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Uveal melanoma

An Author Correction to this article was published on 17 January 2022

This article has been updated

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UMs are usually initiated by a mutation in GNAQ or GNA11, unlike cutaneous melanomas, which usually harbour a BRAF or NRAS mutation. The annual incidence in Europe and the USA is ~6 per million population per year. Risk factors include fair skin, light-coloured eyes, congenital ocular melanocytosis, ocular melanocytoma and the BAP1-tumour predisposition syndrome. Ocular treatment aims at preserving the eye and useful vision and, if possible, preventing metastases. Enucleation has largely been superseded by various forms of radiotherapy, phototherapy and local tumour resection, often administered in combination. Ocular outcomes are best with small tumours not extending close to the optic disc and/or fovea. Almost 50% of patients develop metastatic disease, which usually involves the liver, and is usually fatal within 1 year. Although UM metastases are less responsive than cutaneous melanoma to chemotherapy or immune checkpoint inhibitors, encouraging results have been reported with partial hepatectomy for solitary metastases, with percutaneous hepatic perfusion with melphalan or with tebentafusp. Better insight into tumour immunology and metabolism may lead to new treatments.

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Fig. 1: Development of UM.
Fig. 2: Low eumelanin-to-phaeomelanin ratio in a blue eye.
Fig. 3: Gαq pathway alterations.
Fig. 4: Metastatic UM in the liver.
Fig. 5: Imaging techniques in uveal melanoma.
Fig. 6: Small choroidal melanoma with orange pigment and shallow subretinal fluid in a young man.
Fig. 7: MRI of uveal melanoma.
Fig. 8: Gross appearance of UM.
Fig. 9: Cell composition in UM.
Fig. 10: Iris and ciliary body uveal melanoma.
Fig. 11: A medium-sized and a large choroidal melanoma before and after irradiation.
Fig. 12: LUMPO prognostication tool.

Change history

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Acknowledgements

The Horizon 2020 grant 667787, UM CURE, helped to build international collaborations (M.J.J. and M.-H.S.).

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Contributions

Introduction (M.J.J., C.L.S., C.M.C., M.H.A.-R., H.E.G., M.-H.S., R.D.C., R.J. and B.E.D.); Epidemiology (M.J.J., C.M.C., M.H.A.-R., H.E.G., R.N.B., R.J. and B.E.D.); Mechanisms/pathophysiology (M.J.J., C.M.C., M.H.A.-R., H.E.G., M.-H.S., R.D.C. and R.J.); Diagnosis, screening and prevention (M.J.J., C.L.S., R.D.C., R.N.B., J.A.S. and B.E.D.); Management (C.L.S., R.D.C., J.A.S. and B.E.D.); Quality of life (R.D.C. and B.E.D.); Outlook (M.J.J., C.L.S., H.E.G., R.J. and B.E.D.); Overview of the Primer (M.J.J.).

Corresponding author

Correspondence to Martine J. Jager.

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Competing interests

C.L.S. is a Member of the Scientific Advisory board of Aura Biosciences, Inc. B.E.D. is a part-time consultant for AURA Biosciences Inc., Cambridge Biosciences and Immunocore Ltd. The remaining authors declare no competing interests.

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Nature Reviews Disease Primers thanks M. A. Blasi, U. Keilholz, J. Niederkorn, J. Pe’er, U. Pfeffer, K. Sisley, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Liverpool Uveal Melanoma Prognosticator Online: www.lumpo.net

Oculonco: www.oculonco.com

Uveal Melanoma TNM Staging and Survivorship: www.ocularmelanomaonline.org

Glossary

Congenital ocular melanocytosis

A congenital periocular or ocular pigment condition.

Photopsia

Flashes of light.

Enucleation

Removal of the eye.

Dysplastic naevi

Large and irregularly shaped cutaneous moles.

Punctuated evolution

Rapid bursts of events that drive tumour fitness.

Neoantigen

Antigens arising from expressed mutations in tumour cells.

Fundus

The back of the eye.

Glaucoma

A group of eye disorders characterized by damage to the optic nerve.

Lipofuscin

An insoluble yellow-brown to dark brown pigment derived from incomplete oxidation of lipids.

Bruch’s membrane

The innermost layer of the choroid, also known as the vitreous lamina.

Toxic tumour syndrome

Radiation vasculopathy within the tumour that results in vascular obstruction and incompetence, leading to ischaemia, neovascular complications, fluid leakage, macular oedema and retinal detachment.

Rhegmatogenous retinal detachment

In which a tear in the retina leads to fluid accumulation and separation of the neurosensory retina from the underlying retinal pigment epithelium.

Snellen lines

The Snellen chart has eleven lines of block letters used to measure visual acuity.

Stereopsis

Depth perception.

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Jager, M.J., Shields, C.L., Cebulla, C.M. et al. Uveal melanoma. Nat Rev Dis Primers 6, 24 (2020). https://doi.org/10.1038/s41572-020-0158-0

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