What is the role of biopsy in the workup of choroidal melanoma?

Updated: Feb 18, 2020
  • Author: Enrique Garcia-Valenzuela, MD, PhD; Chief Editor: Andrew A Dahl, MD, FACS  more...
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Fine-needle biopsy and incisional biopsy are not usually required but may be helpful in difficult diagnostic cases, particularly for distinguishing amelanotic melanomas from metastatic tumors, and in situations where the results of other ancillary tests are equivocal. Fine-needle biopsy is increasingly being performed for prognostic purposes.

In experienced hands, both biopsy techniques have an accuracy of more than 95% in tumors larger than 3 mm. Incisional biopsy is more invasive and may have more associated complications, but it has less false-negative and false-positive results. The most common complication for tumor biopsy is intralesional or perilesional hemorrhage.

Risk of spread of cancerous cells in the case of fine-needle biopsy is small for choroidal melanoma (unlike retinoblastoma). Follow biopsy with prompt treatment to prevent extrascleral extension.

Genetic analysis and karyotyping of biopsy specimens have gained increasing attention. Chromosome 3 monosomy and/or amplification of chromosome 8q in the choroidal tumor has been shown to be associated with a significantly greater risk of developing metastases. [4]

Loss of chromosome 1p and gain of chromosome 6p have been linked with a better prognosis.

Specific genetic errors are progressively better understood, such as inactivation of BAP1 (BRCA-associated protein 1), which is associated with metastatic spread, often through monosomy 3.

Gene expression profiling (GEP) outperforms monosomy 3 at predicting metastatic spread. This test is commercially available through DecisionDx-UM (Castle Biosciences).

Analysis of multiple gene expression has led to the subdivision of uveal melanomas into 2 types. Around half of ocular melanomas are class 1, which carry a low risk of metastasis. The other half are class 2, which have a different gene expression pattern, frequently showing chromosome 3 monosomy, and carry a high risk of metastasis. Class 2 tumors have been associated with previously known metastatic risk prognostic features, including ciliary body involvement, larger basal diameter, older age, presence of exudative retinal detachment, and increased tumor height.

Class 1 tumors are further subdivided into class 1a (lowest metastatic risk: low expression of genes CDH1 and RAB31) and class 1b (moderate metastatic risk: high expression of genes CDH1 and RAB31). Class 1b tumors tend to occur in younger individuals and have a posterior location compared with class 1a tumors.

Onken et al, as part of the Collaborative Ocular Oncology Group, evaluated the prognostic performance of a 15-gene expression profiling assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. Tumor tissue was classified by GEP as class 1 or class 2. Patients were managed for their primary tumor and monitored for metastasis. The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Metastasis was detected in 3 (1.1%) class 1 cases and 44 (25.9%) class 2 cases. GEP class had a stronger independent association with metastasis than any other prognostic factor, including tumor size. [5]

This GEP assay can provide prognostic information in eyes with malignant melanoma that have been enucleated.

However, because no effective treatment is available for metastatic disease, the clinical impact of performing routine biopsies on choroidal melanoma is unclear at this point.

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