Clinicopathological Findings in a Growing Optic Nerve Melanocytoma

Br J Ophthalmol: first published as 10.1136/bjo.73.6.410 on 1 June 1989. Downloaded from

British Journal ofOphthalmology, 1989, 73, 410-415

Clinicopathological findings in a growing optic nerve melanocytoma

AHMAD M MANSOUR,' LORENZ ZIMMERMAN,2 FRANCIS G LA PIANA,3 AND GEORGE R BEAUCHAMP4 From the 'Department ofOphthalmology, University of Texas Medical Branch, Galveston, Texas;2 Department ofOphthalmic Pathology, Armed Forces Institute ofPathology, Washington, DC; the 3Ophthalmology Service, Walter Reed Army Medical Center, Washington, DC; and the 3Uniformed Services University ofHealth Services, Bethesda, Maryland, and the 4Cleveland Clinic Foundation, Cleveland, Ohio, USA

SUMMARY We present an unusual case of a melanocytoma of the optic disc that showed documented progressive growth over a period of six years. It reached the largest size of any reported optic nerve melanocytoma and the eye was enucleated because of the possibility of malignant degeneration. Optic nerve melanocytomas are locally invasive but are not known to undergo transformation into malignant melanoma. Follow-up should remain the primary approach in the management of patients with optic nerve melanocytomas, as previously advocated by Zimmerman. copyright.

The management of melanocytomas of the optic disc behaviour of the darkly pigmented tumour of the has changed over the past two decades from enuclea- optic disc." Subsequently Cogan coined the term tion to simple serial observation. Before the pioneer- 4magnocellular nevus" and Reese the term 'benign ing work of Zimmerman,' deeply pigmented lesions melanoma' to describe the same lesion.18

of the optic nerve were considered to be primary Melanocytomas are now thought to be predomi- http://bjo.bmj.com/ malignant melanomas of the optic disc.5 Loewenstein nantly stable lesions with no malignant potential."I suggested that such lesions may represent malignant We present the first clinicopathological study of an transformation in a naevus of the optic nerve.6 optic nerve melanocytoma with prominent growth DeVeer reviewed the literature related to malignant that led to enucleation of the eye because of melanoma of the optic nerve and doubted the exist- suspected malignant transformation. This case along ence of a primary malignant melanoma of the disc, as with a review of the literature helps to establish the

most of the reported lesions showed a peripapillary point that there is no documented case of malignant on September 27, 2021 by guest. Protected origin.7 Seven years later DeVeer examined an eye change in optic nerve melanocytomas, and that enucleated for a so-called malignant melanoma ofthe growth in these tumours reflects simply their locally optic nerve. The cells did not appear to be anaplastic, invasive behaviour. and he concluded that this lesion is benign despite its infiltration into the retina and the optic nerve.8 Case report As a result of a large clinical and histopathological study of such lesions with long-term follow-up The patient was a 42-year-old fair-complexioned Zimmerman established the entity of 'melanocyto- Causasian man who presented for routine physical mas', choosing this term in part to indicate the benign examination in February 1968. The physical exami- This work was partly presented at the Verhoeff Society, 1975, nation gave essentially negative results except for Washington, DC, USA. mild systemic hypertension and a pigmented right optic disc. In April 1968 he presented to his local The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the ophthalmologist with the complaint of sensitivity to views of the Department of the Army or the Department of light in the right eye. An eye examination revealed Defense. 20/20 vision bilaterally, enlarged right blind spot, and Correspondence to A Mansour, MD, Ophthalmology-UTMB, a pigmented lesion over the right optic disc. An Galveston, Texas 77550, USA. examination in May 1968 gave unchanged results, but 410 Br J Ophthalmol: first published as 10.1136/bjo.73.6.410 on 1 June 1989. Downloaded from

Clinicopathologicalfindings in a growing optic nerve melanocytoma 411 copyright.

thegradualgrowth ofthe optic nerve melanocytoma overa totalperiod of64

Fig. 1 Serialfunduscopicfindingsshowing http://bjo.bmj.com/ months. Datesareseriallyasfollows: June1968, Junel970, June1971, Hunel972, August1972, and September1973. it was the impression of the ophthalmologist that the defect was approaching fixation. The pigmented lesion grew in size in June 1968 (Fig. 1-1). lesion was noted to be enlarged inferiorly, with a In August 1968 the patient was referred to the surrounding new nerve fibre layer haemorrhage Walter Reed Army Medical Center for examination. inferiorly. In January 1973 the patient was referred to on September 27, 2021 by guest. Protected The lesion was jet black in colour, with feathery the Edward S Harkness Eye Institute for a B scan edges, covering half the disc and extending inferiorly ultrasonogram. The report stated 'optic tumor at the and nasally over the peripapillary retina. Two senior posterior pole of the right eye, not typical of a consultants agreed on the diagnosis of optic disc melanoma of the choroid, and consistent with melanocytoma and recommended periodic observa- melanocytoma.' The dimensions of the lesion as tion. At follow-up in June of 1970 there was enlarge- determined by ultrasonography were 15 mm in ment of both the pigmented lesion and the visual field elevation, 6 mm in diameter, and with evidence of defect (Fig. 1-2). Vision was 20/20-1 in the right eye. extension of the tumour posterior to the cribriform During subsequent visits in June 1971 (Fig. 1-3) and plate. June 1972 (Fig. 1-4) further enlargement of the In February 1973 the vision was 20/20-2, with the lesion, progressive obscuration of the disc, and optic disc becoming almost totally obscured by the scattering of pigment clumps into the adjacent retinal pigmented lesion. Fluorescein angiography revealed nerve fibre layer were noted. In August 1972 (Fig. blockage of fluorescence of both the choroidal and 1-5) a nerve fibre layer haemorrhage was observed retinal vasculatures by the mass, with absence of adjacent to the tumour temporally. This cleared over leakage around the mass. In September 1973 (Fig. the following two months. In December 1972 the 1-6) the patient presented with decreased vision and patient complained of 'foggy vision'. His vision floaters in the right eye. Vision in the right eye was remained 20/20 in the right eye. An enlarging field 20/40+2. There was a mild afferent pupillary defect. Br J Ophthalmol: first published as 10.1136/bjo.73.6.410 on 1 June 1989. Downloaded from

412 Ahmad M Mansour, Lorenz Zimmerman, Francis G La Piana, and George R Beauchamp copyright. http://bjo.bmj.com/

Fig. 2 Histologicalsections through the optic nerve andmacula. A: Cross section oftheposteriorpole reveals smallgroups of pigmentedcells extending to the level ofthe lamina cribrosa and behind the lamina nasally. The nasaljuxtapapillary choroid is similarly involved. Theperipapillary retina is diffusely thickened especially temporallyfrom tumour infiltration. Haematoxylin and eosin, x 7. The tumour isformed ofsmallspindle cells (upper inset, haematoxyling and eosin, bleached preparation, x600), largepolyhedral heavilypigmented cells (lower inset, haematoxylin and eosin, bleachedpreparation, x600), andpigment laden macrophages. B: Section through thefovea reveals a detachment ofthe retina byproteinaceous on September 27, 2021 by guest. Protected exudate. There is diffuse infiltration ofthe retina bypigmented cells with involvement ofthe retinalsurface andformation ofan epiretinal membrane. Large cystoid spaces in the outerplexiform layerarefilled withproteinaceous material andpigment laden macrophages. .Haematoxylin and eosin, x60.

Dispersed brown and black pigments were noted in enucleation was advised. A P-32 test with readings the vitreous cavity, with layering along the inferior taken at the time of enucleation was negative. The surface of the posterior lens capsule. The tumour had patient remained healthy on his last medical visit in increased in its anteroposterior thickness. There was -March 1986. further encroachment of the field defect on fixation. In April 1974 the patient reported a drastic HISTOPATHOLOGICAL DESCRIPTION decrease in vision. Vision was 20/100-1, and the On gross examination the specimen was seen to enlarging scotoma had covered fixation by visual field consist of a right eyeball with 13 mm segment of testing. The lesion had enlarged, and exudates were attached optic nerve. Transillumination of the eye observed in the macula. No dye leakage was noted on and optic nerve revealed no definite shadow. The fluorescein angiography. Because of the possibility of external examination of the eye revealed no abnor- a malignant melanoma arising in a melanocytoma, mality. A cross section of the optic nerve 1 mm from Br J Ophthalmol: first published as 10.1136/bjo.73.6.410 on 1 June 1989. Downloaded from

Clinicopathologicalfindings in a growing optic nerve melanocytoma 413

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Fig. 2B the sclera revealed no evidence of pigmentation. anterior segment was unremarkable except for the The globe was opened horizontally through the of several foci of presence free pigment granules on September 27, 2021 by guest. Protected optic nerve, revealing a heavily pigmented tumour adherent to the posterior lens capsule, zonular fibres, covering the optic disc and measuring 7 mm in and anterior hyaloid surface. Moderately heavy greatest horizontal dimension. The tumour was pigmentation of the uveal tract was most pronounced raised by a coagulated subretinal exudate. Yellowish posteriorly. Within the optic nerve and extending intraretinal exudates were present along the into the peripapillary area was a very heavily pig- temporal edge of the tumour. Pigmented deposits mented tumour. The tumour lay superficially in the were present in the subretinal space at the temporal optic nerve, though small groups of pigmented cells edge of the optic disc. Very little tumour was seen extended to the level of the lamina cribrosa and a deep in the optic nerve head except for a small patch short distance behind the lamina nasally. The nasal of intense pigmentation behind the lamina cribrosa juxtapapillary choroid showed only a small amount nasally. The vitreous was detached posteriorly and of tumour. The tumour involved the juxtapapillary contained large pigmentary deposits. Moderate pig- retina more extensively in the temporal side, where it mentation and thickening of the nasal peripapillary replaced most of the nasal half of the macula. choroid was noted. The pigmented tumour had The fovea was detached by a large accumulation of spread into the bulging juxtapapillary retina proteinaceous subretinal exudate containing inferiorly and heavily superiorly. Two patches of superficial pigmented macrophages. There was a large accumu- retinal haemorrhages were noted superiorly. lation of serous exudate and foamy histiocytes in the On microscopic examination (Figs. 2A, B) the outer plexiform layer of the foveal region. Between Br J Ophthalmol: first published as 10.1136/bjo.73.6.410 on 1 June 1989. Downloaded from

414 Ahmad M Mansour, Lorenz Zimmerman, Francis G La Piana, and George R Beauchamp the disc and the fovea the retina was severely ing melanocytomas is not known. In one case the thickened, measuring 1-5 mm in thickness as the tumour grew progressively over a period of seven result of the massive infiltration by the pigmented years and became stationary over the next eight years cells. These cells included a mixture of heavily of follow-up.3 In another case the tumour seemed pigmented polyhedral melanocytes with round, to grow over a period of one week.3 Malignant ovoid, and evenly chromatic nuclei like those found melanoma arising in a melanocytoma of the uveal in melanocytomas, large rounded melanophages, tract had been encountered in several of the cases and smaller pigmented spindle cells with irregular, seen at the Ophthalmic Registry ofthe Armed Forces vesicular, and hyperchromatic nuclei resembling the of Pathology, and in several case reports.'92' spindle A melanoma cells ofthe iris. The spindle cells However, there is still no documented case of a were the predominant cells at the junction between malignant melanoma arising from an optic nerve the tumour and normal retina nasally. melanocytoma. Apple et al.2' described the first case The internal limiting membrane was infiltrated in of malignant transformation of an optic nerve the temporal peripapillary area by the pigmented melanocytoma. However, the initial grey mass at the cells to form a thin placoid pigmented layer along the superior aspect of the disc was not recorded and inner retinal surface. Tumour cells infiltrated along seemed atypical in location and discolouration for a the retinal vessels in the peripapillary area and the primary optic nerve melanocytoma favouring a peri- major vessels in the optic nerve head. No tumour was papillary choroidal origin. Moreover it was not clear noted in the cross sections of the optic nerve, if the melanoma arose originally from the choroidal meninges, or orbital tissues. Special stains revealed or the optic nerve part of the naevus. It has been dropout of axons and foci of demyelinisation, especi- estimated that there is one in 5000 chance for a ally on the temporal side of the optic nerve. choroidal naevus to develop into a malignant Transmission electron microscopic findings have melanoma.22 If this is applied to the optic nerve been reported previously.12 melanocytoma, an uncommon form of naevus,

The final pathological diagnosis was melanocy- malignant transformation would be extremely rare. copyright. toma of the optic nerve head. Growth in melanocytomas reflects their known locally invasive behaviour.3 Discussion The causes of visual loss in melanocytomas of the optic disc are multiple. There have been seven cases Several features in our case are typical of an optic of decreased vision from 20/50 or less2381123 up to nerve melanocytoma. They include the jet black hand motion3 and to no light perception,'6 with two of

colouration, the feathery edges, the origin from the these cases having a sudden loss of vision.3 16 http://bjo.bmj.com/ optic disc as noted on initial presentation, the Papilloedema followed by occlusion of the central relatively well preserved vision and visual fields for a retinal artery was the initial manifestation of a deeply long period of follow-up, and the findings on ultra- seated optic nerve melanocytoma. 16 Similarly, ocular sonography and fluorescein angiography. Unusual pain was the presenting sign of a partially necrotic features include the relatively very large size of the optic nerve melanocytoma that showed vasco- mass, its growth pattern, infiltration of the macular occlusive disease of the optic nerve, ischaemic region, the presence of retinal haemorrhages, and necrosis of the tumour, hypoxic retinopathy, and the formation of a preretinal pigmented plaque. neovascular glaucoma.24 Zimmerman3 described one on September 27, 2021 by guest. Protected Melanocytomas of the optic nerve have been case showing ischaemic necrosis of an optic nerve characterised as stable or slowly growing lesions."I A melanocytoma that invaded deeply into the nerve total of 38 cases followed up for five years or more and was related to an occlusion of an anomalous showed no evidence of growth3 3I'l and no evidence vascular supply to the tumour and temporal retina. of metastasis following enucleation.3 Joffe et al." Loss of vision with subsequent progressive partial followed up 27 cases for more than one year and recovery was described in one case of optic nerve found no change in size in 22 eyes. Mild enlargement melanocytoma, though the mechanisms of recovery of the melanocytoma has been recorded in a total of were not clear.'5 Disciform scarring over a choroidal 11 cases,3 10 11 16 17 usually after several years of follow- melanocytoma may lead to decrease in vision and up. The average size of the lesion was calculated from simulate a choroidal melanoma.25 No disciform the series of 40 cases reported by Joffe et al. to be lesion has been seen overlying an optic disc melano- around 40% of the optic disc size." Complete cytoma. obscuration of the optic disc was found in nine Despite these isolated reports, the major cause of cases.3 10 11'8 The three largest reported tumours were decreased vision is attributed to the swelling of axons around 2 disc diameters in diameter.31' 18 from compression of the nerve fibres and their The pattern of growth in the occasionally expand- vascular supply by the tumour.26 This explains why Br J Ophthalmol: first published as 10.1136/bjo.73.6.410 on 1 June 1989. Downloaded from

Clinicopathologicalfindings in a growing optic nerve melanocytoma 415 deeply seated optic nerve melanocytomas, despite 8 DeVeer JA. Melanotic tumors of the optic nerve head: a their small result in visual pathologic study. Arch Ophthalmol 1961; 65: 536-41. apparent size, may loss.34 9 Cogan DG. Discussion: Pigmented ocular tumors. In: Boniuk Computed tomography and ultrasonography can M, ed. Ocular and adnexal tumours: new and controversial help in delineating the posterior extension of aspects. St Louis: Mosby, 1964: 385. melanocytomas, and such investigations should be 10 Reese AB. Congenital melanomas. Am J Ophthalmol 1974; 77: carried out if the visual are not commen- 798-808. symptoms 11 Joffe L, Shields JA, Osher RH, Gass JDM. Clinical and follow- surate with the fundus picture. Sectorial optic nerve up studies of melanocytomas of the optic disc. Ophthalmology atrophy in such lesions has been demonstrated 1979; 86:1067-78. histopathologically.27 Direct infiltration of the nerve 12 Juarez CP, Tso MOM. An ultrastructural study of melano- fibre layer by the mass, with cytomas (magnocellular nevi) of the optic disk and uvea. Am J along pressure atrophy Ophthalmol 1980; 90: 48-62. of the nerve axons, can explain the not infrequent 13 Francois J, De Laey JJ, Kluyskens J, Goes F, Lentini F, occurrence of nasal steps, arcuate nerve fibre layer Giambastiani R. Melanocytome de la papille optique. Bull Soc visual defects, and the Marcus Gunn pupillary sign in Belge Ophtalmol 1980; 187: 111-26. optic nerve melanocytomas. Our case is unique in 14 Reidy JJ, Apple DJ, Steinmetz RL, et al. Melanocytoma: nomenclature, pathogenesis, natural history and treatment. Surv that the nasal macula was infiltrated by the tumour Ophthalmol 1985; 29: 319-27. and the temporal macula was elevated by a serous 15 Wiznia RA, Price J. Recovery of vision in association with a subretinal fluid. Moreover the surface of the macula melanocytoma of the optic disc. Am J Ophthalmol 1974; 78: was covered by a pigmented layer and pigment 236-8. 16 Takahashi T, Isayama Y, Okuzawa I. Unusual case of melano- dispersion from the melanocytoma was found in the cytoma in optic disk. Jpn J Ophthalmol 1984; 28: 171-5. anterior aspect of the posterior segment. This disper- 17 Bischler V, Franceschetti MA. Les colorations noires et grises de sion of pigment granules and pigmented cells should la papille. Bull Soc Fr Ophtalmol 1956; 69: 408-22. not be taken as a sign of active tumour as 18 Patterson MW. Melanoma of the optic disk. Br J Ophthalmol growth, 1952; 36: 447-52. previously noted by Reese. 10 19 Roth AM. Malignant change in melanocytomas of the uveal tract. Surv Ophthalmol 1978; 22: 404-12. copyright. This work was supported by a UNESCO research grant (Dr 20 Barker-Griffith AE. McDonald PR, Green WR. Malignant Mansour). melanoma arising in a choroidal magnocellular nevus (melanocytoma). Can J Ophthalmol 1976; 11: 140-6. 21 Apple DJ, Craythorn JM, Reidy JJ, Steinmetz RL, Brady SE, References Bohart WA. Malignant transformation of an optic nerve melanocytoma. Can J Ophthalmol 1984; 19: 320-5. 1 Zimmerman LE. Pigmented tumours of the optic nerve head 22 Ganley JP, Comstock GW. Benign nevi and malignant (22d annual deSchweinitz lecture). Am J Ophthalmol 1960; 50: melanomas of the choroid. Am J Ophthalmol 1973; 76: 19-25. 338. 23 Taskahashi T. Klinische und histopathologische Beobachtungen 2 Zimmerman LE, Garron, LK. Melanocytoma of the optic disc. beim Melanozytom der Papille. Klin Monatsble Augenheilkd http://bjo.bmj.com/ Int Ophthalmol Clin 1962; 2: 431-40. 1979; 175: 47-55. 3 Zimmerman LE. Melanocytes, melanocytic nevi, and melano- 24 Croxatto JO, Ebner R, Crovetto L, Morales AG. Angle closure cytomas. The Jonas S. Friedenwald Memorial Lecture. Invest glaucoma as initial manifestation of melanocytoma of the optic Ophthalmol Vis Sci 1965; 4: 11-41. disc. Ophthalmology 1983; 90: 830-4. 4 Zimmerman LE. Changing concepts concerning the malignancy 25 Rubin ML. Disciform lesion overlying melanocytoma simulating of ocular tumours. Arch Ophthalmol 1967; 78: 166-73. progression of choroidal melanoma. Trans Am Ophthalmol Sol 5 Cordes FC, Hogan MJ. Primary malignant melanoma of the 1977; 74: 282-94. optic disc: report of a case. Trans Am Ophthalmol Soc 1948; 46: 26 Osher RH, Shields JA, Layman PR. Pupillary and visual field 201-17. evaluation in patients with melanocytoma of the optic disc. Arch on September 27, 2021 by guest. Protected 6 Lowenstein A. Aberrant optic nerve fibres found between retina Ophthalmol 1979; 97:1096-9. and hexagonal cells. BrJ Ophthalmol 1945; 29: 180-5. 27 O'Donnell F Jr, Green WR. Naevus of the optic nerve. 7 DeVeer JA. Juxtapapillary malignant melanoma of the choroid Ophthalmic Res 1976; 8: 276-82. and so-called malignant melanoma of the optic disc. Arch Ophthalmol 1954; 51: 147-60. Acceptedforpublication 4June 1987.