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Brief Report
October 3, 2019

Intraocular Metastasis in Unilateral Multifocal Uveal Melanoma Without Melanocytosis or Germline BAP1 Mutations

Author Affiliations
  • 1Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • 2Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida
  • 3Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • 4Cizik Eye Clinic, University of Texas Health Sciences Center at Houston, Houston
  • 5Retina Consultants of Houston, Houston, Texas
  • 6Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas
JAMA Ophthalmol. Published online October 3, 2019. doi:10.1001/jamaophthalmol.2019.3941
Key Points

Question  What is the explanation for multiple uveal melanomas arising in the same eye?

Findings  In this case series, 4 patients were found to have unilateral multifocal uveal melanomas without ocular or oculodermal melanocytosis. In all cases, the initial and subsequent tumors exhibited class 2 gene expression profiles and identical driver mutations.

Meaning  Cases of unilateral multifocal uveal melanoma in the absence of melanocytosis may represent intraocular metastasis, which may be associated with increased risk for systemic metastasis.

Abstract

Importance  There has been speculation on the pathogenesis of unilateral multifocal uveal melanoma, but there remains no convincing explanation. Genetic analysis suggests that unilateral multifocal uveal melanoma may represent intraocular metastasis with increased risk of systemic metastasis.

Objective  To evaluate the pathogenesis of unilateral multifocal uveal melanoma.

Design, Setting, and Participants  This clinical case series was conducted in tertiary academic ocular oncology referral centers and included patients with unilateral multifocal uveal melanoma.

Main Outcomes and Measures  Gene expression and mutation profiling of tumor samples.

Results  Four patients (all male; age range, 54-77 years) who were diagnosed with uveal melanoma were treated with plaque brachytherapy, and subsequently developed a second discrete uveal melanoma in the same eye were included. None demonstrated ocular or oculodermal melanocytosis. All 8 tumors available for analysis exhibited class 2 gene expression profiles. In all 4 cases, the initial and subsequent tumors were available for targeted DNA sequencing and identical driver mutations were present in both tumors. Data were collected from September 2015 to August 2018.

Conclusions and Relevance  Unilateral multifocal uveal melanoma in the absence of ocular melanocytosis appears to occur preferentially in tumors with the class 2 gene expression profile and a BRCA1-associated protein 1 gene (BAP1) mutation. The presence of identical BAP1 mutations in multiple tumors in the same eye in the absence of a germline BAP1 mutation suggests intraocular metastasis rather than independent primary tumors. These findings indicate that the first site of metastasis can be within the eye itself and suggest that patients with unilateral multifocal uveal melanoma may be at increased risk of systemic metastasis.

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