Introduction
Background
The most common form of skin cancer and the most common epithelial tumor is basal cell carcinoma (BCC), accounting for 80-90% of skin malignancies. Although it is the most common skin cancer, it accounts for fewer than 0.1% of patient deaths due to cancer. BCCs are more likely to occur in white or light-skinned individuals who have had significant unprotected exposure to UV (sunexposed) radiations and are more common in the southern latitudes of the northern hemisphere.
The overall cure rate is directly related to the histologic staging of the disease, time of diagnosis, and treatment modality used. The cure rate is suggested to be approximately 95%. However, since BCC is not a reportable disease, the precise 5-year cure rate (survival rate) is not known.
Pathophysiology
Radiation has proven to be tumorigenic by two mechanisms. The first mechanism entails the initiations of prolonged cellular proliferation, thereby increasing the likelihood of transcription errors that can lead to cellular transformation. The second mechanism is direct damage of DNA replication, leading to cellular mutation that may activate proto-oncogenes or deactivate tumor suppressor genes.
BCC of the eyelid is the most common epithelial tumor, but its molecular-genetic pathogenesis is unclear. Mutation of p53 (in this case, an overexpression of the p53 gene) may form an integral part of the pathogenetic sequence and may attempt to explain the pathogenesis of BCC. A published article by Zhang et al demonstrates that the UV-specific nucleotide changes in 2 tumor suppressor genes, p 53 and PTCH, are both implicated in the development of early-onset BCC.
Immunologically, the mechanism by which prolonged UV radiation exposure leads to the development of BCC includes suppression of the cutaneous immune system and immunologic unresponsiveness to cutaneous tumors. This local effect includes a decrease in Langerhans cells, dendritic epidermal T cells, and Thy1+ cells. Furthermore, systemic proliferation of suppressor T cells and the release of immunosuppressive factors (eg, tumor necrosis factor-a [TNF-a], interleukin 1 [IL-1], prostaglandin [PG], interleukin 10 [IL-10]) are believed to be pathogenic to the development of BCC.
Frequency
United States
Solar radiation exposure is the most important etiologic factor in the genesis of BCC. The tumor most commonly arises in the lower eyelid (48.9-72.1%), followed by the medial canthus (25-30%), the upper eyelid (15%), and the lateral canthus (5%). Review of the literature showed all authors agreed that BCC most commonly occurs in the lower eyelid; however, the remaining anatomical locations and the incidence of occurrence differ among authors.
In the United States, the prevalence of BCC is approximately 1 million with more than 900,000 cases developing in the head or the neck. The age- and sex-adjusted incidence rates for BCC are 14.25 cases per 100,000 individuals per year.
Patients with AIDS are at a greater risk of developing BCC.
Mortality/Morbidity
BCC is slow growing, locally invasive and destructive, and rarely metastasizes (0.0028-0.1%); thus, a metastatic workup often is not indicated. However, cases of metastatic lesions arising from a primary BCC lesion have been reported; Patel et al reported a case of BCC metastasizing to the lung.
- Death from BCC is extremely rare; however, if BCC is allowed to progress, it can result in significant morbidity, and cosmetic disfigurement is not uncommon.
- BCC arising in the medial canthus tends to be deep and invasive and may result perineural extension and loss of nerve function.
- Pieh et al reported a recurrence rate of 5.36% after the first excision of the tumor; the rate increased to 14.7% after the second operation, and the rate reached 50% after the third and fourth operations. The highest recurrence, approximately 60%, was seen with lesions arising from the medial canthus, since these lesions tend to be more invasive and difficult to manage.
- The incidence of BCC increases in patients who are immunocompromised.
Race
BCC occurs more commonly in white or light-skinned individuals than in blacks or in Asians.
Sex
BCC is slightly more common in males than in females with a male-to-female ratio of 3:2.
- The lifetime risk for developing BCC approaches 40% in men and 30% in women.
- Cook et al reported the incidence of BCC to be equal for both men and women.
- Also, according to Cook et al, the age-adjusted incidence rates for all malignant tumors of the eyelid in men were 19.6 cases per 100,000 population per year, and, in women, the rates were 13.3 cases per 100,000 population per year. The age-adjusted incidence rates for BCC of the eyelid for men and women were 16.9 and 12.4, respectively, per 100,000 population per year, as reported by Cook et al.
Age
The incidence of BCC increases with advancing age and tends to occur in the seventh decade of life. The median age at diagnosis is 67 ± 2.5 years, and the mean age is 64.4 ± 5.6 years (age range, 20-90 y). Approximately 5-15% of cases of BCC occur in patients aged 20-40 years.
Clinical
History
- Patients often present complaining of a nonhealing ulcer that often bleeds with mild trauma (eg, wiping or drying after a shower).
- History also may elicit a long history to sun exposure early in life and/or an outdoor occupation.
- Presenting symptoms are often painless.
Physical
Clinically, several variants of BCC exist. However, most tumors present with the following characteristics: painless nodule, shiny and waxy, indurated, firm and immobile, pearly, rolled border, and with fine (small) telangiectatic vessels on the surface.
Clinically, BCC can be grouped into 3 types: nodular, nodulo-ulcerative (rodent ulcer), and morpheaform or sclerosing.
- Nodular
- Most common
- Presents as a firm, shiny, pearly nodule with fine telangiectasia
- Slow growing, 0.5 cm in 1-2 years
- May become pigmented due to the presence of melanin (secondary melanosis) and can be misinterpreted clinically as malignant melanoma
- Fine vessels may bleed, resulting in hemosiderin deposition.
- Tumor may present as a cyst, which can be mistaken for inclusion cysts of the eyelid.
- Undetected or left untreated, the tumor nodule may undergo central ulceration to become an early form of nodulo-ulcerative BCC.
- Nodulo-ulcerative
- Characterized by central ulceration, which can be extensive in neglected cases; hence, rodent ulcer, the other name for this type of BCC
- Tumor margin is raised with rolled pearly borders.
- Dilated blood vessels course over tumor borders.
- If left untreated, the tumor can involve and erode a large portion of the eyelid.
- Morpheaform (sclerosing)
- Least common
- Tumor appears as a pale, well-defined, indurated plaque.
- Tumor borders are ill defined.
- Tumor tends to grow laterally beneath the epidermis; therefore, the lesion may be more extensive on palpation than on inspection.
Causes
The risk factors for developing BCC include the following:
- Prolonged unprotected exposure to the sun
- White race
- Lightly pigmented skin, eyes, and hair
- Increased age (usually seen in the sixth and seventh decades)
- Freckling
- Inability to tan
- Male
- Prolonged redness after exposure to sunlight
- Exposure to ionizing radiation and environmental exposures (eg, hydrocarbons, pesticides)
- Genetic determinants, such as inherited defects in DNA replication and/or repair (eg, xeroderma pigmentosa)
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Further Reading
Keywords
eyelid basal cell carcinoma, BCC, skin tumors, skin malignancies, skin cancer, epithelial tumors
