BCC is the most common nonmelanoma skin cancer (NMSC) in the United States. UV radiation exposure is considered the biggest contributing risk factor for BCC as evidenced by the common sites of occurrence on sun-exposed areas such as the scalp, face, neck, chest, and distal parts of extremities. The malignant nature of BCC is demonstrated by expansive growth, destruction, and invasion of local structures including bone. BCC often remains local with low metastatic potential, and it’s highly curable.
A. Definition: BCC is a malignant epithelial neoplasm arising from the basal cells (in the basal layer) of the epidermis and its appendages.
B. Incidence:
1. Over 3.5 million cases of NMSC among more than 2 million people annually.
2. Highest incidence among Caucasians and individuals with fair skin, approximately 75%
to 80% of NMSC.
3. Greater than 70% occurrences are on the face, 15% on the trunk, and rare occurrences on non–sun-exposed areas including genital or perianal areas.
C. Etiology:
1. UV radiation exposure
a. Intermittent episodes of intense UV exposure and recreational sun exposure at any age.
b. Depletion of earth’s protective ozone layer allows dangerous UV rays to penetrate the atmosphere.
2. Ionizing radiation exposure through occupation or therapeutic radiation for disorders such as facial acne, tinea capitis, psoriasis, eczema, or skin cancer.
3. Arsenic and carcinogenic exposures from contaminated drinking water, seafood, agricultural insecticides, or pharmacological mixtures (Fowler solution).
4. Genetic disorders and DNA repair capability:
a. Nevoid basal cell carcinoma syndrome (NBCCS) (also known as Gorlin syndrome)
—a rare autosomal dominant genetic disorder, caused by the germline mutations (Figure 16-3)
(1) Affected individuals have multiple developmental anomalies in body systems (e.g., skin, bone, endocrine, and nervous system), unusual facial appearance, and predisposition for tumors including multiple BCCs at an early age.
b. Xeroderma pigmentosum (XP)—an autosomal recessive genetic disorder with defective DNA repair mechanism. Inability to repair UV radiation–induced DNA damage and mutations results in development of BCC.
5. BCC may arise in nevus sebaceous, a congenital hamartoma of the skin.
D. Pathogenesis:
1. The mutations in PTCH1, PTCH2, SMO and SUFU genes are well known to associate with the development of BCC. Over 70% of BCC development is caused by alteration in PTCH1 gene on chromosome 9q. PTCH1 is a tumor suppressor gene, functioning as the controller of proliferation and differentiation.
2. PTCH1 gene mutation causes loss of normal function and disruption in signaling pathways, resulting in uncontrolled growth in BCC tumorigenesis.
3. The mutations in P53 gene (early during carcinogenesis) and the MC1R gene are uncommonly involved in the development of BCC.
4. UV irradiation–induced skin inflammation: UV exposure results in inflammation of the skin, which leads to increased synthesis of prostaglandin and induction of cyclooxygenase-2 (COX-2). The key role of COX-2 inhibitors induced by the inflammation is to decrease the incidence of carcinogenesis in NMSC.
5. Langerhans cells, found in the basal layer of the epidermis, are functionally impaired by UVB and PUVA treatment leading to morphologic changes within the cell.
a. PUVA, PUVB, broadband UVB, and narrow band UVB phototherapy are types of UV radiation treatments for many severe skin diseases.
(1) PUVA is a UV radiation treatment using a photosensitizing agent called Psoralens (P), such as methoxsalen (8-methoxypsoralen), 5-methoxypsoralen, and trisoralen orally or topically. Once the medication is applied (or taken orally 2 hours prior to the treatment), expose the treatment areas of the skin to UVA (long UV wavelength, 320 to 400nm) or UVB (290 to 320nm) in a therapeutic light box, a cabinet containing multiple fluorescent light bulbs to administer controlled amount of UV radiation, 2 to 3 times a week until optimal therapeutic outcomes are achieved.
(2) Since 2008 however, lack of supplies in Psoralens caused infrequent use of PUVA or PUVB; currently the most common form of phototherapy is Narrowband UVB phototherapy (NB-UVB). NB-UVB (311 to 312mn) is known to have lower risk associated with phototherapy in comparison to formerly used broadband UVB (290 to 320nm).
(3) Patients must use protective eyewear and cover sensitive skin areas (i.e. face and genitalia) for whole body exposure to limit UV radiation associated irritations, burning, and other damages during the treatment. Currently there are localized treatment instruments available for scalp, extremities, hands and feet.
FIGURE 16-3. Nevoid basal cell carcinoma syndrome. (From DeVita, V. T., et al. (2008).
DeVita, Hellman, and Rosenberg’s cancer: Principles and practice of oncology.
Philadelphia, PA: Wolters Kluwer.)
II. CLINICAL VARIANTS
A. Superficial BCC (Figure 16-4): pearly pink, reddish, or eczematous, with a slightly scaling patch or slightly raised plaque.
B. Papulonodular BCC (Figure 16-5): pearly, shiny, or semitranslucent pink papule or nodule with a crater-like central umbilication and visible surrounding telangiectasia.
C. Sclerotic or morpheaform BCC (Figure 16-6): pale, atrophic, occasionally eroded, or crusting, cicatricial-appearing plaque.
D. Pigmented BCC (Figure 16-7): shiny papule, nodule, or plaque with focally speckled or entirely dark brown, blue-black, or black pigmentation while having pearly, semitranslucent rolled border at the base.
E. Basosquamous cell carcinoma: rarely occurring tumor but aggressive in nature and often classified as an SCC. This type must be confirmed by skin biopsy and histologic study.
FIGURE 16-4. Superficial basal cell carcinoma. (From Dr. Barankin Dermatology Collection.)
FIGURE 16-5. Nodular basal cell carcinoma. (From Lugo-Somolinos, A., et al. (2011).
VisualDx: Essential dermatology in pigmented skin. Philadelphia, PA: Wolters Kluwer.)
FIGURE 16-6. Morpheaform basal cell carcinoma. (From Khan, F. M., & Gerbi, B. J. (2011).
Treatment planning in radiation oncology. Philadelphia, PA: Wolters Kluwer.)
FIGURE 16-7. Pigmented basal cell carcinoma. (From Goodheart, H. P. (2003). Goodheart’s photoguide of common skin disorders (2nd ed.). Philadelphia, PA: Lippincott Williams &
Wilkins.)
III. LABORATORY AND DIAGNOSTIC TESTS
A. Clinical evaluation and skin biopsy for a confirmation of diagnosis.
B. Skin biopsy is highly recommended for patients with atypical features of a lesion for BCC, no prior history of BCC, or other risk factors contributing to possible recurrence of BCC.
IV. DIFFERENTIAL DIAGNOSIS
A. Amelanotic melanoma B. Dermal nevi
C. Eczema
D. Keratoacanthoma E. Nodular melanoma F. Nummular eczema G. Psoriasis
H. Scar/cicatricial plaque I. Squamous cell carcinoma
V. TREATMENT MODALITIES
Treatment modalities are decided by the location and size of the tumor.
Cryosurgery
1. A noninvasive procedure using liquid nitrogen.
2. Useful in small superficial BCC treatment on trunk and extremities.
3. Liquid nitrogen is administered by cone spray apparatus or by use of cryoprobes that conduct cold evenly.
4. May result in postinflammatory hypo- or hyperpigmentation (PIH).
5. No specimen available for evaluation of margins.
Electrosurgery (electrodessication and curettage)
1. Local anesthesia, minimal equipment, and quick office procedure.
2. Useful in treatment of well-differentiated primary BCCs located on trunk and extremities and on patients who are not candidates for invasive surgical procedures.
3. Disadvantages include lack of specimen for margin evaluation and possible hypertrophic scar development.
4. Contraindicated in patients with pacemaker or defibrillator implant, BCCs 2 cm or larger, recurrent BCC, or a BCC located in high-risk location for recurrence.
5. Electrodessication and curettage offers cure rate of 97% to 98%.
Carbon dioxide laser (CO2)
1. May be used in conjunction with a curette in place of electrocautery.
2. Advantages include minimal nonspecific thermal injury to adjacent cells with more rapid healing and less pain postoperatively.
Surgical excision
1. Office procedure using local anesthetic
2. Useful for well-differentiated primary BCC lesions
3. Provides specimen for random evaluation of surgical margins
4. Time-consuming procedure requiring surgical skill, assistants, and more equipment 5. Highly efficacious with cure rate of 96.8% to 99% depends on the types, sizes, depths,
and locations of the lesions.
Radiation therapy
1. Superficial x-ray or high-energy electron beam radiation.
2. Useful for BCCs on the head and neck, with chance of metastasis 3. May cause radionecrosis over bone
Mohs micrographic surgery, named after Frederic Mohs, MD, is defined as excision of skin cancer with histological margin control of deep and peripheral margins.
1. Office procedure using local anesthesia.
2. Indications:
a. Primary BCC on cosmetic sensitive areas (e.g., face and ears).
b. Morpheaform BCC or tumors with indistinct margins.
c. Incompletely excised and recurrent BCC.
d. Certain anatomic areas best treated by the precision of Mohs surgery include central
“H” zone of the face comprising the upper lip, nose, medial canthus, and temple.
3. Tumor is debulked and a layer of tissue is removed to be processed for margin evaluation in an on-site laboratory.
4. Tissue specimen is marked with color-coding inks to maintain the orientation of the specimen and the defect (surgical site).
5. The specimen is then frozen, sliced, and fixed on glass slides and treated in series of chemicals for staining.
6. Surgeon or dermatopathologist reads slides observing the base and epidermal edges of the specimen for the total clearance of the tumor; if BCC persists at one or more color-coded margins, another layer from the corresponding site(s) is harvested from the defect. (Same steps are repeated until the margins are free of tumor.)
7. Precise margin control and conservative removal of the benign skin surrounding the tumor offer advantage in cosmetic sensitive areas and higher cure rate.
8. Disadvantages include possible lengthy procedures with waiting periods; requires special training of surgeon, assistants, and technicians and specialized equipment.
Other treatment modalitiesTopical 5-fluorouracil and imiquimod are effective treatments for superficial BCC and multifocal BCC. May also be used as pretreatment method prior to Mohs or excision surgery for ill-defined BCC lesions on diffuse sun-damaged skin.
Photodynamic therapy (PDT) for superficial BCC, which selectively destroys tumor cells by the administration of a photosensitizing topical agent that is activated by light creating oxygen products capable of cell destruction.
a. Beneficial for patients with nevoid BCC syndrome
VI. PROGNOSIS
BCCs’ viability is dependent on the integumentary system (e.g., pilosebaceous units and loose connective tissue stroma). Therefore, they have low chance of metastasis and highly curable.
Occasionally occurring metastases are associated with long-standing history of neglecting and untreating a large, ulcerating, and aggressively growing, nonhealing lesions.