Ординатура / Офтальмология / Английские материалы / Tumors of the Eye and Ocular Adnexa_Char_2001

80 TUMORS OF THE EYE AND OCULAR ADNEXA

Figure 4–56. Caruncular amelanotic malignant melanoma.

Tissue orientation is crucial. For accurate histologic evaluation, it is vital to relate the neoplasm to normal structures and ensure that the specimen is not folded into itself. We always place conjunctival samples on a sterile ocular map (see Figure 3–1) and label the superior edge of the specimen with a long 4-0 silk suture and the inferior edge with a short 4-0 silk suture. In lesions that extend into the superficial cornea, we have not found frozen section control of that margin to be useful, since usually only tissue anterior to stroma is removed, often in a piecemeal manner. The bulk of the tumor is removed and the underlying corneal stroma is treated with double freeze-thaw cryotherapy.

In general, surgery is not effective management for diffuse conjunctival malignancies that exten-

sively involve both bulbar and palpebral conjunctiva (see Figure 4–26). In tumors that superficially involve the corneal epithelium but not stroma, a Took knife is useful to perform a lamellar scleral and corneal dissection (Figure 4–58).

A number of unique problems are associated with resection of large areas of conjunctiva for either diffuse conjunctival squamous cell carcinoma or melanoma. Tumors that involve a large enough area so that loss of goblet cells results in inadequate tear film, tumors that completely surround the cornea, tumors that involve both bulbar and palpebral conjunctiva, and tumors in the area of the lacrimal ductules are difficult to manage surgically with longterm retention of a useful eye. Although in one heroic case at our institution, the entire conjunctiva was removed and replaced with vaginal mucosa, usually eyes with diffuse tumors that involve both palpebral and bulbar conjunctiva eventually are lost. Some of the surgical techniques discussed below are shown on the CD-ROM accompanying this book.

In some diffuse neoplasms, we combine surgery with irradiation. The perilimbal and corneal tumor is resected so that the cornea and lens can be shielded with a lead contact lens; ionizing radiation is delivered to the remainder of the conjunctival malignancy. Unfortunately, the amount of radiation necessary to sterilize a diffuse tumor usually results in a dry, painful eye that eventually needs anterior exenteration.

In diffuse acquired melanosis with focal areas of malignant degeneration, the melanoma is resected with frozen section control and adjunctive double

freeze-thaw cryotherapy. In the operating room, we use either liquid nitrogen spray, or a hammerhead probe (Figure 4–59) without a thermocouple. The temperature on the control console is brought to

–40° C, the tissue is allowed to thaw, then it is frozen to –40° C again. For larger areas, we use a liquid nitrogen spray. As mentioned previously, these areas of malignant transformation can usually be identified by their increased thickness, vascularity, inflammation, or new spread of pigment. If there is malignant melanoma in association with diffuse acquired melanosis after the malignancy is excised, flat areas of pigmentation are treated with double freeze-thaw cryotherapy after the epithelium is elevated from underlying tissue using a 30-gauge needle and local anesthesia.

Five methods can be used to restore ocular integrity after tumor removal. These are primary closure, bare sclera, advancement conjunctival flaps, free autologous conjunctival grafts, and free buccal mucosa grafts. As previously discussed, when over 40 percent of the cornea is involved, we use a free limbal graft from the opposite eye.

In diffuse perilimbal tumors, if the defect cannot be closed primarily, a bare sclera approach is adequate. It is less satisfactory to leave the bare sclera if tumor resection extends < 5 mm from the limbus. While strabismologists routinely have left even larger areas of extraocular muscles denuded of conjunctival epithelium, it has been our experience that if adjunctive cryotherapy has been used (with its associated inflammation), significant complications occur. In small defects, the conjunctiva can be undermined, mobilized, and closed primarily. In larger defects, we obtain a free conjunctival graft, either from the superior nasal quadrant of that eye (if that area is uninvolved) or from the contralateral superior nasal quadrant. If the conjunctiva is harvested correctly, there should be neither postoperative discomfort nor scarring.

Topical anesthesia is applied to the donor area of the conjunctiva, and a 30-gauge needle is placed directly under the conjunctival epithelium. A conjunctival intraepithelial bleb is created with either balanced salt solution (if the patient is under general anesthesia) or 2 percent lidocaine with 1:100,000 epinephrine. The objective is to obtain only epithe-

Figure 4–59. Hammerhead cryotherapy probe. Alternatively, a liquid nitrogen applicator or spray can be used.

lium, without disturbing the underlying Tenon’s capsule. The conjunctival graft should be approximately 25 percent larger than is needed to fill the defect. The donor area of the graft is removed with Steven’s scissors and forceps. It is often difficult to differentiate the epithelial surface from the subepithelial surface, and care is taken to orient the conjunctival epithelium on a wet tongue depressor with the superficial surface away from the board.

The conjunctival graft is sutured into the area of tumor resection, using 8-0 vicryl cardinal sutures and running 10-0 nylon suture. Figure 4–60A and B demonstrates a conjunctival melanoma before and after resection with a free autologous conjunctival graft.

If a defect > 15 mm is present, buccal mucosa is obtained from the inner surface of the lip. If an extensive conjunctival resection with buccal mucosal graft is anticipated, the operation is usually performed under general anesthesia. Two towel clips are placed just below the vermilion border at the nasal and lateral aspects of the lower lip (Figure 4–61). The lip is everted over a rolled sponge. Two percent lidocaine with 1:100,000 epinephrine is used to infiltrate just under the epithelial surface of the buccal mucosa (Figure 4–62). Either a Davol dermatome (Figure 4–63) or a free buccal mucosal graft is obtained. The author prefers this method, since harvesting a graft with scissors and forceps is slower and the tissue is both thicker and uneven. The

A

B

Figure 4–60. A, Conjunctival melanoma treated with resection under frozen section control, double freeze-thaw cryotherapy and a free, conjunctival graft. B, One week postoperative appearance.

Figure 4–62. Subepithelial infiltration prior to obtaining graft.

towel clips are removed, and a thrombin-soaked sponge is placed between the front surface of the lower teeth and the posterior aspect of the lip. The buccal defect is not closed and results in surprisingly little postoperative discomfort or complications.278 If the conjunctival defect extends into the fornix, deep mattress 5-0 chromic gut sutures are used to construct the fornix; at the end of the procedure, a vault conformer (also known as a symblepharon

Figure 4–61. Placement of towel clips to evert lower lip in preparation for obtaining buccal mucous membrane graft.

Figure 4–63. The use of Davol dermatome to obtain a buccal mucous membrane graft.

conformer) is placed in the space, and a Frost or reverse Frost suture of 4-0 silk is placed in the lid to tightly close the eye for 48 hours. We have found that if this is not done when the fornix is reconstructed, symblepharon is almost inevitable.

In Figures 4–64 A and B, a case of a large fornix palpebral conjunctival melanoma in a patient who refused exenteration is shown prior to surgery and 5 years after resection, cryotherapy, and placement of a large mucous membrane graft.

REFERENCES

1.Ash JE. Epibulbar tumors. Am J Ophthalmol 1950;33: 1203–19.

2.Reese AB. Tumors of the eye, 3rd ed. Hagerstown, MD: Harper and Row; 1976. p. 257.

3.Quillen DA, Goldberg SH, Rosenwasser GO, Sassani JW. Basal cell carcinoma of the conjunctiva. Am J Ophthalmol 1993;116:244–5.

4.Grosssniklaus HE, Green WR, Luckenbach M, Chan CC. Conjunctival lesions in adults. A clinical and histopathologic review. Cornea 1987;6:78–116.

5.Newton R. A review of the etiology of squamous cell carcinoma of the conjunctiva. Br J Cancer 1996;74: 1511–3.

6.Sun EC, Fears TR, Goedert JJ. Epidemiology of squamous cell conjunctival cancer. Cancer Epidemiol Biomarkers Prev 1997;6:73–7.

7.McCarthy JN, Rootman J, Horseman D, White BA. Conjunctival and uveal melanoma in dysplastic nevus syndrome. Surv Ophthalmol 1993;37:377–86.

8.Dahlenfors R, Tornquist GU, Wettrell K, Mark J. Cytogenetic observations in nine ophthalmic malignant melanomas. Anticancer Res 1993;13:415–20.

9.Aubert C, Rouge F, Reilaudou M, Metge P. Establishment and characterization of human ocular melanoma cell lines. Int J Cancer 1993;54:784–92.

10.Ash JE, Wilder HC. Epithelial tumors of the limbus. Am J Ophthalmol 1942;25:926–32.

11.Noojin RO. Multiple ophthalmic verrucae. Arch Dermatol 1968;97:176–7.

12.Petrelli R, Cotlier E, Robins S, Stoessel K. Dinitrochlorobenzene immunotherapy of recurrent squamous papilloma of the conjunctiva. Ophthalmology 1981;88:1221–5.

13.Harkey ME, Metz HS. Cryotherapy of conjunctival papillomata. Am J Ophthalmol 1968;66:872–4.

14.Burns RP, Wankum G, Giangiacoma J, Anderson PC. Dinitrochlorobenzene and debulking therapy of conjunctival papilloma. J Pediatr Ophthalmol Strabismus 1983;20:221–6.

15.Shields CL, Lally MR, Singh AD, et al. Oral cimetidine (Tagamet) for recalcitrant, diffuse conjunctival papillomatosis. Am J Ophthalmol 1999;128:362–4.

16.Lass JH, Grove AS, Papale JJ, et al. Detection of human papillomavirus DNA sequences in conjunctival papilloma. Am J Ophthalmol 1983;96:670–4.

17.McDonnell JM, McDonnell PJ, Mounts P, et al. Demonstration of papillomavirus capsid antigen in human conjunctival neoplasia. Arch Ophthalmol 1986;104: 1801–5.

18.Odrich MG, Jakobiec FA, Lancaster WD, et al. A spectrum of bilateral squamous conjunctival tumors associated with human papillomavirus type 16. Ophthalmology 1991;98:628–35.

19.McDonnell JM, McDonnell PJ, Sun YY. Human papillomavirus DNA in tissues and ocular surface swabs of patients with conjunctival epithelial neoplasia. Invest Ophthalmol Vis Sci 1992;33:184–9.

20.Uy HS, Pineda R, Shore JW, et al. Hypertropic discoid lupus erythematosis of the conjunctiva. Am J Ophthalmol 1999;127:604–5.

84TUMORS OF THE EYE AND OCULAR ADNEXA

21.Kessing SV. Ectopic lacrimal gland tissue at the corneal limbus (glands of Manz?). Acta Ophthalmol 1966; 46:398–403.

22.Young TL, Buchi ER, Kaufman LM, et al. Respiratory epithelium in a cystic choristoma of the limbus. Arch Ophthalmol 1990;108:1736–9.

23.Blodi FC, Apple DJ. Localized conjunctival amyloidosis. Am J Ophthalmol 1979;88:346–50.

24.Boockvar W, Wessely Z, Ballen P. Recurrent granuloma pyogenicum of limbus. Arch Ophthalmol 1974;91: 42–4.

25.Minckler D. Pyogenic granuloma of the cornea simulating squamous cell carcinoma. Arch Ophthalmol 1979;97:516–7.

26.Ortiz JM, Yanoff M. Epipalpebral conjunctival osseous choristoma. Br J Ophthalmol 1979;63:173–6.

27.Martinez LM, Cohen KL. Conjunctival dermoid cyst seen on examination as a chronically red eye. Arch Ophthalmol 1998;116:1109–11.

28.Mansour AM, Barber JC, Reinecke RD, Wang FM. Ocular choristomas. Surv Ophthalmol 1989;33:339–58.

29.Jakobiec FA, Bonanno P, Sigelman J. Conjunctival adnexal cysts and dermoids. Arch Ophthalmol 1978; 96:1404–9.

30.Emamy H, Ahmadian H. Limbal dermoid with ectopic brain tissue. Report of a case and review of the literature. Arch Ophthalmol 1977;95:2201–2.

31.Crawford JS. Benign tumors of the eyelid and adjacent structures: should they be removed? J Pediatr Ophthalmol Strabismus 1979;16:246–50.

32.Frucht-Pery J, Sugar J, Baum J, et al. Mitomycin C treatment for conjunctival-cornea intraepithelial neoplasia. Ophthalmology 1997;104:2085–93.

33.Elsas FJ, Green WR. Epibulbar tumors in childhood. Am J Ophthalmol 1975;79:1001–7.

34.Ferry AP. Synthetic fiber granuloma. ‘Teddy Bear’ granuloma of the conjunctiva. Arch Ophthalmol 1994;112:1339–41.

35.Terry A, Patrinely JR, Anderson RL, Smithwick W IV. Orbital meningioencephalocele manifesting as a conjunctival mass. Am J Ophthalmol 1993;115:46–9.

36.Iwamoto T, Jakobiec FA, Darrell RW. Fibrous histiocytoma of the corneoscleral limbus: the ultrastructure of a distinctive inclusion. Ophthalmology 1981;88: 1260–8.

37.Jakobiec FA. Fibrous histiocytoma of the corneoscleral limbus. Am J Ophthalmol 1974;78:700–6.

38.Faludi JE, Kenyon K, Green WR. Fibrous histiocytoma of the corneoscleral limbus. Am J Ophthalmol 1975; 80:619–24.

39.Litricin O. Fibrous histiocytoma of the corneosclera. Arch Ophthalmol 1983;101:426–8.

40.Perry HD. Isolated episcleral neurofibroma. Ophthalmology 1982;89:1095–8.

41.Dabezies OH Jr, Penner R. Neurofibroma or neurilem-

moma of the bulbar conjunctiva. Arch Ophthalmol 1961;66:73–5.

42.Kalina PH, Bartley GB, Campbell RJ, Buettner H. Isolated neurofibromas of the conjunctiva. Am J Ophthalmol 1991;111:694–8.

43.Pe’er J, Ilsar M, Hidayat A. Conjunctival myxoma: a case report. Br J Ophthalmol 1984;68:618–22.

44.Patrinely JR, Green WR. Conjunctival myxoma. Arch Ophthalmol 1983;101:1416–20.

45.Ferry AP, Sherman FE. Nodular fasciitis of the conjunctiva apparently originating in the fascia bulbi (Tenon’s capsule). Am J Ophthalmol 1974;78: 514–7.

46.Rohrbach JM, Wohlrab TM, Kuper K. Lymphangioma of the conjunctiva. Klin Monatsbl Augenheilkd 1997;311:211–2.

47.Graham CM, McCartney ACE, Buckley RJ. Intrascleral neurilemmoma. Br J Ophthalmol 1989;73:378–81.

48.Shields CL, Shields JA, Varenhorst P. Transscleral leiomyoma. Ophthalmology 1991;98:84–7.

49.Charles NC, Fox DM, Avendano JA, et al. Conjunctival neurilemmoma. Arch Ophthalmol 1997;115:547–9.

50.Charles NC, Fox DM, Glasberg SS, Swicki J. Epibulbar granular cell tumor. Ophthalmology 1997;104: 1444–56.

51.McLeod SD, Edward DP. Benign lymphoid hyperplasia of the conjunctiva in children. Arch Ophthalmol 1999;117:832–5.

52.Cook BE Fr, Bartley GB. Acute lymphoblastic leukemia manifesting in an adult as a conjunctival mass. Am J Ophthalmol 1997;124:104–5.

53.Jakobiec FA, Perry HD, Harrison W, Krebs W. Dacryoadenoma. A unique tumor of the conjunctiva epithelium. Ophthalmology 1989;96:1014–20.

54.Allaire GS, Hidayat AA, Zimmerman LE, Minardi L. Reticulohistiocytoma of limbus and cornea. A clinicopathologic study of two cases. Ophthalmology 1990;97:1018–22.

55.Urbak SF. Infectious mononucleosis presenting as a unilateral conjunctival tumour. Acta Ophthalmologica 1993;71:133–5.

56.Stopak SS, Dreizen NG, Zimmerman LE, O’Neill JF. Sinus histiocytosis presenting as an epibulbar mass. A clinicopathologic case report. Arch Ophthalmol 1988;106:1426–8.

57.Migliori ME, Putterman AM. Recurrent conjunctival papilloma causing nasolacrimal duct obstruction. Am J Ophthalmol 1990;110:17–22.

58.Streeten BW, Carrillo R, Jamison R, et al. Inverted papilloma of the conjunctiva. Am J Ophthalmol 1979;88:1062–6.

59.Grossniklaus HE, Martin DF, Solomon AR. Invasive conjunctival tumor with keratoacanthoma features. Am J Ophthalmol 1990;109:736–8.

60.Munro S, Brownstein S, Liddy B. Conjunctival keratoacanthoma. Am J Ophthalmol 1993;116:654–5.

61.McGavic JS. Intraepithelial epithelioma of the cornea and conjunctiva (Bowen’s disease). Am J Ophthalmol 1942;25:167–76.

62.Arbesman H, Ransohoff DF. Is Bowen’s disease a predictor for the development of internal malignancy? A methodological critique of the literature. JAMA 1987;257:516–8.

63.Sun EC, Fears TR, Goedert JJ. Epidemiology of squamous cell conjunctival cancer. Cancer Epidemiol Biomarkers Prev 1997;6:73–7.

64.Pizzarello LD, Jakobiec FA. Bowen’s disease of the conjunctiva: a misnomer. In: Jakobiec FA, editor. Ocular and adnexal tumors. Birmingham, AL: Aesculapius; 1978. p. 553–71.

65.Erie JC, Campbell RJ, Liesegang TJ. Conjunctival and corneal intraepithelial and invasive neoplasia. Ophthalmology 1986;93;176–83.

66.Waring GO III, Roth AM, Ekins MB. Clinical and pathologic description of 17 cases of corneal intraepithelial neoplasia. Am J Ophthalmol 1984;97:547–59.

67.Zimmerman LE. Squamous cell carcinoma and related lesions of the bulbar conjunctiva. In: Boniuk M, editor. Ocular and adnexal tumors, St Louis, MO: CV Mosby Co; 1964. p 49–74.

68.Char DH. The management of lid and conjunctival malignancies. Surv Ophthalmol 1980;24:679–89.

69.Boone CW, Kelloff GJ, Steele VE. Natural history of intraepithelial neoplasia in humans with implications for cancer chemoprevention strategy. Cancer Res 1992;52:1651–9.

70.Lee GA, Hirst LW. Incidence of ocular surface epithelial dysplasia in metropolitan Brisbane. Arch Ophthalmol 1992;110:525–7.

71.Newton R, Ferlay J, Reeves G, et al. Effects of ambient solar ultraviolet radiation on incidence of squamouscell carcinoma of the eye. Lancet 1996;347:1450–1.

72.Newton R. A review of the etiology of squamous cell carcinoma of the conjunctiva. Br J Cancer 1996;74: 1511–3.

73.Marc’hadour FL, Romanet JP, Fdilia A, et al. Schwannoma of the bulbar conjunctiva. Arch Ophthalmol 1996;114:1258–60.

74.Macarez R, Bossis S, Robinet A, et al. Conjunctival epithelial neoplasias in organ transplant patients receiving cyclosporine therapy. Cornea 1999;18: 495–7.

75.Li G, Ho VC, Berean K, Tron VA. Ultraviolet radiation induction of squamous cell carcinomas in p53 transgenic mice. Cancer Res 1995;55:2070–4.

76.Jha PK, Beral V, Hack S, et al. Antibodies to human papillomavirus and to other genital infectious agents and invasive cervical cancer risk. Lancet 1993;341: 1116–8.

77.Liang J, Mei Q, Da-Zhi C, et al. Indole-3-carbinol prevents cervical cancer in human papilloma virus type

16 (HPV16) transgenic mice. Cancer Res 1999;59:

3991–7.

78.Sauter ER, Nesbit M, Litwin S, et al. Antisense cyclin D1 induces apoptosis and tumor shrinkage in human squamous carcinomas. Cancer Res 1999;59: 4876–81.

79.Tabandeh H, Gopal S, Teimory M, et al. Conjunctival involvement in malignancy-associated acanthosis nigricans. Eye 1993;7:648–51.

80.Tan DTH, Lim ASM, Goh H-S, Smith DR. Abnormal expression of the p53 tumor suppressor gene in the conjunctiva of patients with pterygium. Am J Ophthalmol 1997;123:404–5.

81.Clear AS, Chirambo MC, Hutt MS. Solar keratosis, pterygium, and squamous cell carcinoma of the conjunctiva in Malawi. Br J Ophthalmol 1979;63:102–9.

82.Alani RM, Munger K. Human papillomaviruses and associated malignancies. J Clin Oncol 1998;330–7.

83.Koss LG. Human papillomavirus—passenger, driver, or both? Hum Pathol 1998;29;309–10.

84.Karcioglu ZA, Issa TM. Human papilloma virus in neoplastic and non-neoplastic conditions of the external eye. Br J Ophthalmol 1997;81:595–8.

85.Iliff WJ, Marback R, Green WR. Invasive squamous cell carcinoma of the conjunctiva. Arch Ophthalmol 1975;93:119–22.

86.Jauregui HO, Klintworth GK. Pigmented squamous cell carcinoma of cornea and conjunctiva: a light microscopic, histochemical, and ultrastructural study. Cancer 1976;38:778–88.

87.Verderber L, Wesley RE, Glick AD. Malignant peripheral nerve sheath tumor presenting at the limbal conjunctiva. Orbit 1995;14:81–6.

88.Cameron JA, Hidayat AA. Squamous cell carcinoma of the cornea. Am J Ophthalmol 1991;111:571–4.

89.Steinhorst U, von Domarus D. Carcinoma in situ of the cornea. Ophthalmologica 1990;200:107–10.

90.Daxecker F, Philipp W, Mikuz G. Corneal carcinoma. Ophthalmologica 1989;198:163–5.

91.Spinak M, Friedman AH. Squamous cell carcinoma of the conjunctiva. Value of exfoliative cytology and diagnosis. Surv Ophthalmol 1977;21:351–5.

92.Tsubota K, Kajiwara K, Ugajin S, Hasegawa T. Conjunctival brush cytology. Acta Cytologica 1990; 34:233–5.

93.Nadjari B, Kersten A, Ross B, et al. Cytologic and DNA cytometric diagnosis and therapy monitoring of squamous cell carcinoma in situ and malignant melanoma of the cornea and conjunctiva. Anal Quant Cytol Histol 21:387-96, 1999.

94.Wilson FM II. Rose bengal staining of epibulbar squamous neoplasms. Ophthalmic Surg 1976;7:21–3.

95.Morsman CD. Spontaneous regression of a conjunctival intraepithelial neoplastic tumor. Arch Ophthalmol 1989;107:1490–1.

86TUMORS OF THE EYE AND OCULAR ADNEXA

96.Irvine AR Jr. Dyskeratotic epibulbar tumors. Trans Am Ophthalmol Soc 1963;61:243–73.

97.Carroll JM, Kuwabara T. A classification of limbal epitheliomas. Arch Ophthalmol 1965;73:545–51.

98.Seitz B, Fischar M, Holbach LM, Naumann GOH. Differential diagnosis and progress of 122 excised epibulbar epithelial neoplasias. Klin Monatsvl Augenheilkd 1995;207:239–46.

99.Tabin G, Lewvin S, Snibson G, et al. Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia. Ophthalmology 1997;104:485–92.

100.Spraul CW, Lang GK. Oncocytoma of the conjunctiva. Klin Monatsbl Augenheildkd 1996;209:176–7.

101.Sanders N, Bedotto C. Recurrent carcinoma in situ of the conjunctiva and cornea (Bowen’s disease). Am J Ophthalmol 1972;74:688–93.

102.Stokes JJ. Intraocular extension of epibulbar squamous cell carcinoma of limbus. Tr Acad Ophthalmol 1955;59:143–6.

103.Nicholson DH, Herschler J. Intraocular extension of squamous cell carcinoma of the conjunctiva. Arch Ophthalmol 1977;95:843–6.

104.Li WW, Pettit TH, Zakka KA. Intraocular invasion by papillary squamous cell carcinoma of the conjunctiva. Am J Ophthalmol 1980;90:697–701.

105.Wexler SA, Wallow IH. Squamous cell carcinoma of the conjunctiva presenting with intraocular extension. Arch Ophthalmol 1985;103:1175–7.

106.Blodi FC. Squamous cell carcinoma of the conjunctiva. Doc Ophthalmol 1973;34:93–108.

107.Shields JA, Shields CL, Gunduz K, Eagle RC. Intraocular invasion of conjunctival squamous cell carcinoma in five patients. Ophthal Plast Reconstr Surg 1999;15:153–60.

108.Lindenmuth KA, Sugar A, Kincaid MC, et al. Invasive squamous cell carcinoma of the conjunctiva presenting as necrotizing scleral perforation and uveal prolapse. Surv Ophthalmol 1998;33:50–4.

109.Char DH, Crawford JB, Howes EL Jr, Weinstein AJ. Resection of intraocular squamous cell carcinoma. Br J Ophthalmol 1992;76:123–5.

110.Brownstein S. Mucoepidermoid carcinoma of the conjunctiva with intraocular invasion. Ophthalmology 1981;88:1226–30.

111.Cohen BH, Green WR, Iliff NT, et al. Spindle cell carcinoma of the conjunctiva. Arch Ophthalmol 1980;98:1809–13.

112.Seregard S, Kock E. Squamous spindle cell carcinoma of the conjunctiva. Fatal outcome of a pterygiumlike lesion. Acta Ophthalmol Scand 1995;73:464–6.

113.Fraunfelder FT, Wingfield D. Management of intraepithelial conjunctival tumors and squamous cell carcinomas. Am J Ophthalmol 1983;95:359–63.

114.Dutton JJ, Anderson RL, Tse DT. Combined surgery

and cryotherapy for scleral invasion of epithelial malignancies. Ophthalmic Surg 1984;15:289–94.

115.Divine RD, Anderson RL. Nitrous oxide cryotherapy for intraepithelial epithelioma of the conjunctiva. Arch Ophthalmol 1983;101:782–6.

116.Peksayar G, Soyturk MK, Demiryont M. Long-term results of cryotherapy on malignant epithelial tumors of the conjunctiva. Am J Ophthalmol 1989; 107:337–40.

117.Fraunfelder FT, Wingfield D. Therapy of intraepithelial epitheliomas and squamous cell carcinoma of the limbus. Trans Am Ophthalmol Soc 1980;78: 290–300.

118.Kenyon KR, Wagoner MD, Hettinger ME. Conjunctival autograft transplantation for advanced and recurrent pterygium. Ophthalmology 1985;92:1461–70.

119.Turgeon PW, Nauheim RC, Roat MI, et al. Indications for keratoepithelioplasty. Arch Ophthalmol 1990; 108:233–6.

120.Copeland RA Jr, Char DH. Limbal autograft reconstruction after conjunctival squamous cell carcinoma. Am J Ophthalmol 1990;110:412–5.

121.Tseng SC, Prabhasawat P, Lee SH. Amniotic membrane transplantation for conjunctival surface reconstruction. Am J Ophthalmol 1997;124:765–74.

122.Maloney RK, Thompson V, Ghiselli G, et al. A prospective multicenter trial of excimer laser phototherapeutic keratectomy for corneal visual loss. Am J Ophthalmol 1996;122:149–60.

123.Buus DR, Tse DT, Folberg R. Microscopically controlled excision of conjunctival squamous cell carcinoma. Am J Ophthalmol 1994;117:97–102.

124.Lommatzsch P. Beta-ray treatment of malignant epithelial tumors of the conjunctiva. Am J Ophthalmol 1976;81:198–206.

125.Cerezo L, Otero J, Aragon G, et al. Conjunctival intraepithelial and invasive squamous cell carcinomas treated with strontium-90. Radiother Oncol 1990;17:191–7.

126.Behrendt S, Bernsmeier H, Randzio G. Fractionated beta-irradiation of a conjunctival lymphangioma. Ophthalmologica 1991;203:161–3.

127.Jones DB, Wilhelmus KR, Font RL. Beta radiation of recurrent corneal intraepithelial neoplasia. Trans Am Ophthal Soc 1991;89:285–91.

128.Zehetmayer M, Menapace R, Kulnig W. Combined local excision and brachytherapy with ruthenium106 in the treatment of epibulbar malignancies. Ophthalmologica 1993;207:133–9.

129.Ullman S, Augsburger JJ, Brady LW. Fractionated epibulbar I-125 plaque radiotherapy for recurrent mucoepidermoid carcinoma of the bulbar conjunctiva. Am J Ophthalmol 1995;119:102–3.

130.Kearsley JH, Fitchew RS, Taylor RG. Adjunctive radiotherapy with strontium-90 in the treatment of con-

junctival squamous cell carcinoma. Int J Radiat Oncol Biol Phys 1988;14:435–43.

131.Moriarty AP, Crawford GJ, McAllister IL, Constable IJ. Severe cornealscleral infection: a complication of beta irradiation scleral necrosis following pterygium excision. Arch Ophthalmol 1993;111:947–51.

132.Green MO, Brannen AL. Hyperbaric oxygen therapy for beta- irradiation-induced scleral necrosis. Ophthalmology 1995;102:1038–41.

133.Maskin SL. Regression of limbal epithelial dysplasia with topical interferon. Arch Ophthalmol 1994;112: 1145–6.

134.Dausch D, Landesz M, Schroder E. Phototherapeutic keratectomy in recurrent corneal intraepithelial dysplasia. Arch Ophthalmol 1994;112:22–3.

135.Frucht-Pery J, Rozenman Y. Mitomycin C therapy for corneal intraepithelial neoplasia. Am J Ophthalmol 1994;117:164–8.

136.Rubinfeld RS, Pfister RR, Stein RM, et al. Serious complications of topical mitomycin-C after pterygium surgery. Ophthalmology 1992;99:1647–54.

137.Midena E, Boccato P, Degli Angeli DC. Conjunctival squamous cell carcinoma treated with topical 5-fluorouracil. Arch Ophthalmol 1997;115:1600–1.

138.Frucht-Perry J, Assil K, Ziegler E, et al. Fibrinenmeshed tobramycin liposomes: single application topical therapy of Pseudomonas keratitis. Cornea 1992;11:393–7.

139.Wilson MW, Hungerford JL, George SM, Madraperla SA. Topical mitomycin C for the treatment of conjunctival and corneal epithelial dysplasia and neoplasia. Am J Ophthalmol 1997;124:303–11.

140.Grossniklaus HE, Aaberg TM. Mitomycin C treatment of conjunctival intra-epithelial neoplasia. Am J Ophthalmol 1997;124:381–3.

141.Heigle TJ, Stulting RD, Palay DA. Treatment of recurrent conjunctival epithelial neoplasia with topical mitomycin C. Am J Ophthalmol 1997;124:397–401.

142.Vann RR, Karp CL. Lesional perilesional entopical interferon alpha-B for conjunctival and corneal neoplasia. Ophthalmology 1999;106:91–7.

143.Wolter JR, Bromley WC. Intraepithelial sebaceous epithelioma of lids, conjunctiva, and cornea treated with minimal orbital exenteration. Ophthal Surg 1991;22:341–4.

144.Johnson TE, Tabbara KF, Weatherhead RG, et al. Secondary squamous cell carcinoma of the orbit. Arch Ophthalmol 1997;115:75–8.

145.Margo CE, Groden LR. Intraepithelial neoplasia of the conjunctiva with mucoepidermoid differentiation. Am J Ophthalmol 1989;108:600–1.

146.Carrau RL, Stillman E, Canaan RE. Mucoepidermoid carcinoma of the conjunctiva. Ophthal Plast Reconst Surg 1994;10:163–8

147.Huntington AC, Langloss JM, Hidayat AA. Spindle

cell carcinoma of the conjunctiva. An immunohistochemical and ultrastructural study of six cases. Ophthalmology 1990;97:711–7.

148.Campanella PC, Goldberg SH, Erlichman K, Abendroth C. Squamous cell tumors and ocular prostheses. Ophthalmol Plast Reconstr Surg 1998;14:45–9.

149.Keller AZ. Histology, survivorship and related factors in the epidemiology of eye cancers. Am J Epidemiol 1973;97:386–93.

150.Scotto J, Fraumeni JF Jr, Lee JA. Melanomas of the eye and other noncutaneous sites: epidemiologic aspects. J Natl Cancer Inst 1976;56:489–91.

151.Seregard S, Kock E. Conjunctival malignant melanoma in Sweden 1969–1991. Acta Ophthalmol 1992;70: 289–96.

152.Chang AE, Karnell LH, Menck HR. The national cancer data base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. Cancer 1998;83:1664–78.

153.Verhoeff FH, Loring RG. A case of primary epibulbar sarcoma with secondary growths in limbus and sclera, and invasion of the choroid, ciliary body, and iris. Arch Ophthalmol 1903;32:97–102.

154.Stefani FH. A prognostic index for patients for malignant melanoma of the conjunctiva. Graefe’s Arch Clin Exp Ophthalmol 1986;224:580–2.

155.Jay B. A follow-up study of limbal melanomata. Proc R Soc Med 1964;57:497–500.

156.Reese AB. Precancerous and cancerous melanosis of conjunctiva. Am J Ophthalmol 1955;39:96–100.

157.Silvers DN, Jakobiec FA, Freeman TR, et al. Melanoma of the conjunctiva: a clinical pathologic study. In: Jakobiec, editor. Ocular and adnexal tumors, Birmingham, AL: Aesculapius; 1978. p. 585–99.

158.Folberg R, McLean IW, Zimmerman LE. Malignant melanoma of the conjunctiva. Hum Pathol 1985;16: 136–43.

159.Tucker MA, Shields JA, Hartge P, et al. Sunlight exposure as risk factor for intraocular malignant melanoma. N Engl J Med 1985;313:789–92.

160.Swerdlow AJ. Epidemiology of eye cancer in adults in England and Wales, 1962-1977. Am J Epidemiol 1983;118:294–300.

161.Jay V, Ho M, Hunter W, et al. Expression of p53 in conjunctival melanocytic nevi. An immunohistochemical study. Arch Pathol Lab Med 1996;120:378–9.

162.Seregard S. Cell growth and p53 expression in primary acquired melanosis and conjunctival melanoma. J Clin Pathol 1996;49:338–42.

163.McDonnell JM, Carpenter JD, Jacobs P, et al. Conjunctival melanocytic lesions in children. Ophthalmology 1989;96:986–93.

164.Margo CE, Roper DL, Hidayat AA. Borderline melanocytic tumor of the conjunctiva: diagnostic and theraputic considerations. J Pediatr Ophthalmol Strabismus 1991;28:268–70.

88 TUMORS OF THE EYE AND OCULAR ADNEXA

165.Strempel I, Kroll P. Conjunctival malignant melanoma in children. Ophthalmology 1999;213:129–32.

166.Hitzer S, Bialasiewica AA, Richard G. Immunohistochemical markers for cytoplasmic antigens in acquired melanosis, malignant melanomas, and nevi of the conjunctiva. Klin Monatsbl Augenheilkd 1998;213:230–7.

167.Soong HK, McKeeney MJ, Wolter JR. Adrenochrome staining of senile plaque resembling malignant melanoma. Am J Ophthalmol 1986;101:380.

168.Bartley GB, Buller CR, Campbell RJ, Bullock JD. Pigmented episcleral mass from argyrosis following strabismus surgery. Arch Ophthalmol 1991;109:775–6.

169.Kennedy RH, Flanagan JC, Eagle RC Jr, Carney JA. The Carney complex with ocular signs suggestive of cardiac myxoma. Am J Ophthalmol 1991;111:699–702.

170.Crawford JB, Howes EL Jr, Char DH. Combined nevi of the conjunctiva. Arch Ophthalmol 1999;117: 1121–7.

171.Charles NC, Stenson S, Taterka HB. Epibulbar malignant melanoma in a black patient. Arch Ophthalmol 1979;97:316–8.

172.Welsh NH, Jhavery Y. Malignant melanoma of the cornea in an African patient. Am J Ophthalmol 1971;72:796–800.

173.Reese AB. Precancerous and cancerous melanosis. Am J Ophthalmol 1966;61:1272–7.

174.Gloor P, Alexandrakis G. Characteristics of primary choroidal melanosis. Invest Ophthalmol Basic Sci 1995;36:721–9.

175.Jay B. Naevi in melanomata of the conjunctiva. Br J Ophthalmol 1965;49:169–204.

176.Jakobiec FA. Conjunctival melanoma. Arch Ophthalmol 1980;98:1378–84.

177.Hofbauer GF, Schaefer C, Noppen C, et al. MAGE-3 immunoreactivity in formalin-fixed, paraffinembedded primary and metastatic melanoma: frequency and distribution. Am J Pathol 1997;151: 1549–53.

178.Grossniklaus HE, Margo CE, Solomon AR. Indeterminate melanocytic proliferations of the conjunctiva. Arch Ophthalmol 1999;117:1131–6.

179.Folberg R, Jakobiec FA, Bernardino VB, Iwamoto T. Benign conjunctival melanocytic lesions. Clinicopathologic features. Ophthalmology 1989;96:436–61.

180.Kantelip B, Boccard R, Nores JM, Bacin F. A case of conjunctival spitz nevus: review of literature and comparison with cutaneous locations. Ann Ophthalmol 1989;21:176–9.

181.Weiss JS, Perusse P, Reale F. Tear cytology in conjunctival melanoma. Am J Ophthalmol 1991;111:648–49.

182.Glasgow BJ, McCall LC, Foos RY. HMB-45 antibody reactivity in pigmented lesions of the conjunctiva. Am J Ophthalmol 1990;109:696–700.

183.McDonnell JM, Sun YY, Wagner D. HMB-45 immuno-

histochemical staining of conjunctival melanocytic lesions. Ophthalmology 1991;98:453–8.

184.Zimmerman FA. Criteria for management of melanosis. Arch Ophthalmol 1966;76:307–8.

185.Jakobiec FA, Folberg R, Iwamoto T. Clinicopathologic characteristics of premalignant and malignant melanocytic lesions of the conjunctiva. Ophthalmology 1989;96:147–66.

186.Jay V, Font RL. Conjunctival amelanotic malignant melanoma rising in the primary melanosis sine pigmento. Ophthalmol 1998;105:91–4.

187.Clune JP. Primary malignant melanoma of the cornea. Am J Ophthalmol 1963;55:147–50.

188.Guillen FJ, Albert DM, Mihm MC Jr. Pigmented melanocytic lesions of the conjunctiva — a new approach to their classification. Pathology 1985;17: 275–80.

189.Jeffrey IJ, Lucas DR, McEwan C, Lee WR. Malignant melanoma of the conjunctiva. Histopathology 1986;10:363–78.

190.Crawford JB. Conjunctival melanomas: prognostic factors. A review and an analysis of a series. Trans Am Ophthalmol Soc 1980;78:467–502.

191.Seregard S. Cell proliferation as a prognostic indicator in conjunctival malignant melanoma. Am J Ophthalmol 1993;116:93–7.

192.Lommatzsch PK, Lommatzsch RE, Kirsch I, Fuhrmann P. Therapeutic outcome of patients suffering from malignant melanomas of the conjunctiva. Br J Ophthalmol 1990;74:615–9.

193.Seregard S. Conjunctival melanoma. Surv Ophthalmol 1998;42:321–50.

194.Norregaard JC, Gerner N, Jensen OA, Prause JU. Malignant melanoma of the conjunctiva: Reoccurrence and survival following surgery and radiotherapy in a Danish population. Graefes Arch Clin Exp Ophthalmol 1996;234:569–72.

195.Desjardins L, Poncet P, Levy C, et al. Prognostic factors in malignant melanoma of the conjunctiva. An anatomo-clinical study of 56 patients. J Fr Ophtalmol 1999;22:315–21.

196.Liesegang TJ, Campbell RJ. Mayo Clinic experience with conjunctival melanomas. Arch Ophthalmol 1980;98:1385–9.

197.Lederman M. Radiotherapy of malignant melanomata of the eye. Br J Radiol 1961;34:21–42.

198.Lederman M. Discussion of pigmented tumors of the conjunctiva. In: Boniuk M, editor. Ocular and adnexal tumors. St Louis, MO: CV Mosby; 1964. p. 24–48.

199.Lommatzsch PK. Beta-ray treatment of malignant epibulbar melanoma. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1978;209:111–24.

200.Napel JA. Conjunctival melanoma, a retrospective study. Doc Ophthalmol 1977;42:321–8.

201.Lederman M, Wybar K, Busby E. Malignant epibulbar melanoma: natural history and treatment by radiotherapy. Br J Ophthalmol 1984;68:605–17.

202.Kreusel KM, Wiegel T, Bechrakis NE, et al. Treatment of advanced conjunctival melanoma by external beam irradiation. Front Radiat Ther Oncol 1997; 30:150–3.

203.Zografos L, Uffer S, Bercher L, Gailloud C. Chirurgie, cryocoagulation et radiotherapie combinee pour le traitmement des melanomes de la conjonctive. Klin Monatsbl Augenheilkd 1994;204:385–90.

204.Matthaus W, Lange G, Roitzsch E. Cryotherapy of eyelid and conjunctival tumors. Ophthalmologica 1976;173:53–62.

205.Jakobiec FA, Brownstein S, Wilkinson RD, et al. Combined surgery and cryotherapy for diffuse malignant melanoma of the conjunctiva. Arch Ophthalmol 1980;98:1390–6.

206.Jakobiec FA, Brownstein S, Albert W, et al. The role of cryotherapy in the management of conjunctival melanoma. Ophthalmology 1982;89:502–15.

207.Brownstein S, Jakobiec FA, Wilkinson RD, et al. Cryotherapy for precancerous melanosis (atypical melanocytic hyperplasia) of the conjunctiva. Arch Ophthalmol 1981;99:1224–31.

208.Freedman J, Rohm G. Surgical management and histopathology of invasive tumours of the cornea. Br J Ophthalmol 1979;63:632–5.

209.Engin K, Leeper DB, Tupchong L, Waterman FM. Thermoradiotherapy in the management of superficial malignant tumors. Clin Cancer Res 1995;1:139–45.

210.Akpek EK, Ertoy D, Kalayci D, Hasiripi H. Postoperative topical mitomycin C in conjunctival squamous cell neoplasia. Cornea 1999;18:59–62.

211.Frucht-Pery J, Pe’er J. Use of mitomycin C in the treatment of conjunctival primary acquired melanosis with atypia. Arch Ophthalmol 1996;114:1261–4.

212.Werschnik C, Lommatzsch PK. Mitomycin C in treatment of conjunctival melanoma and primary acquired melanosis. Klin Monatsbl Augenheilkd 1998;212:465–8.

213.Finger PT, Cxechonska G, Liarikos S. Topical mitomycin C chemotherapy for conjunctival melanoma and PAM with atypia. Br J Ophthalmol 1998;82:476–9.

214.Gow JA, Spencer WH. Intraocular extension of an epibulbar malignant melanoma. Arch Ophthalmol 1993;90:57–9.

215.Werschnik C, Lommatzsch PK. Mitomycin C in treatment of conjunctival melanoma and primary acquired melanosis. Klin Monatsbl Augenheilkd 1998;212:465–8.

216.Travis LW, Rice DH, McClatchey KD, Wallace SW. Malignant melanoma of the conjunctiva metastatic to parotid gland. Reports of cases and discussion of surgical management. Laryngoscope 1977;87:2000–7.

217.Robertson DM, Hungerford JL, McCartney A. Pigmentation of the eyelid margin accompanying conjunctival melanoma. Am J Ophthalmol 1989;108:435–9.

218.Jakobiec FR, Buckman G, Zimmerman LE, et al. Metastatic melanoma within and to the conjunctiva. Ophthalmology 1989;96:999–1005.

219.Robertson DM, Hungerford JL, McCartney AL. Malignant melanomas of the conjunctiva, nasal cavity, and paranasal sinuses. Am J Ophthalmol 1989; 108:440–2.

220.Paridaens AD, Minassian DC, McCartney AC, Hungerford JL. Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathologic study of 256 cases. Br J Ophthalmol 1994;78:252–9.

221.Birns JW, Jenkins HA. Melanoma of the conjunctiva

—a rational approach to management. Head Neck Surg 1979;2:99–106.

222.Fuchs U, Kivela T, Leisto K, Tarkkanen A. Prognosis of conjunctival melanoma in relation to histopathologic features. Br J Cancer 1989;59:261–7.

223.Folberg R, McLean IW, Zimmerman LE. Primary acquired melanosis of the conjunctiva. Hum Pathol 1985;16:129–35.

224.Paridaens AD, Seregard S, Minassian D, et al. AgNOR counts in conjunctival malignant melanoma lack prognostic value. Br J Ophthalmol 1992;76:621–3.

225.Kirkwood JM. Systematic adjuvant treatment of highrisk melanoma: the role of interferon alfa-2b and other immunotherapies. Eur J Cancer 1998;34:S12–7.

226.Holland GN, Pepose JS, Pettit TH, et al. Acquired immune deficiency syndrome. Ocular manifestations. Ophthalmology 1983;90:859–73.

227.Kalinske M, Leone CR Jr. Kaposi’s sarcoma involving eyelid and conjunctiva. Ann Ophthalmol 1982;14: 497–9.

228.Lieberman PH, Llovera IN. Kaposi’s sarcoma of the bulbar conjunctiva. Arch Ophthalmol 1972;88:44–5.

229.Bedrick JJ, Savino PJ, Schatz NJ. Conjunctival Kaposi’s sarcoma in a patient with myasthenia gravis. Arch Ophthalmol 1981;99:1607–9.

230.Chang Y, Cesarman E, Pessin MS, et al. Identification of Herpes virus-like DNA sequences in AIDS-asso- ciated Kaposi’s sarcoma. Science 1994;266:1865–9.

231.Macher AM, Palestine A, Masur H, et al. Multicentric Kaposi’s sarcoma of the conjunctiva in a male homosexual with the acquired immunodeficiency syndrome. Ophthalmology 1983;90:879–84.

232.Weiter JJ, Jakobiec FA, Iwamoto T. The clinical and morphologic characteristics of Kaposi’s sarcomas of the conjunctiva. Am J Ophthalmol 1980;89:546–52.

233.Ghabrial R, Quivey JM, Dunn JP Jr, Char DH. Radiation therapy of acquired immunodeficiency syndrome related Kaposi’s sarcoma of the eyelids and conjunctiva. Arch Ophthalmol 1992;110:1423–6.

234.Kurumety UR, Lustbader JM. Kaposi’s sarcoma of the