A 21-year-old woman with xeroderma pigmentosum (XP), who presented with corneal neovascularization (NV) and lipid keratopathy in her left eye. She has a history of skin squamous cell carcinomas (SCC) and basal cell carcinomas that have required more than 20 excisions and full-thickness skin grafts (Figure 1A). She also received penetrating keratoplasty in her right eye 8 years ago for XP-related keratopathy and maintained a clear corneal graft.
The corneal NV and lipid keratopathy in her left eye progressed over 3 years and obscured the optical axis (Figure 1B). Treatments with therapeutic contact lens, topical mitomycin C application, lamellar keratectomy, and subconjunctival injection of bevacizumab were unsuccessful. Finally, penetrating keratoplasty was performed with a 8.25-mm full-thickness donor corneal graft that was secured with interrupted 10–0 Nylon sutures to a 7.75-mm recipient bed. The corneal graft was obtained from a 65-year-old man who had no history of ocular malignancy and died of lung cancer.
The patient engaged in whole body sun protection perioperatively and 1 drop of topical 0.1% betamethasone (Fusone, AIM Inc, Taiwan) was applied 4 times a day after the surgery. There was no visible ocular surface neoplasm preoperatively (Figure 1C). However, a rapidly growing tumor at the nasal bulbar conjunctiva was noticed 1 month after corneal transplantation (Figure 1D) and doubled in size in 2 weeks (Figure 1E).
The patient received excision of conjunctival tumor and cryotherapy on the bulbar conjunctiva close to the excisional site. Pathology confirmed the diagnosis of moderately differentiated SCC. The conjunctival wound healed within 10 days, and no tumor recurrence was noted during a 5-month follow-up (Figure 1F).
Xeroderma pigmentosum is a rare, autosomal recessive disease caused by defective DNA repair.1,2 Ocular surface manifestations of XP include eyelid abnormalities, corneal NV, and scarring, as well as corneal or conjunctival tumors.1-3 Xeroderma pigmentosum patients can have 2000 times the usual frequency of ocular tumors.1
In our patient, no leukoplakia or other signs of ocular malignancy was noted before corneal transplantation. Nevertheless, we cannot exclude the possibility of an occult tumor. Whether this is a case of de novo neoplasm or the rapid progression of an existing tumor, it shows that conjunctival malignancy may develop rapidly after corneal transplantation in a predisposed patient.
Ramasubramanian et al4 studied 4 patients who developed ocular surface squamous neoplasm between 2 and 72 months after corneal grafting and attributed the occurrence of malignancy to long-term topical steroid use.4 In addition, surgical trauma and prolonged wound healing were reported to be possible risk factors of skin SCC in scarred areas.5 We therefore hypothesize that the surgical trauma of corneal transplantation, the wound healing process, the immunosuppression, and the patient’s inherited defect in DNA repair may be factors relevant to the rapid tumor growth.
1. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol. 1987;123:241–250.
2. Goyal JL, Rao VA, Srinivasan R, et al. Oculocutaneous manifestations in xeroderma pigmentosa. Br J Ophthalmol. 1994;78:295–297.
3. Brooks BP, Thompson AH, Bishop RJ, et al. Ocular manifestations of xeroderma pigmentosum: long-term follow-up highlights the role of DNA repair in protection from sun damage. Ophthalmology. 2013;120:1324–1336.
4. Ramasubramanian A, Shields CL, Sinha N, et al. Ocular surface squamous neoplasia after corneal graft. Am J Ophthalmol. 2010;149:62–65.
5. Edwards MJ, Hirsch RM, Broadwater JR, et al. Squamous cell carcinoma arising in previously burned or irradiated skin. Arch Surg. 1989;124:115–117.