444 BritishJournalofOphthalmology, 1992,76,444-446 Recurrent malignant melanoma of the corneal stroma: a case of 'black ' Br J Ophthalmol: first published as 10.1136/bjo.76.7.444 on 1 July 1992. Downloaded from

A D A Paridaens, C M Kirkness, A Garner, J L Hungerford

Abstract capsule, and inferior fornix. A donor corneal A 39-year-old Caucasian woman with a history graft was then sutured to the edges ofthe corneal of recurrent conjunctival melanoma of her host defect using interrupted 10/0 Nylon. The right developed an intrastromal heavily was closed over the bare scleral pigmented malignant melanoma, which component ofthe donor corneal graft, so that the involved the whole corneal diameter. The graft was covered to the level ofthe host limbus. patient was treated by corneoscleral lamellar Postoperatively, there was a mild corneal keratoplasty and there has been no evidence of stromal haze and the epithelial defect of the recurrent neoplasm during 4 years of foliow- donor graft healed within 2 weeks. Some pigment up. This apparently unique presentation of and interface irregularity was noted at the graft malignant melanoma ofthe cornea is illustrated host interface at 10 o'clock and both superficial and the differential diagnosis of corneal and deep neovascularisation were seen at 6 pigmentation is discussed. o'clock. One year after the surgery, the cosmetic result was very satisfactory (Fig 1B) and no noticeable changes of the pigmentation and vascularisation were observed, except for a small Malignant melanoma of the cornea is very area of flat pigmentation of the corneal edge at uncommon. Though primary corneal melanoma the 10-11 o'clock position. The best corrected has been reported'"5 this neoplasm is usually seen visual acuity was 6/9 (20/30) with - 5 D. Because in association with an adjacent limbal or con- of anisekonia the patient was fitted with a daily junctival melanocytic lesion. We describe a wear soft contact , which was well tolerated. patient with a history of recurrent conjunctival Topical steroid therapy has been continued in melanoma who presented with a black cornea gradually decreasing dosage (currently predni- due to extensive malignant melanocytic invasion solone drops, 3% twice daily). into corneal stroma. On her last visit in May 1991, 4 years after removal of the corneal malignant melanoma, the

visual acuity was 6/9 and there was no evidence of http://bjo.bmj.com/ Case report recurrence offrank malignancy. In February 1987 a 39-year-old Caucasian woman was referred to Moorfields Eye Hospital with a 9- year history of recurrent malignant melanoma of HISTOPATHOLOGY her right conjunctiva. The diagnosis had been Histopathological examination of sections of the established by excision biopsies of temporal cornea and adjacent showed a small focus perilimbal pigmented tumours in 1983 and 1985, of residual or recurrent malignant melanoma at on October 1, 2021 by guest. Protected copyright. which showed that the melanoma originated the periphery of the cornea within the superficial from an area of primary acquired melanosis stroma (Figs 3 and 4). Heavily pigmented cells with atypia. No additional cryotherapy or were observed between stromal lamellae across e irradiation had been given. the entire corneal diameter, almost reaching the She complained of having had right photo- resection margin on the opposite side. The Institute of phobia and blurred vision for several months. was atrophic but otherwise Ophthalmology, On examination there was extensive and dense normal and there was no appreciable stromal Department of Pathology of the entire cornea, A D A Paridaens pigmentation interfering vascularisation. Some infiltration of the adjacent A Garner with the central visual axis (Fig IA). Slit-lamp bulbar conjunctiva by neoplastic cells was also examination showed involvement of superficial seen together with mild inflammation in the Moorfields Eye Hospital, corneal stroma. There was evidence ofmelanosis underlying stroma. Within the conjunctiva the Cornea Clinic C M Kirkness* of the temporal limbus but no nodular disease tumour was intraepithelial. Separate specimens was noted. No further areas of conjunctival from the vicinity ofthe , the Moorfields Eye Hospital, pigmentation were seen. The right visual acuity inferior Tenon's capsule, and from the nasal Oncology Clinic was 6/18 with pinhole and 6/36 unaided. The left conjunctiva showed no abnormality. J L Hungerford unaided visual acuity was 6/6. The intraocular *Cuffent address: pressure was 10 mm Hg in both . The left eye Tennent Institute of Ophthalmology, showed no abnormalities. Discussion University ofGlasgow, In June 1987 a corneoscleral lamellar Pigmentation of the cornea is grossly or Glasgow keratoplasty was performed. More than two biomicroscopically visible and is of several Correspondence to: thirds of the thickness of the whole cornea were origins including ocular inflammation, conjunc- Dr A D A Paridaens, Institute of Ophthalmology, excised en bloc with a scleral component in the tival melanocytic lesions, anterior segment Department of Pathology, inferotemporal quadrant, which resulted in a trauma, the pigment dispersion syndrome,6 and 17/25 Cayton Street, London EC1V 9AT. keyhole shaped defect with a diameter of 15 mm drugs.78 Depositions of metals, blood pigments, Accepted for publication by 24 mm (Fig 2). In addition diagnostic biopsies lipids, and lipofuscin9 may mimic the gold- 12 December 1991 were taken from nasal conjunctiva, Tenon's brown to black melanin pigmentation. Recurrent malignant melanoma ofthe corneal stroma: a case of'black cornea' 445 Br J Ophthalmol: first published as 10.1136/bjo.76.7.444 on 1 July 1992. Downloaded from

Fig 3A

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9 V I Fig IA 'A

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Fig 3B Figure 3 (A) Histological examination ofbiopsy specimens ofthe right temporal limbus and conjunctiva shows conjunctival malignant melanoma (arrow) originatingfrom areas ofprimary acquired melanosis with atypia (haematoxylin and eosin, x20). The maximal thickness ofthis nodule is 1 8mm. (B) Higher power examination shows heavily pigmented, large pleomorphic cells and spindle cells (haematoxylin andeosin, x200). The location of corneal pigmentation depends on the underlying cause. Posterior corneal melanin pigmentation has been described in association with congenital melanosis oculi,'° http://bjo.bmj.com/ melanocytic proliferation,"' endothelial phago- cytosis offree melanin pigment, and the presence ofmelanophages or iris pigment epithelial cells.'12 Melanin pigmentation of the anterior cornea has been shown to increase with age and to be related Fig 1B to melanosis of the bulbar conjunctiva.'3 Other on October 1, 2021 by guest. Protected copyright. Figure I (A) 'Black cornea': extensive and dense pigmentation ofthe entire right cornea ofa causes include the presence of melanin in 39-year-old woman with a 9-year history ofrecurrent conjunctival malignant melanoma ofher Langerhans cells, melanophages, neoplastic right eye. (B) Oneyear after lamellar keratoplasty, the cosmetic result is very satisfactory. squamous cells, or in the extracellular space.'4 Exceptfor a small area offlat corneal pigmentation (big arrow) between the 10 and 11 o'clock meridian, no pigmentary changes are noted. The edge of the lamellar graft (small arrow) and Healthy corneal tissue is transparent and does some stitches (curved arrows) can be identified. not harbour melanocytes, with the exception of the corneal limbus. Limbal melanocytes may migrate into the corneal epithelium upon exposure to sunlight or chemicals,'5 and both Position of host limbus adjacent malignant melanosis and frank melanoma may spread locally to the cornea. When the population of atypical melanocytes is confined to the epithelium the condition is defined as 'corneal primary acquired melanosis with atypia'; when there is invasion of Bowman's layer and stroma of tLhe cornea the lesion is by definition a 'corneal malignant melanoma'. Primary corneal melanoma'-5 may be unassoci- ated with limbal or conjunctival neoplasia, but is thought to originate from melanocytes, which have migrated from limbus or conjunctiva. A corneal malignant melanoma may vary in its appearance from nodular and amelanotic' to flat Figure 2 A donor graft was used to cover the keyhole shaped and pigmented as in our case. defect with a diameter of15 mm by 24 mm, which was the invasion result ofen bloc excision ofmore than two thirds ofthickness Melanocytic complicating conjunc- ofthe entire cornea with a scleral component in the tival melanoma rarely occupies more than one inferotemporal quadrant. quadrant of the cornea. The presentation of Br J Ophthalmol: first published as 10.1136/bjo.76.7.444 on 1 July 1992. Downloaded from 446 Paridaens, Kirkness, Garner, Hungerford

recurrent disease as described in the above case of damaged Bowman's membrane to regenerate report was unique in our experience and has in results in a defective barrier to cellular invasion. our knowledge not been reported before. Histo- The compact lamellar architecture ofthe cornea, pathological examination showed absence of which limits both intraocular tumour spread and atypical melanocytes in the corneal epithelium or its associated blood supply, may underly the between Bowman's layer and the basal relatively good prognosis for corneal malignant membrane. The direct spread of melanocytes melanomas. into the corneal stroma may have been assisted There may be several approaches to the by previous excisions of limbal melanomas that treatment of corneal melanoma or primary were removed with an en bloc lamellar dissection acquired melanosis. Melanocytic tumours that of the involved cornea and sclera. The inability are confined to the corneal epithelium may be treated by sliding off the epithelium using absolute alcohol. Lesions involving the super- ficial corneal stroma may be treated by either superficial keratectomy and freeze-thaw ..... - -.. cryotherapy or lamellar keratoplasty. Deeper stromal tumours may be managed by penetrating keratoplasty.'6 A more radical approach in the management of invasive corneal melanoma ib secondary to primary conjunctival disease is exenteration ofthe . In our case the relatively young woman, who was tfeated conservatively, has not only been able to keep her eye, which is cosmetically excellent, butalso she has essentially normal visual acuity. Furthermore, in the 4 years of follow-up, no signs of local or distant recurrence ofher tumour have been noted.

Dr A D A Paridaens was supported by the Dr F P Fischer Foundation, Utrecht, The Netherlands.

Fig4A 1 Schlieter F, Kleifeld 0. Uber das maligne Melanom der http://bjo.bmj.com/ Hornhaut und seine Therapie. Klin Monatsbl Augenheilkd 1975; 167: 404-12. Figure 4 (A) A smallfocus 2 Tragakis M, Pollalis S, Karantinos D, Athanassiadis P, ofresidual or recurrent Paraskevakou E. Me1anome primitif malin de lacornee. Fr malignant melanoma (big Ophtalmol 1979; 2: 29-31. arrow) is seen at the 3 Welsh NH, Jhavery Y. Malignant melanoma of the cornea in an African patient. AmJIOphthalmol 1971; 72: 796-800. periphery ofthe cornea 4 Tokuda K, Ishibashi T, Oshida N, Kobayashi H. A huge within the superficial malignant melanoma of the cornea. Nippon-Ganka-Kiyo stroma. Tumour cells are 1970; 21: 295-301. present in the corneal stroma 5 Paridaens ADA, McCartney ACE, Hungerford JL. Multifocal on October 1, 2021 by guest. Protected copyright. (small arrow) but the corneal amelanotic conjunctival melanoma and acquired melanosis epithelium (curved arrow) sine pigmento. BrJ Ophthalmol 1992; 76: 163-5. shows no evidence of 6 Kampik A, Patrinely JR, Green WR. Morphologic and clinical melanocytic featuresofretrocorneal melanin pigmentation and pigmented infiltration pupillary membranes: review of 225 cases. Surv Ophthalmol (haematoxylin and eosin, 1982; 27: 161-80. x 120). (B) Pigmented 7 Calmettes L, Deodati F, Bechac G. Pigmentation corneene par atypical melanocytes le bitartrate d'epinephrine. Arch Ophtalmol (Paris) 1968; 28: (arrows) have invaded the 303-5. cornea between the stromal 8 Domarus D. Adrenochromeinlagerungen in die Kornea lamellae. The melanocytic ('Schwarze Hornhaut'). Klinisch-pathologischer Fall- bericht. Ophthalmologica 1977; 175: 166-70. invasion involves more than 9 Hedges TR III, Kenyon KR, Hanninen LA, Mosher DB. halfthe corneal thickness Corneal and conjunctival effects of monobenzone in patients and the entire corneal with vitiligo. Arch Ophthalmol 1983; 101: 64-8. diameter to almost reach the 10 Hamilton RF, Weiss JS, Gelender H. Posterior corneal resection margin on the ,4;0 _0 pigmentationin melanosis oculi. Arch Ophthalmol 1983; 101: medial side (haematoxylin ...Jo f1k *4 4_r 1909-11. -dgw 11 Bloomfield SE, Jakobiec FA, Iwamoto T, Harrison WG. and eosin, x320). :_ w * W ~~~~ 'w;L,f. ii Retrocorneal pigmentation secondary to iris stromal melano- .. AOm .~~~~~~~~~~~~~~~~~~~~~~~~~% cytic proliferation. Ophthalmnwogy 1981; 88: 1274-80. N4 tGO9.11, Wk. "k...': 12 Snip RC, Green WR, Kreutzer EW, Hirst LW, Kenyon KR. mi Posterior corneal pigmentation and fibrous proliferation by iris melanocytes. Arch Ophthalmol 1981; 99: 1232-8. 13 Norn MS. Corneal and superficial conjunctival pigmentation in Eskimos, Mongols, and Caucasians. Acta Ophthalmol (Kbh) 1985; 63: 454-8. 14 Jauregui HO, Klintworth GK. Pigmented squamous cell .$ 5II; carcinoma of cornea and conjunctiva: a light microscopic, histochemical, and ultrastructural study. Cancer 1976; 38: 778-88. 4O 15 McCracken JS, Klintworth GK. Ultrastructural observations on experimentally produced melanin pigmentation of the corneal epithelium. AmJ3 Pathol 1976; 85: 167-82. 16 Tarkkanen A, Vannas S. Corneoscleral grafting in the treatment of malignant melanoma of the limbus. Ann Chir Fi'g 4B Gynaecol Fenn 1967; 56: 327-9.