The two most common forms of skin cancer
According to the American Cancer Society, skin cancer is the most common cancer in the United States.1 While melanoma is the deadliest form of skin cancer, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are much more common.
BCC overview
BCCs account for approximately 80% of all skin cancers.2 These epithelial tumors develop from basal cells, located in the lower layer of the epidermis. BCCs are slow-growing and rarely metastasize. They are seen most frequently, but not exclusively, in fair-skinned individuals with a history of actinic exposure.
The most common sites of BCC are sun-exposed areas such as the face, ears, and chest. The majority of BCCs—70%—occur on the face, particularly on the nose.2 Another 25% of BCCs occur on the trunk or the extremities, and the remaining 5% on the penis, vulva, or perianal skin, suggesting that there is more to the development of BCC than simply actinic exposure, although actinic exposure is carcinogenic and can lead to mutations directly related to the development of BCCs.
Clinical appearance. BCCs can have various presentations, with the most common being a pearly papule with telangiectases in the lesion and a rolled edge. These tumors often bleed. Many patients present with a chief complaint of a nonhealing pimple.
The pathology of these classically appearing BCCs are reported as “nodular” BCCs on histologic analysis. Infiltrative BCCs often appear clinically the same as nodular BCCs; however, infiltrative BCCs are difficult to read at the margins because they do not have distinct borders under the microscope.
This makes treatment more challenging. Micronodular BCCs have a more distinct border both to the naked eye and under the microscope, and appear as classically described but tend not to ulcerate.
Three forms of BCC can have a more variable clinical appearance that makes diagnosis difficult: morpheaform BCC, pigmented BCC, and superficial BCC.
Morpheaform BCC appears yellowish and waxy with a tinge of pink, and is often more sclerotic, lacking any ulcercation. These lesions often feel firm on palpation. This finding illustrates the point that a skin examination is often tactile as well as visual.
Pigmented BCC resembles a traditional BCC but has specks of pigment in it, giving it an almost peppered appearance.
Superficial BCC can be much more subtle and appear as an erythematous patch or plaque with or without scale. Superficial BCC occurs most commonly on the upper trunk and shoulders. These lesions are easily misdiagnosed or overlooked as being an eczema patch or psoriasis patch.
A superficial BCC should be considered in the differential diagnosis if a patient presents with red, flaky patches, particularly if that patient has a history of significant sun exposure. Any person with a history of significant sun exposure should be a candidate for a complete skin examination with a dermatology professional.
Diagnosis. The diagnosis of a BCC is made by biopsy. A shave, tangential, or saucerization biopsy is adequate to make the diagnosis and treatment plan. A punch biopsy can be performed if a melanoma is in the differential diagnosis.
Treatment. BCCs typically are treated surgically. Surgical options include excision with appropriate margins, electrodesiccation and curettage (ED&C), and Mohs micrographic surgery. ED&C, the most commonly performed treatment, is done only after the lesion has been debulked during biopsy.
This treatment may result in bleeding and scarring; patients are often left with a white or pink annular scar that is larger than the original lesion. Also, because the clinician performing the ED&C cannot discern the margins of the BCC (with no tissue being sent away for pathology in this procedure, the clinician cannot be sure that all cancerous cells are being cleared), he or she may not go wide or deep enough, or, conversely, may go wider or deeper than is necessary.
The depth and width covered by ED&C are operator-dependent but do rely on the different feel and sound of normal tissue versus cancerous tissue during curettage: Cancerous tissue is often softer; the feel of its removal can be likened to the removal of softened butter. In comparison, normal, healthy tissue is resilient and firm.
Despite the procedure’s drawbacks, ED&C is the most cost-effective treatment option for BCC. The recurrence rate of a BCC 5 years after ED&C is 7.7%.2 Skin also may heal more easily following ED&C than following a procedure that requires stitches.
Mohs micrographic surgery should be considered as a treatment option for skin cancers that are located in cosmetically sensitive areas, are close to adjacent structures that could cause anatomical dysfunction (such as lesions that pull down on the lower eyelid, creating chronic eye-moisture issues; or lesions that pull up the lip border), are larger lesions, or are BCC subtypes with a high incidence of recurrence.
Named after the physician who invented the technique in the 1930s, Mohs micrographic surgery is a stepwise procedure in which layers of the involved tissue are removed, fixed on-site by a histology technician, and then mapped by a pathologist (often the dermatologist performing the procedure).
The margins are read immediately, and a complex repair, such as a flap or a graft, is done on-site by the same physician that day or the next day. Although this procedure can be relatively costly, it is associated with the lowest recurrence rate of all treatment options for BCC.
In addition, Mohs micrographic surgery often provides the most elegant cosmetic result, and in some cases is the only good option for maintaining normal function of surrounding structures. The 5-year recurrence rate of BCC following Mohs surgery has been reported to be as low as 1% in some studies.2
Radiation therapy is an option for patients who have large, advanced BCC lesions or who are not candidates for surgery based on location of the tumor or the person’s general health status. Both topical 5-fluorouracil (Carac, Efudex, Fluoroplex) and imiquimod (Aldara, Zyclara) are FDA-approved for the treatment of basal cell skin cancers, and often are used to treat diffuse areas of sun damage in patients who have a history of BCC or who are at high risk for BCC or SCC.
These agents should be applied only to superficial BCC in low-risk areas, such as the arms and the back, and require close clinical follow-up by a dermatology provider following use.
5-fluorouracil typically is applied twice a day for 3 to 6 weeks. Crusting, erythema, and stinging of the skin are common and expected reactions to 5-fluorouracil.3 Cure rates for the treatment of superficial BCC with 5-fluorouracil vary, but a 90% clearance rate has been reported.4
Imiquimod has various dosing regimens, but a common routine is to apply the cream 5 days a week for 6 to 12 weeks. Inflammation, irritation, and crusting are expected side effects during treatment with imiquimod as with all topical therapies for BCC.4 (When skin does not react this way during such treatment, it is an indication that the area has become cancer-free.)
Studies suggest that cure rates with topical imiquimod range from 73% to 82%. Selection of this treatment option should be based on the tumor’s histologic subtype and location, and a careful analysis of risk-to-benefit ratio that requires the clinician to take into account the risk of recurrence of the original lesion.
A recurrence of BCC on the back, for example, is less of a concern than a recurring lesion on the ear, where there is very little spare tissue. In addition, certain subtypes are more vulnerable to topical therapy. Superficial basal cells are much more responsive to topical therapy than are micronodular BCCs, which tend to be more aggressive and go deeper.
Whereas some providers use imiquimod as their first-line agent, others prefer 5-fluorouracil, which is less expensive (albeit still costly) and has been observed by some anecdotally to have better clearance.
Vismodegib (Erivedge), an oral therapy, was approved in January 2012 as a once-a-day capsule, representing the first FDA-authorized treatment for advanced forms of BCC.
This inhibitor of the Hedgehog signaling pathway is intended for the treatment of adults with metastatic BCC or with locally advanced BCC that has recurred after surgery, and for adults who are not candidates for surgical or radiation therapy.5
Long-term follow-up. Regardless of the type of BCC therapy used, patients need to be educated about proper sun-protective behaviors. Instruct these individuals to apply sunscreen—with a sun-protection factor (SPF) of 30 or higher—20 minutes before sun exposure and to reapply it every two hours, or more often if they have been in the water or are sweating.
Sunscreens generally work in one of two ways, depending on their ingredients. The more traditional formulations, which contain metals such as zinc oxide or titanium dioxide, reflect light. Other sunscreens use different chemicals, such as avobenzone or ecamsule, which actually absorb the UV radiation and disperse the energy as heat. Heat is currently believed to be harmless to cells and certainly less harmful than true UV radiation.
Also advise patients to avoid peak sunlight hours (10 a.m.-2 p.m.), to seek shade when possible, to wear clothing that protects the skin from ultraviolet (UV) light, and to wear hats.
Routine clinical monitoring in the form of complete skin examinations for BCC and other skin cancers is essential. A person who has had one BCC has as high as a 44% risk of developing another BCC within the first three years following initial diagnosis.6
For persons with a new diagnosis of BCC, a common recommendation is to undergo skin examinations every 6 months for the first 5 years depending on the patient’s history, risk level, and ability to monitor his or her own skin. The most common histologic types of BCCs to recur are micronodular, infiltrative, morpheaform, and superficial carcinomas.2 Tumors that are larger than 2 cm or that have been treated more than once have a higher recurrence rate.2 Recurrence is most common on the nose and elsewhere on the face.2
The following are warning signs of a BCC recurrence:
- Breakdown of previously healed scar tissue
- Enlargement of the scar tissue
- Formation of a papule or nodule within the scar tissue
- Development of crusting or scale on the scar tissue
- Bleeding or ulceration of the scar tissue.
Any change at the site of a previously treated BCC must be evaluated pathologically. Patients with a history of BCC are at an increased risk of developing cutaneous melanoma.7 making the need for regular skin examinations for these patients even more vital.
SCC overview
SCC accounts for 16% of all skin cancers. Compared with BCC, this type of skin cancer can grow faster, is more aggressive, and carries a greater risk for metastasis. Although cutaneous SCC is rarely fatal, these lesions can become large and bleed or ulcerate on a daily basis to the point of causing discomfort and pain.
Additionally, cutaneous SCC often develops on the head or neck, so lesion removal can result in disfigurement and can impair local structure functioning. The most common cause of SCC is UV radiation damage to p53 tumor suppressor gene.
Keratinocytes in the skin then undergo rapid and uncontrolled cloning and growth. Further genetic defects are acquired during this process, leading to the invasion of SCC. Many other genetic abnormalities are associated with or are being studied in the development of SCC.
Immunosuppression resulting from immunosuppressive therapy following organ transplantation can lead to multiple SCCs. Therefore, all organ recipients should undergo full clinical skin examinations as part of their long-term follow up care. In addition, any form of chronic immunosuppression, such as that caused by human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS), predisposes a person to SCC.
Other risk factors for the development of SCC include exposure to not just UV radiation but other forms of radiation as well, exposure to known human carcinogens, and human papillomavirus (HPV) infection.
Clinical appearance. SCC often appears on sun-exposed parts of the body as an ulcerate plaque or papule with scaling or crusting, or as a horny wartlike growth. Symptoms suggestive of nerve involvement include numbness, twitching, and visual changes (if the lesion is on the head or face).8 SCC can be painful even if there is no nerve involvement.
Diagnosis. SCC is diagnosed by skin biopsy. A shave, tangential, or saucerization biopsy is adequate for the diagnosis of a solitary small lesion.
A punch biopsy would provide full thickness analysis and depth of invasion. Computed tomography (CT) imaging should be performed to investigate concerns of local soft-tissue involvement, and magnetic resonance imaging (MRI) should be performed to investigate concerns of nerve involvement. A fine-needle biopsy is required to evaluate nodule or local lymph node involvement.
If the pathology report describes the lesion as poorly differentiated, the level of atypia is most severe and may even make histology diagnosis difficult to differentiate between mesenchymal tumors, melanoma, or lymphoma. Both acantholytic (adenoid) SCC and spindle cell SCC have a more aggressive clinical course, and management should reflect that.8
Other SCC lesions associated with more aggressive behavior include those that involve the lips, ears, anogenital region, or nerves; those that develop within a scar or chronic wound; those larger than 2 cm; those that have invaded the subcutaneous fat; those with poor differentiation; and those representing a recurrent disease.9 SCCs in the following locations are associated with high rates of metastasis: scalp, forehead, temple, eyelid, nose, dorsal surface of the hands, penis, and scrotum.8
Unlike BCC, SCC on an eyelid can invade the ocular nerve or the bone of the orbit, or can metastasize to more distant locations, to become fatal.10 Of clinical importance is squamous cell in situ (Bowen disease), a cancerous malignancy that will progresses to invasive SCC if left untreated. SCC in situ often appears as a pink or mildly scaly plaque, patch, or macule.
An actinic keratosis (AK) is a common skin lesion that can progress to SCC. AKs can be subtle to obvious. They are often rough or scaly macules or plaques of pink, tan, or brown color. These lesions often wax and wane but rarely resolve on their own. AKs can be diagnosed clinically and treated, but because a clinical diagnosis can be wrong, patients should be followed for complete resolution of a treated AK.
A lesion identified as an AK that does not resolve may in fact be an SCC. A more definitive way to differentiate between an AK and SCC would be to biopsy the lesion.
Once an AK is diagnosed, treatment options include liquid nitrogen cryotherapy, photodynamic therapy, and topical prescription chemotherapy. Patients using topical prescription chemotherapeutic agents such as topical 5-fluorouracil, imiquimod cream, and ingenol mebutate (Picato) can expect to experience irritation, redness, swelling, and scabbing of the skin during cutaneous treatment of AK.
However, ingenol mebutate and other new topical agents require as few as 3 days of application, compared with up to 12 weeks of application required by some older medications, and the skin normally returns to baseline (the AK resolves, as does any inflammation or crusting) in 14 to 21 days.
Correctly identifying AK is important in terms of preventing SCC, which can have much more devastating treatment and life-expectancy outcomes.
Treatment. Uncomplicated, solitary, small lesions caught early can be treated with ED&C. However, excision or Mohs surgery excision are the more commonly used treatments due to the potentially aggressive nature of SCC. Chemotherapy or radiation therapy may be used adjunctively or for patients who are not surgical candidates.
Persons who present with early SCC lesions and who receive adequate treatment have a 5-year survival rate of greater than 90%. Conversely, patients with advanced SCC tumors with lymph node involvement have a dramatically lower 5-year survival rate, of 25% to 45%.8
Long-term follow-up. Persons with SCC should be counseled similarly to persons with BCC in terms of using sun protection, taking other steps to prevent recurrence, and undergoing skin examinations. Persons with SCC also should undergo regional lymph node examinations.7
Clinicians should be aware that like persons with a history of BCC, persons with a history of SCC are at increased risk for cutaneous melanoma.7
Both groups of patients also should be counseled to avoid the carcinogenic exposure of tanning beds: Utilizing indoor tanning devices more than doubles an individual’s risk of developing SCC.8
Summary
Primary-care clinicians are in a unique and critical position of being able to flag patients with risk factors for BCC and/or SCC. These providers also often can identify clinically abnormal lesions that require a biopsy and a subsequent treatment plan. There are two common themes when talking about BCC and SCC: Early detection is key, and prevention is essential.
Abby Jacobson, PA-C, is a physician assistant practicing in dermatology at Delaware Valley Dermatology Group in Wilmington, Delaware, and at Dermatology and Skin Surgery Center of York in York, Pennsylvania.
References
- American Cancer Society. Skin cancer. Available at
- Bader RS. Basal cell carcinoma. Medscape. Updated March 27, 2014. Available at emedicine.medscape.com/article/276624-overview.
- National Institutes of Health National Library of Medicine. Fluorouracil topical. MedlinePlus website. Available at www.nlm.nih.gov/medlineplus/druginfo/meds/a605010.html
- Love WE, Bernhard JD, Bordeaux JS. Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review.Arch Dermatol. 2009;145(12):1431-1438.
- Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-2179. Available at www.nejm.org/doi/full/10.1056/NEJMoa1113713#t=articleTop.
- Levi F, Randimbison L, Maspoli M, et al. High incidence of second basal cell skin cancers. Int J Cancer.2006;119(6):1505-1507. Available at
- National Comprehensive Cancer Network, Inc. Guidelines Version 2.2014: Basal Cell and Squamous Cell Skin Cancers. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). 2014; p. MS-3.
- Monroe MM. Cutaneous squamous cell carcinoma. Medscape. Updated April 7, 2014. Available at emedicine.medscape.com/article/1965430-overview.
- Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection.
- Cook BE Jr, Bartley GB. Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmsted County, Minnesota. Ophthalmology. 1999;106(4):746-750.
All electronic documents accessed June 09, 2014.
