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Choroidal Melanoma in Association with Juxtapapillary ...Choroidal Melanoma in Association with...
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Choroidal Melanoma in Association with Juxtapapillary Melanocytoma Saba Al-Rashaed, MD; Hind M. Alkatan, MD King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia Introduction Melanocytoma, also known as magnocellular nevus, is a benign, heavily pigmented tumor that may develop wherever uveal melanocytes are present 1. Melanocytomas most commonly arise on/adjacent to the optic disc and are traditionally considered benign and stationary lesions with little potential for growth; Zimmerman and Garron 1,2 reported instances of limited growth of melanocytomas. However, other reports have highlighted cases in which melanocytomas enlarge rapidly and lead to sudden visual loss and necrosis 1, 3, 4, 7 . Few cases of melanoma arising from melanocytoma of the optic disc were reported previously 8, 9, 10 . One large series of optic disc melanocytoma done by Shields et al 10 recently showed that the rate of malignant transformation was 1%-2%. We report an example a case of malignant choroidal melanoma associated with optic disc melanocytoma that was documented by histopathological study. Abstract Purpose: To report a rare example case of choroidal melanoma associated with juxtapapillary melanocytoma. Method: Clinical data including visual acuity, color fundus photographs, fluorescein angiography, ultra sonogram and histopathologic studies of this case were reviewed. Result: A 68-year-old Saudi man was evaluated for sudden painless loss of vision in left eye for duration of 4 months. His vision in the affected eye was counting fingers near the face. Fundus examination showed an elevated dark brown lesion with jet black color partially overlying the optic disc infero-temporally with an associated sub-retinal and vitreous hemorrhage. Ultrasound showed moderate internal reflectivity with moderate sound attenuation of a vascular mass. The eye was enucleated and histopathological section showed two types of cells: 1) round to oval with abundant cytoplasm, pigment granules and small nucleus representing melanocytoma cells and 2) spindle-B cells representing the developing melanoma with atypical mitotic figures identified, which invade the adjacent optic nerve. This was further supported by positive immunostaining with HMB45. Conclusion: This is one of the few documented cases of choroidal melanoma that was associated with juxtapapillary melanocytoma. Periodic follow-up of the patient with optic disc melanocytoma is necessary. Key words: Choroidal melanoma, melanocytomas, histopathology, follow-up Case Report A 68-year-old Saudi man presented with reduced vision of his left eye for duration of 4 months duration. On examination, his vision in the affected eye was counting fingers near the face. The left fundus (fig1) showed an elevated round choroidal mass, partially overlying the optic disc infero-temporally. The lesion was dark brown with jet black color peripherally with an associated sub retinal hemorrhage. The view of the fundus was hazy secondary to significant vitreous hemorrhage and posterior sub capsular cataract . Ultrasound showed a dome shaped posterior lesion surrounding the optic disc, maximum elevation of the lesion was 6mm infero-temporally and had moderate internal reflectivity with moderate sound attenuation. Doppler ultrasound showed a vascular mass. Intravenous flourescein angiography was not conclusive because of poor fundus view. The case was diagnosed as choroidal melanoma probably evolving from pre-existing juxtapapillary melanocytoma. Radiological studies did not show extra-ocular extension, hepatomegaly or evidence of lung metastasis; however, MRI of the left orbit was suggestive of extension of the lesion into the optic nerve head. The case was discussed and enucleation of the globe was decided (fig 2, 3). Histopathology showed a darkly pigmented peripapillary choroidal tumor with overlying retinal detachment and collection of sub retinal fluid (fig 4). Bleached sections showed two types of cells: 1) round to oval with abundant cytoplasm, pigment granules and small nucleus representing melanocytoma cells (fig 5) and spindle-B cells representing the developing melanoma with atypical mitotic figures identified (fig 6). Some balloon cells were also seen (fig 7). The tumor invaded the adjacent optic nerve head (fig 8, 9). Diagnosis was choroidal melanoma arising in association with a pre-existing juxtapapillary melanocytoma. This was further supported by positive immunostaining with HMB45 (fig 10). Based on our finding, we presume that the patient had pre-existing asymptomatic juxtapapillary melanocytoma and the recent deterioration of the patient’s vision was caused by the rapid tumor growth, which caused retinal detachment, vitreous and sub-retinal hemorrhage. However, we do not have any documentation that the patient had a pre-existing melanocytoma lesion previously. P.O. Box 7191, Riyadh 11462 Kingdom Saudi Arabia (+966-1) 482-1234 x 3777 (O) (+966-1) 482-9311 (F) King Khaled Eye Specialist Hospital Discussion Dendritic melanocytes, which are derived from the neural crest, are considered to be the origin of pigmented intraocular growths such as nevi, melanocytoma and melanoma. Melanocytoma is a characteristic darkly pigmented tumor which can occur anywhere in the uvea where melanocytes are present, and classically in the optic nerve head 1, 2 . A few cases of choroidal melanoma arising from optic nerve melanocytoma have been reported but this issue for some authors was controversial. Apple and associates 11 reported a case of malignant transformation from optic nerve melanocytoma. The initial gray mass at the superior aspect of the disk was not recorded and seemed atypical in location. It was not clear if melanoma originated from the choroid or from the optic nerve. At the Verhoeff Ophthalmic Pathology Society meeting, in 1975, Zimmerman presented a case that was initially diagnosed as low-grade melanoma arising from a melanocytoma of the optic disk, but the final pathological diagnosis was melanocytoma of the optic nerve head as reported by Mansour and associates 12 . Shields and associates 9 reported a choroidal melanoma developing from a melanocytoma that affected both the optic disk and juxtapapillary choroid. The malignant tumor in their case was of the mixed-cell type. De Potter and associates 13 reported a mixed-cell malignant melanoma confined to the optic disk. It was considered a rare example of malignant transformation of a melanocytoma even without residual focus of visible melanocytoma cells histologically. In 1992, Loeffler 14 reported a similar case of an ophthalmoscopically typical melanocytoma of the optic disc which turned into a malignant melanoma of spindle-B cell type located within the choroid just next to the optic disc over 7 years. Tumor extension through Bruch’s membrane and in the nerve fiber layer of the optic nerve head was noted. On the other hand, no “melanocytoma cells” were seen within the choroid. They were able to identify two types of cells by ultra structure studies: one of macrophage origin with large melanosomes, and the other with elongated nuclei, many cytoplasmic organelles and smaller melanosomes. The pre-melanosomes showed a granular or filamentous substructure. However the two distinct types of melanocytoma cells described by Juarez and Tso 15 couldn’t be Figure 1: Color picture of the left fundus showing an elevated dark brown lesion with jet black color partially overlying the optic disc infero-temporally with sub retinal and vitreous hemorrhage. Figure 4. Peripapillary darkly pigmented choroidal tumor with overlying retinal detachment and collection of sub retinal fluid. (Hematoxylin & Eosin x25) Figure 5. Bleached section showing Melanocytoma cells. (Hematoxylin & Eosin x400)s Figure 6. Bleached section showing spindle-B melanoma cells with atypical mitotic figures. (Hematoxylin & Eosin x400) Figure 7. Bleached section showing ballooned cells. (Hematoxylin & Eosin x200) Figure 8. Optic nerve tumor involvement. (Hematoxylin & Eosin x100) Figure 9. Bleached section of the optic nerve involvement. (Hematoxylin & Eosin x100) Figure 10. HMB45 positive tumor. (Hematoxylin & Eosin x100) Figure 11. Electron Microscopy showing melanocytoma cell with indented nucleus (original magnification 3,800) Figure 12 A. Electron Microscopy showing macrophage with eccentric nucleu. (original magnification 3,800) Figure 12 B. Electron Microscopy showing phagosomes in a macrophage with irregular melanin granules (original magnification 18,500) Figure 2&3: The enucleated globe showing a peripapillary choroidal mass. demonstrated in his case. Meyer and his colleagues 9 reported a typical melanocytoma of the optic disc with documented change in color and size eventually with dramatic visual loss 5.5 years after the initial diagnosis. The histopathology demonstrated spindle-B malignant melanoma cells interwoven with the population of the melanocytoma cells which extended to the lamina crib Rosa of the optic nerve. Therefore, they strongly recommended regular examination with serial fundus photographs of melanocytoma cases. More recently, in large study, Shields and associates 10 showed the rate of malignant transformation of the disk melanocytoma 1% to 2%. Our patient presented at a later stage with recent onset of visual loss and an elevated lesion suggestive of malignancy. Unfortunately, no previous clinical or photographic documentation of his original melanocytoma was available; however, there was enough histopathologic and ultra structural evidence of a pre-existing peripapillary melanocytoma within the infero-temporal choroid which is the usual location as has been observed by Zimmerman. The typical polyhedral large heavily pigmented cells were mixed with spindle-B melanoma cells. The malignant cells superficially invaded the optic nerve head. The untrastructural studies showed mainly type 2 melanocytoma cells with a markedly indented nucleus and relatively smaller melanosomes (fig 11). Few macrophages with phagosomes containing irregular melanin granules were identified (fig 12). Our case further supports the necessity of close follow-up of pigmented lesions within the optic nerve or the adjacent choroid. On the other hand the rare occurrence of primary malignant melanoma of the optic nerve as reported by De Veer 16 should be taken into consideration. Such lesions should be recognized and followed-up regularly as they may simulate growing melanocytomas 13, 17 . In Conclusion, we report one of the few well documented cases of choroidal melanoma that was associated with juxtapapillary melanocytoma and was confirmed by histopathological study. We believe that periodic follow-up of the patient with optic disc melanocytoma is necessary. References 1. Zimmerman LE, Garron LK. Melanocytoma of the optic disc. Int Ophthalmol Clin 1962;2:431-440. 2. Zimmerman LE. Melanocytes, melanocytic nevi, and melanocytoma. Invest Ophthalmol 1965;4:11-41. 3. Shields JA, Shields CL, Eagle RC, Singh AD, Berrocal MH, Berrocal JA.Central retinal vascular obstruction secondary to melanocytoma of the optic disc. Arch Ophthalmol 2001;119:129-133. 4. Croxatto JO, Ebner R, Crovetto L, Morales AG. Angle closure glaucoma as initial manifestation of melanocytoma of the optic disc. Ophthalmology 1983;90:830-834. 5. Takahashi T, Isayama Y, Okuzuawa I. Unusual case of melanocytoma in the optic disk. Jpn J Ophthalmol 1984;28:171-175. 6. Usui T, Shirakashi M, Kurosawa A, Abe H, Iwata K. Visual disturbance in patients with melanocytoma of the optic disc. Opthalmologica 1990;201:92-98. 7. Shuey TF, Blacharski PA. Pigmented tumor and visual loss. Surv Ophthalmol 1988;33:121-126. 8. Shields JA, Shields CL, Eagle RC, Lieb WE, Stern S. Malignant melanoma associated with melanocytoma of the optic disc. Ophthalmology 1990;97:225-230. 9. Meyer D, Jayne GE, Blinder KJ, Sinard J, Xu S Malignant transformation of an optic disc melanocytoma. AmJ Ophthalmol 1999;127:710-714. 10. Shields JA, Demirci H, Mashayekhi A, Shields CL. Melanocytoma of optic disc in 115 cases: The Samuel Jackson Memorial Lecture, Part 1. Ophthalmology 2004;111(9):1739-1746. 11. 12.Apple DJ, Craythom JM, Reidy JJ et al. “Malignant transformation of an optic nerve melanocytoma”. Can J Ophthalmol 1984; 19:320-8. 12. Mansour AM, Zimmerman L, LaPiana FG and Beauchamp GR. “Clinicopathological findings in a growing optic nerve melanocytoma” British J of Ophthalmology 1989; 73: 410-415. 13. De Potter P, Shields CL, Eagle RC, Shields JA and Lipkowitz JL. “Malignant melanoma of the optic nerve”. Archives of Ophthalmology 1996; 114: 608-612. 14. Loeffler KU and Tecklenborg H. “Melanocytoma-like growth of a juxtapapillary malignant melanoma”, Retina 1992; 12 (1): 29-34. 15. Juarez CP and Tso MOM. “An ultrastructural study of melanocytomas”, Magnocellular nevi of the optic disc and uvea. Am J Ophthalmol 1980; 90: 48-62. 16. De Veer JA and Brooklyn NY. “Melanotic tumors of the the optic nerve head: a pathologic study”. Archives of Ophthalmology 1961; 65: 536-541. 17. Erzurum SA, Jampol LM, Territo C and O’Grady R. “Primary malignant melanoma of the optic nerve simulating a melanocytoma”. Archives of Ophthalmology 1962; 110: 486-684.
Transcript of Choroidal Melanoma in Association with Juxtapapillary ...Choroidal Melanoma in Association with...
Choroidal Melanoma in Association with Juxtapapillary MelanocytomaSaba Al-Rashaed, MD; Hind M. Alkatan, MDKing Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
IntroductionMelanocytoma, also known as magnocellular nevus, is a benign, heavily pigmented tumor that may develop wherever uveal melanocytes are present1. Melanocytomas most commonly arise on/adjacent to the optic disc and are traditionally considered benign and stationary lesions with little potential for growth; Zimmerman and Garron1,2 reported instances of limited growth of melanocytomas. However, other reports have highlighted cases in which melanocytomas enlarge rapidly and lead to sudden visual loss and necrosis1, 3, 4, 7. Few cases of melanoma arising from melanocytoma of the optic disc were reported previously8, 9, 10. One large series of optic disc melanocytoma done by Shields et al10
recently showed that the rate of malignant transformation was 1%-2%.
We report an example a case of malignant choroidal melanoma associated with optic disc melanocytoma that was documented by histopathological study.
AbstractPurpose: To report a rare example case of choroidal melanoma associated with juxtapapillary melanocytoma.
Method: Clinical data including visual acuity, color fundus photographs, �uorescein angiography, ultra sonogram and histopathologic studies of this case were reviewed.
Result: A 68-year-old Saudi man was evaluated for sudden painless loss of vision in left eye for duration of 4 months. His vision in the affected eye was counting �ngers near the face. Fundus examination showed an elevated dark brown lesion with jet black color partially overlying the optic disc infero-temporally with an associated sub-retinal and vitreous hemorrhage. Ultrasound showed moderate internal re�ectivity with moderate sound attenuation of a vascular mass. The eye was enucleated and histopathological section showed two types of cells: 1) round to oval with abundant cytoplasm, pigment granules and small nucleus representing melanocytoma cells and 2) spindle-B cells representing the developing melanoma with atypical mitotic �gures identi�ed, which invade the adjacent optic nerve. This was further supported by positive immunostaining with HMB45.
Conclusion: This is one of the few documented cases of choroidal melanoma that was associated with juxtapapillary melanocytoma. Periodic follow-up of the patient with optic disc melanocytoma is necessary.
Key words: Choroidal melanoma, melanocytomas, histopathology, follow-up
Case ReportA 68-year-old Saudi man presented with reduced vision of his left eye for duration of 4 months duration. On examination, his vision in the affected eye was counting �ngers near the face. The left fundus (�g1) showed an elevated round choroidal mass, partially overlying the optic disc infero-temporally. The lesion was dark brown with jet black color peripherally with an associated sub retinal hemorrhage. The view of the fundus was hazy secondary to signi�cant vitreous hemorrhage and posterior sub capsular cataract . Ultrasound showed a dome shaped posterior lesion surrounding the optic disc, maximum elevation of the lesion was 6mm infero-temporally and had moderate internal re�ectivity with moderate sound attenuation. Doppler ultrasound showed a vascular mass. Intravenous �ourescein angiography was not conclusive because of poor fundus view. The case was diagnosed as choroidal melanoma probably evolving from pre-existing juxtapapillary melanocytoma.
Radiological studies did not show extra-ocular extension, hepatomegaly or evidence of lung metastasis; however, MRI of the left orbit was suggestive of extension of the lesion into the optic nerve head.
The case was discussed and enucleation of the globe was decided (�g 2, 3). Histopathology showed a darkly pigmented peripapillary choroidal tumor with overlying retinal detachment and collection of sub retinal �uid (�g 4). Bleached sections showed two types of cells: 1) round to oval with abundant cytoplasm, pigment granules and small nucleus representing melanocytoma cells (�g 5) and spindle-B cells representing the developing melanoma with atypical mitotic �gures identi�ed (�g 6). Some balloon cells were also seen (�g 7). The tumor invaded the adjacent optic nerve head (�g 8, 9). Diagnosis was choroidal melanoma arising in association with a pre-existing juxtapapillary melanocytoma. This was further supported by positive immunostaining with HMB45 (�g 10).
Based on our �nding, we presume that the patient had pre-existing asymptomatic juxtapapillary melanocytoma and the recent deterioration of the patient’s vision was caused by the rapid tumor growth, which caused retinal detachment, vitreous and sub-retinal hemorrhage. However, we do not have any documentation that the patient had a pre-existing melanocytoma lesion previously.
P.O. Box 7191, Riyadh 11462Kingdom Saudi Arabia(+966-1) 482-1234 x 3777 (O)(+966-1) 482-9311 (F)
King Khaled Eye SpecialistHospital
DiscussionDendritic melanocytes, which are derived from the neural crest, are considered to be the origin of pigmented intraocular growths such as nevi, melanocytoma and melanoma. Melanocytoma is a characteristic darkly pigmented tumor which can occur anywhere in the uvea where melanocytes are present, and classically in the optic nerve head1, 2. A few cases of choroidal melanoma arising from optic nerve melanocytoma have been reported but this issue for some authors was controversial. Apple and associates11 reported a case of malignant transformation from optic nerve melanocytoma. The initial gray mass at the superior aspect of the disk was not recorded and seemed atypical in location. It was not clear if melanoma originated from the choroid or from the optic nerve. At the Verhoeff Ophthalmic Pathology Society meeting, in 1975, Zimmerman presented a case that was initially diagnosed as low-grade melanoma arising from a melanocytoma of the optic disk, but the �nal pathological diagnosis was melanocytoma of the optic nerve head as reported by Mansour and associates12. Shields and associates9 reported a choroidal melanoma developing from a melanocytoma that affected both the optic disk and juxtapapillary choroid. The malignant tumor in their case was of the mixed-cell type.
De Potter and associates13 reported a mixed-cell malignant melanoma con�ned to the optic disk. It was considered a rare example of malignant transformation of a melanocytoma even without residual focus of visible melanocytoma cells histologically. In 1992, Loef�er14 reported a similar case of an ophthalmoscopically typical melanocytoma of the optic disc which turned into a malignant melanoma of spindle-B cell type located within the choroid just next to the optic disc over 7 years. Tumor extension through Bruch’s membrane and in the nerve �ber layer of the optic nerve head was noted. On the other hand, no “melanocytoma cells” were seen within the choroid. They were able to identify two types of cells by ultra structure studies: one of macrophage origin with large melanosomes, and the other with elongated nuclei, many cytoplasmic organelles and smaller melanosomes. The pre-melanosomes showed a granular or �lamentous substructure. However the two distinct types of melanocytoma cells described by Juarez and Tso15 couldn’t be
Figure 1: Color picture of the left fundus showing an elevated dark brown lesion with jet black color partially overlying the optic disc infero-temporally with sub retinal and vitreous hemorrhage.
Figure 4. Peripapillary darkly pigmented choroidal tumor with overlying retinal detachment and collection of sub retinal �uid. (Hematoxylin & Eosin x25)
Figure 5. Bleached section showing Melanocytoma cells. (Hematoxylin & Eosin x400)s
Figure 6. Bleached section showing spindle-B melanoma cells with atypical mitotic �gures. (Hematoxylin & Eosin x400)
Figure 7. Bleached section showing ballooned cells. (Hematoxylin & Eosin x200)
Figure 8. Optic nerve tumor involvement. (Hematoxylin & Eosin x100)
Figure 9. Bleached section of the optic nerve involvement. (Hematoxylin & Eosin x100)
Figure 10. HMB45 positive tumor. (Hematoxylin & Eosin x100)
Figure 11. Electron Microscopy showing melanocytoma cell with indented nucleus (original magni�cation 3,800)
Figure 12 A. Electron Microscopy showing macrophage with eccentric nucleu. (original magni�cation 3,800)
Figure 12 B. Electron Microscopy showing phagosomes in a macrophage with irregular melanin granules (original magni�cation 18,500)
Figure 2&3: The enucleated globe showing a peripapillary choroidal mass.
demonstrated in his case. Meyer and his colleagues9 reported a typical melanocytoma of the optic disc with documented change in color and size eventually with dramatic visual loss 5.5 years after the initial diagnosis. The histopathology demonstrated spindle-B malignant melanoma cells interwoven with the population of the melanocytoma cells which extended to the lamina crib Rosa of the optic nerve. Therefore, they strongly recommended regular examination with serial fundus photographs of melanocytoma cases.
More recently, in large study, Shields and associates10 showed the rate of malignant transformation of the disk melanocytoma 1% to 2%.
Our patient presented at a later stage with recent onset of visual loss and an elevated lesion suggestive of malignancy. Unfortunately, no previous clinical or photographic documentation of his original melanocytoma was available; however, there was enough histopathologic and ultra structural evidence of a pre-existing peripapillary melanocytoma within the infero-temporal choroid which is the usual location as has been observed by Zimmerman. The typical polyhedral large heavily pigmented cells were mixed with spindle-B melanoma cells. The malignant cells super�cially invaded the optic nerve head. The untrastructural studies showed mainly type 2 melanocytoma cells with a markedly indented nucleus and relatively smaller melanosomes (�g 11). Few macrophages with phagosomes containing irregular melanin granules were identi�ed (�g 12). Our case further supports the necessity of close follow-up of pigmented lesions within the optic nerve or the adjacent choroid. On the other hand the rare occurrence of primary malignant melanoma of the optic nerve as reported by De Veer16 should be taken into consideration. Such lesions should be recognized and followed-up regularly as they may simulate growing melanocytomas13, 17.
In Conclusion, we report one of the few well documented cases of choroidal melanoma that was associated with juxtapapillary melanocytoma and was con�rmed by histopathological study. We believe that periodic follow-up of the patient with optic disc melanocytoma is necessary.
References 1. Zimmerman LE, Garron LK. Melanocytoma of the optic disc. Int Ophthalmol Clin 1962;2:431-440.2. Zimmerman LE. Melanocytes, melanocytic nevi, and melanocytoma. Invest Ophthalmol 1965;4:11-41.3. Shields JA, Shields CL, Eagle RC, Singh AD, Berrocal MH, Berrocal JA.Central retinal vascular obstruction secondary to melanocytoma of the optic disc. Arch Ophthalmol 2001;119:129-133.4. Croxatto JO, Ebner R, Crovetto L, Morales AG. Angle closure glaucoma as initial manifestation of melanocytoma of the optic disc. Ophthalmology 1983;90:830-834.5. Takahashi T, Isayama Y, Okuzuawa I. Unusual case of melanocytoma in the optic disk. Jpn J Ophthalmol 1984;28:171-175.6. Usui T, Shirakashi M, Kurosawa A, Abe H, Iwata K. Visual disturbance in patients with melanocytoma of the optic disc. Opthalmologica 1990;201:92-98.7. Shuey TF, Blacharski PA. Pigmented tumor and visual loss. Surv Ophthalmol 1988;33:121-126.8. Shields JA, Shields CL, Eagle RC, Lieb WE, Stern S. Malignant melanoma associated with melanocytoma of the optic disc. Ophthalmology 1990;97:225-230.9. Meyer D, Jayne GE, Blinder KJ, Sinard J, Xu S Malignant transformation of an optic disc melanocytoma. AmJ Ophthalmol 1999;127:710-714.
10. Shields JA, Demirci H, Mashayekhi A, Shields CL. Melanocytoma of optic disc in 115 cases: The Samuel Jackson Memorial Lecture, Part 1. Ophthalmology 2004;111(9):1739-1746.11. 12.Apple DJ, Craythom JM, Reidy JJ et al. “Malignant transformation of an optic nerve melanocytoma”. Can J Ophthalmol 1984; 19:320-8.12. Mansour AM, Zimmerman L, LaPiana FG and Beauchamp GR. “Clinicopathological findings in a growing optic nerve melanocytoma” British J of Ophthalmology 1989; 73: 410-415.13. De Potter P, Shields CL, Eagle RC, Shields JA and Lipkowitz JL. “Malignant melanoma of the optic nerve”. Archives of Ophthalmology 1996; 114: 608-612. 14. Loeffler KU and Tecklenborg H. “Melanocytoma-like growth of a juxtapapillary malignant melanoma”, Retina 1992; 12 (1): 29-34.15. Juarez CP and Tso MOM. “An ultrastructural study of melanocytomas”, Magnocellular nevi of the optic disc and uvea. Am J Ophthalmol 1980; 90: 48-62.16. De Veer JA and Brooklyn NY. “Melanotic tumors of the the optic nerve head: a pathologic study”. Archives of Ophthalmology 1961; 65: 536-541.17. Erzurum SA, Jampol LM, Territo C and O’Grady R. “Primary malignant melanoma of the optic nerve simulating a melanocytoma”. Archives of Ophthalmology 1962; 110: 486-684.
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