Choroidal tumors may assume a mushroom or collar-button configuration due to extension of the lesion through Bruch’s membrane and growth into the subretinal space. The mechanism for this extension is unclear and may involve rapid vertical growth, large overall tumor size, enzymatic degradation,1 or retinal pigment epithelium (RPE) abnormalities.2 Sites of eruption have been associated with areas of focal hyperfluorecence seen on fluorescein angiography, suggesting an association with areas of more intense growth activity.3 Interestingly, while 87.7% of choroidal melanoma show microscopic invasion of Bruch’s membrane,4 choroidal metastases rarely do, with less than 0.5% exhibiting a mushroom-shaped growth pattern.5 In this case report, a choroidal metastasis from a pancreatic neuroendocrine tumor adopted a mushroom configuration with subretinal and breakthrough vitreous hemorrhage. This unique finding may provide some clues for the mechanism by which choroidal tumors extend through Bruch’s membrane.
A 72-year-old man with metastatic neuroendocrine tumor presented with vision loss and a large mushroom-shaped choroidal mass with subretinal and vitreous hemorrhage in the right eye. He had been diagnosed 1 year prior with metastatic neuroendocrine tumor from the pancreas after undergoing a laparoscopic cholecystectomy for gallbladder-type gastrointestinal symptoms. At the time of diagnosis, computed tomography (CT) imaging showed multiple nodular liver and lung metastases with hilar and mediastinal lymphadenopathy, for which he was treated initially with octreotide acetate followed by palliative radiation therapy when brain and spinal metastases were later discovered. At the time of presentation to the Duke University Eye Center, he reported a 4-month history of progressive vision decline followed by sudden vision loss in the right eye for several days. On examination, he was found to have only light perception vision and an IOP of 28 mm Hg in the affected eye. Anterior segment examination showed moderate conjunctival injection and pseudophakia, with no view to the fundus due to dense vitreous hemorrhage. B-scan ultrasonography demonstrated a large, 10.4 × 10.5 × 8.6 mm mushroom-shaped choroidal mass with medium internal reflectivity and no intralesional vascular pulsations, as well as dense subretinal and vitreous hemorrhage (Figure 1A). Due to the mushroom configuration, choroidal melanoma was suggested, although choroidal metastasis was suspected due to the internal reflectivity, breakthrough hemorrhages, and extensive history of metastatic disease. Given the lesion size, enucleation with implant placement was performed. Gross examination of the specimen revealed an amelanotic, mushroom-shaped endophytic choroidal mass and dense vitreous hemorrhage corresponding to the ultrasonographic findings (Figure 1B). Histologic examination showed a nested organoid pattern of the tumor (Figure 2A) and immunopositivity for synatophysin (Figure 2B), consistent with a diagnosis of metastatic neuroendocrine carcinoma. The patient continued to receive palliative radiation therapy at the time of diagnosis.
(A) B-scan ultrasound image of the right eye demonstrating a large mushroom-shaped choroidal mass with medium internal hyperreflectivity and a funnel-shaped interface suggestive of a total retinal detachment with both vitreous and subretinal hemorrhages. (B) Gross pathologic examination of the enucleated globe confirms the firm, fibrous mushroom-shaped mass with dense vitreous hemorrhage.
(A) Hematoxylin- and eosin-stained histological section of the choroidal mass shows a nested organoid pattern. (B) Immunohistochemical staining for synaptophysin is positive.
A mushroom- or collar-button-shaped choroidal mass is classically suggestive for melanoma. This growth pattern results from the propensity of choroidal malignant melanoma to extend through Bruch’s membrane into the subretinal space. In contrast, choroidal metastases are typically placoid, diffuse, or dome-shaped. Few case reports exist describing mushroom-shaped choroidal metastases arising from lung adenocarcinoma.6,7 However, mushroom-shaped choroidal metastasis from a neuroendocrine tumor has not been previously described in the literature.
Neuroendocrine tumors are derived from highly differentiated neuroendocrine cells that often produce biogenic amines or polypeptide hormones such as gastrin, serotonin, or adrenocorticotrophic hormone (ACTH). They are identified by the presence of secretory granules and specific cell markers such as neuron-specific enolase, chromogranin, and synaptophysin.8 Neuroendocrine tumors arise from various primary sites along the gastrointestinal, bronchopulmonary, and urogenital tracts and can metastasize to lung, liver, spleen, bone, and lymph nodes, and only rarely to the eye and orbit.9 The site of intraocular metastasis is usually the choroid, although both ciliary body and iris metastases have been reported.9 The most common appearance is a characteristic orange color,8–10 while some may be simply amelanotic8 or even pigmented in one report.11 Treatment of these rare metastases has included external beam radiotherapy, plaque brachytherapy, argon laser photocoagulation, and local resection, varying by individual case.9
The neuroendocrine choroidal metastasis reported in the current report differs from prior reports in that the site of origin was the pancreas, whereas the primary site reported in the literature is typically the lung.6,9,11 It is unclear whether or how a gastrointestinal neuroendocrine metastasis may differ from bronchopulmonary metastatic lesions to result in this distinct growth pattern. Nevertheless, this unusual case presentation should alert clinicians to the possibility of choroidal metastases simulating the mushroom configuration that is more commonly associated with melanoma. Further studies on the pathobiology of metastatic neuroendocrine tumors, particularly from the pancreas, may help expand our understanding of the mechanism by which uveal tumors extend through Bruch’s membrane.
- Lai K, Conway RM, Crouch R, Jager MJ, Madigan MC. Expression and distribution of MMPs and TIMPs in human uveal melanoma. Exp Eye Res. 2008;86(6):936–941. doi:10.1016/j.exer.2008.03.010 [CrossRef]
- Hainsworth DP, Sommerville DN, Ranson NT, Todd KC, Gigantelli JW. Bruch’s membrane abnormalities in dome-shaped and mushroom-shaped choroidal melanomas. Ann Acad Med Singapore. 2006;35(2):87–88.
- Leff SR, Augsburger JJ, Shields JA. Focal fluorescence of choroidal melanoma. Br J Ophthalmol. 1986;70(2):104–106. doi:10.1136/bjo.70.2.104 [CrossRef]
- Histopathologic characteristics of uveal melanomas in eyes enucleated from the Collaborative Ocular Melanoma Study. COMS report no. 6. Am J Ophthalmol. 1998;125(6):745–766.
- Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology. Aug1997;104(8):1265–1276. doi:10.1016/S0161-6420(97)30148-1 [CrossRef]
- Shields JA, Shields CL, Brown GC, Eagle RC Jr, . Mushroom-shaped choroidal metastasis simulating a choroidal melanoma. Retina. 2002;22(6):810–813. doi:10.1097/00006982-200212000-00024 [CrossRef]
- Ward SD, Byrne BJ, Kincaid MC, Mann ES. Ultrasonographic evidence of a mushroom-shaped choroidal metastasis. Am J Ophthalmol. 2000;130(5):681–682. doi:10.1016/S0002-9394(00)00604-8 [CrossRef]
- Trichopoulos N, Augsburger JJ. Neuroendocrine tumours metastatic to the uvea: diagnosis by fine needle aspiration biopsy. Graefes Arch Clin Exp Ophthalmol. 2006;244(4):524–528. doi:10.1007/s00417-005-0113-5 [CrossRef]
- Harbour JW, De Potter P, Shields CL, Shields JA. Uveal metastasis from carcinoid tumor. Clinical observations in nine cases. Ophthalmology. 1994;101(6):1084–1090. doi:10.1016/S0161-6420(94)38030-4 [CrossRef]
- Krema H, McGowan H, Tanzer H, Simpson R, Laperriere N. Unusual orange-colored choroidal metastases. J Ophthalmic Vis Res. 2013;8(1):53–57.
- Eagle RC Jr, Ehya H, Shields JA, Shields CL. Choroidal metastasis as the initial manifestation of a pigmented neuroendocrine tumor. Arch Ophthalmol. 2000;118(6):841–845. doi:10.1001/archopht.118.6.841 [CrossRef]