Basal Cell Carcinoma – Causes, Symptoms, Diagnosis, Treatment and Ongoing care
Incidence in US: ∼1,000,000 cases/year and is increasing about 10% each year
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
- Greater frequency in geriatric patients (ages 55–75 have 100 times incidence of age <20)
- The incidence is rapidly increasing in 20–40-year-olds.
Rare in children, but childhood sun exposure is important in adult disease.
Worldwide, the most common form of cancer.
- Incidence in US: 1,000,000 cases/year and is increasing about 10% each year
- Predominant age: Generally >40, but incidence is increasing in younger populations
- Predominant sex: Male > Female (although incidence is increasing in females)
- Lifetime risk of white North Americans: 30%
- 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
- 3–4 decades after chronic arsenic exposure
- 2 decades after therapeutic radiation
- Chronic immunosuppression: Transplant recipients (10 times higher incidence), patients with HIV or lymphomas
Several genetic conditions increase the risk of developing BCC:
- Albinism (recessive alleles)
- Xeroderma pigmentosum (autosomal recessive)
- Bazex syndrome (rare, x-linked dominant)
- Nevoid basal cell carcinoma syndrome/Gorlin syndrome (rare, autosomal dominant)
- Cytochrome P-450 CYP2D6 and glutathione S-transferase detoxifying enzyme gene mutations (especially in truncal basal cell carcinoma, marked by clusters of basal cell carcinomas and a younger age of onset)
- 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 a.m. and 4 p.m. as well as wearing wide-brimmed hats and long-sleeved shirts.
- Avoid tanning and sunburns (including tanning salons).
- UV-induced inflammation and cyclooxygenase activation in skin
- Mutation of PTCH1 (patched homolog 1), a tumor-suppressor gene that inhibits the hedgehog signaling pathway
- Mutation of the SMO (smoothened homolog) gene, which is also involved in the hedgehog signaling pathway
- UV-induced mutations of the TP53 (tumor protein 53), a tumor-suppressor gene
- Activation of BCL2, an antiapoptosis proto-oncogene
Commonly Associated Conditions
- Cosmetic disfigurement since 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.
Exposure to risk factors, family history
- 80% on face and neck, 20% on trunk and lower limbs (mostly women) (1)[B]
- Nodular: Most common (60%); presents as pinkish, 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: (30%); light red, scaly papule or plaque with atrophic center, ringed by translucent micropapules, usually on trunk or extremities; more common in men
- Morpheaform: (5–10%); firm, smooth, flesh-colored, scarlike papule or plaque with ill-defined borders
Diagnostic Tests & Interpretation
- Clinical diagnosis and histological subtype are confirmed through skin biopsy and pathological 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.
- Nodular BCC:
- Extending from the epidermis are nodular aggregates of basaloid cells.
- Tumor cells are uniform; rarely have mitotic figures; and have 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
- Morpheoform BCC:
- Thin cords and strands of basaloid cells, embedded in dense, fibrous, “scarlike” stroma
- Less peripheral palisading and retraction, greater subclinical involvement
- Infiltrating BCC:
- Like morpheoform BCC, but no “scarlike” 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
- Sebaceous hyperplasia
- Epidermal inclusion cyst
- Intradermal nevi (pigmented and nonpigmented)
- Molluscum contagiosum
- Squamous cell carcinoma
- Nummular dermatitis
- Melanoma (pigmented lesions)
- Atypical fibroxanthoma
- Rare adnexal neoplasms
- May be especially useful in those who cannot tolerate surgical procedures and in those who refuse to have surgery
- 5-fluorouracil cream inhibits thymidylate synthetase, interrupting DNA synthesis for superficial lesions in low-risk areas; primary treatment only 5% applied b.i.d. for 3–10 weeks
- Imiquimod (Aldara) cream approved for treatment of low-risk superficial BCC; daily dosing for 6–12 weeks; 90% histologic cure
- Radiation therapy:
- Useful for patients who cannot or will not undergo surgery
- Used following surgery, particularly if margins of tumor were not cleared
- Cure rate is approximately 90%.
- Tumors that recur in areas previously treated with radiation are harder to treat, and the area is more difficult to reconstruct.
- Photodynamic therapy (PDT) (2)[A]:
- 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
- Generally 1st choice; specific treatment selection varies with extent and location of lesion as well as tumor border demarcation (3)[A]
- High-risk areas:
- Inner canthus, nasolabial sulcus, philtrum, preauricular area, retroauricular sulcus, lip, temple
- Curettage and electrodesiccation:
- If nodular lesion <1 cm, in low-risk area, not deeply invasive
- Useful for lesions in high-risk areas
- Not as dependent on lesion size
- Reserved for small lesions in low-risk areas
- May want pre- and post-treatment biopsies
- Mohs surgery:
- Preferred microsurgically controlled surgical treatment for lesions in high-risk areas, recurrent lesions, and lesions exhibiting an aggressive growth pattern
- Requires referral to appropriately trained dermatologic surgeon
Outpatient unless extensive lesion
- Avoid sun exposure.
- Oral retinoids may prevent the development of new basal cell carcinomas in patients with Gorlin syndrome, renal transplant patients, and patients with severe actinic damage.
- Every month for 3 months, then twice yearly for 5 years; yearly thereafter
- Increased risk of other skin cancers (4)[C]
- Teach patient appropriate sun-avoidance techniques, sunscreens, etc.
- Monthly self skin exam
- Educate patients concerning adequate calcium and vitamin D intake.
- Proper treatment yields 90–95% cure.
- Most recurrences happen within 5 years.
- Development of new BCCs: Patients (36%) will develop a new lesion within 5 years.
- Local recurrence and spread
- Usually, recurrences will appear within 5 years.
- Metastasis: Rare (<0.1%), but metastatic disease usually fatal within 8 months
1. Wong CS, Strange RC, Lear JT. Basal cell carcinoma. BMJ. 2003;327:794–8.
2. Soler AM, Angell-Petersen E, Warloe T, et al. Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources. Photochem Photobiol. 2000;71:724–9.
3. Bath FJ, Bong J, Perkins W, et al. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev. 2003;CD003412.
4. Friedman GD, Tekawa IS. Association of basal cell skin cancers with other cancers (United States). Cancer Causes Control. 2000;11:891–7.
- 173.0 Other malignant neoplasm of skin of lip
- 173.1 Other malignant neoplasm of skin of eyelid, including canthus
- 173.2 Other malignant neoplasm of skin of ear and external auditory canal
- 173.3 Other malignant neoplasm of skin of other and unspecified parts of face
- 173.4 Other malignant neoplasm of scalp and skin of neck
- 173.5 Other malignant neoplasm of skin of trunk, except scrotum
- 173.6 Other malignant neoplasm of skin of upper limb, including shoulder
- 173.7 Other malignant neoplasm of skin of lower limb, including hip
- 173.8 Other malignant neoplasm of other specified sites of skin
- 173.9 Other malignant neoplasm of skin, site unspecified
- 254701007 Basal cell carcinoma of skin (disorder)
- 402819001 basal cell carcinoma of skin of lip (disorder)
- 231832009 basal cell carcinoma of eyelid (disorder)
- 402820007 basal cell carcinoma of ear (disorder)
- 402519009 basal cell carcinoma of face (disorder)
- 403915004 basal cell carcinoma of scalp (disorder)
- 402509003 basal cell carcinoma of neck (disorder)
- 402523001 basal cell carcinoma of truncal skin (disorder)
- 402521004 basal cell carcinoma of upper extremity (disorder)
- 402522006 basal cell carcinoma of lower extremity (disorder)
- Use diagnostic keys above to differentiate between BCC and cutaneous squamous cell carcinoma (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 there is insufficient evidence to recommend for or against routine total body skin exams for melanoma, BCC, or SCC. Exams should be based on risk factors, including exposures and family and prior medical history. All patients may receive education about risks and self-exam.