Introduction
Fine-needle aspiration (FNA) biopsy of choroidal melanoma is an old diagnostic technique that is currently enjoying renewed interest. It involves inserting a small-gauge needle (25- or 27-gauge, most commonly) into an intraocular tumor via either a transcleral or transvitreal approach in order to obtain a tissue sample for diagnostic purposes.
Risks of this procedure vary with technique but include hemorrhage, seeding of the needle tract with tumor cells, retinal break, retinal detachment, infection, and vision loss.1-3 However, many questions remain regarding FNA, among them, how common are these risks, and are they justified? This article explores the risks and benefits of this diagnostic technique and describes how its risk-to-benefit ratio is changing with our evolving understanding of choroidal melanomas.
Historically, FNA biopsy was reserved for select eyes with atypical intraocular tumors, specifically for those eyes where the tumor diagnosis remains unclear and the treatment options are diverse.1 In these patients, the potential risks of the procedure, including intraocular hemorrhage and tumor seeding, are justified by the need to establish an appropriate and effective treatment plan. While the exact incidence of hemorrhage and tumor seeding is unknown, studies suggest that FNA biopsy obtains a diagnosis in up to 90% of such cases.2,3
In contrast, FNA biopsy is not usually performed on eyes with typical choroidal melanomas. In these cases, FNA biopsy provides little additional diagnostic or prognostic information beyond that obtained from the clinical exam alone, yet it still involves all of the same risks of the procedure.4
New Roles for FNA Biopsy
New molecular tests for choroidal melanoma may soon allow FNA biopsy to provide beneficial diagnostic and prognostic information in all cases of choroidal melanoma. One such test employs gene expression profiling on tumor RNA to separate choroidal melanomas into 2 groups, class I and class II. Class I tumors are associated with a low risk for metastatic disease, while class II tumors are associated with a high risk for metastatic death. Onken et al suggest that this classification system is so accurate that its negative and positive predictive power for metastatic disease is superior to any other current prognostic method.5. Another test that can provide prognostic information is cytogenetic analysis of chromosomes 3 and 8 from a tumor.6
Fine-needle biopsy will enjoy an improved risk-to-benefit ratio if it can accurately and reliably provide tumor samples for these molecular tests.
Methods to Evaluate FNA Biopsy
We now have an excellent opportunity to formally evaluate the risks and benefits of FNA biopsy. Molecular biology labs can rapidly perform RNA and cytogenetic analyses on tumor samples obtained from FNA biopsy. Surgical tools and techniques are available to help minimize the potential risks of the biopsy. Such techniques include using small-bore needles and placing the FNA biopsy site under a scleral flap in the bed of the plaque just prior to brachytherapy treatment.
Plaque brachytherapy is now well established as being comparable to enucleation in terms of patient survival7 which allows clinicians to ethically perform FNA biopsy in combination with plaque brachytherapy in order to optimize globe and vision preservation. Widespread networks of clinical centers can be readily created to permit timely data collection from a large number of patients with this rare tumor. Accurate information on the clinical history of treated choroidal melanomas is available, enabling statisticians to design a prospective study with adequate power.7
Finally, the field of medical oncology is evolving to where oncologists may soon be capable of designing effective anti-tumor regimens based on a neoplasm's molecular footprint.
Current Studies on FNA Biopsy
Currently, several FNA biopsy studies are under way, including one sponsored by Washington University School of Medicine in St. Louis. While this study is investigating whether FNA biopsy can be used in conjunction with gene expression profiling of tumor RNA to prospectively predict metastatic disease, it will also obtain accurate information on the exact risks of FNA biopsy when performed in combination with plaque brachytherapy. However, clinicians must remember that the ultimate goal for FNA biopsy is to help improve patient survival from choroidal melanoma, and all studies on FNA biopsy should be working toward this goal.
It is exciting to imagine that soon FNA biopsy might allow clinicians to treat subclinical metastatic choroidal melanoma disease using regimens based on a specific tumor's molecular biology footprint and also enable patients with benign lesions to avoid any treatments associated with high ocular morbidity.
Conclusion
While I cannot determine whether FNA biopsy is currently "worth the risk," I believe that formal studies into the risk-to-benefit ratio of FNA biopsy for choroidal melanoma are indicated and justified. It is disheartening that ocular oncology has not improved the survival rate of choroidal melanoma during the last 25 years8 and that no other reasonable prospect for improved treatment of choroidal melanoma is on the horizon. Only formal FNA biopsy studies will tell us whether FNA biopsy is worth the risk.
References
1. Augsburger JJ. Diagnostic biopsy of selected intraocular tumors. Am J Ophthalmol. 2005;140(6):1094-1095.
2. Glascow BJ, Brown HH, Zargoza AM, Foos RY. Quantitation of tumor seeding from fine needle aspiration of ocular melanomas. Am J Ophthalmol. 1988;105(5):538-546.
3. Shields JA, Shields CL, Ehya H, Eagle RC Jr, De Potter P. Fine-needle aspiration biopsy of suspected intraocular tumors. The 1992 Urwick Lecture. Ophthalmology. 1993;100(11):1677-1684.
4. Collaborative Ocular Melanoma Study Group. Accuracy of diagnosis of choroidal melanoma in the Collaborative Ocular Melanoma Study. COMS report no. 1. Arch Ophthalmol. 1990;108(9):1268-1273.
5. Onken MD, Worley LA, Ehlers JP, Harbour JW. Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res. 2004;64(20):7205-7209.
6. Damato B, Duke C, Coupland SE, Hiscott P, et al. Cytogenetics of uveal melanoma: a 7-year clinical experience. Ophthalmology. 2007;114(10):1925-1931.
7. Collaborative Ocular Melanoma Study Group. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol. 2006;124(12):1684-1693.
8. Singh AD, Topham A. Survival rates with uveal melanoma in the United States: 1973-1997. Ophthalmology. 2003;110(5):962-965.
Author Disclosure
Dr. Wirostko states that he has no financial relationship with the manufacturer of any product discussed in this article or with the manufacturer of any competing product. The writing of this manuscript is supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York.