depth of the lesion to be accurately determined. There are a number of different types of biopsies: 

  • Shave Biopsy: A blade is used to shave off the top layers of skin.  
  • Punch Biopsy: A tool that looks similar to a small, round cookie cutter is used to remove a deep sample of skin.  
  • Incisional Biopsy: A scalpel is used to remove part of the lesion. 
  • Excisional Biopsy: A scalpel is used to remove the entire lesion.  

The sample of lesion is sent to a lab to be looked at by a pathologist who determines if the lesion is cancerous and if cancerous what type of skin cancer it is. Along with the biopsy your provider will do a full physical exam and health history. Your provider may order further testing to see if the cancer has spread. Imaging tests like MRI, CT and chest x-rays may be used.  

Staging of Non-Melanoma Skin Cancers 

The depth of the lesion determines prognosis and treatment, so it is important for this to be accurate. This depth is described by Clark's level, which describes depth of invasion by the tissue it invades (levels I-V). Clark's level is an indication of the depth of penetration only, not the stage of disease.   

  • Clark's Level I involves the epidermis only (outermost level).  
  • Clark's Level II involves the epidermis and the layer of skin immediately below, the papillary dermis.  
  • Clark's Level III goes one layer deeper into the reticular dermis.  
  • Clark's Level IV involves the deep dermis.  
  • Clark's Level V invades beyond the skin layers into the subcutaneous fat.  

Non-melanoma skin cancer is most commonly staged using the TNM staging system, which is determined by the American Joint Committee on Cancer 7th edition (2010) The "T stage" represents the extent of the primary tumor itself. The "N stage" represents the degree of involvement of the lymph nodes. The "M stage" represents whether or not there is spread of the cancer to distant parts of the body. These are scored as follows: >2 cm or has greater than 2 high-risk features.  

Primary Tumor (T) 

TX 

The primary tumor cannot be assessed. 

T0 

No evidence of primary tumor.  

Tis 

Carcinoma in situ (tumor remained in epidermis). 

T1 

The tumor is 2cm across or smaller and has only 1 high risk feature. 

T2 

The tumor is larger than 2cm across, or is any size with 2 or more high-risk features. 

T3 

The tumor has grown into the facial bones. 

T4 

The tumor has grown into other bones in the body or into the base of the skull.  

High risk features: These features help distinguish between some T1 and T2 tumors.  

  • The tumor is thicker than 2mm. 
  • The tumor has invaded down into the lower dermis or subcutis. 
  • The tumor has grown into tiny nerves in the skin. 
  • The tumor is on the ear or on part of the lip.  
  • The tumor cells look very abnormal under a microscope.  

Regional Lymph Nodes (N) 

NX 

Nearby lymph nodes cannot be assessed.  

N0 

The cancer has not spread to nearby lymph nodes. 

N1 

The cancer has spread to 1 nearby lymph node, which is on the same side of the body as the main tumor and is 3cm or less across. 

N2a 

The cancer has spread to 1 nearby lymph node, which is on the same side of the body as the main tumor and is larger than 3cm but not larger than 6cm across. 

N2b 

The cancer has spread to more than 1 nearby lymph node on the same side of the body as the main tumor, none of which are larger than 6cm across. 

N2c 

The cancer has spread to nearby lymph node(s) on the other side of the body from the main tumor, none of which are larger than 6cm across. 

N3 

The cancer has spread to any nearby lymph node that is larger than 6cm across. 

Metastasis (M) 

M0 

The cancer has not spread. 

M1 

The cancer had spread to other parts of the body.  

Stages 

Tis, N0, M0 

T1, N0, M0 

II 

T2, N0, M0 

III 

T3, N0, M0 

T1 to T3, N1, M0 

IV 

T1 to T3, N2, M0 

Any T, N3, M0 

T4, any N, M0 

Any T, any N, M1 

 

Although this system of cancer staging is quite complicated, it is designed to help physicians describe the extent of the cancer, and therefore, helps to direct what type of treatment is given.

How is non-melanoma skin cancer treated?

The treatment of SCC and BCC is dependent on location of the tumor, the age of the individual at diagnosis, the extent of disease, and whether the area has been treated before. Non-melanoma skin cancers are generally addressed with local treatments, including surgery, cryotherapy, and radiation. When lesions are discovered and thought to be suspicious, they are frequently biopsied to ensure they are not a more aggressive type of skin cancer. For lesions that are small and not locally progressive, the treatment options are numerous and include Moh’s surgery, excisional surgery, cryotherapy, curettage and electrodessication, photodynamic therapy, topical chemotherapy, and radiation therapy. In some instances, more than one treatment modality will be used to treat the cancer.

Cryotherapy

This type of treatment involves freezing off the lesions with liquid nitrogen. Cryotherapy is best for very small, well-defined superficial BCC and well-demarcated SCC. It is frequently used in patients that are not ideal surgical candidates.

Excisional surgery

This traditional simple surgical resection involves numbing the area with local anesthesia and removing the entire area of concern with a border or margin of healthy tissue, generally 3-10 mm. The skin is then closed with sutures (stitches) and the tissue is sent to a laboratory for a pathologist to ensure all the cancer has been removed. 

Curettage and Electrodessication

The type of therapy is the most common method for treating BCC. The treatment involves local anesthesia followed by removal of the tumor by curettage (scraping). The abnormality is scooped out with a curette until normal skin is appreciated. The entire area is then treated with an electrical current to stop any bleeding. The difficulty with curettage is found in evaluating the margins (edges) and depth of the tumor. Similar to cryotherapy, this technique is best for very small, well-defined superficial BCC and well-demarcated SCC. 

Moh's Surgery

Moh’s surgery is a procedure often performed by a dermatologist or a trained specialist in the office under local anesthesia. With Moh’s surgery, very precise surgery is performed with attempts to remove the least amount of tissue while the margins, or edges, of the resection are examined under a microscope immediately to ensure all of the cancer is removed. While other types of resection can have recurrence rates as high as 50%, Moh’s cure rates have been documented higher than 90%. This type of surgery is also very useful in traditionally difficult areas, including the face. Indications for Moh’s surgery include large lesions where cosmesis can be difficult and maximum skin preservation is crucial.

Radiation Therapy

Radiation therapy, which involves the use of non-invasive, painless, highly focused beams of ionizing energy, is often used when lesions are in locations that are not easily addressed with surgery, such as eyelids, lips, the nose, or ears. Radiation therapy involves daily treatments for several weeks. Radiation is used in the primary treatment of non-melanoma skin cancers, achieving local control nearing 90%. Radiation is more frequently used for skin cancers in the head and neck region as it offers improved cosmetic outcomes. The effectiveness of radiation as a primary treatment is related to tumor size, with smaller tumors generally responding better. As late skin effects from radiation are a concern, radiation is generally reserved for older patients. Radiation therapy can also be used in conjunction with surgery when tumors are considered high risk or have positive margins as well as with recurrent tumors.

Topical medications and Chemotherapies

Topical medications are occasionally used to treat BCC. Fluorouracil (5-FU) is a type of chemotherapy often used intravenously for other types of cancer; however, it is also approved for topical use for basal cell carcinomas. The 5-FU cream is applied to the area twice daily for several weeks. Imiquimod is also an approved topical medication for BCC. This cream, which is thought to work by stimulating the immune system, is applied to the tumor five times a week for 6 weeks. This type of therapy is reserved for pre-malignant and very superficial lesions.

Photodynamic Therapy  

Photodynamic therapy is a treatment in which a topical photosensitizing agent is put on the lesion and then the lesion is exposed to a to a wavelength of light. When the light is activated the photosensitizer reacts with the oxygen causing destruction of the cancer cells.  

Advanced Lesions 

Locally advanced lesions that involve invasion into adjacent areas, the treatments are typically more aggressive. Frequently, the surgery will involve reconstruction if a large amount of tissue will be removed. When reconstruction must occur, a skin graft or muscle is often used to aid healing and reach an acceptable cosmetic outcome. Radiation therapy will be used in addition to surgery to improve local control for lesions that are large and / or total resections are not possible. When tumors recur at the primary (original) site, treatment becomes more complex and is often referred to specialists. The majority of recurrences occur within the first few years following diagnosis. When possible, surgery to achieve negative margins is the best option. However, as lesions often occur on the face near important structures such as the nose, lips, ears, and eyes, radiation is often used when surgery would result in disfigurement.  

Clinical Trials 

Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your healthcare provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow-up Care and Survivorship 

Patients with a history of non-melanoma skin cancer have been documented to be at greater risk of developing a secondary skin cancer. Therefore, all patients require close follow-up. Patients with BCC should be evaluated with a complete skin exam every 6 to 12 months for life. Patients with localized SCC should be evaluated with a complete skin exam every 3 to 6 months for the first 2 years after diagnosis, then every 6 to 12 months for 3 years, and then annually.  

It is important for patients to continue to examine his or her own skin for any changes or new lesions. As soon as you notice any changes you should contact your provider. It is also very important to practice sun safety.  

Fear of recurrence, financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by non-melanoma skin cancer survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer. 

Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.  

This article is meant to give you a better understanding of non-melanoma skin cancer. Use this knowledge when meeting with your healthcare provider, making treatment decisions, and continuing your search for information.  

Resources for more information: 

Skin Cancer Foundation 

Strive to education the public and medical professionals about the dangers of skin cancer, prevention methods and sun protection. Provides information on skin cancer and treatment. 

http://www.skincancer.org/skin-cancer-information 

National Institute of Health Medline Plus 

The United States medical research agency. Provides information on treatment and research, much of it in Spanish. http://www.nlm.nih.gov/medlineplus/skincancer.html

References

American Cancer Society. Non-Melanoma Skin Cancer. 2016. Found at: https://www.cancer.org/cancer/skin-cancer.html 

Lucena SR et al. Combined treatments with photodynamic therapy for non-melanoma skin cancer. Journal of Molecular Science. 2015; 16(10):25912-25933.  

National Cancer Institute. Non-melanoma skin cancer treatment. Jan 2016. Found at: https://www.cancer.gov/types/skin/hp/skin-treatment-pdq#link/_369 

NCCN. Non-Melanoma Skin Cancer. Basal and Squamous Cell Cancer. 2016. Found at: https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf

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