Skip to main content
SpringerLink
Log in

Ocular Melanoma

  • Reference work entry
  • First Online:
Melanoma

  • 839 Accesses

Abstract

Approximately 5% of all melanomas arise in the eye. Of these ocular melanomas, about 97% are of uveal origin and 3% are conjunctival. Uveal and conjunctival melanomas are biologically and clinically distinct diseases. Uveal melanomas are mostly initiated by GNAQ and GNA11 mutations and progress via SF3B1, EIF1AX, and BAP1 mutations, the latter greatly enhancing metastatic potential. Conjunctival melanomas are biologically similar to cutaneous melanomas, with common mutations of BRAF or NRAS as initiating mutations. The first choice of treatment for primary uveal melanomas is radiotherapy in most centers, whereas conjunctival melanomas are treated by excision with adjunctive radiotherapy and/or topical chemotherapy. With uveal melanomas, the prognosis for survival is mostly based on genetic studies, whereas with conjunctival melanomas tumor size and location are more predictive. There currently is no effective treatment for metastatic uveal melanoma, whereas conjunctival melanomas, like cutaneous melanomas, can be treated with targeted therapy and/or immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 799.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Al-Jamal RT, Kivela T (2011) Prognostic associations of insulin-like growth factor-1 receptor in primary uveal melanoma. Can J Ophthalmol 46(6):471–476

    Article  PubMed  Google Scholar 

  • All-Ericsson C, Girnita L, Seregard S, Bartolazzi A, Jager MJ, Larsson O (2002) Insulin-like growth factor-1 receptor in uveal melanoma: a predictor for metastatic disease and a potential therapeutic target. Invest Ophthalmol Vis Sci 43(1):1–8

    PubMed  Google Scholar 

  • Augsburger JJ, Correa ZM, Trichopoulos N (2011) Surveillance testing for metastasis from primary uveal melanoma and effect on patient survival. Am J Ophthalmol 152(1):5–9 e1

    Article  PubMed  Google Scholar 

  • Aziz HA, Gastman BR, Singh AD (2015) Management of conjunctival melanoma: critical assessment of sentinel lymph node biopsy. Ocul Oncol Pathol 1(4):266–273

    Article  PubMed  PubMed Central  Google Scholar 

  • Blum ES, Yang J, Komatsubara KM, Carvajal RD (2016) Clinical management of uveal and conjunctival melanoma. Oncology (Williston Park) 30(1):29–32, 34–43, 48.

    Google Scholar 

  • Callejo SA, Dopierala J, Coupland SE, Damato B (2011) Sudden growth of a choroidal melanoma and multiplex ligation-dependent probe amplification findings suggesting late transformation to monosomy 3 type. Arch Ophthalmol 129(7):958–960

    Article  PubMed  Google Scholar 

  • Chattopadhyay C, Kim DW, Gombos DS, Oba J, Qin Y, Williams MD, Esmaeli B, Grimm EA, Wargo JA, Woodman SE, Patel SP (2016) Uveal melanoma: from diagnosis to treatment and the science in between. Cancer 122(15):2299–2312

    Article  PubMed  Google Scholar 

  • Collaborative Ocular Melanoma Study, G (2001) Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the Collaborative Ocular Melanoma Study (COMS): COMS report no. 15. Arch Ophthalmol 119(5):670–676

    Article  Google Scholar 

  • Collaborative Ocular Melanoma Study, G (2006) The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol 124(12):1684–1693

    Article  Google Scholar 

  • Coupland SE, Campbell I, Damato B (2008) Routes of extraocular extension of uveal melanoma: risk factors and influence on survival probability. Ophthalmology 115(10):1778–1785

    Article  PubMed  Google Scholar 

  • Coupland SE, Lake SL, Zeschnigk M, Damato BE (2013) Molecular pathology of uveal melanoma. Eye (Lond) 27(2):230–242

    Article  CAS  Google Scholar 

  • de la Cruz PO Jr, Specht CS, McLean IW (1990) Lymphocytic infiltration in uveal malignant melanoma. Cancer 65(1):112–115

    Article  PubMed  Google Scholar 

  • Damato B (2001) Detection of uveal melanoma by optometrists in the United Kingdom. Ophthalmic Physiol Opt 21(4):268–271

    Article  CAS  PubMed  Google Scholar 

  • Damato B (2007) Legacy of the collaborative ocular melanoma study. Arch Ophthalmol 125(7):966–968

    Article  PubMed  Google Scholar 

  • Damato B (2008) Choroidal melanoma endoresection, dandelions and allegory-based medicine. Br J Ophthalmol 92(8):1013–1014

    Article  PubMed  Google Scholar 

  • Damato B, Coupland SE (2008a) Clinical mapping of conjunctival melanomas. Br J Ophthalmol 92(11):1545–1549

    Article  CAS  PubMed  Google Scholar 

  • Damato B, Coupland SE (2008b) Conjunctival melanoma and melanosis: a reappraisal of terminology, classification and staging. Clin Experiment Ophthalmol 36(8):786–795

    Article  PubMed  Google Scholar 

  • Damato B, Coupland SE (2009a) An audit of conjunctival melanoma treatment in Liverpool. Eye (Lond) 23(4):801–809

    Article  CAS  Google Scholar 

  • Damato B, Coupland SE (2009b) A reappraisal of the significance of largest basal diameter of posterior uveal melanoma. Eye (Lond) 23(12):2152–2160; quiz 2161–2152.

    Article  CAS  PubMed  Google Scholar 

  • Damato BE, Coupland SE (2012) Differences in uveal melanomas between men and women from the British Isles. Eye (Lond) 26(2):292–299

    Article  CAS  Google Scholar 

  • Damato B, Heimann H (2013) Personalized treatment of uveal melanoma. Eye (Lond) 27(2):172–179

    Article  CAS  Google Scholar 

  • Damato B, Lecuona K (2004) Conservation of eyes with choroidal melanoma by a multimodality approach to treatment: an audit of 1632 patients. Ophthalmology 111(5):977–983

    Article  PubMed  Google Scholar 

  • Damato B, Duke C, Coupland SE, Hiscott P, Smith PA, Campbell I, Douglas A, Howard P (2007) Cytogenetics of uveal melanoma: a 7-year clinical experience. Ophthalmology 114(10):1925–1931

    Article  PubMed  Google Scholar 

  • Damato B, Dopierala JA, Coupland SE (2010) Genotypic profiling of 452 choroidal melanomas with multiplex ligation-dependent probe amplification. Clin Cancer Res 16(24):6083–6092

    Article  CAS  PubMed  Google Scholar 

  • Damato B, Eleuteri A, Taktak AF, Coupland SE (2011) Estimating prognosis for survival after treatment of choroidal melanoma. Prog Retin Eye Res 30(5):285–295

    Article  PubMed  Google Scholar 

  • Damato BE, Groenewald C, Foulds WS (2013) Surgical resection of choroidal melanoma. In: Ryan SJ (ed) Retina, vol 3. Elsevier, London, pp 2298–2306

    Chapter  Google Scholar 

  • Decatur CL, Ong E, Garg N, Anbunathan H, Bowcock AM, Field MG, Harbour JW (2016) Driver mutations in uveal melanoma: associations with gene expression profile and patient outcomes. JAMA Ophthalmol 134(7):728–733

    Article  PubMed  PubMed Central  Google Scholar 

  • De Paris SW, Taktak A, Eleuteri A, Enanoria W, Heimann H, Coupland SE, Damato B (2016) External validation of the liverpool uveal melanoma prognosticator online. Invest Ophthalmol Vis Sci 57(14):6116–6122

    Article  Google Scholar 

  • Eleuteri A, Damato B, Coupland SE, Taktak AFG (2012) Enhancing survival prognostication in patients with choroidal melanoma by integrating pathologic, clinical and genetic predictors of metastasis. IJBET 8:18–35

    Article  Google Scholar 

  • Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R (2005) The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell 122(6):835–847

    Article  CAS  PubMed  Google Scholar 

  • Field MG, Durante MA, Decatur CL, Tarlan B, Oelschlager KM, Stone JF, Kuznetsov J, Bowcock AM, Kurtenbach S, Harbour JW (2016) Epigenetic reprogramming and aberrant expression of PRAME are associated with increased metastatic risk in Class 1 and Class 2 uveal melanomas. Oncotarget 7(37):59209–59219

    Google Scholar 

  • Goh AY, Layton CJ (2016) Evolving systemic targeted therapy strategies in uveal melanoma and implications for ophthalmic management: a review. Clin Experiment Ophthalmol 44(6):509–519

    Article  PubMed  Google Scholar 

  • Gomez D, Wetherill C, Cheong J, Jones L, Marshall E, Damato B, Coupland SE, Ghaneh P, Poston GJ, Malik HZ, Fenwick SW (2014) The Liverpool uveal melanoma liver metastases pathway: outcome following liver resection. J Surg Oncol 109(6):542–547

    Article  CAS  PubMed  Google Scholar 

  • Griewank KG, Westekemper H, Murali R, Mach M, Schilling B, Wiesner T, Schimming T, Livingstone E, Sucker A, Grabellus F, Metz C, Susskind D, Hillen U, Speicher MR, Woodman SE, Steuhl KP, Schadendorf D (2013) Conjunctival melanomas harbor BRAF and NRAS mutations and copy number changes similar to cutaneous and mucosal melanomas. Clin Cancer Res 19(12):3143–3152

    Article  CAS  PubMed  Google Scholar 

  • Grixti A, Angi M, Damato BE, Jmor F, Konstantinidis L, Groenewald C, Heimann H (2014) Vitreoretinal surgery for complications of choroidal tumor biopsy. Ophthalmology 121(12):2482–2488

    Article  PubMed  Google Scholar 

  • Harbour JW, Roberson ED, Anbunathan H, Onken MD, Worley LA, Bowcock AM (2013) Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 45(2):133–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussain RN, Kalirai H, Groenewald C, Kacperek A, Errington RD, Coupland SE, Heimann H, Damato B. (2016) Prognostic Biopsy of Choroidal Melanoma after Proton Beam Radiation Therapy. Ophthalmology 123 (10):2264–5

    Article  PubMed  Google Scholar 

  • Hawkins BS, G. Collaborative Ocular Melanoma Study (2004) The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma: IV. Ten-year mortality findings and prognostic factors. COMS report number 24. Am J Ophthalmol 138(6):936–951

    Article  PubMed  Google Scholar 

  • Henriquez F, Janssen C, Kemp EG, Roberts F (2007) The T1799A BRAF mutation is present in iris melanoma. Invest Ophthalmol Vis Sci 48(11):4897–4900

    Article  PubMed  Google Scholar 

  • Hoglund M, Gisselsson D, Hansen GB, White VA, Sall T, Mitelman F, Horsman D (2004) Dissecting karyotypic patterns in malignant melanomas: temporal clustering of losses and gains in melanoma karyotypic evolution. Int J Cancer 108(1):57–65

    Article  PubMed  CAS  Google Scholar 

  • Kalirai H, Dodson A, Faqir S, Damato BE, Coupland SE (2014) Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing. Br J Cancer 111(7):1373–1380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim IK, Lane AM, Gragoudas ES (2010) Survival in patients with presymptomatic diagnosis of metastatic uveal melanoma. Arch Ophthalmol 128(7):871–875

    Article  PubMed  Google Scholar 

  • Kivela T, Makitie T, Al-Jamal RT, Toivonen P (2004) Microvascular loops and networks in uveal melanoma. Can J Ophthalmol 39(4):409–421

    Article  PubMed  Google Scholar 

  • Kivela TT, Piperno-Neumann S, Desjardins L, Schmittel A, Bechrakis N, Midena E, Leyvraz S, Zografos L, Grange JD, Ract-Madoux G, Marshall E, Damato B, Eskelin S (2016) Validation of a prognostic staging for metastatic uveal melanoma. A Collaborative Study of the European Ophthalmic Oncology Group. Am J Ophthalmol 168:217–226

    Article  PubMed  Google Scholar 

  • Krishna Y, Kalirai H, Thornton S, Damato BE, Heimann H, Coupland SE (2016) Genetic findings in treatment-naive and proton-beam-radiated iris melanomas. Br J Ophthalmol 100(7):1012–1016

    Article  PubMed  Google Scholar 

  • Kujala E, Damato B, Coupland SE, Desjardins L, Bechrakis NE, Grange JD, Kivela T (2013) Staging of ciliary body and choroidal melanomas based on anatomic extent. J Clin Oncol 31(22):2825–2831

    Article  PubMed  Google Scholar 

  • Larsen AC (2016) Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile. Acta Ophthalmol 94 Thesis 1:1–27

    Article  PubMed  CAS  Google Scholar 

  • Larsen AC, Dahl C, Dahmcke CM, Lade-Keller J, Siersma VD, Toft PB, Coupland SE, Prause JU, Guldberg P, Heegaard S (2016) BRAF mutations in conjunctival melanoma: investigation of incidence, clinicopathological features, prognosis and paired premalignant lesions. Acta Ophthalmol 94(5):463–470

    Article  CAS  PubMed  Google Scholar 

  • Makitie T, Summanen P, Tarkkanen A, Kivela T (1999) Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma. Invest Ophthalmol Vis Sci 40(11):2471–2480

    CAS  PubMed  Google Scholar 

  • Makitie T, Summanen P, Tarkkanen A, Kivela T (2001) Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma. Invest Ophthalmol Vis Sci 42(7):1414–1421

    CAS  PubMed  Google Scholar 

  • Manschot WA, Lee WR, van Strik R (1995) Uveal melanoma: updated considerations on current management modalities. Int Ophthalmol 19(4):203–209

    Article  PubMed  Google Scholar 

  • Marshall E, Romaniuk C, Ghaneh P, Wong H, McKay M, Chopra M, Coupland SE, Damato BE (2013) MRI in the detection of hepatic metastases from high-risk uveal melanoma: a prospective study in 188 patients. Br J Ophthalmol 97(2):159–163

    Article  PubMed  Google Scholar 

  • Missotten GS, Keijser S, De Keizer RJ, De Wolff-Rouendaal D (2005) Conjunctival melanoma in the Netherlands: a nationwide study. Invest Ophthalmol Vis Sci 46(1):75–82

    Article  PubMed  Google Scholar 

  • Moore AR, Ceraudo E, Sher JJ, Guan Y, Shoushtari AN, Chang MT, Zhang JQ, Walczak EG, Kazmi MA, Taylor BS, Huber T, Chi P, Sakmar TP, Chen Y (2016) Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma. Nat Genet 48(6):675–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nathan P, Cohen V, Coupland S, Curtis K, Damato B, Evans J, Fenwick S, Kirkpatrick L, Li O, Marshall E, McGuirk K, Ottensmeier C, Pearce N, Salvi S, Stedman B, Szlosarek P, Turnbull N (2015) Uveal melanoma UK national guidelines. Eur J Cancer

    Google Scholar 

  • Oliva M, Rullan AJ, Piulats JM (2016) Uveal melanoma as a target for immune-therapy. Ann Transl Med 4(9):172

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Onken MD, Worley LA, Ehlers JP, Harbour JW (2004) Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Cancer Res 64(20):7205–7209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ophthalmic Oncology Task, F (2016) Local recurrence significantly increases the risk of metastatic uveal melanoma. Ophthalmology 123(1):86–91

    Article  Google Scholar 

  • Parrella P, Sidransky D, Merbs SL (1999) Allelotype of posterior uveal melanoma: implications for a bifurcated tumor progression pathway. Cancer Res 59(13):3032–3037

    CAS  PubMed  Google Scholar 

  • Raja V, Russo A, Coupland S, Groenewald C, Damato B (2011) Extraocular seeding of choroidal melanoma after a transretinal biopsy with a 25-gauge vitrector. Retin Cases Brief Rep 5(3):194–196

    Article  PubMed  Google Scholar 

  • Sellam A, Desjardins L, Barnhill R, Plancher C, Asselain B, Savignoni A, Pierron G, Cassoux N (2016) Fine needle aspiration biopsy in uveal melanoma: technique, complications, and outcomes. Am J Ophthalmol 162(28–34):e21

    Google Scholar 

  • Sen J, Groenewald C, Hiscott PS, Smith PA, Damato BE (2006) Transretinal choroidal tumor biopsy with a 25-gauge vitrector. Ophthalmology 113(6):1028–1031

    Article  PubMed  Google Scholar 

  • Shah CP, Weis E, Lajous M, Shields JA, Shields CL (2005) Intermittent and chronic ultraviolet light exposure and uveal melanoma: a meta-analysis. Ophthalmology 112(9):1599–1607

    Article  PubMed  Google Scholar 

  • Shain AH, Bastian BC (2016) From melanocytes to melanomas. Nat Rev Cancer 16(6):345–358

    Article  CAS  PubMed  Google Scholar 

  • Sheng X, Li S, Chi Z, Si L, Cui C, Mao L, Lian B, Tang B, Wang X, Yan X, Kong Y, Dai J, Guo J (2015) Prognostic factors for conjunctival melanoma: a study in ethnic Chinese patients. Br J Ophthalmol 99(7):990–996

    Article  PubMed  Google Scholar 

  • Shields CL, Shields JA, Gunduz K, Cater J, Mercado GV, Gross N, Lally B (2000) Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Arch Ophthalmol 118(11):1497–1507

    Article  CAS  PubMed  Google Scholar 

  • Stannard C, Sauerwein W, Maree G, Lecuona K (2013) Radiotherapy for ocular tumours. Eye (Lond) 27(2):119–127

    Article  CAS  Google Scholar 

  • Tschentscher F, Husing J, Holter T, Kruse E, Dresen IG, Jockel KH, Anastassiou G, Schilling H, Bornfeld N, Horsthemke B, Lohmann DR, Zeschnigk M (2003) Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. Cancer Res 63(10):2578–2584

    CAS  PubMed  Google Scholar 

  • Tuomaala S, Eskelin S, Tarkkanen A, Kivela T (2002) Population-based assessment of clinical characteristics predicting outcome of conjunctival melanoma in whites. Invest Ophthalmol Vis Sci 43(11):3399–3408

    PubMed  Google Scholar 

  • van Essen TH, van Pelt SI, Versluis M, Bronkhorst IH, van Duinen SG, Marinkovic M, Kroes WG, Ruivenkamp CA, Shukla S, de Klein A, Kilic E, Harbour JW, Luyten GP, van der Velden PA, Verdijk RM, Jager MJ (2014) Prognostic parameters in uveal melanoma and their association with BAP1 expression. Br J Ophthalmol 98(12):1738–1743

    Article  PubMed  Google Scholar 

  • Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O’Brien JM, Simpson EM, Barsh GS, Bastian BC (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457(7229):599–602

    Article  PubMed  CAS  Google Scholar 

  • Voelter V, Schalenbourg A, Pampallona S, Peters S, Halkic N, Denys A, Goitein G, Zografos L, Leyvraz S (2008) Adjuvant intra-arterial hepatic fotemustine for high-risk uveal melanoma patients. Melanoma Res 18(3):220–224

    Article  CAS  PubMed  Google Scholar 

  • Wang A, Papneja A, Hyrcza M, Al-Habeeb A, Ghazarian D (2016) BAP1: gene of the month. J Clin Pathol 69(9):750–3

    Article  CAS  PubMed  Google Scholar 

  • Zimmerman LE, McLean IW, Foster WD (1978) Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells. Br J Ophthalmol 62(6):420–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vitreoretinal Surgery and Ocular Oncology, Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA

    Armin R. Afshar

  2. Ocular Oncology Service, Departments of Ophthalmology and Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA

    Bertil E. Damato

  3. Departments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA

    Boris C. Bastian

Authors
  1. Armin R. Afshar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bertil E. Damato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Boris C. Bastian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bertil E. Damato .

Editor information

Editors and Affiliations

  1. Department of Dermatology, Harvard/MGH Cutaneous Biology Research Center, and Melanoma Program, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David E. Fisher

  2. Departments of Dermatology and Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA

    Boris C. Bastian

Section Editor information

  1. Departments of Dermatology and Pathology, University of California, San Francisco, San Francisco, CA, USA

    Boris Bastian

  2. Auburndale, MA, USA

    Hensin Tsao

  3. Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA

    Hensin Tsao

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Afshar, A.R., Damato, B.E., Bastian, B.C. (2019). Ocular Melanoma. In: Fisher, D., Bastian, B. (eds) Melanoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7147-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-7147-9_2

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-7148-6

  • Online ISBN: 978-1-4614-7147-9

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation