Malignant Melanoma Associated with Melanocytoma of the Optic Disc JERRY A. SHIELDS, MD,t CAROL L. SHIELDS, MD,t RALPH C. EAGLE, Jr., MD/ WOLFGANG E. LIEB, MD, 1 SHELDON STERN, MD 3
Abstract: A 61-year-old white man underwent enucleation because of pro gressive growth of a pigmented epipapillary tumor that was diagnosed 9 years earlier as an optic nerve and juxtapapillary melanocytoma. Histopathologic stud ies showed the tumor was a malignant melanoma of the optic disc and juxta papillary retina and choroid. Foci of typical melanocytoma cells were within the tumor. The tumor produced segmental atrophy of the optic nerve. This is a rare example of a malignant melanoma developing in conjunction with a lesion that possessed typical clinical and histopathologic features of a melanocytoma of the optic disc. Ophthalmology 1990; 97:225-230
The melanocytoma is a well-known ophthalmic tumor that has typical clinical and pathologic features. I-s Clin ically, the melanocytoma is characteristically a dark brown to black lesion that involves the optic disc. Histopatho logically, it is composed of deeply pigmented round to oval cells with abundant cytoplasm and small, round, bland nuclei that are best appreciated on bleached prep arations. The melanocytoma is a benign, stationary tumor with almost no propensity to undergo malignant trans formation. I-s We report a rare example of a clinically typ ical melanocytoma that grew progressively over 8 years and was found histopathologically to have transformed into a malignant melanoma. Originally received: July 3, 1989. Revision accepted: August 7, 1989. 1
Ocular Oncology Service, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University, Philadelphia. 2 Pathology Department, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University, Philadelphia. . 3 Kresge Eye Institute, Wayne State University, and the Sinai Hospital, Detroit. Presented at the annual meeting of the Midwestern Ophthalmic Pathology Society (Theobald Society) Oklahoma City, Oklahoma, May 1989. Supported in part by the Ocular Oncology Fund and the Oncology Research Fund, Wills Eye Hospital and in part by the Black Patch Invitational Golf Tournament, Downingtown, Pennsylvania. Reprint requests to Jerry A. Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 9th and Walnut Sts, Philadelphia, PA 19107.
CLINICAL HISTORY A 53-year-old white man was found on routine ophthalmologic examination in January 1980 to have a heavily pigmented lesion in the posterior fundus of the right eye. The black lesion covered the temporal fourth of the optic disc and had a fibrillar margin that extended into the adjacent nerve fiber layer of the retina. A flat juxtapapillary choroidal portion of the lesion measured approximately 3 X 2 mm in basal dimensions (Fig 1, top left). Based on its clinical appearance, the lesion was di agnosed as a melanocytoma of the optic disc with in volvement of the juxtapapillary choroid. The patient was advised to have periodic examinations. Results of a follow-up examination in November I 982 showed only slight enlargement of the epipapillary and retinal portions of the lesion but no appreciable change in the choroidal portion. Additional slight progression of the lesion was documented in February 1984 (Fig 1, bot tom left). Two years later, the patient complained of pain less, progressive visual loss in the affected eye and marked enlargement of the lesion was noted (Fig 1, top right). It was more elevated and had enlarged to cover the entire optic disc. The possibility of enucleation was discussed with the patient, but he declined. In October I 988, the patient was referred to the On cology Service at Wills Eye Hospital for evaluation and possible enucleation because of progressive visual loss, 225
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Fig 1. Clinical photographs show progression of the lesion. Top left. 1980; bottom lefi. 1984; top right, 1986; bottom right, 1988.
Fig 2. Fluorescein angiogram in the venous phase shows intense hypo fluorescence of the lesion. This hypofluorescence persisted into the late angiograms.
further enlargement of the tumor, and vitreous seeding. The best-corrected visual acuities were 6/60 in the right eye and 6/6 in the left. Intraocular pressures were 18 226
mmHg in each eye. Slit-lamp biomicroscopy of the right eye showed scattered golden-brown pigment clumps in the anterior vitreous cavity. Indirect ophthalmoscopy dis closed a dome-shaped brown mass that obscured the optic disc and juxtapapillary choroid. It was estimated clinically to be approximately 5 X 5 mm in basal dimensions and 4 mm in elevation. Clumps of brown cells extended from the irregular surface of the mass into the vitreous cavity inferiorly (Figs 1, bottom right). The vitreous cells settled on the retinal surface inferiorly at the posterior aspect of the vitreous base. Fluorescein angiography disclosed hypofluorescence of the mass in the early and late phases (Fig 2). A-scan ul trasonography showed the mass to have high internal re flectivity and B-scan ultrasonography demonstrated acoustic solidity without choroidal excavation. Computed tomography and magnetic resonance imaging demon strated a rounded mass in the optic disc area, but these studies could not determine whether the lesion was benign or malignant. The clinical diagnosis was probable malignant mela noma arising from a melanocytoma of the optic disc and juxtapapillary choroid. The patient was again advised of the suspected diagnosis of malignant melanoma, and he elected to have enucleation of the affected eye. A gentle,
SHIELDS et al
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Fig 3. Low-power photomi crograph shows tumor in volving peripapiUary choroid, optic nerve tissue, and jux tapapillary retina. Arrows depict Bruch's membrane (hematoxylin-eosin; original magnification X10).
minimal manipulation enucleation was performed and a long section of optic nerve was obtained. The patient is alive and well almost 1 year after enucleation.
PATHOLOGY The globe was normal externally and measured 24
X 24 X 23 mm. At gross examination, the 20-mm segment
of optic nerve appeared normal. Transillumination find ings were unremarkable. The globe was sectioned hori zontally. There was a dark brown tumor that measured 5 X 5 X 4 mm that obscured the optic disc and involved the adjacent sensory retina. The tumor surface had an irregular granular appearance and liberated pigment ap peared to emanate from the tumor into the inferior por tion of the vitreous. The pertinent histopathologic findings were confined to the posterior segment of the globe. Here, a maximally pigmented, dome-shaped mass involved the epipapillary region, the optic nerve head, and the temporal peripapil lary choroid (Fig 3). The bulk of the tumor, which was nodular in configuration, was situated anterior to the optic disc and sensory retina. This epipapillary nodule was composed predominantly of interweaving fascicles of moderately pigmented spindle cells with large oval nuclei and conspicuous nucleoli consistent with spindle-B ma lignant melanoma cells (Fig 4). Occasional epithelioid cells also were present. The mitotic index of the melanoma was low with only one equivocal mitotic figure being ob served in 40 high-power fields. The choroidal portion of the tumor contained a prom
inent population of large round or oval cells that had an abundant quantity of maximally pigmented cytoplasm that obscured nuclear details. Results of examination of depigmented sections disclosed that many of the nuclei were small, round, and relatively bland in appearance, consistent with magnocellular nevus or melanocytoma cells (Fig 5). Spindle and rare epithelioid malignant mel anoma cells also were observed focally in the choroidal portion of the tumor. There was no evidence of extra scleral extension. At the temporal margin of the optic disc, the tumor extended around the end of Bruch's membrane, perfo rating the retina and communicating with the epipapillary portion of the tumor. More than half of the temporal portion of the prelaminar optic disc was totally infiltrated and replaced by a mixed population of cells similar to that found in the peripapillary choroid. The retrolaminar portion of the nerve was tumor-free. Segmental atrophy, characterized by gliosis and marked widening of the pial septae, involved the retrolaminar optic nerve on the side of the tumor and ·retinal perforation. Melanophages occurred in aggregates throughout the mass and were particularly abundant near the apex of the tumor (Fig 6) where focal perforation of the internal lim iting membrane provided ready access to the vitreous cavity. The pigmented cells seen clinically and macro scopically in the vitreous were not present in available histologic sections. The primary histopathologic diagnoses were ( 1) epi papillary malignant melanoma, mixed-cell type, predom inantly spindle, associated with melanocytoma ofthejux tapapillary choroid and optic disc and (2) segmental optic atrophy. 227
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Fig 4. Photomicrograph shows spindle melanoma cells in optic disc region (he matoxylin-eosin; bleached, original magnification, X I00).
Fig 5. Photomicrograph shows melanocytoma cells in the choroid (hematoxylin eosin; bleached, original magnification, X 100).
DISCUSSION The term melanocytoma 1- 5 (magnocellular nevus) 6 designates a rather specific intraocular tumor that appears clinically as a deeply pigmented lesion that classically af fects a portion of the optic nerve head. Before the reports 228
of Zimmerman and associates, 1•2 this tumor was often misinterpreted as a malignant melanoma both clinically and histopathologically.7 Zimmerman popularized the concept that the lesion is almost always dormant clinically and does not demonstrate the active proliferation that characterizes most malignant melanomas. It is also rec ognized that melanocytomas can occur in the iris,8 ciliary body, 9 and choroid. 10
SHIELDS et al
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Fig 6. Photomicrograph of melanophages near vitreal surface of the tumor (he matoxylin-eosin; bleached, original magnification, X I00).
Joffe and associates, 5 in a 19-year follow-up study of 40 patients from the Wills Eye Hospital and the Bascom Palmer Eye Institute, stressed the clinical variations of this lesion. They showed that the lesion is confined to the optic nerve head in 13% of patients, extends into the nerve fiber layer of the retina in 77%, has a juxtapapillary cho roidal nevus component in 47%, and demonstrates min imal enlargement in 15%. Osher and associates 11 showed that 90% of affected patients have an associated visual field defect and that 30% have an afferent pupillary defect in the affected eye. Despite the fact that a melanocytoma can show minimal clinical enlargement, visual field loss, and afferent pupillary defects, the tumor is generally con sidered to be benign. Although malignant transformation of extrapapillary uveal melanocytomas has occasionally been recog nized, 12 • 13 malignant transformation of a true melano cytoma affecting the optic disc has rarely, if ever, been documented. Zografos and associates 14 reported a case that was similar to the case reported here. At the Verhoeff Ophthalmic Pathology Society in 1975, Zimmerman pre sented a case that was initially diagnosed as a low-grade melanoma arising from a melanocytoma of the optic disc. That case, which has been the subject ofconsiderable dis cussion by ophthalmic pathologists, was recently reported as documented growth of a melanocytoma without ma lignant transformation. 15 Apple and associates 16 reported a case of presumed malignant transformation of a me lanocytoma of the optic nerve, but there were no clinical photographs to confirm that a lesion compatible with a melanocytoma was present on the optic disc. Based on our review of that article, we believe that the lesion was probably a juxtapapillary choroidal melanoma that grew over the optic nerve head. Others also questioned the va
lidity of that case and speculated that it may have origi nated from a melanocytoma ofthe peripapillary choroid. 15 Reidy and associates 17 recently reviewed the literature on the subject and discounted many of the earlier reports of malignant melanoma of the optic disc, indicating that they actually represented benign melanocytomas, an ob servation that was earlier stressed by Zimmerman. 1 Ac cording to the most recent report from the Armed Forces Institute of Pathology, "there is still no documented case of a malignant melanoma arising from an optic nerve melanocytoma." 15 Clinically, the tumor reported here possessed all of the characteristics of a melanocytoma. It was deeply pig mented, involved the optic disc, extended into the nerve fiber layer of the juxtapapillary retina, and involved the juxtapapillary choroid. Furthermore, sequential fundus photographs disclosed that the lesion was relatively sta tionary, showing only minimal growth over several years of close clinical follow-up. Results of histopathologic ex amination disclosed that the choroidal component of the tumor contained numerous large, round, deeply pig mented cells with . small round bland nuclei, consistent with the diagnosis of melanocytoma. The epipapillary and retinal portions of the tumor were characterized by a mixed-cell-type melanoma composed mainly of spindle B malignant melanoma cells with occasional melanocy toma cells. Based on the histopathologic findings, it is possible that the tumor reported here arose from a melanocytoma that affected both the optic disc and juxta papillary choroid. It is also feasible, however, that it arose in the juxtapapillary choroid and invaded the optic disc and sensory retina secondarily. If so, then there is still no unequivocal case ofa malignant melanoma arising in a pure melanocytoma
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of the optic disc. Nevertheless, the lesion that we report here, which was clinically compatible with a melanocy toma, underwent malignant transformation into a malig nant melanoma. Thus, this is one of the few well-docu mented cases of malignant transformation of a lesion that showed typical clinical characteristics ofa melanocytoma affecting the optic disc.
7. 8. 9. 10.
REFERENCES
11.
12. 1. Zimmerman LE. Melanocytes, melanocytic nevi, and melanocytomas. the Jonas S. Friedenwald Memorial Lecture. Invest Ophthalmol 1965; 4:11-41. 2. Zimmerman LE, Garron LK. Melanocytoma of the optic disc. lnt Ophthalmol Clin 1962; 2:431-40. 3. Shields JA. Diagnosis and Management of Intraocular Tumors. St. Louis: CV Mosby, 1983; 595-616. 4. Shields JA. Melanocytoma of the optic nerve head: a review. lnt Ophthalmol1978; 1:31-7. 5. Joffe L, Shields JA, Osher RH, Gass JDM. Clinical and follow-up studies of melanocytomas of the optic disc. Ophthalmology 1979; 86:1067 78. 6. Cogan DG. Discussion of pigmented ocular tumors. In: Boniuk M, ed. Ocular and Adnexal Tumors: New and Controversial Aspects (Sym
230
13. 14. 15.
16. 17.
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posium sponsored by Department of Ophthalmology, Baylor University College of Medicine). St. Louis: CV Mosby, 1964; 385. Shields JA, Zimmerman LE. Lesions simulating malignant melanomas of the posterior uvea. Arch Ophthalmol1973; 89:466-71. Shields JA, Annesley WH Jr, Spaeth Gl. Necrotic melanocytoma of iris with secondary glaucoma. Am J Ophthalmol1977; 84:826-9. Shields JA, Augsburger JJ, Bernardino V Jr, et al. Melanocytoma of the ciliary body and iris. Am J Ophthalmol1980; 89:632-5. Shields JA, Font Rl. Melanocytoma of the choroid clinically simulating a malignant melanoma. Arch Ophthalmol1972; 87:396-400. Osher RH, Shields JA, Layman PR. Pupillary and visual field evaluation in patients with melanocytoma of the optic disc. Arch Ophthalmol 1979; 97:1096-9. Barker-Griffith AE, McDonald PR, Green WR. Malignant melanoma arising in a choroidal magnacellular nevus (melanocytorna). Can J Ophthalmol1976; 11:140-6. Roth AM. Malignant change in rnelanocytomas of the uveal tract. Surv Ophthalmol 1978; 22:404-12. Zografos L, Uffer S, Gailloud C, Kohli M. Le rnelanome de Ia papille, nouvelle observation. Klin Monatsbl Augenheilkd 1982; 180:503-9. Mansour AM, Zimmerman LE, LaPiana F, Beauchamp GR. Clinico pathological findings in a growing optic nerve rnelanocytoma. Br J Ophthalmol1989; 73:410-5. Apple DJ, Craythorn JM, Reidy JJ, et al. Malignant transformation of an optic nerve melanocytorna. Can J Ophthalrnol1984; 19:320-5. Reidy JJ, Apple DJ, Steinmetz RL, et al. Melanocytorna: nomenclature, pathogenesis, natural history and treatment. Surv Ophthalrnol 1985; 29:319-27.
Abstract: A 61-year-old white man underwent enucleation because of pro gressive growth of a pigmented epipapillary tumor that was diagnosed 9 years earlier as an optic nerve and juxtapapillary melanocytoma. Histopathologic stud ies showed the tumor was a malignant melanoma of the optic disc and juxta papillary retina and choroid. Foci of typical melanocytoma cells were within the tumor. The tumor produced segmental atrophy of the optic nerve. This is a rare example of a malignant melanoma developing in conjunction with a lesion that possessed typical clinical and histopathologic features of a melanocytoma of the optic disc. Ophthalmology 1990; 97:225-230
The melanocytoma is a well-known ophthalmic tumor that has typical clinical and pathologic features. I-s Clin ically, the melanocytoma is characteristically a dark brown to black lesion that involves the optic disc. Histopatho logically, it is composed of deeply pigmented round to oval cells with abundant cytoplasm and small, round, bland nuclei that are best appreciated on bleached prep arations. The melanocytoma is a benign, stationary tumor with almost no propensity to undergo malignant trans formation. I-s We report a rare example of a clinically typ ical melanocytoma that grew progressively over 8 years and was found histopathologically to have transformed into a malignant melanoma. Originally received: July 3, 1989. Revision accepted: August 7, 1989. 1
Ocular Oncology Service, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University, Philadelphia. 2 Pathology Department, Wills Eye Hospital, Jefferson Medical College, Thomas Jefferson University, Philadelphia. . 3 Kresge Eye Institute, Wayne State University, and the Sinai Hospital, Detroit. Presented at the annual meeting of the Midwestern Ophthalmic Pathology Society (Theobald Society) Oklahoma City, Oklahoma, May 1989. Supported in part by the Ocular Oncology Fund and the Oncology Research Fund, Wills Eye Hospital and in part by the Black Patch Invitational Golf Tournament, Downingtown, Pennsylvania. Reprint requests to Jerry A. Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 9th and Walnut Sts, Philadelphia, PA 19107.
CLINICAL HISTORY A 53-year-old white man was found on routine ophthalmologic examination in January 1980 to have a heavily pigmented lesion in the posterior fundus of the right eye. The black lesion covered the temporal fourth of the optic disc and had a fibrillar margin that extended into the adjacent nerve fiber layer of the retina. A flat juxtapapillary choroidal portion of the lesion measured approximately 3 X 2 mm in basal dimensions (Fig 1, top left). Based on its clinical appearance, the lesion was di agnosed as a melanocytoma of the optic disc with in volvement of the juxtapapillary choroid. The patient was advised to have periodic examinations. Results of a follow-up examination in November I 982 showed only slight enlargement of the epipapillary and retinal portions of the lesion but no appreciable change in the choroidal portion. Additional slight progression of the lesion was documented in February 1984 (Fig 1, bot tom left). Two years later, the patient complained of pain less, progressive visual loss in the affected eye and marked enlargement of the lesion was noted (Fig 1, top right). It was more elevated and had enlarged to cover the entire optic disc. The possibility of enucleation was discussed with the patient, but he declined. In October I 988, the patient was referred to the On cology Service at Wills Eye Hospital for evaluation and possible enucleation because of progressive visual loss, 225
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Fig 1. Clinical photographs show progression of the lesion. Top left. 1980; bottom lefi. 1984; top right, 1986; bottom right, 1988.
Fig 2. Fluorescein angiogram in the venous phase shows intense hypo fluorescence of the lesion. This hypofluorescence persisted into the late angiograms.
further enlargement of the tumor, and vitreous seeding. The best-corrected visual acuities were 6/60 in the right eye and 6/6 in the left. Intraocular pressures were 18 226
mmHg in each eye. Slit-lamp biomicroscopy of the right eye showed scattered golden-brown pigment clumps in the anterior vitreous cavity. Indirect ophthalmoscopy dis closed a dome-shaped brown mass that obscured the optic disc and juxtapapillary choroid. It was estimated clinically to be approximately 5 X 5 mm in basal dimensions and 4 mm in elevation. Clumps of brown cells extended from the irregular surface of the mass into the vitreous cavity inferiorly (Figs 1, bottom right). The vitreous cells settled on the retinal surface inferiorly at the posterior aspect of the vitreous base. Fluorescein angiography disclosed hypofluorescence of the mass in the early and late phases (Fig 2). A-scan ul trasonography showed the mass to have high internal re flectivity and B-scan ultrasonography demonstrated acoustic solidity without choroidal excavation. Computed tomography and magnetic resonance imaging demon strated a rounded mass in the optic disc area, but these studies could not determine whether the lesion was benign or malignant. The clinical diagnosis was probable malignant mela noma arising from a melanocytoma of the optic disc and juxtapapillary choroid. The patient was again advised of the suspected diagnosis of malignant melanoma, and he elected to have enucleation of the affected eye. A gentle,
SHIELDS et al
•
MELANOCYTOMA
Fig 3. Low-power photomi crograph shows tumor in volving peripapiUary choroid, optic nerve tissue, and jux tapapillary retina. Arrows depict Bruch's membrane (hematoxylin-eosin; original magnification X10).
minimal manipulation enucleation was performed and a long section of optic nerve was obtained. The patient is alive and well almost 1 year after enucleation.
PATHOLOGY The globe was normal externally and measured 24
X 24 X 23 mm. At gross examination, the 20-mm segment
of optic nerve appeared normal. Transillumination find ings were unremarkable. The globe was sectioned hori zontally. There was a dark brown tumor that measured 5 X 5 X 4 mm that obscured the optic disc and involved the adjacent sensory retina. The tumor surface had an irregular granular appearance and liberated pigment ap peared to emanate from the tumor into the inferior por tion of the vitreous. The pertinent histopathologic findings were confined to the posterior segment of the globe. Here, a maximally pigmented, dome-shaped mass involved the epipapillary region, the optic nerve head, and the temporal peripapil lary choroid (Fig 3). The bulk of the tumor, which was nodular in configuration, was situated anterior to the optic disc and sensory retina. This epipapillary nodule was composed predominantly of interweaving fascicles of moderately pigmented spindle cells with large oval nuclei and conspicuous nucleoli consistent with spindle-B ma lignant melanoma cells (Fig 4). Occasional epithelioid cells also were present. The mitotic index of the melanoma was low with only one equivocal mitotic figure being ob served in 40 high-power fields. The choroidal portion of the tumor contained a prom
inent population of large round or oval cells that had an abundant quantity of maximally pigmented cytoplasm that obscured nuclear details. Results of examination of depigmented sections disclosed that many of the nuclei were small, round, and relatively bland in appearance, consistent with magnocellular nevus or melanocytoma cells (Fig 5). Spindle and rare epithelioid malignant mel anoma cells also were observed focally in the choroidal portion of the tumor. There was no evidence of extra scleral extension. At the temporal margin of the optic disc, the tumor extended around the end of Bruch's membrane, perfo rating the retina and communicating with the epipapillary portion of the tumor. More than half of the temporal portion of the prelaminar optic disc was totally infiltrated and replaced by a mixed population of cells similar to that found in the peripapillary choroid. The retrolaminar portion of the nerve was tumor-free. Segmental atrophy, characterized by gliosis and marked widening of the pial septae, involved the retrolaminar optic nerve on the side of the tumor and ·retinal perforation. Melanophages occurred in aggregates throughout the mass and were particularly abundant near the apex of the tumor (Fig 6) where focal perforation of the internal lim iting membrane provided ready access to the vitreous cavity. The pigmented cells seen clinically and macro scopically in the vitreous were not present in available histologic sections. The primary histopathologic diagnoses were ( 1) epi papillary malignant melanoma, mixed-cell type, predom inantly spindle, associated with melanocytoma ofthejux tapapillary choroid and optic disc and (2) segmental optic atrophy. 227
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Fig 4. Photomicrograph shows spindle melanoma cells in optic disc region (he matoxylin-eosin; bleached, original magnification, X I00).
Fig 5. Photomicrograph shows melanocytoma cells in the choroid (hematoxylin eosin; bleached, original magnification, X 100).
DISCUSSION The term melanocytoma 1- 5 (magnocellular nevus) 6 designates a rather specific intraocular tumor that appears clinically as a deeply pigmented lesion that classically af fects a portion of the optic nerve head. Before the reports 228
of Zimmerman and associates, 1•2 this tumor was often misinterpreted as a malignant melanoma both clinically and histopathologically.7 Zimmerman popularized the concept that the lesion is almost always dormant clinically and does not demonstrate the active proliferation that characterizes most malignant melanomas. It is also rec ognized that melanocytomas can occur in the iris,8 ciliary body, 9 and choroid. 10
SHIELDS et al
•
MELANOCYTOMA
Fig 6. Photomicrograph of melanophages near vitreal surface of the tumor (he matoxylin-eosin; bleached, original magnification, X I00).
Joffe and associates, 5 in a 19-year follow-up study of 40 patients from the Wills Eye Hospital and the Bascom Palmer Eye Institute, stressed the clinical variations of this lesion. They showed that the lesion is confined to the optic nerve head in 13% of patients, extends into the nerve fiber layer of the retina in 77%, has a juxtapapillary cho roidal nevus component in 47%, and demonstrates min imal enlargement in 15%. Osher and associates 11 showed that 90% of affected patients have an associated visual field defect and that 30% have an afferent pupillary defect in the affected eye. Despite the fact that a melanocytoma can show minimal clinical enlargement, visual field loss, and afferent pupillary defects, the tumor is generally con sidered to be benign. Although malignant transformation of extrapapillary uveal melanocytomas has occasionally been recog nized, 12 • 13 malignant transformation of a true melano cytoma affecting the optic disc has rarely, if ever, been documented. Zografos and associates 14 reported a case that was similar to the case reported here. At the Verhoeff Ophthalmic Pathology Society in 1975, Zimmerman pre sented a case that was initially diagnosed as a low-grade melanoma arising from a melanocytoma of the optic disc. That case, which has been the subject ofconsiderable dis cussion by ophthalmic pathologists, was recently reported as documented growth of a melanocytoma without ma lignant transformation. 15 Apple and associates 16 reported a case of presumed malignant transformation of a me lanocytoma of the optic nerve, but there were no clinical photographs to confirm that a lesion compatible with a melanocytoma was present on the optic disc. Based on our review of that article, we believe that the lesion was probably a juxtapapillary choroidal melanoma that grew over the optic nerve head. Others also questioned the va
lidity of that case and speculated that it may have origi nated from a melanocytoma ofthe peripapillary choroid. 15 Reidy and associates 17 recently reviewed the literature on the subject and discounted many of the earlier reports of malignant melanoma of the optic disc, indicating that they actually represented benign melanocytomas, an ob servation that was earlier stressed by Zimmerman. 1 Ac cording to the most recent report from the Armed Forces Institute of Pathology, "there is still no documented case of a malignant melanoma arising from an optic nerve melanocytoma." 15 Clinically, the tumor reported here possessed all of the characteristics of a melanocytoma. It was deeply pig mented, involved the optic disc, extended into the nerve fiber layer of the juxtapapillary retina, and involved the juxtapapillary choroid. Furthermore, sequential fundus photographs disclosed that the lesion was relatively sta tionary, showing only minimal growth over several years of close clinical follow-up. Results of histopathologic ex amination disclosed that the choroidal component of the tumor contained numerous large, round, deeply pig mented cells with . small round bland nuclei, consistent with the diagnosis of melanocytoma. The epipapillary and retinal portions of the tumor were characterized by a mixed-cell-type melanoma composed mainly of spindle B malignant melanoma cells with occasional melanocy toma cells. Based on the histopathologic findings, it is possible that the tumor reported here arose from a melanocytoma that affected both the optic disc and juxta papillary choroid. It is also feasible, however, that it arose in the juxtapapillary choroid and invaded the optic disc and sensory retina secondarily. If so, then there is still no unequivocal case ofa malignant melanoma arising in a pure melanocytoma
229
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of the optic disc. Nevertheless, the lesion that we report here, which was clinically compatible with a melanocy toma, underwent malignant transformation into a malig nant melanoma. Thus, this is one of the few well-docu mented cases of malignant transformation of a lesion that showed typical clinical characteristics ofa melanocytoma affecting the optic disc.
7. 8. 9. 10.
REFERENCES
11.
12. 1. Zimmerman LE. Melanocytes, melanocytic nevi, and melanocytomas. the Jonas S. Friedenwald Memorial Lecture. Invest Ophthalmol 1965; 4:11-41. 2. Zimmerman LE, Garron LK. Melanocytoma of the optic disc. lnt Ophthalmol Clin 1962; 2:431-40. 3. Shields JA. Diagnosis and Management of Intraocular Tumors. St. Louis: CV Mosby, 1983; 595-616. 4. Shields JA. Melanocytoma of the optic nerve head: a review. lnt Ophthalmol1978; 1:31-7. 5. Joffe L, Shields JA, Osher RH, Gass JDM. Clinical and follow-up studies of melanocytomas of the optic disc. Ophthalmology 1979; 86:1067 78. 6. Cogan DG. Discussion of pigmented ocular tumors. In: Boniuk M, ed. Ocular and Adnexal Tumors: New and Controversial Aspects (Sym
230
13. 14. 15.
16. 17.
•
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posium sponsored by Department of Ophthalmology, Baylor University College of Medicine). St. Louis: CV Mosby, 1964; 385. Shields JA, Zimmerman LE. Lesions simulating malignant melanomas of the posterior uvea. Arch Ophthalmol1973; 89:466-71. Shields JA, Annesley WH Jr, Spaeth Gl. Necrotic melanocytoma of iris with secondary glaucoma. Am J Ophthalmol1977; 84:826-9. Shields JA, Augsburger JJ, Bernardino V Jr, et al. Melanocytoma of the ciliary body and iris. Am J Ophthalmol1980; 89:632-5. Shields JA, Font Rl. Melanocytoma of the choroid clinically simulating a malignant melanoma. Arch Ophthalmol1972; 87:396-400. Osher RH, Shields JA, Layman PR. Pupillary and visual field evaluation in patients with melanocytoma of the optic disc. Arch Ophthalmol 1979; 97:1096-9. Barker-Griffith AE, McDonald PR, Green WR. Malignant melanoma arising in a choroidal magnacellular nevus (melanocytorna). Can J Ophthalmol1976; 11:140-6. Roth AM. Malignant change in rnelanocytomas of the uveal tract. Surv Ophthalmol 1978; 22:404-12. Zografos L, Uffer S, Gailloud C, Kohli M. Le rnelanome de Ia papille, nouvelle observation. Klin Monatsbl Augenheilkd 1982; 180:503-9. Mansour AM, Zimmerman LE, LaPiana F, Beauchamp GR. Clinico pathological findings in a growing optic nerve rnelanocytoma. Br J Ophthalmol1989; 73:410-5. Apple DJ, Craythorn JM, Reidy JJ, et al. Malignant transformation of an optic nerve melanocytorna. Can J Ophthalrnol1984; 19:320-5. Reidy JJ, Apple DJ, Steinmetz RL, et al. Melanocytorna: nomenclature, pathogenesis, natural history and treatment. Surv Ophthalrnol 1985; 29:319-27.
