Updated: Mar 9, 2007
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.
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.
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.
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.
BCC occurs more commonly in white or light-skinned individuals than in blacks or in Asians.
BCC is slightly more common in males than in females with a male-to-female ratio of 3:2.
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.
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.
The risk factors for developing BCC include the following:
Blepharitis, Adult
Chalazion
Hordeolum
Pigmented Lesions of the Eyelid
Sebaceous Gland Carcinoma
Squamous Cell Carcinoma, Eyelid
Actinic keratosis
Sebaceous hyperplasia
Nevi malignant melanoma
Keratoacanthoma
Seborrheic keratosis
Bowen disease
Cutaneous T-cell lymphoma (mycosis fungoides)
Metastatic malignancies
Nodular type: The nodular type accounts for more than 70% (73.4%) of the histologic type. Nests of basaloid cells in different sizes are present. Tumor cells show peripheral palisading. Cells have large, oval or elongated nuclei with scant cytoplasm. Cells may be pleomorphic or atypical and may contain mitotic figures. Sharp demarcation between normal cells and neoplastic cells is well visualized on microscopy. Contraction artifact at the periphery of the tumor lobules is seen; this histologic feature results from shrinkage of the mucin-rich stroma during specimen processing. Desmoplasia (pseudocarcinomatous changes) of the surrounding stroma is seen.
Variants of the nodular type include the following:
Paavilainen et al recently described nodular subtypes, to include micronodular (4.9%) and superficial (1.9%), both with a low incidence of occurrence compared to the nodular form.
Morpheaform (fibrosing) type: Tumor cells grow in thin, elongated strands or cords. Usually, this type is one cell layer thick (Indian file pattern). This type lacks desmoplasia. Proliferation of connective tissue into dense fibrous stroma is seen. Contraction artifact is observed histologically. This type tends to be more aggressive, invades deeper into the underlying tissue, and is likely to recur.
Unlike other carcinomas (eg, colorectal cancer), BCC is not commonly staged because it rarely metastasizes. Staging BCC often is reserved for large or widespread basal cell cancers. If staging is necessary, the most widely used method is the TNM system.
Histologic type, size, and location are important factors that must be taken into account when treating BCC. Traditionally, treatment modalities have included cryosurgery, radiation therapy, electrodesiccation and curettage, and surgical excision. Each method is useful in specific clinical situations, and depending on the preference and/or expertise (familiarity) of the ophthalmologist, these methods have cure rates ranging from 85-95%.
Mohs micrographic surgery has the highest 5-year cure rates for surgical treatment of both primary BCC (96%) and recurrent BCC (90%). This method uses microscopic control to evaluate the extent of tumor invasion. The 5-year recurrence rates for treated BCC after Mohs micrographic surgery was 1%, 7.5% after cryosurgery, 7.7% after desiccation and curettage, 8.7% after radiotherapy, and 10.1% after surgical excision.
A published paper in Ophthalmology reported a 5-year recurrence rate of 0% for primary tumors and of 7.8% for recurring tumors after Mohs microsurgery.
Small margin excision (ie, 2-mm margin instead of traditional 3- to 4-mm margin) with delayed primary closure is another viable option in surgical management. This procedure has been shown to be safe and efficacious with preservation of healthy tissue, allowing for less radical reconstructive surgery and/or labor intensive Mohs microsurgery.
Although there are no proven topical or systemic medications to combat BCC, tazarotene has been shown to decrease tumor size, and, in 50% of the studied cases, it has been shown to eliminate the tumor.
Decrease cohesiveness of abnormal hyperproliferative keratinocytes and may reduce potential for malignant degeneration. Modulate keratinocyte differentiation.
Retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; also may have anti-inflammatory and immunomodulatory properties. Not FDA approved for treating BCC.
Apply 0.1% to affected area qhs
Not approved
None reported
Documented hypersensitivity
X - Contraindicated in pregnancy
May cause burning or stinging sensations; discontinue if excessive irritation; rinse thoroughly if contact with eyes, eyelids, or mouth; may cause severe irritation in eczematous skin; photosensitivity may occur; may cause skin irritation; may worsen eczema
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eyelid basal cell carcinoma, BCC, skin tumors, skin malignancies, skin cancer, epithelial tumors
Hon-Vu Q Duong, MD, Ophthalmologist, Department of Ophthalmology, Westfield Eye Center
Hon-Vu Q Duong, MD is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.
Robert Copeland, MD, Chair, Associate Professor, Department of Ophthalmology, Howard University College of Medicine
Robert Copeland, MD is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.
Ron W Pelton, MD, PhD, Private Practice, Colorado Springs, Colorado
Ron W Pelton, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Ophthalmic Plastic and Reconstructive Surgery, Colorado Medical Society, Utah Medical Association, and Wilderness Medical Society
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.
Mark T Duffy, MD, PhD, Consulting Staff, Division of Oculoplastic, Orbito-facial, Lacrimal, and Reconstructive Surgery, Green Bay Eye Clinic, BayCare Clinic
Mark T Duffy, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Ophthalmic Plastic and Reconstructive Surgery, Sigma Xi, and Society for Neuroscience
Disclosure: Allergan - Botox Cosmetic Consulting fee Consulting; Quest medical - lacrimal balloons Honoraria Speaking and teaching
Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.
Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.
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