Gene Expression Profiling as an Adjunctive Measure to Guide the Management of Indeterminate, High-Risk Choroidal Melanocytic Lesions: A Pilot Study

Abstract

Purpose: To describe our early experience with gene expression profiling (GEP) assessment for juxtafoveal, subfoveal, and peripapillary indeterminate high-risk melanocytic lesions to assist in making early treatment decisions in patients who did not feel comfortable with either close observation or definitive treatment. Methods: A prospective cohort of patients with indeterminate lesions who underwent GEP were enrolled. Nonparametric statistical analysis was utilized given the small sample size. Results: Fifteen patients were included in this series. Six (40%) were class 1A and 9 (60%) class 1B. Class 1A and 1B lesions had a median of three and four clinical risk factors, respectively (p = 0.27). There was no statistically significant difference for the largest basal diameter between the classes (p = 0.31); however, class 1B lesions were thicker than class 1A lesions (p = 0.03). None of the class 1A lesions showed definite growth or metastasis over a mean follow-up period of 17.1 ± 1.8 months from fine needle aspiration biopsy. All class 1B patients opted for plaque brachytherapy, and to date none of these patients have developed metastasis, with a mean follow-up of 18.7 ± 8.4 months. Conclusion: There may be a role for GEP assessment in high-risk, indeterminate, posteriorly located choroidal lesions to assist in treatment planning.

Small High-Risk Uveal Melanomas Have a Lower Mortality Rate

“…On this basis, it is conventional practice in many ocular oncology centers to monitor small, indeterminate uveal melanocytic tumors for months (or even years) until growth is documented [ 68 , 69 , 70 , 71 , 72 ]. Weis et al demonstrated that most of these indeterminate lesions are low-risk D3-UM [ 73 ]. Our current study supports these findings, with 73% of the small melanocytic tumors being D3; however, importantly, we demonstrate that over one quarter (i.e., 27%) of these small lesions are M3-UM, and therefore have a high metastatic risk.…”

What’s in a Name? Large Choroidal Nevus, Small Choroidal Melanoma, or Indeterminate Melanocytic Tumor

“…Although with recent innovations in imaging we are able to detect subtle changes such as orange pigmentation and subretinal fluid that were barely detectable on clinical examination, the diagnostic dilemma persists [2, 3]. The issue has become more relevant with the use of commercially available molecular prognostic tests (which have been validated only for survival prognosis) [4], as a surrogate for diagnosis of small choroidal melanomas [5-7]. For the purpose of this commentary, the complex clinical situation could be broken down to certain key components.…”

Small Choroidal Melanoma: Correlation between Clinical Characteristics and Metastatic Potential

“…Few attempts have been made to correlate growth [23] or growth “risk factors” (clinical characteristics) across various AJCC stages [24] and more specifically in small choroidal melanoma with a prognostic class (indicator for metastasis) using 2 commercially available prognostic tests, MLPA (Impact Genetics, Toronto, Canada) [25] and GEP (DecisionDx-UM; Castle Biosciences, Inc., Phoenix, AZ, USA) [26] (Table 1) [27, 28]. The limited data indicate that the growth “risk factors” such as presence of orange pigment, subretinal fluid (SRF), and lack of drusen/ retinal pigment epithelial (RPE) changes are not statistically significantly associated with metastatic potential as identified by GEP class [24, 28].…”

“…The limited data indicate that the growth “risk factors” such as presence of orange pigment, subretinal fluid (SRF), and lack of drusen/ retinal pigment epithelial (RPE) changes are not statistically significantly associated with metastatic potential as identified by GEP class [24, 28]. Relationship with tumor height seems to be conflicting between the studies [24, 27, 28]. Even documented growth, considered as a hallmark diagnostic feature of small choroidal melanoma [29-33], was not associated with the GEP class although the definition of observed growth was not specified in the study [28].…”

“…Even documented growth, considered as a hallmark diagnostic feature of small choroidal melanoma [29-33], was not associated with the GEP class although the definition of observed growth was not specified in the study [28]. Ignoring the risk factors altogether, GEP class has been tested as an adjunctive measure to guide treatment with the intent of observing indeterminate choroidal melanocytic tumors with low metastatic potential (Class 1A) and promptly treating those with moderate or high metastatic potential (Class 1B and 2) [27].…”