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Basal Cell Carcinoma
William Farkas, DO, CPT, MC, USA
Sean R. Wise, MD
image BASICS
DESCRIPTION
Basal cell carcinoma (BCC) is the most common cancer, originating from the basal cell layer of the skin appendages.
  • Rarely metastasizes but capable of local tissue destruction
Geriatric Considerations
Greater frequency in geriatric patients (ages 55 to 75 years have 100 times the incidence when compared with those aged <20 years)
Pediatric Considerations
  • Rare in children, but childhood radiation treatment is contributory, as are frequent or severe sunburns.
  • The Centers for Disease Control and Prevention recommend against using tanning beds and lamps in their guidelines for cancer prevention in school-age children.
EPIDEMIOLOGY
Worldwide, the most common form of cancer
Incidence
  • Incidence in the United States: with squamous cell carcinoma, over 2 million cases each year. 4 to 5 times more common than squamous cell carcinoma.
  • Predominant age: generally >40 years, although incidence increasing in younger populations
  • Predominant sex: male > female (2:1 ratio)
ETIOLOGY AND PATHOPHYSIOLOGY
  • UV-induced inflammation and cyclooxygenase activation in skin
  • In chromosome 9q22, mutation of PTCH1 (patched homolog 1), a tumor-suppressor gene that inhibits the hedgehog signaling pathway
  • UV-induced mutations of the TP53 (tumor protein 53), a tumor-suppressor gene
  • Activation of BCL2, an antiapoptosis proto-oncogene
Genetics
  • Several genetic conditions increase the risk of developing BCC:
    • Albinism (recessive alleles)
    • Xeroderma pigmentosum (autosomal recessive)
    • Bazex syndrome (rare, X-linked dominant)
    • Nevoid BCC syndrome/Gorlin syndrome (rare, autosomal dominant)
    • Cytochrome P-450 CYP2D6 and glutathione S-transferase detoxifying enzyme gene mutations (especially in truncal BCC, marked by clusters of BCCs and a younger age of onset)
RISK FACTORS
  • Chronic sun exposure (UV radiation). Most common in the following phenotypes
    • Light complexion: skin type I (burns but does not tan) and skin type II (usually burns, sometimes tans)
    • Red or blond hair
    • Blue or green eyes
  • Tendency to sunburn
  • Male sex, although increasing risk in women due to lifestyle changes, such as tanning beds
  • History of nonmelanoma skin cancer
    • After initial diagnosis of skin cancer, 35% risk of new nonmelanoma skin cancer at 3 years and 50% at 5 years
  • Family history of skin cancer
  • 3 to 4 decades after chronic arsenic exposure
  • 2 decades after therapeutic radiation
  • Chronic immunosuppression: transplant recipients (10 times higher incidence), patients with HIV or lymphomas
GENERAL PREVENTION
  • Use broad-spectrum sunscreens of at least SPF 30 daily and reapply after swimming or sweating.
  • Avoid overexposure to the sun by seeking shade between 10 AM and 4 PM, and wearing wide-brimmed hats and long-sleeved shirts.
  • The American Cancer Society recommends cancer related checkups every 3 years in patients 20 to 40 years old, and yearly in patients older than 40 years.
COMMONLY ASSOCIATED CONDITIONS
  • Cosmetic disfigurement because head and neck most often affected
  • Loss of vision with orbital involvement
  • Loss of nerve function due to perineural spread or extensive and deep invasion
  • Ulcerating neoplasms are prone to infections.
image DIAGNOSIS
PHYSICAL EXAM
  • 80% on face and neck, 20% on trunk and lower limbs (mostly women)
  • Nodular: most common (60%); presents as pinkish, pearly papule, plaque, or nodule, often with telangiectatic vessels, ulceration, and a rolled periphery usually on face (1)
    • Pigmented: presents as a translucent papule with “floating pigment”; more commonly seen in darker skin types; may give a blue, brown, or black appearance and be confused with melanoma (1)
  • Superficial: 30%; light red, scaly plaque resembling eczema or psoriasis, but with raised, pearly white borders similar to the nodular subtype, usually on trunk or extremities; least invasive of BCC subtypes
  • Morpheaform: 5-10%; resembles localized scleroderma; mass is ill-defined and often extends beyond visible lesion.
DIFFERENTIAL DIAGNOSIS
  • Sebaceous hyperplasia
  • Epidermal inclusion cyst
  • Intradermal nevi (pigmented and nonpigmented)
  • Molluscum contagiosum
  • Squamous cell carcinoma (SCC)
  • Nummular dermatitis
  • Psoriasis
  • Melanoma (pigmented lesions)
  • Atypical fibroxanthoma
  • Rare adnexal neoplasms
DIAGNOSTIC TESTS & INTERPRETATION
Diagnostic Procedures/Other
  • Clinical diagnosis and histologic subtype are confirmed through skin biopsy and pathologic examination.
  • Shave biopsy is typically sufficient; however, punch biopsy is more useful to assess depth of tumor and perineural invasion.
  • If a genetic disorder is suspected, additional tests may be needed to confirm it.
Test Interpretation
  • Nodular BCC
    • Extending from the epidermis are nodular aggregates of basaloid cells.
    • Tumor cells are uniform; rarely have mitotic figures; large, oval, hyperchromatic nuclei with little cytoplasm, surrounded by a peripheral palisade
    • Early lesions are usually connected to the epidermis, unlike late lesions.
    • Increased mucin in dermal stroma
  • Cleft formation (retraction artifact) common between BCC “nests” and stroma due to mucin shrinkage during fixation and staining
  • Superficial BCC
    • Appear as buds of basaloid cells attached to undersurface of epidermis
    • Peripheral palisading
  • Morpheaform BCC
    • Thin cords and strands of basaloid cells; embedded in dense, fibrous, scar-like stroma
    • Less peripheral palisading and retraction, greater subclinical involvement
  • Infiltrating BCC
    • Like morpheaform BCC but no scar-like stroma and thicker, more spiky, irregular strands
    • Less peripheral palisading and retraction, greater subclinical involvement
  • Micronodular BCC
    • Small, nodular aggregates of tumor cells
    • Less retraction artifact and higher subclinical involvement than nodular BCC
image TREATMENT
MEDICATION
  • May be especially useful in those who cannot tolerate surgical procedures and in those who refuse to have surgery,as well as for low risk superficial and/or nodular BCC
  • 5-fluorouracil cream inhibits thymidylate synthetase, interrupting DNA synthesis for superficial lesions in low-risk areas; primary treatment only; 5% applied BID for 3 to 10 weeks.
  • P.115

  • Imiquimod (Aldara) cream approved for treatment of low-risk superficial BCC; daily dosing for 6 to 12 weeks; 90% histologic cure (1,2)[A]
  • Neither imiquimod nor 5-FU is considered appropriate primary monotherapy for infiltrative or nodular BCC (1)[A].
  • Topical treatment failure may yield skip lesions that yield false negative margins, making Mohs and excisional surgery potentially less effective (1)[A].
  • Emerging therapies:
    • Vismodegib, a sonic hedgehog pathway inhibitor; for patients with advanced BCC when other options are exhausted; not considered appropriate therapy for low-risk tumors (1)[A].
    • Intralesional IFN-a-2B injection: some efficacy for small (<1 cm) nodular and superficial BCCs; relatively high cost, and frequent side effects (1,3)[A]
ADDITIONAL THERAPIES
  • Radiation therapy
    • Useful for patients, typically older, who cannot or will not undergo surgery (1)[C]
    • Used following surgery, particularly if margins of tumor were not cleared
    • Cure rate is ˜90%.
    • Tumors that recur in areas previously treated with radiation are harder to treat, and the area is more difficult to reconstruct.
    • Local treatment
    • Recurrence rates are 7-8%
  • Photodynamic therapy (PDT)
    • 5-aminolevulinic acid, a photosensitizer, is activated by specific wavelengths of light, creating singlet oxygen radicals that destroy local tissue (no damage to surrounding or deep tissues).
    • Useful in areas where tissue preservation is cosmetically or functionally important; considered inferior to surgical excision in terms of efficacy (2)
    • When examining 5-year recurrence rates, may be equivalent to cryotherapy
SURGERY/OTHER PROCEDURES
  • Surgical excision is first line treatment (3)[A]; specific treatment selection varies with extent and location of lesion as well as tumor border demarcation.
  • High-risk areas
    • Inner canthus, nasolabial sulcus, philtrum, preauricular area, retroauricular sulcus, lip, temple, “mask areas” of the face (2)[C]
  • Curettage and electrodesiccation
    • If nodular lesion <1 cm, in low-risk area, not deeply invasive
    • Avoid in the hair-bearing areas due to risk of the tumor extending down follicular structures.
    • 5-year cure rate of 92%; recurrence as high as 27% for high risk lesions
  • Excision with postoperative margin assessment
    • Treatment of choice for low risk lesions <2 cm in diameter
    • Goal is 4 mm margin
    • 5-year cure rate of 98%
  • Cryosurgery
    • Reserved for nodular and superficial BCC, not indicated for tumors with depth exceeding 3 mm
    • Typically for tumors with low risk of recurrence
    • May want pre- and posttreatment biopsies (2)[C]
    • 5-year cure rate of 99%
  • Mohs surgery
    • Preferred microsurgically controlled surgical treatment for lesions in high-risk areas, recurrent lesions, and lesions exhibiting an aggressive growth pattern (1,2)[A]
    • Gold standard for maximizing tissue sparing for functional or cosmetic reasons (1)[A]
    • 5-year survival rate of 99%
    • Requires referral to appropriately trained dermatologic surgeon
INPATIENT CONSIDERATIONS
Outpatient, unless extensive lesion
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Avoid sun exposure.
  • Oral retinoids may prevent the development of new BCCs in patients with Gorlin syndrome, renal transplant recipients, and patients with severe actinic damage.
Patient Monitoring
  • Every 6 to 12 months for life
  • Increased risk of other skin cancers
  • Recurrence:
    • Local: follow NCCN 2015 guidelines for primary treatment
    • Regional: surgery and/or radiation therapy
    • Metastatic: multidisciplinary tumor board consultation
PATIENT EDUCATION
  • Teach patient-appropriate sun-avoidance techniques, sunscreens, and so forth.
  • Monthly skin self-exam
  • Educate patients concerning adequate vitamin D intake.
PROGNOSIS
  • Proper treatment yields 90-95% cure.
  • Most recurrences happen within 5 years.
  • Development of new BCCs: Some patients (36%) will develop a new lesion within 5 years.
REFERENCES
1. Firnhaber JM. Diagnosis and treatment of basal cell and squamous cell carcinoma. Am Fam Physician. 2012;86(2):161-168.
2. Clark CM, Furniss M, Mackay-Wiggan JM. Basal cell carcinoma: an evidence-based treatment update. Am J Clin Dermatol. 2014;15(3):197-216.
3. Bath-Hextall FJ, Perkins W, Bong J, et al. Interventions for basal carcinoma of the skin. Cochrane Database Syst Rev. 2007;(1):CD003412.
Additional Reading
  • Kundu RV, Patterson S. Dermatologic conditions in skin of color: part I. Special considerations for common skin disorders. Am Fam Physician. 2013;87(12):850-856.
  • Wong CS, Strange RC, Lear JT. Basal cell carcinoma. BMJ. 2003;327(7418):794-798.
Codes
ICD10
  • C44.91 Basal cell carcinoma of skin, unspecified
  • C44.31 Basal cell carcinoma of skin of other and unspecified parts of face
  • C44.41 Basal cell carcinoma of skin of scalp and neck
Clinical Pearls
  • Nodular: pearly papule, plaque, or nodule often with telangiectatic vessels, ulceration, and a rolled periphery, usually on face
  • Pigmented: presents as a translucent papule with “floating pigment”; more commonly seen in darker skin types
  • Superficial: scaly papule or plaque with atrophic center, ringed by translucent micropapules, usually on trunk or extremities; more common in men
  • Morpheaform: firm, smooth, flesh-colored, scar-like papule or plaque with ill-defined borders
  • Use diagnostic keys above to differentiate between BCC and cutaneous SCC. SCC arises from actinic keratosis in 60% of cases and generally presents as an asymptomatic hyperkeratotic lesion. If unsure, biopsy or refer to a specialist.
  • Some hyperpigmented BCCs may appear similar to melanoma. Remember the ABCDEs of melanoma recognition: Asymmetry, Border irregularities, Color variability, Diameter >6 mm, Enlargement. If unsure, refer to a specialist.
  • The USPSTF concludes insufficient evidence and recommends for or against routine total body skin exams for melanoma, BCC, or SCC. Exams should be based on risk factors, including exposure and family and prior medical history. All patients should receive education about risks and self-exam.