Patient referred for evaluation of a white lesion in the inferior fornix

The lesion was previously removed and grew back. The patient said the eye was red and sore.

Mark E. Patron

Andre J. Witkin

A 60-year-old man presented to our oculoplastics clinic for evaluation of a white raised lesion in his right inferior fornix. The lesion had first been noted by the patient 6 months ago.

He had been seen by a general ophthalmologist, who thought it was a chalazion and performed an incision and curettage of the lesion. The lesion grew back and was excised again 2 months later. The patient continued to have redness and irritation in the same area, and he was given a course of doxycycline with no improvement. He was then referred to our clinic. The patient noted that for the past few weeks, the right eye had been red and felt sore.

His medical history was significant only for benign prostate hypertrophy, for which he took Flomax (tamsulosin, Boehringer Ingelheim), as well as a remote history of seizures, for which he took Dilantin (phenytoin, Pfizer) and Neurontin (gabapentin, Pfizer). He had no significant ocular history. A review of systems was negative. He worked as an electrical engineer and had been smoking up to a pack of cigarettes a day for 45 years. He denied alcohol or drug abuse.

Examination

On examination, the patient was 20/20 in both eyes without corrective lenses. There was no afferent pupillary defect. Intraocular pressures were 15 mm Hg in both eyes. Visual fields were full to confrontation.

Figure 1. An elevated white plaque-like lesion, with some irregularity and hypertrophy of the adjacent palpebral conjunctiva, was seen on the right inferior fornix. Images: Batta P, Goldstein M, Kapadia M

External examination revealed no abnormalities, including normal appearance and position of the eyelids. Inspection of the right inferior fornix revealed an elevated white plaque-like lesion, with some irregularity and hypertrophy of the adjacent palpebral conjunctiva (Figure 1). The inferior bulbar conjunctiva was injected. The remainder of the anterior segment examination was normal. Funduscopic evaluation was normal except for a small flat choroidal nevus in the right eye.

What is your diagnosis?

White lesion

The differential diagnosis for lesions of the palpebral conjunctiva includes cystic, inflammatory, infiltrative and neoplastic processes. This particular lesion was relatively unusual because it was white, and there are relatively few conjunctival lesions that are white in appearance.

A common lesion seen in the inferior fornix is an epithelial inclusion cyst. These lesions are typically clear, although recurrent ones may have thicker cyst walls and appear slightly white in appearance. They frequently recur after excision. Another frequently recurrent lesion is a pyogenic granuloma. These lesions often occur in an area of prior chalazia and thus are commonly seen in the inferior fornix. Pyogenic granulomas are actually reactive hemangiomas containing extremely vascular granulation tissue; they are therefore typically reddish in color. Less common conditions in the conjunctival fornix include ocular amyloidosis, manifested by yellowish amyloid plaques, with or without systemic involvement. However, these are more diffuse, rather than focal, lesions.

The differential for an atypical, recurrent lesion should always include neoplastic processes. This lesion could represent squamous cell carcinoma of the conjunctiva (or its noninvasive precursor, conjunctival intraepithelial neoplasia), as the white appearance is suggestive of leukoplakia. It is highly unusual to have squamous cell carcinoma on the palpebral conjunctiva; typically, squamous dysplasia is seen on the sun-exposed bulbar conjunctiva. Another possibility is sebaceous cell carcinoma. However, sebaceous cancers usually involve the lid margin, where sebaceous glands are abundant, and because they contain sebum, are usually more yellow in color.

Diagnosis

An incisional biopsy was performed, and pathology results were consistent with squamous cell carcinoma of the conjunctiva. This is the most common malignant tumor of the conjunctiva. A more general term frequently used for these lesions is ocular surface squamous neoplasia, which also includes conjunctival intraepithelial neoplasia in addition to squamous cell carcinoma. Risk factors include age, male gender, sun exposure, HPV infection and smoking.

As mentioned before, it is much more commonly seen on the bulbar interpalpebral conjunctiva. Corneal involvement is present in up to 50% of patients. Intraocular invasion is rare, affecting less than 8% of patients, and orbital invasion is seen in up to 15%. It is rare to see metastatic disease with conjunctival squamous cell carcinoma. Treatment options include surgical resection, cryotherapy and topical chemotherapy with either interferon or mitomycin; frequently, a combination of these is employed. Prognosis depends on such factors as size and depth of tumor.

Follow-up

The patient’s lesion was surgically excised via a Mohs micrographic technique, with cryotherapy applied to the tumor margins. Topical interferon was subsequently employed; however, this was discontinued early secondary to side effects that included malaise and flu-like symptoms. The patient was monitored closely and after approximately 6 months was noted to have inferior forniceal foreshortening and symblepharon formation, as well as an irregular appearance to the inferior bulbar conjunctiva (Figure 2). This area was biopsied and found to be negative for recurrence; however, given the unusual appearance, he was treated with two cycles of topical mitomycin C 0.04%. Upon completing the mitomycin C treatment, his condition seemed to have worsened, with a more distinctly leukoplakic lesion present on the bulbar surface (Figure 3).

Figure 2. Six months after surgery, the patient was noted to have inferior forniceal foreshortening and symblepharon formation, as well as an irregular appearance to the inferior bulbar conjunctiva.

Figure 3. After mitomycin C treatment, there was a more distinctly leukoplakic lesion present on the bulbar surface.

A large surgical resection with amniotic membrane grafting was performed, with pathology results suggesting possible lymphovascular invasion. In light of this, the patient underwent radiation treatment to the orbit. A few months after completing his radiation treatment, he presented with another small white lesion on the right lower eyelid margin, with biopsy positive for recurrent squamous cell carcinoma. He then had a PET scan, suggesting possible spread to a regional lymph node. He underwent another extensive surgical resection with reconstructive eyelid surgery, as well as a regional lymph node dissection, which did not reveal any metastatic spread. He is currently undergoing a second round of radiation treatment. He will continue to be closely monitored for recurrence, with future plans for further reconstruction of the right eyelids and inferior fornix.

References:

• Basti S, Macsai MS. Ocular surface squamous neoplasia: a review. Cornea. 2003;22(7):687-704.
• Holcombe DJ, Lee GA. Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia. Am J Ophthalmol. 2006;142(4):568-571.
• 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. 2005;123(1):109-113.
• Shields CL, Naseripour M, Shields JA. Topical mitomycin C for extensive, recurrent conjunctival-corneal squamous cell carcinoma. Am J Ophthalmol. 2002;133(5):601-606.
• Sturges A, Butt AL, Lai JE, Chodosh J. Topical interferon or surgical excision for the management of primary ocular surface squamous neoplasia. Ophthalmology. 2008;115(8):1297-1302.
• 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, Michael Goldstein, MD, and Mitesh Kapadia, MD, PhD, 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.

• Edited by Mark E. Patron, MD, and Andre J. Witkin, MD. Drs. Patron and Witkin 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.