Imaging results. A, Fundus photograph of the left eye showing choroidal melanoma involving the macula. B, Late-phase fluorescein angiography showing hyperfluorescence and internal circulation within the tumor. C, Vertical (top) and horizontal (bottom) optical coherence tomographic scans through the tumor (small arrows) revealing adjacent subretinal (large arrow) and intraretinal (arrowhead) fluid. D, B-scan ultrasonography showing an elevated mass measuring 3.2 × 1.5 mm with acoustic hollowness (white arrows) and medium internal reflectivity on A-scan waves (blue arrows).
Microscopy results. A, In the retina, a dumbbell-shaped tumor arises from the choroid (arrow) and reaches into the macula (arrowhead) (hematoxylin-eosin, bar = 200 μm). Inset, A high-power view of the tumor cells (hematoxylin-eosin, original magnification ×100). B, Tumor cells resemble a mixed-pattern human melanoma consisting of epithelioid and spindle A cells. Rare cells resembling spindle B cells are also noted (hematoxylin-eosin, bar = 70 μm). C, The ciliary body epithelium. Several displaced, rounded, enlarged, and less pigmented cells are shown (arrowheads). These dysplastic cells disrupt the integrity of the epithelium (hematoxylin-eosin, bar = 50 μm). D, A transmission electron micrograph reveals malignant epithelioid cells in sheets (bar = 5 μm). Inset, A subpopulation of malignant cells contain fully matured melanosomes (bar = 2 μm).
Albert DM, Dubielzig RR, Li Y, Lin T, Neekhra A, Orilla W, Ramos M, Salamat MS, Burke JA. Choroidal Melanoma Occurring in a Nonhuman Primate. Arch Ophthalmol. 2009;127(8):1080-1082. doi:10.1001/archophthalmol.2009.173
Copyright 2009 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2009
A cynomolgus monkey had a choroidal melanoma. The clinical findings, ophthalmic and systemic investigations, and histopathological examination are described.
A 7-year-old female cynomolgus monkey (Macaca fascicularis) was obtained in January 2006. Results of the prearrival screening tests for tuberculosis and simian retrovirus were negative. Mild hepatomegaly and moderate dental tartar were present on physical examination on arrival. Minimal hypochromic, normocytic anemia, neutropenia, and lymphocytosis were found on clinicopathological examination. The serum chemistry data, including levels of hepatic enzymes, were unremarkable.
A prestudy ocular examination was performed in May 2006. Results of the external and anterior segment examinations of both eyes were unremarkable. The dilated examination showed a healthy retina in the right eye and an elevated choroidal mass involving the macula with some intrinsic peripheral pigmentation in the left eye (Figure 1A). Fluorescein angiography showed an intrinsic circulation within the mass with areas of hyperfluorescence (Figure 1B). Optical coherence tomography revealed a choroidal mass with high reflectivity and adjacent subretinal and intraretinal fluid (Figure 1C). B-scan ultrasonography showed acoustic hollowness with medium internal reflectivity. There was excavation of the underlying sclera (Figure 1D). The differential diagnosis included primary intraocular tumor or metastatic spread of a systemic malignant neoplasm as well as rare peripheral nerve sheath tumors such as schwannoma; however, the clinical presentation suggested a choroidal melanoma. The animal was euthanized 2 years after initial presentation, and a necropsy was done with enucleation. No significant change was noticed in the tumor on imaging prior to euthanasia. No other abnormalities were observed. The eye was fixed in Davidson solution prior to its transfer to 70% ethanol.
The histopathological examination of the eye showed a dumbbell-shaped mass arising from the choroid, penetrating the Bruch membrane, and involving the overlying retina at the macula (Figure 2A). It measured 3.2 × 1.5 mm. The tumor was composed of epithelioid and spindle cells (Figure 2B). Rare mitotic figures were noted. The pigmented epithelium of the ciliary body was disorganized with numerous displaced, dysplastic, and lightly pigmented cells present (Figure 2C). Results of immunohistochemical staining of the specimen with HMB-45 and for MART-1 were negative. Transmission electron microscopy, however, confirmed the diagnosis of choroidal melanoma by revealing melanosomes in tumor cells (Figure 2D).
Uveal melanoma is the most common primary intraocular malignant tumor in humans.1 Although it constitutes only about 5% of all melanomas,1 it contributes to 13% of melanoma deaths owing to the high rate of metastasis and poor response to treatment.2 Kaspareit et al3 reported spontaneous neoplasms of endocrine organs, the respiratory system, and the female genital system and lymphoma involving multiple organs but no choroidal melanoma in cynomolgus monkeys during a 15-year period. Searches on PubMed (a service of the National Library of Medicine and the National Institutes of Health), PrimateLit (a database that is the collaborative project of the Wisconsin Primate Research Center, the Washington National Primate Research Center, and the University of Wisconsin–Madison Libraries), IndexCat (a National Library of Medicine database), the CAB Abstracts (a database covering veterinary science literature), JSTOR (digital interdisciplinary archives for scholarship), and SciFinder Scholar (a large interdisciplinary database going back the mid 1800s) did not reveal any published report of uveal melanoma in a nonhuman primate. To our knowledge, this is the first reported case of a primary choroidal melanoma in a cynomolgus monkey.
In addition to histopathological findings similar to those of human uveal melanoma, similar clinical features were observed in the choroidal mass. These features include a dumbbell shape, adjacent subretinal and intraretinal fluid, internal vascularity on fluorescein angiography, and medium internal reflectivity on B-scan ultrasonography. Although the tumor cells failed to stain for HMB-45 and MART-1, they have an appearance similar to the epithelioid and spindle cell type of human choroidal melanoma as described in the Callender classification modified by the Armed Forces Institute of Pathology.4 We attribute the absence of immunohistochemical staining to cross-reactivity of antibodies (that are directed against human antigens) with cynomolgus tissues related to the nonhuman species. The finding of neoplastic melanocytes containing fully melanized mature melanosomes on transmission electron microscopy further supports the diagnosis of choroidal melanoma. Additionally, the presence of dysplastic pigmented epithelial cells in the ciliary body of this animal is interesting but of unknown significance. There is no known relationship between ocular melanoma and ciliary epithelial dysplasia in humans or animals. No evidence of metastasis was evident in this monkey and no other abnormalities were found at the time of euthanasia. Uveal melanoma research groups are currently using various human uveal melanoma cell lines that can be injected into experimental animal models to simulate intraocular melanoma. Transgenic mouse models of spontaneously occurring uveal melanoma or melanomalike tumors are also available.5,6 However, there is lack of a nonhuman primate model of uveal melanoma that has a close phylogenetic relationship to humans and would be a better alternative than currently available uveal melanoma models. The proven occurrence of spontaneous uveal melanoma in a nonhuman primate will hopefully lead to the identification and study of additional choroidal melanomas in other nonhuman primate species, thereby opening the possibility of further genetic studies and breeding opportunities for primate model development that will advance our knowledge of human uveal melanoma.
Correspondence: Dr Albert, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, K6/412 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3220 (firstname.lastname@example.org).
Author Contributions: Dr Albert 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 grant P30 EY016665 (Core Grant for Vision Research) and an unrestricted department award from Research to Prevent Blindness.