Patient seen for redness in left eye

Jeffrey Chang

Vivek Chaturvedi

A 47-year-old man with a history of AIDS was referred to the New England Eye Center for a red left eye, noted for the past 2 days by his caretaker. The patient had poor mental status and could not provide much information; however, he did note mild to moderate pain in the left eye.

In addition to AIDS (CD4 count less than 50), the patient’s medical history was significant for progressive multifocal leukoencephalopathy and disseminated cytomegalovirus. He had no ocular history. His medications included multiple HAART medications and psychiatric medications. His social history and family history were not well-known.

Examination

On examination, the patient’s best corrected visual acuity was 20/30 in the right eye and 20/70 in the left eye. His pupils were equal and reactive with no afferent pupillary defect. He had a severe left exotropia; motility otherwise was grossly full. IOPs were within normal limits in both eyes.

Slit lamp examination revealed a papillomatous lesion on the nasal bulbar conjunctiva, approaching the limbus, with prominent dilated episcleral blood vessels. A gray gelatinous lesion extended circumferentially around the limbus from approximately 5 o’clock to 2 o’clock (total 9 clock-hours), with “frosted-glass” extensions on the corneal surface. Additionally, there were multiple areas of melanosis within the lesion (Figures 1 to 3).

Figures 1-3. Anterior segment photos of the left eye demonstrating a gray gelatinous lesion extended circumferentially around the limbus with dilated episcleral blood vessels, “frosted-glass” extensions on the corneal surface and multiple areas of melanosis within the lesion. Images: Batta P, Keshet M, Hu D

What is your diagnosis?

Conjunctival lesion

The differential diagnosis for conjunctival surface lesions includes both benign and malignant entities.

Among the benign lesions is squamous papilloma, the most common benign neoplasm of the conjunctiva. It is associated with human papillomavirus and appears as clumps of pink fibrovascular fronds of tissue, either sessile or pedunculated, with marked hyperkeratosis and acanthosis on pathology. Other benign lesions include keratoacanthoma, an elevated fleshy lesion resulting from hyperkeratosis and inflammation; keratotic plaques, which are rare and may be accompanied by leukoplakia; and actinic keratosis, a frothy white lesion usually seen over a pinguecula or pterygium. Although benign, these lesions are usually excised in order to relieve irritation, improve cosmesis and rule out malignancy.

The primary malignancy of concern in this patient’s case is squamous cell carcinoma, as well as its precursor, conjunctival intraepithelial neoplasia. Conjunctival intraepithelial neoplasia, also called carcinoma in situ, refers to partial or full-thickness replacement of the conjunctival squamous epithelium by dysplastic, rapidly proliferating cells. Conjunctival intraepithelial neoplasia, as the full name implies, is entirely intraepithelial; the abnormal cells do not extend past the basement membrane of the epithelium. In invasive squamous cell carcinoma, the tumor cells have broken through the basement membrane to invade underlying stroma, and these lesions are therefore capable of metastasis. Squamous cell carcinoma and conjunctival intraepithelial neoplasia are clinically indistinguishable; biopsy and histopathology are required for differentiation between the two. On examination, these malignant squamous lesions can have papillomatous, gelatinous and leukoplakic components.

Figure 4. Anterior segment photo of the left eye, post-excision, showing recurrence of disease at the nasal limbus.

Management includes several options. Larger lesions generally should be excised, and topical chemotherapy, such as mitomycin C or interferon, can be used either as adjuvant treatment or subsequent to the excision in order to prevent recurrence. However, some tumors can be treated with only topical chemotherapy without excision, with repeat cycles until the tumor regresses; several studies have shown that this is effective particularly for smaller lesions. Notably, patients with AIDS or other immunocompromised conditions tend to present with more aggressive squamous lesions.

Other less likely malignant lesions to consider in this patient’s case include sebaceous cell carcinoma and malignant melanoma. Sebaceous cell carcinoma originates from glandular components of the eyelid but may display pagetoid spread to the bulbar conjunctiva. Melanoma is usually a darkly pigmented lesion but may exhibit features that mimic squamous cell lesions. Both of these cancers are more aggressive, display higher rates of metastasis and have a poorer prognosis than squamous cell carcinoma.

Diagnosis and management

This patient’s lesion was clinically suspected to be squamous cell carcinoma. Surgical excision was performed, with cryotherapy applied to its margins. The tumor base extended about 20 mm nasally, superiorly and inferiorly from the limbus, with about 10 clock hours involved. Given the extent of conjunctival excision, an amniotic membrane was applied. Histopathology showed conjunctival intraepithelial neoplasia; despite the wide excision, tumor cells were found at the margins of the excised tissue. After 1 month, the patient was noted to have recurrence of disease at the nasal limbus (Figure 4). He is currently receiving topical chemotherapy with mitomycin C.

References:

• Frucht-Pery J, Rozenman Y, Pe’er J. Topical mitomycin-C for partially excised conjunctival squamous cell carcinoma. Ophthalmology. 2002;109(3):548-552.
• Karp CL, Moore JK, Rosa RH Jr. Treatment of conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b. Ophthalmology. 2001;108(6):1093-1098.
• McKelvie PA, Daniell M, McNab A, Loughnan M, Santamaria JD. Squamous cell carcinoma of the conjunctiva: a series of 26 cases. Br J Ophthalmol. 2002;86(2):168-173.
• Peksayar G, Altan-Yaycioglu R, Onal S. Excision and cryosurgery in the treatment of conjunctival malignant epithelial tumours. Eye. 2003;17(2):228-232.
• Shields CL, Shields JA. Tumors of the conjunctiva and cornea. Surv Ophthalmol. 2004;49(1):3-24.
• Tunc M, Char DH, Crawford B, Miller T. Intraepithelial and invasive squamous cell carcinoma of the conjunctiva: analysis of 60 cases. Br J Ophthalmol. 1999;83(1):98-103.

• Priti Batta, MD, Maayan Keshet, MD, and Daniel Hu, MD, can be reached at Tufts Medical Center, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.

• Edited by Jeffrey Chang, MD, and Vivek Chaturvedi, MD.Drs. Chang and Chaturvedi 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.