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Ophthalmology > CONJUNCTIVA
Squamous Cell Carcinoma, Conjunctival
Article Last Updated: Feb 7, 2008
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Christopher DeBacker, MD, Volunteer Faculty, Department of Ophthalmology, California Pacific Medical Center; Consulting Staff, Ophthalmic Medical Associates
Christopher DeBacker is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Ophthalmology, American Society of Ophthalmic Plastic and Reconstructive Surgery, and Phi Beta Kappa
Coauthor(s):
Robert M Dryden, MD, FACS, Clinical Professor, Department of Ophthalmology, University of Arizona School of Medicine
Editors: Jerre Freeman, MD, Founder, Chairman, Memphis Eye and Cataract Associates; Clinical Professor, Department of Ophthalmology, University of Tennessee Health Science Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Hospital; 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:
conjunctival squamous cell carcinoma, squamous cell carcinoma of the conjunctiva, conjunctival intraepithelial neoplasia, CIN, SCC
Background
Squamous cell carcinoma of the conjunctiva is a malignant epithelial neoplasm characterized by basement membrane invasion or distant metastasis. Epithelial tumors of the conjunctiva are similar to conjunctival intraepithelial neoplasia (CIN).
Squamous cell carcinoma of the conjunctiva represents a form of CIN that has either broken through the basement membrane to involve the subepithelial tissue or has metastasized. Morbidity is related primarily to local involvement of the conjunctiva and cornea, although regional spread and distant metastasis are possible. Rarely ocular penetration can occur, particularly with the mucoepidermoid type.
Pathophysiology
Squamous cell carcinoma is believed to arise from limbal stem cells and presents as a mass in the interpalpebral fissure at the nasal or temporal limbus. It may have a gelatinous and velvety, papilliform, or leukoplakic appearance. Given its variable appearance, it may pose a diagnostic challenge as a masquerade syndrome.
Frequency
United States
Squamous cell carcinoma is the most common conjunctival malignancy in the United States.
International
Patients who live close to the equator tend to present at a younger age than patients who live more distant from the equator. The incidence of the disease varies geographically, 0.03-3.5 cases per 100,000 people per year.
Mortality/Morbidity
The morbidity from squamous cell carcinoma of the conjunctiva relates to the ocular side effects of the disease and its treatment, as well as regional orbital sequelae, periorbital spread, periorbital sinus involvement, and intracranial involvement. Death may result from distant or regional metastases, as well as intracranial spread.
Race
Squamous cell carcinoma of the conjunctiva is most common in Caucasian individuals.
Sex
Squamous cell carcinoma is more common in males (75%) than in females (25%).
Age
Patients with squamous cell carcinoma of the conjunctiva tend to be elderly, with an average age of 60 years. Patients with acquired immunodeficiency syndrome (AIDS) have a 13-fold increased risk of developing conjunctival epithelial malignancies; these patients also present at a younger age.
History
- Various factors have been shown to be associated with squamous cell carcinoma of the conjunctiva, including human papilloma virus (HPV) infection, cigarette smoking, petroleum products, light hair, European ancestry, actinic exposure, AIDS, and chronic wear of contact lenses.
- Individuals who are HIV positive and patients with xeroderma pigmentosa also are more likely to develop squamous cell carcinoma of the conjunctiva probably because of their diminished immune status.
- Patients may notice a conjunctival mass, which may be enlarging. Often, small conjunctival masses are noted on routine eye examinations.
- Irritation and/or chronic conjunctivitis may also be presenting signs.
Physical
Distinguishing squamous cell carcinoma from CIN is difficult on clinical examination alone.
- Most squamous cell carcinomas involving the conjunctiva manifest as chronic unilateral localized patches of redness or more diffuse conjunctivitis.
- The corneoscleral limbus is the most common location, although the palpebral conjunctiva or cornea may be involved, particularly in the interpalpebral region.
- Usually, the lesions have a gelatinous appearance with a papillomatous vessel pattern, often with overlying keratin deposition (leukoplakia), and prominent feeder vessels.
- Examination should determine the full extent of the lesion.
- Rose bengal dye is helpful for determining the exact extent of the lesion.
- Assess any suspicion for intraocular involvement via slit lamp examination, gonioscopy, and echography.
- Orbital involvement should be investigated with CT scan or MRI.
- Investigate regional spread by palpating for enlarged lymph nodes in the head and neck region.
Causes
- Purported causes of squamous cell carcinoma of the conjunctiva include the following:
- Excessive ultraviolet light
- HPV types 16 and 18
- Long-standing inflammation
- Cigarette smoking
- Petroleum products
- Light hair
- European ancestry
- Chronic wear of contact lenses
- Immunodeficiency syndrome
Burns, Chemical
Dermoid, Limbal
Melanoma, Conjunctival
Pterygium
Other Problems to be Considered
Pseudocancerous lesions - Pseudoepitheliomatous hyperplasia and keratoacanthoma
Conjunctival degeneration - Pinguecula and amyloidosis
Papillomas - HPV-induced papillomas
Cancerous lesions - Sebaceous cell carcinoma, basal cell carcinoma, and rhabdomyosarcoma
Congenital tumors - Dermoids, dermolipomas, and episcleral osseous choristoma
Neuroectodermal tumors - Nevus, primary acquired melanosis, and melanoma
Lymphoid tumors - Lymphoid neoplasia, benign reactive lymphoid hyperplasia, and leukemic infiltrates
Xanthomatous lesions - Juvenile xanthogranuloma and fibrous xanthoma
Hereditary lesions - Benign hereditary intraepithelial dyskeratosis
Vascular lesions - Angioma, lymphangioma, Kaposi sarcoma, and pyogenic granuloma
Lab Studies
- Once there is a suspicion of conjunctival squamous cell carcinoma, excisional biopsy is the treatment of choice.
- For extremely large lesions, incisional biopsy may be performed; however, strict notation of the biopsy site and minimal handling of the surrounding tissues is imperative to prevent seeding of the tumor.
- Recurrence rates as high as 50% are common for incompletely excised tumors.
Imaging Studies
- Assess any suspicion of intraocular invasion with echography.
- Assess any suspicion of orbital involvement with orbital imaging studies, preferably MRI with IV contrast enhancement.
Histologic Findings
Most squamous cell carcinomas have a gelatinous surface on gross inspection, which frequently is permeated by fibrovascular cores, giving it a papillomatous appearance.
On histologic examination, the full thickness of the epithelium is replaced by atypical, pleomorphic epithelial cells. The involved epithelium is typically 2-3 times thicker (acanthosis) than the normal adjacent epithelium. The normal polarity of the epithelial layers is lost (atypia), and mitotic figures are often present. By definition, the epithelial basement membrane layer is invaded by malignant cells, with involvement of the subepithelial tissues, and possibly adjacent eye, eyelids, and orbit. Metastasis, although rare, may occur.
Medical Care
Excisional biopsy is the treatment of choice. Topical cytotoxic therapy (ie, 5-fluorouracil [5-FU], mitomycin C [MMC]) has been used to treat CIN and to debulk large carcinomas prior to surgical excision.
Surgical Care
- Surgical excision is best performed under the operating microscope.
- Removal of a cuff of normal conjunctival tissue surrounding the lesion is prudent, and an episclerectomy at the base of the lesion is also advisable if it is adherent to the sclera in order to remove any superficial cells infiltrating the sclera.
- Involved corneal tissues may be best removed following treatment with 100% ethanol. The tissues superficial to the Bowman layer are removed easily in a single sheet and sent to the laboratory for analysis. Care should be taken not to incise into the Bowman membrane.
- Cryotherapy is performed, in a double freeze-thaw manner, to the edges of the uninvolved conjunctiva and Tenon capsule. It also can be applied to the involved limbal area.
- The exposed sclera occasionally is treated with 100% ethanol to devitalize any remaining tumor cells.
- All excised tissues are submitted for histopathologic analysis.
- Reconstruction is performed with direct closure, local flaps, or free conjunctival grafts.
- Extensive lesions with orbital involvement require exenteration.
- Radiation therapy may be used as adjunctive therapy in cases of extensive lesions with poorly defined margins and as palliative therapy in cases where the patient cannot tolerate extensive surgery.
Consultations
An oncologist should be consulted if metastatic disease is suspected.
Further Outpatient Care
- Patients should be closely observed for any signs of recurrence.
- Recurrent lesions should be treated aggressively. Occasionally, pyogenic granulomas can occur soon after tumor excision in areas of bare sclera. They typically respond quickly to topical steroid treatment and must be differentiated from recurrent tumor.
- Evaluation by the patient's internist is prudent because of the possibility of metastasis.
- Success in treating recurrences with topical mitomycin C drops has been reported.
Complications
- The primary complication is recurrence, which typically occurs within the first year after excision but may occur much later. Intraocular invasion has been demonstrated in 2-8% of cases. Orbital invasion has been reported in 12-16% of cases.
- Poor conjunctival and/or corneal healing may occur, especially if aggressive keratectomy, sclerectomy, or 100% ethanol application were performed. Symblepharon formation is a common surgical complication following tumor resection and ocular surface reconstruction.
- Limbal stem cell damage may result from excision of large lesions
Prognosis
- The prognosis is reasonably good for completely excised lesions. Various mortality rates have been reported; some reported rates are as high as 4-8%. By adhering to a policy of complete excision of all lesions, the recurrence rate should be 10% or less.
Patient Education
- Patients need to be informed that recurrences are possible even years after excision, so they should have routine eye examinations.
- The general public needs to be educated to have suspicious eye lesions, even chronic red eyes, evaluated promptly to rule out early ocular surface malignancies. Educating people who live in tropical areas and in regions with a high degree of solar exposure is particularly important.
Medical/Legal Pitfalls
- An elderly patient presents with a chronic unilateral bulbar conjunctival lesion that is excised via frozen-section control, and shown to be squamous cell carcinoma with episcleral involvement. His immediate postoperative course is uneventful. He informs the office staff that he will be moving out of the state 2 months after the operation. It is critical for the operating physician in this situation to provide the medical record and operative/pathology report to the patient and to encourage the patient to continue frequent follow-up with the new physician. The patient also should be assisted in locating a new physician to provide this care.
- A 32-year-old male patient presents with a leukoplakic lesion, the biopsy of which reveals squamous cell carcinoma. It is important for the surgeon to investigate risk factors for HIV exposure in this patient and to encourage HIV testing and follow-up care with the appropriate specialist.
Special Concerns
- Patients with an atypical pterygium may have a conjunctival tumor. These patients should be observed much more closely than patients with a classic pterygium.
| Media file 1:
Extensive conjunctival squamous cell carcinoma of the left eye. The patient has limbal and corneal involvement temporally, as well as scleral invasion with intraocular spread. A malignant cellular reaction in the anterior chamber was present. The patient was treated with a lid-sparing exenteration. |
 |  View Full Size Image | |
Media type: Photo
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- Akpek EK, Polcharoen W, Chan R, Foster CS. Ocular surface neoplasia masquerading as chronic blepharoconjunctivitis. Cornea. May 1999;18(3):282-8. [Medline].
- Erie JC, Campbell RJ, Liesegang TJ. Conjunctival and corneal intraepithelial and invasive neoplasia. Ophthalmology. Feb 1986;93(2):176-83. [Medline].
- Fraunfelder FT, Wingfield D. Management of intraepithelial conjunctival tumors and squamous cell carcinomas. Am J Ophthalmol. Mar 1983;95(3):359-63. [Medline].
- McKelvie PA, Daniell M, McNab A, Loughnan M, Santamaria JD. Squamous cell carcinoma of the conjunctiva: a series of 26 cases. Br J Ophthalmol. Feb 2002;86(2):168-73. [Medline].
- Pe'er J. Ocular surface squamous neoplasia. Ophthalmol Clin North Am. Mar 2005;18(1):1-13, vii. [Medline].
- Robinson JW, Brownstein S, Jordan DR, Hodge WG. Conjunctival mucoepidermoid carcinoma in a patient with ocular cicatricial pemphigoid and a review of the literature. Surv Ophthalmol. Sep-Oct 2006;51(5):513-9. [Medline].
- Shields CL, Demirci H, Marr BP, Masheyekhi A, Materin M, Shields JA. Chemoreduction with topical mitomycin C prior to resection of extensive squamous cell carcinoma of the conjunctiva. Arch Ophthalmol. Jan 2005;123(1):109-13. [Medline].
- Shields JA, Shields CL, De Potter P. Surgical management of conjunctival tumors. The 1994 Lynn B. McMahan Lecture. Arch Ophthalmol. Jun 1997;115(6):808-15. [Medline].
- Shields JA, Shields CL, Gunduz K, Eagle RC Jr. The 1998 Pan American Lecture. Intraocular invasion of conjunctival squamous cell carcinoma in five patients. Ophthal Plast Reconstr Surg. May 1999;15(3):153-60. [Medline].
- Tunc M, Char DH, Crawford B, Miller T. Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases. Br J Ophthalmol. Jan 1999;83(1):98-103. [Medline].
- Yeatts RP, Engelbrecht NE, Curry CD, Ford JG, Walter KA. 5-Fluorouracil for the treatment of intraepithelial neoplasia of the conjunctiva and cornea. Ophthalmology. Dec 2000;107(12):2190-5. [Medline].
Squamous Cell Carcinoma, Conjunctival excerpt Article Last Updated: Feb 7, 2008
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