Aim: To describe 4 cases of conjunctival squamous cell carcinoma (SCC) with corneal stromal invasion. Methods: Retrospective, clinicopathologic case series. Results: All patients had prior resections of presumed pterygia. The degree of corneal involvement dictated the extent of surgical management. One eye with localized invasion was treated with lamellar keratoplasty and plaque brachytherapy. Another case with widespread invasion warranted penetrating keratoplasty and eventual enucleation. Two cases were treated medically prior to surgical intervention: one with localized invasion was treated with topical interferon and retinoic acid; another with significant inflammation was treated with doxycycline and fluorometholone. The patient who underwent keratoplasty and brachytherapy had no recurrence after 7 years of follow-up. Those initially treated medically had resections of recurrence but ultimately required enucleation. Histologically, specimens demonstrated SCC invading the deep corneal stroma, with 2 tumors of the mucoepidermoid type. Conclusions: This series demonstrates the importance of maintaining clinical suspicion of conjunctival squamous neoplasia in pterygia. We recommend that all excised pterygia be submitted for histopathologic evaluation and be carefully evaluated for dysplasia and variants of SCC associated with increased risk of intraocular invasion. Undetected ocular surface squamous neoplasia may give rise to potentially vision- and eye-threatening invasive corneal SCC.

1.
Chui J, Di Girolamo N, Wakefield D, Coroneo MT: The pathogenesis of pterygium: current concepts and their therapeutic implications. Ocul Surf 2008;6:24-43.
2.
Chui J, Coroneo MT: Pterygium pathogenesis, actinic damage, and recurrence; in Hovanesion JA (ed): Pterygium: Techniques and Technologies for Surgical Success. Thorofare, SLACK Incorporated, 2012, pp 1-26.
3.
Coroneo M: Ultraviolet radiation and the anterior eye. Eye Contact Lens 2011;37:214-224.
4.
Lee GA, Hirst LW: Incidence of ocular surface epithelial dysplasia in metropolitan Brisbane. A 10-year survey. Arch Ophthalmol 1992;110:525-527.
5.
McClellan AJ, McClellan AL, Pezon CF, Karp CL, Feuer W, Galor A: Epidemiology of ocular surface squamous neoplasia in a veterans affairs population. Cornea 2013;32:1354-1358.
6.
Gichuhi S, Sagoo MS, Weiss HA, Burton MJ: Epidemiology of ocular surface squamous neoplasia in Africa. Trop Med Int Health 2013;18:1424-1443.
7.
Lee GA, Hirst LW: Retrospective study of ocular surface squamous neoplasia. Aust NZ J Ophthalmol 1997;25:269-276.
8.
Grossniklaus HE, Green WR, Luckenbach M, Chan CC: Conjunctival lesions in adults. A clinical and histopathologic review. Cornea 1987;6:78-116.
9.
Shields JA, Shields CL, Gunduz K, Eagle RC Jr: The 1998 Pan American Lecture. Intraocular invasion of conjunctival squamous cell carcinoma in five patients. Ophthal Plast Reconstr Surg 1999;15:153-160.
10.
Iliff WJ, Marback R, Green WR: Invasive squamous cell carcinoma of the conjunctiva. Arch Ophthalmol 1975;93:119-122.
11.
Erie JC, Campbell RJ, Liesegang TJ: Conjunctival and corneal intraepithelial and invasive neoplasia. Ophthalmology 1986;93:176-183.
12.
Yousef YA, Finger PT: Squamous carcinoma and dysplasia of the conjunctiva and cornea: an analysis of 101 cases. Ophthalmology 2012;119:233-240.
13.
Roy A, Rath S, Das S, Vemuganti GK, Parulkar G: Penetrating sclerokeratoplasty in massive recurrent invasive squamous cell carcinoma. Ophthal Plast Reconstr Surg 2011;27:e39-e40.
14.
Rootman DB, McGowan HD, Yucel YH, Pavlin CJ, Simpson ER: Intraocular extension of conjunctival invasive squamous cell carcinoma after pterygium surgery and cataract extraction. Eye Contact Lens 2012;38:133-136.
15.
Zhang Z, Li B, Shi J, Xu X, Li L, Gao F: Intraocular extension of conjunctival squamous cell carcinoma. Ophthalmologica 2007;221:200-203.
16.
Brownstein S: Mucoepidermoid carcinoma of the conjunctiva with intraocular invasion. Ophthalmology 1981;88:1226-1230.
17.
Ali MJ, Pujari A, Dave TV, Kaliki S, Naik MN: Clinicopathological profile of orbital exenteration: 14 years of experience from a tertiary eye care center in South India. Int Ophthalmol 2016;36:253-258.
18.
Woods M, Chow S, Heng B, Glenn W, Whitaker N, Waring D, Iwasenko J, Rawlinson W, Coroneo MT, Wakefield D, Di Girolamo N: Detecting human papillomavirus in ocular surface diseases. Invest Ophthalmol Vis Sci 2013;54:8069-8078.
19.
Chui J, Coroneo MT, Tat LT, Crouch R, Wakefield D, Di Girolamo N: Ophthalmic pterygium: a stem cell disorder with premalignant features. Am J Pathol 2011;178:817-827.
20.
Segev F, Mimouni M, Tessler G, Hilely A, Ofir S, Kidron D, Bahar I: A 10-year survey: prevalence of ocular surface squamous neoplasia in clinically benign pterygium specimens. Curr Eye Res 2015;40:1284-1287.
21.
Yeung SN, Kim P, Lichtinger A, Amiran MD, Cote E, Teitel S, Slomovic AR: Incidence of ocular surface squamous neoplasia in pterygium specimens: an 8-year survey. Br J Ophthalmol 2011;95:592.
22.
Hirst LW, Axelsen RA, Schwab I: Pterygium and associated ocular surface squamous neoplasia. Arch Ophthalmol 2009;127:31-32.
23.
Oellers P, Karp CL, Sheth A, Kao AA, Abdelaziz A, Matthews, JL, Dubovy SR, Galor A: Prevalence, treatment, and outcomes of coexistent ocular surface squamous neoplasia and pterygium. Ophthalmology 2013;120:445-450.
24.
Shields JA, Shields CL, De Potter P: Surgical management of conjunctival tumors. The 1994 Lynn B. McMahan Lecture. Arch Ophthalmol 1997;115:808-815.
25.
Tabin G, Levin S, Snibson G, Loughnan M, Taylor H: Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia. Ophthalmology 1997;104:485-492.
26.
Schechter BA, Koreishi AF, Karp CL, Feuer W: Long-term follow-up of conjunctival and corneal intraepithelial neoplasia treated with topical interferon alfa-2b. Ophthalmology 2008;115:1291-1296.
27.
Krilis M, Tsang H, Coroneo M: Treatment of conjunctival and corneal epithelial neoplasia with retinoic acid and topical interferon alfa-2b: long-term follow-up. Ophthalmology 2012;119:1969-1973.
28.
Finger PT, Tran HV, Turbin RE, Perry HD, Abramson DH, Chin K, Della Rocca R, Ritch R: High-frequency ultrasonographic evaluation of conjunctival intraepithelial neoplasia and squamous cell carcinoma. Arch Ophthalmol 2003;121:168-172.
29.
Galor A, Karp CL, Oellers P, Kao AA, Abdelaziz A, Feuer W, Dubovy SR: Predictors of ocular surface squamous neoplasia recurrence after excisional surgery. Ophthalmology 2012;119:1974-1981.
30.
Rao NA, Font RL: Mucoepidermoid carcinoma of the conjunctiva: a clinicopathologic study of five cases. Cancer 1976;38:1699-1709.
31.
Robinson JW, Brownstein S, Jordan DR, Hodge WG: Conjunctival mucoepidermoid carcinoma in a patient with ocular cicatricial pemphigoid and a review of the literature. Surv Ophthalmol 2006;51:513-519.
32.
Shields JA, Eagle RC, Marr BP, Shields CL, Grossniklaus HE, Stulting RD: Invasive spindle cell carcinoma of the conjunctiva managed by full-thickness eye wall resection. Cornea 2007;26:1014-1016.
33.
Mittal R, Rath S, Vemuganti GK: Ocular surface squamous neoplasia - review of etio-pathogenesis and an update on clinico-pathological diagnosis. Saudi J Ophthalmol 2013;27:177-186.
34.
Alkatan HM, Al-Motlak MA, Al-Shedoukhy AA: Metastatic squamous spindle cell carcinoma of the conjunctiva. Saudi J Ophthalmol 2010;24:155-158.
35.
Kamal S, Kaliki S, Mishra DK, Batra J, Naik MN: Ocular surface squamous neoplasia in 200 patients: a case-control study of immunosuppression resulting from human immunodeficiency virus versus immunocompetency. Ophthalmology 2015;122:1688-1694.
36.
Shields CL, Ramasubramanian A, Mellen PL, Shields JA: Conjunctival squamous cell carcinoma arising in immunosuppressed patients (organ transplant, human immunodeficiency virus infection). Ophthalmology 2011;118:2133-2137.
37.
Waddell KM, Lewallen S, Lucas SB, Atenyi-Agaba C, Herrington CS, Liomba G: Carcinoma of the conjunctiva and HIV infection in Uganda and Malawi. Br J Ophthalmol 1996;80:503-508.
38.
Panda A, Sharma N, Sen S: Massive corneal and conjunctival squamous cell carcinoma. Ophthalmic Surg Lasers 2000;31:71-72.
39.
Murillo JC, Galor A, Wu MC, Kye NK, Wong J, Ahmed IO, Joag M, Shalabi N, Lahners W, Dubovy S, Karp CL: Intracorneal and intraocular invasion of ocular surface squamous neoplasia after intraocular surgery: report of two cases and review of the literature. Ocul Oncol Pathol 2017;3:66-72.
40.
Coroneo MT, Chui JJY: Pterygium; in Holland EJ, Mannis MJ, Lee WB (eds): Ocular Surface Disease: Cornea, Conjunctiva and Tear Film. Philadelphia, Saunders Elsevier, 2013, pp 125-144.
41.
Hirst LW: Mitomycin C in the treatment of pterygium. Clin Exp Ophthalmol 2006;34:197-198.
42.
Thomas BJ, Galor A, Nanji AA, El Sayyad F, Wang J, Dubovy SR, Joag MG, Karp CL: Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia. Ocul Surf 2014;12:46-58.
43.
Balestrazzi A, Martone G, Pichierri P, Tosi GM, Caporossi A: Corneal invasion of ocular surface squamous neoplasia after clear corneal phacoemulsification: in vivo confocal microscopy analysis. J Cataract Refract Surg 2008;34:1038-1043.
44.
Walsh-Conway N, Conway RM: Plaque brachytherapy for the management of ocular surface malignancies with corneoscleral invasion. Clin Exp Ophthalmol 2009;37:577-583.
45.
Arepalli S, Kaliki S, Shields CL, Emrich J, Komarnicky L, Shields JA: Plaque radiotherapy in the management of scleral-invasive conjunctival squamous cell carcinoma: an analysis of 15 eyes. JAMA Ophthalmol 2014;132:691-696.
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