Older man presents with elevated conjunctival lesion of right eye
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A 78-year-old man was referred to Tufts Medical Center Cornea Clinic from an outside ophthalmologist for a conjunctival lesion of the right eye.
The patient first noted the lesion 4 months before presentation and stated it had gradually been enlarging in size. He denied eye pain but stated he had ocular surface irritation and now, due to the size, the lesion blocked part of his temporal visual field. He was seen by his general ophthalmologist who started him on topical ofloxacin, prednisolone acetate and neomycin-polymyxin-dexamethasone ointment four times daily. The patient was scheduled for excisional biopsy; however, due to the enlarging size, he was referred to the New England Eye Center cornea department for further management.
Medical history was notable for thyroid cancer and subsequent thyroidectomy, basal cell carcinoma of the scalp, atrial fibrillation, hypertension, hyperlipidemia, osteoarthritis status post total knee replacement and a benign heart murmur. Systemic medications included levothyroxine, apixaban, atorvastatin and metoprolol.
Examination
On examination, uncorrected visual acuity was 20/20 in both eyes. IOP was normal bilaterally, and both pupils were round and briskly reactive to light with no relative afferent pupillary defect. Extraocular motility was full and painless in all directions of gaze. The lids and lashes were unremarkable. In the right temporal conjunctiva, there was a pedunculated pink nodular lesion measuring 5.7 mm vertically by 7.5 mm horizontally, extending 0.3 mm onto the temporal cornea (Figure 1). There was a prominent conjunctival feeder vessel inferonasally supplying the lesion (Figure 2). On the superficial aspect of the lesion medially, there was 0.8 mm of brown pigment. There was no extension onto the palpebral conjunctiva and no forniceal involvement.
Source: Nisha S. Dhawlikar, MD, MPH, and Helen K. Wu, MD
The cornea was otherwise clear, the anterior chamber was without cell or flare, the iris had no transillumination defects, and toric IOLs were noted bilaterally. The left eye examination was unremarkable. The patient’s dilated examination was normal in both eyes.
What is your diagnosis?
See answer below.
Conjunctival lesion
An elevated pink conjunctival lesion with a feeder vessel and rapid growth is most concerning for a neoplasm.
The leading diagnosis was ocular surface squamous neoplasia. The differential also included conjunctival melanoma, although the patient only had superficial conjunctival pigmentation. A pterygium or pinguecula presents in the temporal or nasal conjunctiva, although these are slow growing and do not present with such profound elevation and nodularity. Conjunctival lymphoma is unlikely given the heterogeneity of the lesion, unlike lymphomatous lesions, which usually display a typical salmon patch appearance and are notable for slow growth. Conjunctival hemangioma or pyogenic granuloma may be present in the temporal conjunctiva, although they would appear bright red and appear more homogenous, and the patient did not have a history of conjunctival or strabismus surgery.
Workup and management
Slit lamp photos were obtained for documentation, and anterior segment OCT (AS-OCT) was obtained to evaluate the depth and extent of the lesion (Figure 3). On AS-OCT, hyperreflectivity of the lesion was noted with a thickened epithelium and an abrupt transition from normal to abnormal tissue. Given the concern for ocular surface squamous neoplasia, the patient was promptly scheduled for an excisional biopsy with cryotherapy, mitomycin C and amniotic membrane graft. Surgical pathological examination noted papillary squamous cell carcinoma with clear margins.
Discussion
Ocular surface squamous neoplasia (OSSN) is the most common nonpigmented ocular surface tumor, encompassing mild dysplasia to invasive squamous cell carcinoma. It is more commonly noted in patients older than 60 years of age; however, younger patients with predisposing factors, including HIV or xeroderma pigmentosum, may develop OSSN earlier. Additional risk factors for OSSN include UV light exposure, HPV infection, smoking, male gender and immunosuppression. Classic clinical presentation of OSSN is a gelatinous, fleshy or plaque-like mass. It may also have a papillomatous form, abnormal vascularity such as a feeder vessel or possible leukoplakia.
OSSN encompasses a wide spectrum of disease progression. Conjunctival intraepithelial neoplasia is noninvasive, in which the basement membrane remains intact with no involvement of the underlying substantia propria. Corneal epithelial dysplasia or dysmaturation has slightly abnormal or increased nuclear to cytoplasmic ratios and dyskeratosis. In squamous cell carcinoma (SCC), dysplastic epithelial cells have penetrated the basement membrane with metastatic potential. Mucoepidermoid carcinoma is a rare and aggressive variant of SCC that cannot be distinguished from SCC without histopathology. Systemic workup is oftentimes not required, as metastasis of OSSN occurs in less than 1% of patients.
The gold standard for diagnosis of OSSN has been histopathological analysis via surgical excision. Noninvasive diagnostic techniques such as high-resolution OCT (HR-OCT) have greatly assisted diagnosis and management of OSSN. HR-OCT is noncontact and can be readily obtained and interpreted in clinic. However, limitations include inability to reliably identify invasion in forniceal or caruncular lesions, as well as shadowing of deeper structures in pigmented or large tumors. Small areas of subclinical disease may also be missed by the technician performing the scan. Classic HR-OCT findings of OSSN demonstrate a hyperreflective thickened epithelium with an abrupt transition between normal and abnormal epithelium. Concurrent ocular surface pathology including pterygia and pinguecula may exist, although it has been noted that epithelial thickness greater than 120 µm helps differentiate OSSN from pterygia with high sensitivity and specificity.
Surgical management involves excision with 3- to 4-mm margins and a dry “no-touch” technique. Cryotherapy is used at the limbal/conjunctival borders to reduce the risk for recurrence with a double freeze-thaw technique. In advanced or recurrent tumors, MMC is also applied to the area for 2 minutes and then rinsed thoroughly with balanced salt solution. If any excision margins are positive, either additional surgery or postoperative topical chemotherapeutic agents (5-fluorouracil, interferon alpha-2b or MMC) can be used.
Medical management of OSSN with topical chemotherapeutic agents rather than surgery has been gaining favor. It can treat the whole ocular surface while avoiding surgical complications, including positive margins, limbal stem cell deficiency and scarring. Interferon (IFN) alpha-2b has shown success both as primary and adjuvant therapy for OSSN. It can be given topically (one drop four times daily) or intralesionally (up to three times weekly) until tumor resolution. Although it is expensive, it has a more favorable side effect profile with rare conjunctival hyperemia, follicular conjunctivitis and epithelial microcysts. 5-FU is a pyrimidine analog antimetabolite that is typically dosed topically four times daily for 1 week, followed by 3 weeks without treatment, and requires a total of four to six cycles. 5-FU is less expensive at approximately $38 per month; however, it has more side effects than IFN alpha-2b, including epitheliopathy, conjunctival hyperemia, eyelid swelling and chemosis. MMC is an antineoplastic agent dosed in a similar fashion to 5-FU (four times daily for 1 week, then 2 to 3 weeks off), cycled until lesion resolution. It has faster tumor resolution of 1.5 months compared with 3.5 months with IFN alpha-2b; however, it is associated with worse ocular surface toxicity compared with the other two drugs. Punctal plugs are recommended with therapy due to risk for punctal stenosis.
These three medications have similar resolution rates, with IFN alpha-2b and 5-FU being highest. Most recurrences of OSSN occur within 1 year of treatment, and rates of recurrence are 0% to 28% with 5-FU and 4% to 20% with IFN alpha-2b. In conjunction with clinical examination, HR-OCT can be used to monitor for improvement while on topical agents. HR-OCT has been found to detect subclinical OSSN and thus can also be a useful tool in monitoring for recurrence after medical or surgical intervention.
Clinical case continued
The patient was most recently seen for his 1-month postoperative visit, and his conjunctival surface was well healed. He had completed his prednisolone acetate and ofloxacin taper. As the final pathology report confirmed, the lesion was completely excised, and no topical chemotherapy agent was needed for adjuvant treatment. He will be followed closely in clinic for monitoring of any recurrence.
- References:
- Morkin MI, et al. Ocular surface tumors. Focal Points. 2020;38(6).
- Nanji AA, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2013.11.017.
- Sayed-Ahmed IO, et al. Expert Rev Ophthalmol. 2017;doi:10.1080/17469899.2017.1263567.
- Tran AQ, et al. Eye Vis (Lond). 2019;doi:10.1186/s40662-019-0152-3.
- Venkateswaran N, et al. Am J Ophthalmol. 2019;doi:10.1016/j.ajo.2018.11.007.
- For more information:
- Nisha S. Dhawlikar, MD, MPH, and Helen K. Wu, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Allison V. Coombs, DO, MS, and Nisha S. Dhawlikar, MD, MPH. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.