Laboratory Studies
- No laboratory studies are indicated.
Imaging Studies
- No imaging studies are indicated.
Procedures
- Biopsy (incisional or excisional) is a reasonable and safe method that aids in obtaining a definitive diagnosis. Indications for a biopsy are as follows:
- To rule in or to rule out the possibility of malignancy
- For lesions not obviously benign (symptomatic and/or show growth)
- For neoplasms suggestive of malignancy (HIV-positive patients or chronic unilateral conjunctivitis unresponsive to therapy)
- Therapeutic decision
- To determine the surgical margin in ill-defined lesions
- To exclude the possibility of recurrent neoplastic changes
- To harvest tissue for special studies (ie, flow cytometry)
- Frozen section
- The most common indication for a frozen section is to determine whether surgical margins are free of tumor (ie, to assess the adequacy of tissue excision).
- A frozen section should not be used for an "on-the-spot" diagnosis, since frozen tissue rendered tissue morphology is less optimal for microscopic examination.
- Invasive disease can be excluded, but intraepithelial lesions may not.
- Conjunctival tissue tends to curl after excision; therefore, it is best to examine after fixation and inking the borders. After obtaining the biopsy, place the tissue flat on a piece of firm paper/cardboard before placing in fixation medium.
- Surface tissue sampling
- Exfoliative cytology (tissue scraping)
- This technique is used commonly to aid in the diagnosis of cervical disease. However, this technique and its role in aiding the ophthalmologist in diagnosing ocular surface lesions are less well defined.
- Major limitations include the possibility of false-negative results and its inability to determine the depth of invasion.
- Most benign and inflammatory lesions cannot be identified precisely by cytologic methods.
- It is useful as a guide for where to obtain a biopsy specimen or resect ill-defined conjunctival lesions.
- Impression cytology
- Another technique for collecting surface cells, impression cytology uses a cellulose acetate filter paper. When the filter paper is placed in direct contact with the surface cells, the cells adhere to the paper.
- Impression cytology is less traumatic than exfoliative cytology.
- Intracellular structures are better preserved than with exfoliative cytology.
- Limitations are similar to exfoliative cytology; both are not appropriate for identifying intraepithelial tumors.
- Exfoliative cytology (tissue scraping)
Histologic Findings
Squamous cell papillomas (eg, infectious papilloma, viral conjunctival papilloma) are composed of multiple branching fronds emanating from a narrow pedunculated base. Individual fronds are surrounded by connective tissue, each having a central vascularized core. Acute and chronic inflammatory cells are found within these fronds. The epithelium is acanthotic, nonkeratinized stratified squamous epithelium without atypia. Numerous goblet cells are seen along with acute inflammatory cells. Koilocytosis is exhibited. The basement membrane is intact.
Limbal papillomas are sessile lesions arising from a broad base with a gelatinous appearance. Corkscrew vascular loops and feeder vessels are seen. The epithelium is acanthotic, displaying varying degrees of pleomorphism and dysplasia. The epithelium surface may be keratinized with foci of parakeratosis within the papillary folds. The basement membrane is intact.
Inverted papillomas exhibit exophytic and endophytic growth patterns. Invagination into the underlying stroma instead of the exophytic growth pattern is exhibited by squamous cell or limbal papillomas, whereas some lesions exhibit a mixture of exophytic and endophytic growth patterns. Unlike inverted papilloma arising in the lateral nasal wall or paranasal sinuses, lesions arising from the conjunctiva tend to be less aggressive in malignant transformation. The lesions are composed of lobules of epithelial cells extending down into the stroma. The lesion may be elevated or umbilicated. Epithelial cells do not demonstrate atypia, and dysplastic changes are uncommon for conjunctival inverted papillomas. The cytoplasm is vacuolated in some cells. They may resemble squamous papilloma or pyogenic granuloma. Numerous goblet cells are intermixed with the epithelium. Cysticlike lesions may be seen secondary to the confluence of goblet cells. The lesion may contain melanin granules and/or melanocytes.
Peck N, Lucarelli MJ, Yao M, et al. Human papillomavirus 6a lesions of the lower eyelid and genitalia. Ophthal Plast Reconstr Surg. Jul-Aug 2006;22(4):311-3. [Medline].
Sjo NC, Buchwald CV, Cassonnet P, et al. Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma. Types and frequencies in a large series. Br J Ophthalmol. Dec 13 2006;[Medline].
Minchiotti S, Masucci L, Serapiao Dos Santos M, Perrella E, Graffeo R, Lambiase A. Conjunctival papilloma and human papillomavirus: identification of HPV types by PCR. Eur J Ophthalmol. May-Jun 2006;16(3):473-7. [Medline].
Egbert JE, Kersten RC. Female genital tract papillomavirus in conjunctival papillomas of infancy. Am J Ophthalmol. Apr 1997;123(4):551-2. [Medline].
Lauer SA. Recurrent conjunctival papilloma causing nasolacrimal duct obstruction. Am J Ophthalmol. Nov 15 1990;110(5):580-1. [Medline].
Migliori ME, Putterman AM. Recurrent conjunctival papilloma causing nasolacrimal duct obstruction. Am J Ophthalmol. Jul 15 1990;110(1):17-22. [Medline].
Petrelli R, Cotlier E, Robins S, Stoessel K. Dinitrochlorobenzene immunotherapy of recurrent squamous papilloma of the conjunctiva. Ophthalmology. Dec 1981;88(12):1221-5. [Medline].
Lass JH, Foster CS, Grove AS, et al. Interferon-alpha therapy of recurrent conjunctival papillomas. Am J Ophthalmol. Mar 15 1987;103(3 Pt 1):294-301. [Medline].
Muralidhar R, Sudan R, Bajaj MS, Sharma V. Topical interferon alpha-2b as an adjunctive therapy in recurrent conjunctival papilloma. Int Ophthalmol. Feb 2009;29(1):61-2. [Medline].
de Keizer RJ, de Wolff-Rouendaal D. Topical alpha-interferon in recurrent conjunctival papilloma. Acta Ophthalmol Scand. Apr 2003;81(2):193-6. [Medline].
Falco LA, Gruosso PJ, Skolnick K, Bejar L. Topical interferon alpha 2 beta therapy in the management of conjunctival papilloma. Optometry. Apr 2007;78(4):162-6. [Medline].
Hawkins AS, Yu J, Hamming NA, Rubenstein JB. Treatment of recurrent conjunctival papillomatosis with mitomycin C. Am J Ophthalmol. Nov 1999;128(5):638-40. [Medline].
Shields CL, Lally MR, Singh AD, et al. Oral cimetidine (Tagamet) for recalcitrant, diffuse conjunctival papillomatosis. Am J Ophthalmol. Sep 1999;128(3):362-4. [Medline].
Chang SW, Huang ZL. Oral cimetidine adjuvant therapy for recalcitrant, diffuse conjunctival papillomatosis. Cornea. Jul 2006;25(6):687-90. [Medline].
Schachat A, Iliff WJ, Kashima HK. Carbon dioxide laser therapy of recurrent squamous papilloma of the conjunctiva. Ophthalmic Surg. Nov 1982;13(11):916-8. [Medline].
Jackson WB, Beraja R, Codere F. Laser therapy of conjunctival papillomas. Can J Ophthalmol. Feb 1987;22(1):45-7. [Medline].
Bailey RN, Guethlein ME. Diagnosis and management of conjunctival papillomas. J Am Optom Assoc. May 1990;61(5):405-12. [Medline].
Bosniak SL, Novick NL, Sachs ME. Treatment of recurrent squamous papillomata of the conjunctiva by carbon dioxide laser vaporization. Ophthalmology. Aug 1986;93(8):1078-82. [Medline].
Buggage RR, Smith JA, Shen D, Chan CC. Conjunctival papillomas caused by human papillomavirus type 33. Arch Ophthalmol. Feb 2002;120(2):202-4. [Medline].
Campbell RJ. Tumors of the eyelids, conjunctiva, and cornea. In: Garner A, Klintworth GK, eds. Pathobiology of Ocular Disease - A Dynamic Approach. Marcel Dekker Inc; 1994:1367-8(chap 46).
Chang T, Chapman B, Heathcote JG. Inverted mucoepidermoid papilloma of the conjunctiva. Can J Ophthalmol. Jun 1993;28(4):184-6. [Medline].
Chiemchaisri Y, Dongosintr N, Wasi C, et al. The regression of recurrent conjunctival papillomas by lymphoblastoid interferon treatment. J Med Assoc Thai. Jul 1990;73(7):406-13. [Medline].
Eagle RC. Conjunctiva. In: Eye Pathology - An Atlas and Basic Text. Philadelphia, Pa: WB Saunders Co; 1999:47-8, 59, 61-2(chap 4).
Easty DL, Williams C. Viral and rickettsial disease. In: Garner A, Klintworth GK, eds. Pathobiology of Ocular Disease - A Dynamic Approach. Marcel Dekker Inc; 1994:247(chap 7).
Harkey ME, Metz HS. Cryotherapy of conjunctival papillomata. Am J Ophthalmol. Nov 1968;66(5):872-4. [Medline].
Hsu HC, Lin HF. Eyelid tumors in children: a clinicopathologic study of a 10-year review in southern Taiwan. Ophthalmologica. Jul-Aug 2004;218(4):274-7. [Medline].
Jakobiec FA, Harrison W, Aronian D. Inverted mucoepidermoid papillomas of the epibulbar conjunctiva. Ophthalmology. Mar 1987;94(3):283-7. [Medline].
Khalil MK, Pierson RB, Mihalovits H, et al. Intraepithelial neoplasia of the bulbar conjunctiva clinically presenting as diffuse papillomatosis. Can J Ophthalmol. Oct 1993;28(6):287-90. [Medline].
Kremer I, Sandbank J, Weinberger D, et al. Pigmented epithelial tumours of the conjunctiva. Br J Ophthalmol. May 1992;76(5):294-6. [Medline].
Lass JH, Grove AS, Papale JJ, et al. Detection of human papillomavirus DNA sequences in conjunctival papilloma. Am J Ophthalmol. Nov 1983;96(5):670-4. [Medline].
Lass JH, Jenson AB, Papale JJ, Albert DM. Papillomavirus in human conjunctival papillomas. Am J Ophthalmol. Mar 1983;95(3):364-8. [Medline].
Mantyjarvi M, Syrjanen S, Kaipiainen S, et al. Detection of human papillomavirus type 11 DNA in a conjunctival squamous cell papilloma by in situ hybridization with biotinylated probes. Acta Ophthalmol (Copenh). Aug 1989;67(4):425-9. [Medline].
Margo CE, Mack WP. Therapeutic decisions involving disparate clinical outcomes: patient preference survey for treatment of central retinal artery occlusion. Ophthalmology. Apr 1996;103(4):691-6. [Medline].
McDonnell JM, Lass JH. Human papillomavirus diseases. In: Pepose JS, et al, eds. Ocular Infection and Immunity. New York: Mosby; 1996:857-68(chap 67).
McDonnell JM, McDonnell PJ, Mounts P, et al. Demonstration of papillomavirus capsid antigen in human conjunctival neoplasia. Arch Ophthalmol. Dec 1986;104(12):1801-5. [Medline].
McDonnell PJ, McDonnell JM, Kessis T, et al. Detection of human papillomavirus type 6/11 DNA in conjunctival papillomas by in situ hybridization with radioactive probes. Hum Pathol. Nov 1987;18(11):1115-9. [Medline].
McLean IW, et al. Tumors of the conjunctiva (Chapter 3). In: Tumors of the Eye and Ocular Adnexa. Atlas of Tumor Pathology. Washington, DC: Armed Forces Institute of Pathology;1994:49-52.
Mincione GP, Taddei GL, Wolovsky M, et al. Detection of human papillomavirus (HPV) DNA type 6/11 in a conjunctival papilloma by in situ hybridization with biotinylated probes. Pathologica. Jul-Aug 1992;84(1092):483-8. [Medline].
Miyagawa M, Hayasaka S, Nagaoka S, Mihara M. Sebaceous gland carcinoma of the eyelid presenting as a conjunctival papilloma. Ophthalmologica. 1994;208(1):46-8. [Medline].
Morsman CD. Spontaneous regression of a conjunctival intraepithelial neoplastic tumor. Arch Ophthalmol. Oct 1989;107(10):1490-1. [Medline].
Omohundro JM, Elliott JH. Cryotherapy of conjunctival papilloma. Arch Ophthalmol. Nov 1970;84(5):609-10. [Medline].
Pfister H, Fuchs PG, Volcker HE. Human papillomavirus DNA in conjunctival papilloma. Graefes Arch Clin Exp Ophthalmol. 1985;223(3):164-7. [Medline].
Rumelt S, Pe'er J, Rubin PA. The clinicopathological spectrum of benign peripunctal tumours. Graefes Arch Clin Exp Ophthalmol. Feb 2005;243(2):113-9. [Medline].
Saegusa M, Takano Y, Hashimura M, et al. HPV type 16 in conjunctival and junctional papilloma, dysplasia, and squamous cell carcinoma. J Clin Pathol. Dec 1995;48(12):1106-10. [Medline].
Schechter BA, Rand WJ, Velazquez GE, et al. Treatment of conjunctival papillomata with topical interferon Alfa-2b. Am J Ophthalmol. Aug 2002;134(2):268-70. [Medline].
Slade CS, Katz NN, Whitmore PV, Bardenstein DS. Conjunctival and canalicular papillomas and ichthyosis vulgaris. Ann Ophthalmol. Jul 1988;20(7):251-5. [Medline].
Spencer WH. Neoplasms and related conditions (Chapter 2). In: Ophthalmic Pathology - An Atlas and Textbook. Vol. 1. Philadelphia, Pa: WB Saunders Co;1996:106-11.
Wells GB, Lasner TM, Yousem DM, Zager EL. Lhermitte-Duclos disease and Cowden's syndrome in an adolescent patient. Case report. J Neurosurg. Jul 1994;81(1):133-6. [Medline].
Wilson FM, Ostler HB. Conjunctival papillomas in siblings. Am J Ophthalmol. Jan 1974;77(1):103-7. [Medline].
Yanoff M, Fine BS. Conjunctiva - pseudocancerous lesions. In: Ocular Pathology. 4th ed. New York: Mosby-Wolfe; 1996:220-1(chap 7).

