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A 33-year-old woman presents to the ophthalmology department of a hospital in Tübingen, Germany, following referral for a suspected tumor on the nasal bulbar conjunctiva of her right eye.

Clinical assessment by clinicians notes inflammation involving a gelatinous lesion that measures 2.8×3.0 mm. The tumor appears to be freely mobile over the sclera and is surrounded by markedly dilated blood vessels.

The patient's records show that for the previous 2 weeks, the lesion has been treated topically four times daily with combination corticosteroid and antibiotic eye drops -- 1 mL suspension of 1 mg dexamethasone, 6,000 IU polymyxin B sulphate, and 3,500 IU neomycin sulphate (Maxitrol) -- and artificial tears. The patient notes that this seemed to have no effect, and in fact, the lesion appeared to have grown.

Following consultation with the patient, the decision is made to excise the lesion without further delay.

Two Days Later

The patient undergoes surgery two days after that. Clinicians apply topical anesthesia (five drops of a single dose of 0.4% oxybuprocaine hydrochloride) and subconjunctival anesthesia with 2% mepivacaine. They use Vannas scissors to excise the conjunctival tumor, allowing a wide excisional biopsy with a tumor safety distance of at least 2.0 mm. Cautery is then gently applied to the bleeding vessels.

The primary procedure involves closure of the conjunctival defect, and after undermining and mobilization of the surrounding conjunctiva to cover the bare sclera, the team sutures the conjunctiva by four interrupted Vicryl 9-0 sutures.

The specimen is sent for histopathological analysis, and the results suggest a diagnosis of squamous cell carcinoma (SCC) of the conjunctiva.

Histopathology Findings

Histopathological examination of the invasive SCC of the conjunctiva stained with hematoxylin and eosin (50×, 100×, and 200× magnification) reveals atypical cell nests of varying shapes infiltrating the fibrous tissue beneath the atypical superficial epithelium, which shows an altered maturation and cytologic atypia. The fibrous tissue also shows an increase in elastic fibers (solar elastosis).

Following surgery, the eye is treated with topical mitomycin C (MMC) 0.02% eye drops, administered four times daily for 14 days. This is followed by a 2-week interval when only artificial tears eye drops are administered, and then a second 14-day cycle of treatment with MMC.

In addition, for 2 weeks following surgery, the patient is treated with topical corticosteroid (1.3 mg/mL dexamethasone) eye drops; antibiotic eye drops (0.5% moxifloxacin hydrochloride ophthalmic solution); and artificial tears administered four times daily.

The corticosteroid eye drops are subsequently reduced by one drop each week, while the artificial tears are continued for four times daily for 8 weeks. Assessment reveals reduced inflammation, and the conjunctival lesion appears to be healing. Histopathological examination identifies the surgical margins as tumor free. At the 12-month follow-up, a slit-lamp examination detects no evidence of recurrence (image B).

Discussion

Clinicians reporting this of conjunctival squamous cell carcinoma note that its presentation in a female and in someone so young (age 33) is atypical, since the cancer occurs much more commonly in males and at older ages.

While SCC is a curable cancer, timely and accurate are important to prevent loss of vision, and in the worst case, progression to a life-threatening stage.

SCC of the conjunctiva is the most common non-pigmented malignancy of the ocular surface, and is the end stage of a spectrum of diseases referred to as ocular surface squamous neoplasia (OSSN). The incidence of SCC is about nine to 10 times higher in the African population than in Caucasians.

Other research has identified a different disease pattern specific to equatorial Africa, in which OSSN is more common in younger adults (about age 40) and women. This pattern was recently observed in Kenya, where data also shows that about three-quarters of those with OSSN have been diagnosed with HIV.

The case authors note that SCC usually affects the exposed part of the eyeball in sun-damaged conjunctiva at the limbus. Ultraviolet B radiation is the primary risk factor, with other risk factors including immunosuppression (HIV/AIDS), human papilloma virus, and allergic conjunctivitis, as well as smoking, petroleum product exposure, and genetic predisposition in conditions such as xeroderma pigmentosa.

Common include red eye, photophobia, irritation, foreign body sensation, and a white, painless, progressive growth on the surface of the eye.

Histopathologic examination is considered the optimum approach to diagnosing SCC, and invasive cases are generally managed by excision, along with cryotherapy when adjunctive treatment is indicated.

Treatment

Following resection, topical MMC appears to be a safe and effective therapy for conjunctival and corneal SCC, even when there is extensive recurrence of the tumor. However, there is as yet no general agreement about either the dose or the duration of treatment, the case authors note, adding that loss of time may result in the need for more aggressive treatment as the tumor becomes larger and more invasive.

Chemotherapeutic management has gained acceptance, with increasing use of agents like MMC, interferon-α2b, and fluorouracil, and the authors cite a 2018 case series by Chaugule, et al. that suggests that pure topical chemotherapy without surgery is safe and effective with complete regression in OSSN.

In addition, the case report authors note, their own clinical experience is reflected in previous reports suggesting that chemotherapy is a valuable option for the management of OSSN.

Likewise, post-surgical use of topical MMC is a cost-effective and safe approach to minimizing tumor recurrence, and even in cases of extensive recurrent disease, topical MMC is a successful treatment for conjunctival or corneal squamous-cell carcinoma. MMC is a non-cell-cycle specific alkylating agent, with a mode of action that mimics that of ionizing radiation.

The authors conclude that the case illustrates that effective and successful clinical management of conjunctival SSC is possible with excision and postoperative treatment with MMC 0.02% eye drops.

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