Grand Rounds at the New England Eye Center

Conjunctival lesion in a middle-aged woman

The patient's left eye was previously injured with a mascara brush.

A 50-year-old woman presented to an outside ophthalmologist with a 2-month history of irritation and discharge after injury to the left eye with a mascara brush. Her exam was notable for conjunctival injection and a nasal conjunctival scar. She was treated with erythromycin ointment and a topical steroid with improvement of her symptoms; however, her conjunctival scar remained unchanged, so she was referred to Tufts Medical Center for evaluation. Before this, the patient had no ocular issues. She was otherwise healthy with no medical history or prescribed medications. Her social history was notable for a 30 pack-year smoking history, but she had recently quit smoking.

Examination

On initial examination, the patient’s visual acuity measured 20/20 in the right eye and 20/20 in the left eye. Pupils were symmetrically reactive with no afferent pupil defect. IOP was within normal limits. On anterior segment exam, the bulbar conjunctiva was mildly injected in each eye. In the left eye, a vascularized conjunctival mass was seen in the inferior fornix with thickened and inflamed conjunctiva extending up to the caruncle with mild nasal symblepharon (Figure 1). The remainder of the examination, including dilated fundus exam, was unremarkable in each eye.

Inferonasal vascularized mass with nasal inflammation and symblepharon
Figure 1. Inferonasal vascularized mass (black arrow) with nasal inflammation and symblepharon (yellow arrow).

Source: Sarah Adelson, MD, and Narae Ko, MD

What is your diagnosis?

See answer on next page.

Conjunctival lesion

The differential diagnosis for a vascularized conjunctival mass with inflammation and symblepharon in a 50-year-old woman includes neoplastic processes such as squamous papilloma, ocular squamous surface neoplasia or lymphoma. Inflammatory process such as pyogenic granuloma should be considered given the patient’s history of trauma with a mascara brush. Ocular cicatricial pemphigoid was less likely in this patient given the lack of conjunctival fibrosis or symblepharon in the fellow eye.

Further workup and management

Due to a high suspicion for squamous papilloma secondary to HPV, the patient underwent excisional biopsy of the conjunctival mass and incision biopsy of the inflamed nasal conjunctiva. Double freeze-thaw cryotherapy was performed in the inferior and nasal conjunctiva to reduce the likelihood of HPV recurrence. Biopsy of the conjunctival mass showed squamous intraepithelial neoplasia with moderate to severe dysplasia with positive margins. In situ hybridization was positive for low-risk HPV. The biopsy of the inflamed conjunctiva showed reactive conjunctival epithelium with chronic inflammation. Due to the positive margins, the patient underwent a 4-month course of treatment with topical interferon alfa-2b 1 million IU/mL four times daily, which was supplemented with 0.01% retinoic acid every other day.

Discussion

Ocular surface squamous neoplasia (OSSN) is an umbrella term that describes a spectrum of epithelial neoplasia ranging from mild dysplasia of conjunctival intraepithelial neoplasia (CIN) to invasive squamous cell carcinoma (SCC). The term CIN refers to squamous dysplasia confined to the epithelial layer with no violation of the basement membrane. When the dysplastic neoplasia penetrates the basement membrane, the term invasive SCC is used.

OSSN is a rare tumor in the United States with an annual incidence of 0.3 per 1 million. It largely affects Caucasian men in their sixth decade of life in the United States. Risk factors include older age, male gender, smoking, ultraviolet light and immunocompromised state, including HIV and xeroderma pigmentosum. An association with HPV has been postulated, but its role in OSSN remains controversial.

OSSN is a slow-growing tumor, and intraocular invasion and metastasis are rare. Affected patients typically present with an ocular surface mass or foreign body sensation with conjunctival injection. Clinically, most lesions appear gelatinous, translucent, leukoplakic or papillomatous. Diagnosis of OSSN is suspected based on clinical appearance of the lesion or high-resolution OCT showing a thickened hyperreflective epithelium. In our case, the patient underwent biopsy to confirm the diagnosis as the appearance with significant inflammation and symblepharon was less typical for OSSN.

The traditional treatment of choice for OSSN includes surgical excision with wide margins or cryotherapy using a double freeze-thaw technique. However, topical chemotherapeutic agents have gained popularity with their ability to treat a broader ocular surface area, including areas of microscopic disease. Interferon alfa-2b (IFN) is an effective treatment with rare side effects that include fever, malaise and flu-like symptoms. This agent can be used alone or in combination with 0.01% retinoic acid, an antineoplastic agent. The limitations of IFN include high cost and requirement for refrigeration. Mitomycin C, although effective for OSSN, is not a first-line treatment due to its side effect profile, which includes pain, conjunctival hyperemia and chemosis, epiphora, punctate epithelial keratopathy, limbal stem cell deficiency, recurrent corneal erosion and punctal stenosis. Recently, 5-fluorouracil has been shown to be effective for OSSN with advantages of lower cost and stability at room temperature.

Seven months after excisional biopsy and cryotherapy and 3 months after the completion of treatment with IFN
Figure 2. Seven months after excisional biopsy and cryotherapy and 3 months after the completion of treatment with IFN, showing no recurrence of OSSN and improved nasal conjunctival inflammation.

Follow-up

Our patient completed a 4-month course of IFN treatment without complication. At her most recent follow-up visit (7 months after biopsy and 3 months after the completion of IFN), she remained free of recurrence with significantly improved conjunctival inflammation (Figure 2). She continued to abstain from smoking.

A 50-year-old woman presented to an outside ophthalmologist with a 2-month history of irritation and discharge after injury to the left eye with a mascara brush. Her exam was notable for conjunctival injection and a nasal conjunctival scar. She was treated with erythromycin ointment and a topical steroid with improvement of her symptoms; however, her conjunctival scar remained unchanged, so she was referred to Tufts Medical Center for evaluation. Before this, the patient had no ocular issues. She was otherwise healthy with no medical history or prescribed medications. Her social history was notable for a 30 pack-year smoking history, but she had recently quit smoking.

Examination

On initial examination, the patient’s visual acuity measured 20/20 in the right eye and 20/20 in the left eye. Pupils were symmetrically reactive with no afferent pupil defect. IOP was within normal limits. On anterior segment exam, the bulbar conjunctiva was mildly injected in each eye. In the left eye, a vascularized conjunctival mass was seen in the inferior fornix with thickened and inflamed conjunctiva extending up to the caruncle with mild nasal symblepharon (Figure 1). The remainder of the examination, including dilated fundus exam, was unremarkable in each eye.

Inferonasal vascularized mass with nasal inflammation and symblepharon
Figure 1. Inferonasal vascularized mass (black arrow) with nasal inflammation and symblepharon (yellow arrow).

Source: Sarah Adelson, MD, and Narae Ko, MD

What is your diagnosis?

See answer on next page.

PAGE BREAK

Conjunctival lesion

The differential diagnosis for a vascularized conjunctival mass with inflammation and symblepharon in a 50-year-old woman includes neoplastic processes such as squamous papilloma, ocular squamous surface neoplasia or lymphoma. Inflammatory process such as pyogenic granuloma should be considered given the patient’s history of trauma with a mascara brush. Ocular cicatricial pemphigoid was less likely in this patient given the lack of conjunctival fibrosis or symblepharon in the fellow eye.

Further workup and management

Due to a high suspicion for squamous papilloma secondary to HPV, the patient underwent excisional biopsy of the conjunctival mass and incision biopsy of the inflamed nasal conjunctiva. Double freeze-thaw cryotherapy was performed in the inferior and nasal conjunctiva to reduce the likelihood of HPV recurrence. Biopsy of the conjunctival mass showed squamous intraepithelial neoplasia with moderate to severe dysplasia with positive margins. In situ hybridization was positive for low-risk HPV. The biopsy of the inflamed conjunctiva showed reactive conjunctival epithelium with chronic inflammation. Due to the positive margins, the patient underwent a 4-month course of treatment with topical interferon alfa-2b 1 million IU/mL four times daily, which was supplemented with 0.01% retinoic acid every other day.

Discussion

Ocular surface squamous neoplasia (OSSN) is an umbrella term that describes a spectrum of epithelial neoplasia ranging from mild dysplasia of conjunctival intraepithelial neoplasia (CIN) to invasive squamous cell carcinoma (SCC). The term CIN refers to squamous dysplasia confined to the epithelial layer with no violation of the basement membrane. When the dysplastic neoplasia penetrates the basement membrane, the term invasive SCC is used.

OSSN is a rare tumor in the United States with an annual incidence of 0.3 per 1 million. It largely affects Caucasian men in their sixth decade of life in the United States. Risk factors include older age, male gender, smoking, ultraviolet light and immunocompromised state, including HIV and xeroderma pigmentosum. An association with HPV has been postulated, but its role in OSSN remains controversial.

OSSN is a slow-growing tumor, and intraocular invasion and metastasis are rare. Affected patients typically present with an ocular surface mass or foreign body sensation with conjunctival injection. Clinically, most lesions appear gelatinous, translucent, leukoplakic or papillomatous. Diagnosis of OSSN is suspected based on clinical appearance of the lesion or high-resolution OCT showing a thickened hyperreflective epithelium. In our case, the patient underwent biopsy to confirm the diagnosis as the appearance with significant inflammation and symblepharon was less typical for OSSN.

PAGE BREAK

The traditional treatment of choice for OSSN includes surgical excision with wide margins or cryotherapy using a double freeze-thaw technique. However, topical chemotherapeutic agents have gained popularity with their ability to treat a broader ocular surface area, including areas of microscopic disease. Interferon alfa-2b (IFN) is an effective treatment with rare side effects that include fever, malaise and flu-like symptoms. This agent can be used alone or in combination with 0.01% retinoic acid, an antineoplastic agent. The limitations of IFN include high cost and requirement for refrigeration. Mitomycin C, although effective for OSSN, is not a first-line treatment due to its side effect profile, which includes pain, conjunctival hyperemia and chemosis, epiphora, punctate epithelial keratopathy, limbal stem cell deficiency, recurrent corneal erosion and punctal stenosis. Recently, 5-fluorouracil has been shown to be effective for OSSN with advantages of lower cost and stability at room temperature.

Seven months after excisional biopsy and cryotherapy and 3 months after the completion of treatment with IFN
Figure 2. Seven months after excisional biopsy and cryotherapy and 3 months after the completion of treatment with IFN, showing no recurrence of OSSN and improved nasal conjunctival inflammation.

Follow-up

Our patient completed a 4-month course of IFN treatment without complication. At her most recent follow-up visit (7 months after biopsy and 3 months after the completion of IFN), she remained free of recurrence with significantly improved conjunctival inflammation (Figure 2). She continued to abstain from smoking.