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Ophthalmology > LID
Squamous Cell Carcinoma, Eyelid
Article Last Updated: Aug 14, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Michael T Yen, MD, Associate Professor of Ophthalmology, Department of Ophthalmology, Division of Ophthalmic Plastic, Lacrimal, and Orbital Surgery, Cullen Eye Institute, Baylor College of Medicine
Michael T Yen is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, American Society of Ophthalmic Plastic and Reconstructive Surgery, and Association for Research in Vision and Ophthalmology
Editors: Ron W Pelton, MD, PhD, Private Practice, Colorado Springs, Colorado; Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles; Mark T Duffy, MD, PhD, Consulting Staff, Division of Oculoplastic, Orbito-facial, Lacrimal, and Reconstructive Surgery, Green Bay Eye Clinic, BayCare Clinic; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Author and Editor Disclosure
Synonyms and related keywords:
adenoacanthoma, adenoid squamous cell carcinoma, invasive squamous cell carcinoma, malignant squamous cell carcinoma, pseudoglandular squamous cell carcinoma
Background
Squamous cell carcinoma of eyelid is a relatively rare malignant epithelial tumor that typically affects elderly fair-skinned individuals. Certain benign and malignant epithelial tumors may simulate squamous cell carcinoma both clinically and histopathologically; earlier studies may have overestimated the frequency of squamous cell carcinoma.
Although not nearly as common as basal cell carcinoma of the eyelids, previous studies have found it to be the second or third most common eyelid malignancy, accounting for approximately 5% of all eyelid neoplasms. Squamous cell carcinoma may arise de novo or from preexisting lesions such as actinic keratosis. It also may develop in patients with xeroderma pigmentosum or following radiation therapy to the eyelids.
Pathophysiology
Squamous cell carcinoma is found frequently in areas of the body that are exposed to sunlight. Similarly, many precancerous lesions (eg, actinic keratosis, Bowen dermatosis) also appear to be related to ultraviolet light exposure. Squamous cell carcinoma can develop even if the history of sun exposure occurred decades prior to development of the skin lesion.
Occupations with considerable exposure to oils or tar may be associated with increased incidence of squamous cell carcinoma of eyelids. In patients with xeroderma pigmentosum, defective DNA repair causes predisposition for development of malignant epithelial lesions, including squamous cell carcinoma.
Although typically observed in elderly patients, squamous cell carcinoma may be seen in younger patients with a history of radiotherapy or in patients infected with HIV. Human papillomavirus infection or p53 overexpression may play a role in development of squamous cell carcinoma in patients who are infected with HIV.
Frequency
United States
Incidence of squamous cell carcinoma has been reported in the literature to account for 2.4-30.2% of malignant eyelid tumors. Kwitko found that out of 115 tumors originally diagnosed as squamous cell carcinoma at the Armed Forces Institute of Pathology, only 12 were diagnosed correctly after reevaluation. More recent studies have estimated that squamous cell carcinoma accounts for approximately 5% of malignant eyelid tumors.
Mortality/Morbidity
Unlike basal cell carcinoma of eyelid, squamous cell carcinoma can be an aggressive tumor that has potential to invade the orbit, metastasize to lymph nodes and distant sites, and cause death.
- Incidence of metastasis from cutaneous squamous cell carcinoma has been found to be 0.23-2.4% of cases. However, tumors arising from areas of previous radiation therapy may have an incidence of metastasis as high as 20%.
- Squamous cell carcinoma may be more aggressive in patients who are immunocompromised.
Race
Squamous cell carcinoma is more common in fair-skinned individuals, especially those who have been chronically exposed to sunlight.
Sex
Squamous cell carcinoma may be slightly more common in males than in females. However, this may be due to certain occupations that entail more significant exposure to sunlight or other occupational hazards such as soot, oils, or tars.
- Age-adjusted incidence rates from Olmsted County, Minnesota are 2.42 (men) and 0.67 (women) cases per 100,000 population per year.
- In Sweden, relative incidences are 0.13 (men) and 0.093 (women) per 100,000 population per year.
Age
Incidence of squamous cell carcinoma increases significantly with age.
- Cook and Bartley reported age- and gender-adjusted incidence rate per 100,000 per year to be 0.00 in men aged 40-49 years and 29.99 in men older than 80 years. Incidence rate was 1.21 for women aged 40-49 years and 11.44 in women older than 80 years.
- Dailey found that 80% of their patients with squamous cell carcinoma were older than 60 years.
- Patients who are immunocompromised develop squamous cell carcinoma at a younger age. In a study of cutaneous squamous cell carcinoma, mean age of patients infected with HIV was 49 years, whereas mean age of patients who were not immunocompromised was 75 years.
History
A complete past medical and ocular history should be obtained.
- Existing medical conditions such as xeroderma pigmentosum, or previous history of cutaneous malignancies (basal cell, squamous cell, sebaceous cell carcinoma, malignant melanoma)
- Immunocompetency of patient (HIV risk factors, history of organ transplant, current chemotherapy)
- History of significant sun exposure, occupational exposures (oils, tars, soot)
- Previous history of benign eyelid lesions (actinic keratosis, chalazion); recurrence after treatment of eyelid lesion
- Duration for which eyelid lesion has been present
- Change in size, contour, or color of lesion
- Ocular symptoms (decreased vision, diplopia, increasing proptosis, ocular surface irritation)
Physical
- External examination
- Location of lesion (upper/lower eyelid, medial/lateral/central eyelid); squamous cell carcinoma more common on lower eyelid
- Size of lesion
- Character of lesion (smooth/nodular, vascularity, color); squamous cell carcinoma may appear as plaques or nodules with variable degrees of scale, crust, or ulceration
- Presence of ulceration
- Loss of lashes or destruction of normal eyelid architecture
- Evaluation of subcutaneous tissues (depth of lesion, bony involvement)
- Examination of conjunctiva for involvement (hyperemia, dyskeratosis)
- Hertel exophthalmometry, if orbital extension is suspected
- Palpation of preauricular, submandibular, and cervical lymph nodes
- Ocular examination
- Visual acuity
- Slit lamp examination and fundus examination to exclude other causes of symptoms
Causes
- Risk factors for squamous cell carcinoma include the following:
- Sunlight (ultraviolet light) exposure, especially in fair-skinned individuals
- Soot, chimney sweepers
- Arsenic fumes or medications
- Coal tar
- Paraffin oil
- Radiation exposure
- Precancerous dermatoses
Basal Cell Carcinoma, Eyelid
Blepharitis, Adult
Chalazion
Dermatitis, Atopic
Dermatitis, Contact
Hordeolum
Squamous Cell Carcinoma, Conjunctival
Xanthelasma
Other Problems to be Considered
Actinic keratosis
Eyelid malignant melanoma
Eyelid sebaceous cell carcinoma
Lab Studies
- Liver function tests, if metastasis is suspected
- Genetic analysis for xeroderma pigmentosum, if patient is young and there is no history of occupational exposure or excessive sun exposure
- HIV test, if patient is young and there is no history of occupational exposure or excessive sun exposure, and xeroderma pigmentosum has been excluded
Imaging Studies
- CT scan
- To evaluate depth of extension into orbit and bony erosions
- Liver scans or full body CT scan, if metastasis is suspected
Other Tests
- Photography - To document appearance of lesion
Procedures
- Incisional biopsy for histological diagnosis
Histologic Findings
Squamous cell carcinoma may arise de novo or from premalignant lesions such as actinic keratosis or intraepidermal carcinoma (carcinoma in situ). Intraepidermal squamous cell carcinoma is characterized by full-thickness epidermal atypia (cellular atypia, loss of polarity, pleomorphic and/or hyperchromatic nuclei, mitotic figures, and parakeratosis).
Invasive squamous cell carcinoma is present when cellular atypia penetrates through the epidermal basement membrane.
In well-differentiated squamous cell carcinoma, cells are polygonal with abundant cytoplasm. Dyskeratotic cells with keratin pearls are present. Nuclei are prominent, hyperchromatic, and pleomorphic. Mitotic figures are commonly present; loss of polarity of normal epidermal architecture can be seen. Poorly differentiated lesions may show little or no evidence of keratinization.
Medical Care
- All patients should be advised to protect their eyelids from sun exposure.
- Physical sunblocks with the active ingredients of zinc oxide or titanium oxide provide the most complete protection from UVA and UVB rays.
- Alternatively, a combination chemical sunblock of octocrylene, ecamsule, and avobenzone also provides excellent broad-spectrum UV protection.
- If systemic metastasis is discovered, the patient should be referred to an oncologist for adjunctive chemotherapy.
Surgical Care
- Complete excision of lesion
- Mohs micrographical excision - Fresh tissue technique of Mohs has been advocated as the treatment of choice. Mohs reported a 5-year cure rate of 98.1% in 213 cases of eyelid squamous cell carcinomas that had been treated.
- Wide local excision with frozen-section monitoring of margins may be performed when Mohs micrographical excision is not readily available.
- Radiation therapy - For patients who are unwilling or medically unable to undergo an extensive excision of the lesion
- Photodynamic therapy with 5-aminolevulinic acid (ALA) - For patients with discrete eyelid lesions who are unable or unwilling to undergo an extensive surgical excision of the lesion
- Cryotherapy - For patients who refuse surgery or are poor surgical candidates
- Orbital exenteration - In cases with secondary orbital invasion
Consultations
- Otolaryngologist, if regional lymph node metastasis is present and patient requires lymph node dissection and/or neck dissection
- Oncologist, if systemic metastasis is present
- Radiation oncologist, if patient is unable to undergo surgical excision of lesion and radiotherapy is desired
Activity
- Protection from sunlight may significantly reduce risk of developing squamous cell carcinoma.
- Use of sun block, wearing protective clothing, and avoiding excessive sun exposure should be recommended to all patients, especially fair-skinned elderly patients.
- Even young patients should be advised to take precautions against excessive sun exposure to reduce risk of developing cutaneous malignancies in future.
Further Outpatient Care
- After excision, patients should be observed for the following:
- Recurrence of previously excised malignancy
- Development of other epithelial eyelid tumors (basal cell carcinoma)
Deterrence/Prevention
Prognosis
- Prognosis for cure is excellent if the lesion is detected early and complete excision is performed. However, with exposure to risk factors, patients still require vigilant follow-up care because they continue to be at risk for development of additional cutaneous skin malignancies (basal cell carcinoma and squamous cell carcinoma) of eyelid.
Patient Education
Medical/Legal Pitfalls
- Although rare, squamous cell carcinoma does have the potential to metastasize.
- Delay in diagnosis may result in liability claims against ophthalmologist.
- For definitive diagnosis, a biopsy should be performed on eyelid lesions suggestive of squamous cell carcinoma.
| Media file 1:
This 35-year-old man who is HIV positive presented with a 2-year history of a slowly enlarging, left lower eyelid lesion; incisional biopsy revealed squamous cell carcinoma. |
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Media type: Photo
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| Media file 2:
Axial MRI of a large squamous cell carcinoma of the left lower eyelid with invasion of the anterior orbit. |
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Media type: MRI
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| Media file 3:
External photograph of a large ulcerated invasive squamous cell carcinoma of the left lower eyelid. This patient also had perineural invasion of the infraorbital nerve extending into the cranial base. |
 | View Full Size Image | |
Media type: Photo
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Squamous Cell Carcinoma, Eyelid excerpt Article Last Updated: Aug 14, 2006
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