SQUAMOUS CELL CARCINOMA

Signs and Symptoms

Squamous cell carcinoma (SCC) is the second most common malignant neoplasm of the eyelid (after basal cell carcinoma), accounting for 5% to 10% of all eyelid neoplasms in the United States.1-3 SCC is most often encountered in fair-skinned individuals over 60 years of age, particularly those who have a history of chronic or excessive sun exposure.2-5 Studies have identified a nutritional risk factor for SCC development as well; diets rich in fats (e.g., cream and whole-milk dairy products) are associated with a higher incidence of SCC, whereas high intake of leafy green vegetables appears to be protective for SCC.6,7

Although there is no “classic” presentation, patients often demonstrate a roughened, scaly patch of tissue; the area is typically red, elevated and nodular, with crusted and/or bloody margins. Often, patients will describe the lesion as “a scab that will not heal.” Other signs that may be associated with SCC include a history of rapid growth, asymmetrical shape, telangiectatic vessels, and focal loss of lashes (madarosis). Periocular carcinomas tend to occur most frequently on the lower lid or lid margin, followed by the medial canthus and upper lid or lateral canthus.1,4,5

Patients with SCC are rarely symptomatic beyond cosmetic concerns when the lesions present in their earliest stages (local to the epidermis). When the lesions invade tissue or occur in tissues with mucous membranes such as the conjunctiva or caruncle, unlike basal cell carcinoma, they can present as painful masses.8 As the lesions acquire depth, they have the capability of invading deeply into tissues or transferring into other body cavities by growing along nerves (perineural invasion).9,10 This often leads to malfunction of the affected nerve, causing pain or numbness along its distribution.9,10 Acuity is not affected unless the lesion is so large it obscures the visual axis.

Pathophysiology

Squamous cell carcinoma is a potentially invasive tumor derived from surface epithelium. In the early stages, normal epithelial cells are replaced by atypical squamous cells throughout the epidermis, resulting in a loss of normal maturation. This stage is sometimes referred to as squamous cell carcinoma-in-situ. Continued growth along with the production of matrix metalloproteinases and other factors can bring about disruption of the basement membrane and subsequent tumor spread into the underlying dermis; when this occurs, the lesion is referred to as invasive squamous cell carcinoma.11

While no single causative agent for the development of SCC has been identified, it is clear that ultraviolet radiation is a substantial risk factor and demonstrates a distinct association with this disease.2,11-13 This is supported by the finding that the majority of ocular squamous cell tumors arise on the lower lid margin and medial canthus, the two periocular areas most susceptible to sunlight exposure. Additional risk factors may include exposure to arsenic, hydrocarbons, radiation or immunosuppressive drugs.2,11

Like other malignant forms of skin cancer, invasive squamous cell carcinoma possesses the capacity for both local invasion with destruction of normal periocular architecture, as well as lymphatic, hematogenous and neurotropic spread—a process referred to clinically as metastasis.14

Management

The preferred management of virtually all malignant periocular lesions involves surgery. While radiation therapy, chemotherapy or cryotherapy may achieve some success, the potential for complications combined with high recurrence rates make these options less desirable. Typically, nonsurgical treatment modalities are employed only when the patient refuses surgical intervention or when a procedure is considered intolerable due to other health concerns.

When SCC excision is performed, wide margin excision is recommended with histological confirmation of the surgical margins.15 In one study published in 2006, researchers created a 5mm margin beyond the clinically identifiable borders of the lesion; however, the authors acknowledge that “the actual tumor edge may be difficult to determine clinically, and the result is an increased surgical tissue defect.”15

Mohs micrographic surgery represents an alternative to wide-margin excision.1 The Mohs technique examines en-face frozen-prepared sections of the entire outer surface of excised tissue, rather than just the lateral borders. This procedure carries the lowest reported rate of recurrence for SCC (3.64%) while affording maximal preservation of normal tissue, as compared to all other treatment modalities.1 However, Mohs surgery is also quite time consuming and expensive. Hence, many oculoplastics specialists still prefer wide-margin excision for small, initial or uncomplicated cases of SCC.

Clinical Pearls

SCC in its early stages may be easily confused with a multitude of other eyelid lesions, both malignant and benign. Some of these lesions include basal cell carcinoma, sebaceous gland carcinoma, follicular keratosis, actinic keratosis, seborrheic keratosis and keratoacanthoma.

While SCC is the second most common eyelid malignancy, it is far less common than basal cell carcinoma, which represents about 90% of malignant eyelid neoplasms.16

While squamous cell carcinoma does possess the ability to invade local tissues and metastasize to other organ systems, it is not a particularly aggressive tumor. Its rate of development is quite slow, and metastasis is exceedingly rare. Still, the potential for damage exists in cases where diagnosis and treatment are delayed.

Early biopsy is the key to diagnosis. Suspicious lid lesions, which demonstrate irregular growth, changes in color or appearance, or discharge of a purulent or bloody nature should be biopsied to rule out cancerous entities.

Confirmed malignancies should be referred promptly for treatment by an oculoplastic specialist or, where possible, an ocular oncologist.

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6. Hughes MC, Pols JC, Marks GC, et al. Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study. Int J Cancer. 2006;119(8):1953-60.

7. Ibiebele TI, van der Pols JC, Hughes MC, et al. Dietary pattern in association with squamous cell carcinoma of the skin: a prospective study. Am J Clin Nutr. 2007;85(5):1401-8.

8. Van De Put MA, Haeseker BI, De Wolff-Rouendaal D, De Keizer RJ. Squamous cell carcinoma of the lacrimal caruncle: case reports. Eur J Ophthalmol. 2014;24(3):441-5.

9. Adams CC, Thomas B, Bingham JL. Cutaneous squamous cell carcinoma with perineural invasion: a case report and review of the literature.Cutis. 2014;93(3):141-4.

10. Tyers AG. Orbital exenteration for invasive skin tumours. Eye (Lond). 2006;20(10):1165-70.

11. Sullivan TJ. Squamous cell carcinoma of eyelid, periocular, and periorbital skin. Int Ophthalmol Clin. 2009;49(4):17-24.

12. Melnikova VO, Ananthaswamy HN. Cellular and molecular events leading to the development of skin cancer. Mutat Res. 2005;571(1-2):91-106.

13. Mehta M, Fay A. Squamous cell carcinoma of the eyelid and conjunctiva. Int Ophthalmol Clin. 2009;49(1):111-21.

14. Kerkelä E, Saarialho-Kere U. Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer. Exp Dermatol. 2003;12(2):109-25.

15. Nemet AY, Deckel Y, Martin PA, et al. Management of periocular basal and squamous cell carcinoma: a series of 485 cases. Am J Ophthalmol 2006; 142(2):293-7.

16. Prabhakaran VC, Gupta A, Huilgol SC, Selva D. Basal cell carcinoma of the eyelids. Compr Ophthalmol Update. 2007;8(1):1-14.