Patient presents with mass on right eye

The vascular, pink conjunctival mass was present for 5 years and was increasing in size.

Jane Loman

Zinaria Williams

A 77-year-old man presented to the cornea service complaining of a right eye mass accompanied by redness and tearing for several years. The mass had been present for 5 years and was increasing in size. His vision was unaffected throughout this period. Before this presentation, the patient was evaluated by the oculoplastic service and was scheduled for a biopsy. At that time, he refused and was lost to follow-up. Nine months later, he was referred again by his primary care doctor for re-evaluation.

History

His medical history was significant for several facial basal cell carcinomas, which had been successfully treated with local excision. He had no significant ocular history. The patient was not taking any medications and had no allergies. Family history, social history and review of systems were noncontributory.

Examination

On examination, the patient had visual acuity with correction of 20/30 in the right eye and 20/25 in the left. Pupils were normal in both eyes. IOP was 13 mm Hg in the right eye and 15 mm Hg in the left. Confrontation visual fields and extraocular muscle movements were full in both eyes.

The margin-reflex distance was 0 mm on the right and 3.5 mm on the left. The inferior limbal scleral show was 2 mm in both eyes. No lagophthalmos was present in either eye. Levator function was 11 mm on the right and 15 mm on the left. Hertel exophthalmometry showed excursion of 20 mm in both eyes with a lateral orbital rim distance of 97 mm.

External examination of the right eye revealed a large conjunctival mass involving the superior conjunctiva and extending 5 mm onto the superior cornea (Figures 1a-d). Its appearance was vascular with a non-uniform pink to salmon color and frond-like surface. Slit-lamp examination revealed a thickened right upper eyelid with extensive papillary changes on the upper palpebral conjunctiva. The remainder of the examination including posterior segment was normal except for early nuclear sclerotic cataracts in both eyes.

Large right conjunctival and corneal mass.
Images: Yoon MK, Soukiasian SH

What is your diagnosis?

Eye mass

The differential diagnosis for conjunctival and corneal masses is broad. They are categorized in many topics, such as age of presentation (congenital vs. age-related) and malignant potential (benign vs. malignant). Furthermore, masses can be broken down into their tissue composition.

In this patient, the lesion was clearly not congenital. Based on appearance, many other types of lesions could be excluded. Potential benign lesions in the differential include papilloma, keratoacanthoma, hereditary benign intraepithelial dyskeratosis, epithelial inclusion cyst, dacryoadenoma and actinic keratosis. None of these lesions have the type of fleshy, vascular appearance that the patient’s had.

The most common malignant neoplasm of the conjunctiva is squamous cell carcinoma or conjunctival intraepithelial neoplasia. These are pathologically the same type of neoplasm with different stages. Malignant melanoma typically does not have this gross appearance. Instead, it typically has a dark focal appearance with prominent epibulbar vessels. Only rarely are there amelanotic or hypomelanotic melanomas. Vascular tumors such as pyogenic granuloma are possible because of the red and vascular appearance; however, they usually occur in the setting of previous trauma or inflammation, which this patient did not have on history. Capillary hemangioma and Kaposi’s sarcoma are not likely in this setting because hemangiomas typically appear in childhood and Kaposi’s sarcoma is rare without HIV infection.

Another major type of tumor to consider is lymphoma. Typically described as a salmon-colored mass, lymphoma should be considered when a conjunctival lesion has this appearance. Although rare, given the patient’s history of multiple skin cancers, basal cell carcinoma of the conjunctiva should be considered. The mass appearance, however, was not characteristic of conjunctival basal cell carcinoma.

Diagnosis

The patient consented to undergo incisional biopsy of the mass. Nine of eleven biopsy sites were positive for squamous cell carcinoma. The two negative biopsies were obtained from the inferior fornix and lower palpebral conjunctiva. Subsequently, the patient was seen by otolaryngology for laryngoscopic examination and to rule out regional extension. No spread of the tumor was found.

Discussion

Squamous cell carcinoma is the most common malignant neoplasm of the conjunctiva. It has been reported to occur in 0.02 to 0.35 cases per 100,000 people. Major risk factors for development of squamous cell carcinoma include infection with human papilloma virus type 16 and 18, ultraviolet and sunlight exposure, exposure to petroleum products, cigarette smoking, family history and HIV infection. Men are more commonly affected than women, and average onset is in the sixth and seventh decades. Persons with HIV/AIDS can develop squamous cell carcinoma at a much earlier age, and the disease can be more aggressive.

The appearance of squamous cell carcinoma is variable. It can take on the form of a sessile, gelatinous or papillomatous lesion. If hyperkeratosis is present, it can have a leukoplakic appearance. This tumor is slow-growing and extends via lateral spread. Often, there can be expansion to involve the cornea.

Almost all dysplastic lesions of the conjunctiva or cornea involve the corneoscleral limbus. The limbus is the location of the epithelial stem cells for the cornea and conjunctiva, thus there is high mitotic activity. When in conjunction with infection with human papilloma virus, there is believed to be an increased chance of mutation. This is analogous to the squamocolumnar junction of the cervix, where most cervical cancer begins with co-infection with HPV. Type 16 is most commonly implicated.

Drastic decrease of the tumor with red inflammatory tissue.

There has been recent change in the classification of squamous cell carcinoma. The term conjunctival intraepithelial neoplasm is used to describe the presence of tumor in the spectrum from benign to malignant neoplasms. Dysplasia, a change of cell polarity with possible cell atypia, can be used to histologically describe these types of cells. Carcinoma-in-situ describes the presence of dysplastic cells in the entire thickness of the epithelium. When there is invasion through the basement membrane, the lesion is called squamous cell carcinoma.

Two uncommon subtypes of squamous cell carcinoma are worthy of note: spindle cell carcinoma or pseudosarcomatous carcinoma and mucoepidermoid carcinoma. These are rare, aggressive forms that tend to invade the deeper structures in the eye and orbit. Excision can be curative, but recurrences are common.

Diagnosis of squamous cell carcinoma is made by excisional biopsy. An attempt should be made to find the limits of the lesion through careful examination. In large lesions in which there would be extensive tissue loss, incisional biopsy could be used. However, this must be performed with caution because melanotic tumors can have an increased chance of recurrence if incised. Pathologic diagnosis is the key because clinical appearance is not reliable.

Histologically, the tumor is well differentiated. Atypical epithelial cells with mitotic figures can be found within the lesion. Acanthosis and surface keratinization are common. Inflammatory cells can be found in the surrounding stroma.

Treatment options are diverse and have been shown to have a wide variation in success. The traditional treatment is excisional biopsy with cryotherapy applied to the margins. Multiple techniques for surgical excision have been described. The major criteria for complete excision without recurrence are presence of tumor in the excision margins. Thus, reports of recurrence range between 5% and 56%. This can be difficult, requiring technically difficult Mohs surgery and frozen section analysis.

Beta radiation with strontium 90 has been described in the literature by Lommatzsch. Application is performed via external beam or custom-designed plaque therapy. This is most successful in lymphoma or metastatic carcinoma.

Use of chemotherapeutic agents such as 5-fluorouracil and mitomycin C has been described. Efficacy has been shown in several studies. These treatments work only for epithelial disease and will therefore have limited efficacy with deeper invading tumors. Side effects include local irritation, epithelial defects, pain and irritation, and scleral melt. Intolerance to therapy is also a concern with these agents.

Twelve months after initiation of treatment with resolution of inflammatory tissue.

Finally, interferon alfa-2b has been used to treat squamous cell carcinoma. This medication is a recombinant drug derived from a family of glycoproteins that act as cell surface receptors to produce antiviral and antitumor effects. The exact mechanism of action is unknown. Interferon has also been used to treat condylomata acuminatum, chronic hepatitis, malignant melanoma and hairy-cell leukemia. It can be administered as topical drops (1 million units in 1 mL four times a day) or subconjunctival injection (3 million units in 1 mL). Although prolonged treatment may be necessary, the side effect profiles are favorable. Patients have good tolerance of the medication, there is no corneal toxicity, and there are no known carcinogenic properties. In terms of efficacy, Boehm and Huang reported treating six patients with topical interferon alfa-2b successfully with no evidence of recurrence. Resolution can occur in as little as 3 to 6 weeks.

Patient course

The patient underwent treatment with topical interferon alfa-2b because of its favorable side effect profile and reported efficacy. In addition, the large size of the tumor would have made surgical excision and reconstruction difficult. The patient was treated for 9 months and had careful follow-up.

The presence of biopsy-proven chronic inflammatory tissue without presence of tumor, most likely pyogenic granuloma, was found and treated successfully with prednisolone acetate 1% four times a day for 5 months with complete resolution (Figure 2).

Twelve months after initiation of therapy, the patient remains free of recurrence (Figure 3).

For Your Information:

• Michael K. Yoon, MD, and Sarkis H. Soukiasian, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866.

• Edited by Jane Loman, MD, and Zinaria Williams, MD. Drs. Loman and Williams can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Loman and Williams have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.