The DecisionDx-UM gene expression profiling test is an accurate, popular, and technically simple method for obtaining prognostic information from uveal melanoma tissue. However, this test does not provide diagnostic information and may errantly provide prognostication results for lesions other than uveal melanoma. A 73-year-old woman presented with a uveal metastasis from lung adenocarcinoma, which was misdiagnosed as uveal melanoma. DecisionDx-UM gene expression profiling was performed on tissue obtained from a needle biopsy. A test result was provided regarding the lesion’s metastatic potential even though it was not a uveal melanoma.
[Ophthalmic Surg Lasers Imaging Retina. 2014;45:441–442.]
From the Department of Ophthalmology (MIS, PJS, BED) and the Department of Radiation Oncology (KKM, BED), University of California, San Francisco, California.
Funded in part by NIH-NEI EY002162 Core Grant for Vision Research and an unrestricted grant from Research to Prevent Blindness.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Michael Seider, MD, 10 Koret Way, San Francisco, CA 94143; email:
Received: November 18, 2013
Accepted: April 09, 2014
Posted Online: August 26, 2014
Gene expression profiling (GEP) has recently been validated as a method of predicting the metastatic potential of uveal melanoma.1 Unlike previous methods of prognostic biopsy that require larger amounts of tumor tissue,2,3 GEP may be performed with precision from a fine-needle aspirate.1 Gene expression profiling is commercially available (DecisionDx-UM; Castle Biosciences, Phoenix, AZ) and uses a PCR-based platform to evaluate the expression of 15 genes and classify uveal melanoma into class 1 (lower metastatic risk) or class 2 (higher metastatic risk).1,4
We present the case of a uveal metastasis that was misdiagnosed as uveal melanoma and errantly biopsied for GEP. In this case, GEP provided a result regarding the malignant potential of the lesion even though it was not a uveal melanoma.
A 73-year-old woman presented with complaints of distorted vision in the right eye, worsening over the previous few months. She had no other ocular or systemic complaints. She had no ocular history but had been treated for breast cancer with a right mastectomy 29 years earlier. She had smoked for 5 years but had quit 20 years prior and had a family history of breast cancer in her sister.
On examination, visual acuity was 20/70 in the right eye and 20/25 in the left. IOP was 15 mm Hg in the right eye and 14 mm Hg in the left. Visual field examination revealed a small inferonasal scotoma near fixation in the right eye but otherwise normal findings in both eyes. Motility and pupils were normal in both eyes.
Slit lamp examination revealed mild nuclear sclerotic cataracts in both eyes but yielded otherwise normal findings. Dilated fundus examination of the right eye revealed a large amelanotic mass extending from the fovea to the temporal equator, with associated subretinal fluid and scattered drusen (Figure). Dilated examination of the left eye revealed scattered drusen but otherwise normal findings. B-Scan ultrasonography of the right eye revealed a dome-shaped mass measuring 13.9 mm circumferentially by 13.8 mm radially, with a thickness of 4.9 mm and medium to low internal reflectivity. Fluorescein angiography revealed an absence of intralesional vascularity, with diffuse leakage of the overlying retinal pigment epithelium in the later frames.
Fundus image, right eye. Elevated choroidal metastasis with associated subretinal fluid, right eye.
A misdiagnosis of amelanotic uveal melanoma was made. Tantalum marker clips were placed in preparation for proton beam radiotherapy, and a transscleral tumor biopsy was performed at the time of surgery using a 27-gauge needle. This sample was sent for DecisionDx-UM GEP testing as per the commercial recommendations and resulted in a class 1A gene expression profile with a high “discriminant value” (0.53) and normal confidence.
Soon after tantalum marker placement, a chest x-ray was completed as part of a routine metastatic work-up and revealed several opacities. Positron emission tomography scan revealed many metabolically active lesions in the lungs, spine, brain, abdominal and thoracic lymph nodes, and right globe. The patient underwent fluoroscopic-guided biopsy of a right subclavian lymph node, and a diagnosis of metastatic lung adenocarcinoma was made. The patient was treated with systemic chemotherapy, with dramatic improvement of the choroidal adenocarcinoma metastasis in her right eye.
Our case is a salutary reminder that a prognostication test result may be provided from the DecisionDx-UM test, even if the tumor tested is not a uveal melanoma. Indeed, despite its name, the commercial GEP test is marketed as a prognostic, not diagnostic, tool. The GEP results are routinely provided with a clear statement that the test is only relevant to patients with uveal melanoma and that “these results have not been validated in patients with clinical features different from those described.” Ideally, in all patients, a biopsy large enough to permit histopathological analysis should be performed before interpreting the results of the DecisionDx-UM test, as was performed in the GEP validation study.1
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