Figure 1. Progression of melanocytoma over 33 years. Fundus photographs of the optic disc melanocytoma at the initial visit with visual acuity of 20/20 (A), 12 years later with visual acuity of 20/70 (B), 25 years later with visual acuity of 20/80 (C), 29 years later with visual acuity of 20/150 (D), 31 years later with visual acuity of hand motions (E), and 33 years later with visual acuity of hand motions (F), and optical coherence tomography demonstrating retinal invasion by melanocytoma (G).
Figure 2. Macrophotographs and histologic analysis. A, Macrophotograph of the enucleated specimen shows deeply pigmented convex tumor on the surface of the optic nerve. An epiretinal seed of pigmented cells rests on the slope near the luteal pigment at the left. B, Intensely pigmented tumor infiltrates the swollen nerve head and extends posteriorly behind the lamina cribrosa. A choroidal component is seen at the left (hematoxylin-eosin, original magnification ×5). C, Depigmented section of the residual melanocytomatous component of tumor discloses large cells with copious quantities of cytoplasm. Most nuclei are bland, but some have distinct nucleoli (bleach, original magnification ×250). D, Fascicles of spindle cells arranged in a haphazard whorl-like fashion and containing variably sized and shaped nuclei compose part of the tumor consistent with low-grade melanoma (bleach, original magnification ×250). E, High-magnification macrophotograph shows a seed of spindle cells composing a focal neoplastic epiretinal membrane. F, Histopathologic analysis of the neoplastic epiretinal membrane shows intensely pigmented spindle cells on the inner surface of the internal limiting membrane (top; hematoxylin-eosin, original magnification ×100), and bland nuclei of the spindle cells are disclosed by bleaching (bottom; bleach, original magnification ×250).
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Shukla SY, Shields JA, Eagle RC, Shields CL. Transformation of Optic Disc Melanocytoma Into Melanoma Over 33 Years. Arch Ophthalmol. 2012;130(10):1344–1347. doi:10.1001/archophthalmol.2012.740
Author Affiliations: Ocular Oncology Service (Drs Shukla, J. A. Shields, and C. L. Shields) and Department of Ophthalmic Pathology (Dr Eagle), Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania.
Optic disc melanocytoma is a deeply pigmented variant of benign melanocytic nevus that has been confused with malignant melanoma.1 Although melanocytoma was believed to be benign,1 there are rare reports of transformation into malignant melanoma, heralded by tumor growth or decrease in vision.2-5 A study of 115 patients revealed malignant transformation in 2 of the patients.5 We report the longest documented follow-up, to our knowledge, of an optic disc melanocytoma and provide clinicopathologic correlation following tumor growth and enucleation.
An asymptomatic 23-year-old woman had a pigmented lesion in her right eye. Visual acuity was 20/20 OU. The only abnormal finding was a deeply pigmented mass within the inferonasal portion of the right optic disc (Figure 1A). Fluorescein angiography showed early hypofluorescence and late mild hyperfluorescence of the mass with slight late leakage. These findings were characteristic of optic disc melanocytoma, and observation was advised.
After 12 years, her visual acuity gradually decreased to 20/70 OD without change in tumor appearance (Figure 1B). After 25 years of follow-up, visual acuity was 20/80 and there was minor vitreous seeding without tumor growth (Figure 1C). After 29 years, visual acuity was 20/150 and slight tumor enlargement was documented (Figure 1D). After 31 years, visual acuity was hand motions, the tumor appeared necrotic, and extensive vitreous seeding was noted (Figure 1E). The patient refused fine-needle aspiration biopsy. After 32 years, fine-needle aspiration biopsy was performed, which disclosed cells consistent with melanocytoma and no malignant neoplasm. The patient elected observation.
After 33 years, visual acuity remained hand motions with progressive vitreous seeding and retinal edema (Figure 1F and G). The seeding and vision reduction were suspicious for transformation into malignant melanoma, and enucleation was advised.
Following enucleation, gross examination revealed a dark-brown mass obscuring the optic nerve and invading the retina (Figure 2A). Microscopic examination revealed intensely pigmented tumor within the optic nerve head and retrolaminar portion and peripapillary choroid (Figure 2B). The solid tumor was composed of large polygonal cells with abundant pigmented cytoplasm, compatible with melanocytoma (Figure 2C). Additional sections revealed spindle-cell fascicles containing variably sized and shaped nuclei consistent with low-grade spindle B melanoma (Figure 2D). Pigmented spindle cells were present on the retina, composing a neoplastic epiretinal membrane, and pigmented vitreous cells were noted (Figure 2E and F). The histopathologic diagnosis was optic nerve melanocytoma with malignant transformation into low-grade melanoma. There was no clinical evidence of metastasis.
Melanocytoma of the optic nerve is a benign condition that has rarely undergone malignant transformation.2-6 Most reports have identified transformation within 5 years of the initial manifestation, although cases at 9 years and 17 years have been reported.2,3 Over 33 years, our patient experienced gradual visual acuity loss from 20/20 to hand motions with progressive vitreous seeding of tumor cells. Histopathologic analysis revealed melanocytoma with necrosis and low-grade spindle B melanoma. Genetic heterogeneity of uveal melanoma has been described,7 but genetic analysis was not performed in this case.
The few previous reports of malignant transformation of melanocytoma illustrated an increase in tumor thickness, hinting at the development of melanoma, within a few years of the initial manifestation.2-4 Our case is different because there was little appreciable change in tumor thickness. The main features of concern were progressive vitreous seeding and vision loss. Extensive tumor involvement of the optic disc with vision loss suggests malignant transformation but can occur with ischemic necrosis of benign melanocytoma.6
Visual acuity and melanocytoma enlargement were assessed by Shields et al5 in 116 eyes. By 10 years, they found visual acuity loss of 2 or more lines in 18% of patients and tumor enlargement in 32% of patients. Malignant transformation occurred in 2 eyes. We demonstrate gradual vision loss and minor tumor enlargement over 33 years with transformation into low-grade melanoma. Follow-up of optic disc melanocytoma for malignant transformation, even over several decades, is advised.
Correspondence: Dr J. A. Shields, Ocular Oncology Service, Wills Eye Institute, 840 Walnut St, Ste 1440, Philadelphia, PA 19107 (email@example.com).
Author Contributions: Dr J. A. Shields had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Financial Disclosure: None reported.
Funding/Support: This work was supported by Eye Tumor Research Foundation, Philadelphia, Pennsylvania (Drs J. A. Shields and C. L. Shields).
Role of the Sponsor: The sponsor had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.