Melanoma
Figure 2: B-scan Ultrasound Image of a Dome-shaped and Mushroom-shaped Choroidal Melanoma
between choroidal hemorrhage and CM. It is also used to localize CM prior to endoresection when there are opaque media. Both MRI and CT are essential in evaluating extrascleral, intraneural, or intracranial CM extension.
A B
B-scan ultrasound Image of a dome-shaped choroidal melanoma (a) and a mushroom-shaped choroidal melanoma (b). Note that the internal reflectivity of both tumors is moderately low (arrows), though the head of the mushroom is relatively hyperechoic.
were employed by the COMS and thus established low internal reflectivity and dome shape as the most common presenting characteristics of CM (see Figure 2a).30
PET/CT has recently been used to characterize CM. Using 18-fluorodeoxyglucose uptake, PET/CT allows in vivo measurements of metabolic activity within CM, though only relatively large CMs were found to be specific uptake value (SUV)-positive. However, this characteristic may be a biomarker for metastasis. In one study, an SUV greater than 4.0 was correlated to such currently accepted tumor high-risk factors as epithelioid cell type, high-risk vascular loops, extrascleral tumor extension and metastases.10
A recent report found
that plaque irradiation extinguished SUV positivity and therefore metabolic activity of CM.35
Intraocular Tumor Biopsy
Mushroom-shaped CM were noted in only 25 % of cases and found to be more common among larger tumors (see Figure 2b). The COMS report number 29, describing baseline echographic characteristics of 2,320 patients with medium and large tumors, found that 1,268 patients (54 %) had a tumor apex located posterior to the equator (27 % equator-posterior, 22 % posterior-equator, and only 5 % posterior).30
A-scan imaging is the most sensitive method to assess a tumor’s internal acoustic reflectivity. This characteristic has been exploited to differentiate between types of tumors and to monitor response to therapy. For example, internal reflectivity is typically high with choroidal hemangioma, moderate with metastases, and low with CM.31
Non-hemorrhagic retinal
pigment epithelial detachments and choroidal effusions are typically echolucent. During the years after radiation therapy for choroidal melanoma, A-scan typically reveals increasing internal reflectivity.
B-scan imaging has become an essential tool for measuring tumor dimensions. Commonly, CMs are measured to be larger by ultrasound compared with fundus photography. This information is vital for treatment planning (accurate plaque size selection) and for assessing response to radiotherapy. Furthermore, both dynamic A- and B-scan imaging can be used to assess a tumor’s intrinsic vascularity at diagnosis and document post-treatment reductions over time.
Ophthalmic ultrasound imaging has been recognized as an integral method for evaluating and T-staging uveal melanomas by both the American Joint Committee on Cancer and the International Union Against Cancer.20,32–34
Intraocular Radiographic Imaging
MRI and radiographic CT have limited diagnostic value for the diagnosis of CM. In special circumstances, MRI can be used to help differentiate
64
Biopsy methods have been reported to employ a fine needle or vitreous cutter. Approaches include the pars plana, cornea (for anterior segment
US OPHTHALMIC REVIEW
Use of 3D B-scan ultrasound imaging has proved invaluable for evaluating disorganized eyes (e.g. those containing occult CM). Interactive sectioning of the 3D block has allowed for post-enucleation ultrasonographic-histopathologic reconstruction. Lastly, such sectioning also allows for simultaneous longitudinal and transverse views of ophthalmic plaques in vivo, aiding intra-operative evaluations of plaque placement.25
With advances in cytogenetics, in recent years it appeared likely that biopsy would also be used to grade uveal melanomas. In the 1990s, it was discovered that uveal melanomas tend to develop several chromosomal abnormalities, the most important of which re monosomy 3, isochromosome 6p, trisomy 8, and isochromosome 8q.37 A landmark article by Prescher et al. showed monosomy 3 to correlate strongly with metastatic death, data indicating a reduction in the five-year survival from 100 to less than 50 %.38
However, these initial
expectations regarding the sensitivity and specificity of monosomy 3 tests in predicting metastatic death were found to be overly optimistic. Perhaps cytogenetic prognostication may require taking into account the complex pathway we call metastasis and that immune status, tumor size, and access to routes of egress may also play a role.
More recently, Harbour and Onken have introduced the concept of RNA-based analysis, dividing CM into ‘type 1’ and ‘type 2’ tumors. According to their study, type 1 tumors carry a low risk of metastasis, while type 2 are mostly lethal.39
These data are admittedly preliminary
and require validation by a large clinical study. In the interim, we know of no ophthalmic oncologist who would deny treatment to a type 1 CM based on genetic testing. In summary, cytogenetic classification (both monosomy 3 and RNA analysis) should be considered investigational.
Since CM can be diagnosed by clinical evaluation and testing in over 99 % of cases, one must question the need for biopsy. On the other hand, if there existed a risk-free method to retrieve a piece of tumor, such tissue would serve to confirm the clinical diagnosis as well as offering helpful histopathologic, genetic, and molecular information. Unfortunately, choroidal biopsy carries the risks (albeit small) of endophthalmitis, vitreous hemorrhage, retinal detachment, and CM dissemination. Therefore, we must weigh the risks versus such potential benefits. Most ophthalmic oncologists agree that biopsy is indicated for atypical tumors where the diagnosis is unclear, when the tumor is probably metastatic with no known primary, and when the patient requires a biopsy to proceed with treatment.36
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