Article

Fine Needle Aspiration Biopsy for Uveal Melanoma

Part 1, Technique and complications

Fine Needle Aspiration Biopsy for Uveal Melanoma

Part 1, Technique and complications

AMY C. SCHEFLER, MD, FACS • PRITHVI MRUTHYUNJAYA, MD, FACS

In recent years, there has been an explosion of knowledge in the field of cancer molecular genetics. Compared to the 1980s, when the Collaborative Ocular Melanoma Study (COMS) was conceived and initiated,1 ocular oncologists are significantly more sophisticated in their understanding of which mutations lead to both the initial development and the eventual metastasis of this potentially fatal cancer.

As a result of these advances, there has been a recent rise in the number of fine needle aspiration biopsies (FNABs) performed on a routine clinical basis for uveal melanoma patients. Many authors have reported on techniques for this procedure and on the ability to successfully extrapolate useful prognostic information from these biopsies.2-6

Typically, the tissue extracted from these procedures is used for three purposes: 1) cytologic confirmation of the diagnosis; 2) genomic analysis to predict individual patient survival; and 3) research studies.

In part 1 of this review, we will review different techniques and complications associated with FNAB for uveal melanoma.

Amy C. Schefler, MD, FACS, practices with Retina Consultants of Houston and Houston Methodist Hospital in Texas. Prithvi Mruthyunjaya, MD, FACS, is associate professor of ophthalmology at the Duke University Eye Center in Durham, NC. Neither author reports any financial interests in products mentioned in this article. Dr. Schefler can be reached via e-mail at acsmd@houstonretina.com.

TRANS-SCLERAL BIOPSIES

Technique

Trans-scleral biopsy techniques have been used routinely since the initiation of early cytogenetic studies of uveal melanoma in the 1990s.7 This technique is most useful for tumors that are located anterior to the equator.

The approach requires three basic components: a needle, an optional tubing extender, and a syringe (with or without a suction control device). Regarding needle choice, most large series have reported the use of either a 23-gauge or a 25-gauge needle.

The steps of the procedure typically include the following.

    1. Transillumination is necessary for delineation of tumor margins with marking of the sclera using a sterile marking pen or indirect ophthalmoscopy, with a scleral depressor/marker for amelanotic tumors (Figure 1).

    Figure 1. Transcleral fine needle aspiration biopsy after tumor transillumination and delineation.

    2. A biopsy site is chosen based on knowledge of the location of the greatest tumor thickness (most commonly at the geographic center of the tumor).

    3. The needle is inserted into the tumor. Some surgeons perform a triangular or square-shaped partial-thickness scleral flap prior to insertion of the needle. The clinician must be aware of the needle depth relative to the tumor height and should angle the needle appropriately. For smaller tumors, sharper entry angles are used.

    4. Suction is created, and cells are extracted, either by having an assistant pull on the syringe plunger or by creating suction with a suction control device, such as the Inrad (Kentwood, MI) breast biopsy gun (Figure 2). We find the gun to be helpful in controlling the amount of suction, as well as in situations in which an experienced assistant is not available. The tubing extender is helpful in minimizing the amount of unintended movement transmitted from the assistant to the surgeon.

    Figure 2. Inrad Biopsy Gun, used for both trans-scleral and transvitreal approaches.

    5. The needle is withdrawn from the site. Some surgeons perform cryotherapy to the needle site in an attempt to eradicate any tumor cells that may be present at the biopsy site.

    6. The scleral flap is closed, if one was created.

    7. The plaque or tantalum rings are placed.

Complications

Potential complications of this procedure include: penetration of the apex of the tumor with vitreous hemorrhage and extraocular extension of tumor. Penetration of the apex of the tumor can be easily avoided with careful marking of the biopsy needle with a marking pen and accounting for approximately 1 mm of the sclera in cases in which a scleral flap is not created. When this complication occurs, the retinal break typically seals on its own, as in the case of transvitreal biopsies because the tumor acts as a buckle supporting the break.

Extrascleral extension caused by FNAB is a serious concern that has received much attention in recent years. Schefler et al reported that, in a survey of ocular oncologists at the International Society of Ocular Oncology, only four cases could be identified, and all of those patients received open biopsies and multiple procedures, had an infusion line, did not undergo plaque therapy or proton beam therapy afterward, and/or underwent vitrectomy.8

Since that report, two additional cases have been reported, and a series of six total additional cases is in preparation. Given the number of biopsies that have been performed worldwide in recent years, it is apparent that this complication is extremely rare, although possible. We recommend counseling patients to this effect.

Tissue Yield

Ensuring adequate tissue yield after a biopsy is critical for prognostication and patient satisfaction. Published rates of negative biopsies have varied from 5% to 15%.6,9 Methods for improving these rates include having a pathologist present in the operating room at the time of the procedure for an “adequacy check” ensuring that an adequate-sized needle is used and that the entire bevel tip is buried within the tumor.

TRANSVITREAL BIOPSIES

Technique

This approach is typically recommended for tumors that are located posterior to the equator and cannot be accessed directly through the sclera. Depending on the orbital anatomy of the particular patient and whether the tumor is located on the nasal side (and thus is more difficult to access due to obstruction of the surgical space by the nose), some tumors at the equator or slightly anterior to the equator will also be most easily accessed via this approach.

There are two basic approaches that can be used for transvitreal biopsies: an indirect ophthalmoscope-guided approach and a microscopic approach (Table). For surgeons who use the indirect ophthalmoscope, the procedure consists of the following steps: 1) a long 23- or 25-gauge needle is inserted through the pars plana toward the tumor with partial thickness penetration of the tumor while under indirect viewing via the indirect ophthalmoscope and a 20 D or 28 D lens; and 2) cryotherapy is applied to the needle entry/exit site for reasons outlined above.

Table. Transvitreal Biopsies: Indirect Technique vs Microscope Technique
ADVANTAGES OF INDIRECT OPHTHALMOSCOPIC APPROACH ADVANTAGES OF MICROSCOPE APPROACH
Faster Magnified view
Less expensive Upright view
No special equipment required Better sampling
  Better video/teaching capabilities
  Ability to use various instruments if needed (if trocar system is used)

For a microscope approach, the procedure consists of these steps (Figure 3).

Figure 3. Transvitreal biopsy setup using the operating microscope and a biopsy gun held by a surgical assistant.

    1. An operating microscope is used, as well as a contact or noncontact retinal viewing system, such as the BIOM, EIBOS, or contact lens viewing systems.

    2. Optionally, a 25- or 23-gauge trocar and chandelier or light pipe can be inserted.

    3. A long 23- or 25-gauge needle is inserted through the trocar or through the sclera toward the tumor with partial thickness penetration of the tumor. Some surgeons use a 23-, 25-, or 27-gauge vitrector to extract cells from the tumor, especially in cases of thin tumors.

    4. Bleeding is controlled with observation only, injection of balanced saline solution into the vitreous cavity, or diathermy inserted through a trocar. We do not recommend the placement of an infusion line because several rare cases of extraocular extension of tumor after a biopsy have been reported in cases in which infusion lines were present.

    5. The trocar is removed (if present), with optional application of cryotherapy to the needle exit site and/or closing and suturing of the trocar site.

Complications

The potential complications of this procedure include: preretinal/vitreous hemorrhage, retinal tear and/or detachment, and extraocular tumor extension. Preretinal, subretinal, and vitreous hemorrhages are very common, reported in some series to occur as often as 50% of the time.10

Retinal tear and retinal detachment are significantly more rare, as the tumor typically acts as a buckle, supporting the break created by the biopsy. Some surgeons have reported that retinal detachments are more likely to occur when regression of the tumor after plaque therapy is especially rapid, before a buckle effect takes place.

Tissue Yield

In our experience, transvitreal biopsies are more challenging technically than the trans-scleral approach. In some series, negative yield occurs in as many as 34% of transvitreal biopsies.6 Many surgeons have reported that the use of a vitrector improves the likelihood of successful tissue acquisition.

CONCLUSION

Fine needle aspiration biopsies for uveal melanoma have become common in the daily practice of ocular oncology at major centers. Complication rates are low, and tissue yield rates are currently in the 90% to 100% range, due to improvements in instrumentation and surgeon experience. Extraocular extension, the most feared complication of the procedure, is extremely rare, and most cases have been reported only in the context of vitrectomy or open biopsy or with the use of infusion lines.

Molecular genomic testing is evolving and offers patients the opportunity to access information about the likelihood of metastasis and entry into clinical trials. In the next article in this series, we will discuss the controversies surrounding the type of molecular testing that should be done and how the information should be used to guide clinical care. RP

REFERENCES

1. Diener-West M, Earle JD, Fine SL, et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18. Arch Ophthalmol. 2001;119:969-982.

2. Augsburger JJ. Diagnostic biopsy of selected intraocular tumors. Am J Ophthalmol. 2005;140:1094-1095.

3. Onken MD, Worley LA, Tuscan MD, Harbour JW. An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma. J Mol Diagn. 2010;12:461-468.

4. Shields CL, Ganguly A, Materin MA, et al. Chromosome 3 analysis of uveal melanoma using fine-needle aspiration biopsy at the time of plaque radiotherapy in 140 consecutive cases: the Deborah Iverson, MD, Lectureship. Arch Ophthalmol. 2007;125:1017-1024.

5. Midena E, Bonaldi L, Parrozzani R, Radin PP, Boccassini B, Vujosevic S. In vivo monosomy 3 detection of posterior uveal melanoma: 3-year follow-up. Graefes Arch Clin Exp Ophthalmol. 2008;246:609-614.

6. Chang MY, McCannel TA. Comparison of uveal melanoma cytopathologic sample retrieval in trans-scleral versus vitrectomy-assisted transvitreal fine needle aspiration biopsy. Br J Ophthalmol. 2014;98:1654-1658.

7. Prescher G, Bornfeld N, Becher R. Two subclones in a case of uveal melanoma. Relevance of monosomy 3 and multiplication of chromosome 8q. Cancer Genet Cytogenet. 1994;77:144-146.

8. Schefler AC, Gologorsky D, Marr BP, Shields CL, Zeolite I, Abramson DH. Extraocular extension of uveal melanoma after fine-needle aspiration, vitrectomy, and open biopsy. JAMA Ophthalmol. 2013;131:1220-1224.

9. Medina CA, Biscotti CV, Singh N, Singh AD. Diagnostic cytologic features of uveal melanoma. Ophthalmology. 2015 May 23. [Epub ahead of print]

10. Klufas MA, Itty S, McCannel CA, Glasgow BJ, Moreno C, McCannel TA. Variable results for uveal melanoma-specific gene expression profile prognostic test in choroidal metastasis. JAMA Ophthalmol. 2015 Jun 18. [Epub ahead of print]