What should every doctor know about ocular melanoma? - review of literature
DOI:
https://doi.org/10.12775/JEHS.2025.77.56890Keywords
melanoma malignum, ocular melanoma, uveal melanoma, iris melanoma, ciliary body melanoma, choroidal melanomaAbstract
The following paper aims to discuss melanoma located in the eye. Melanoma is a malignant tumor arising from melanocytes, in which a mutation has occurred in the DNA and pathological cells have developed. In most cases, this tumor is located on the skin exposed to sunlight, but it is also rarely located in the structures of the eye, especially in the part called uvea. It consists of the anterior and posterior parts, and in each of them the process of carcinogenesis can occur. The disease can cause very non-specific symptoms, mainly pain, visual disturbances, floaters and photopsia, or exophthalmos, but almost half of the cases are asymptomatic. Treatment is complicated and depends on many factors, radiation therapy, laser therapy, local resection and enucleation are used. Most patients are diagnosed when the changes are already extensive, or metastases occur. In the case of liver metastases, the prognosis is unfavorable. For this reason, we want every doctor to pay attention to the eye symptoms reported by the patient in order to be able to recognize this disease as soon as possible and treat it effectively.
References
Cui YZ, Man XY. Biology of melanocytes in mammals. Front Cell Dev Biol. 2023 Nov 22;11:1309557.
Cichorek M, Wachulska M, Stasiewicz A, et al. Skin melanocytes: biology and development. Postepy Dermatol Alergol. 2013 Feb;30(1):30-41.
Ahmed B, Qadir MI, Ghafoor S. Malignant Melanoma: Skin Cancer-Diagnosis, Prevention, and Treatment. Crit Rev Eukaryot Gene Expr. 2020;30(4):291-297.
Ostrowski SM, Fisher DE. Biology of Melanoma. Hematol Oncol Clin North Am. 2021 Feb;35(1):29-56.
Govindarajan B, Bai X, Cohen C, et al. Malignant transformation of melanocytes to melanoma by constitutive activation of mitogen-activated protein kinase kinase (MAPKK) signaling. J Biol Chem. 2003 Mar 14;278(11):9790-5.
Uong A, Zon LI. Melanocytes in development and cancer. J Cell Physiol. 2010 Jan;222(1):38-41.
Ottaviano M, Giunta EF, Tortora M, et al. BRAF Gene and Melanoma: Back to the Future. Int J Mol Sci. 2021 Mar 27;22(7):3474.
Puckett Y, Wilson AM, Farci F, et al. Melanoma Pathology. [Updated 2024 Jul 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459367/
Situm M, Buljan M, Kolić M, et al. Melanoma--clinical, dermatoscopical, and histopathological morphological characteristics. Acta Dermatovenerol Croat. 2014;22(1):1-12. [10] Marghoob AA, Koenig K, Bittencourt FV, et al. Breslow thickness and clark level in melanoma: support for including level in pathology reports and in American Joint Committee on Cancer Staging. Cancer. 2000 Feb 1;88(3):589-95.
Owen SA, Sanders LL, Edwards LJ, et al. Identification of higher risk thin melanomas should be based on Breslow depth not Clark level IV. Cancer. 2001 Mar 1;91(5):983-91.
Wee E, Wolfe R, Mclean C, et al. The anatomic distribution of cutaneous melanoma: A detailed study of 5141 lesions. Australas J Dermatol. 2020 May;61(2):125-133.
Stanienda-Sokół K, Salwowska N, Sławińska M, et al. Primary Locations of Malignant Melanoma Lesions Depending on Patients’ Gender and Age. Asian Pac J Cancer Prev. 2017 Nov 26;18(11):3081-3086.
Stanienda-Sokół K, Salwowska N, Sławińska M, et al.. Primary Locations of Malignant Melanoma Lesions Depending on Patients’ Gender and Age. Asian Pac J Cancer Prev. 2017 Nov 26;18(11):3081-3086.
Heistein JB, Acharya U, Mukkamalla SKR. Malignant Melanoma. 2024 Feb 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–.
Davis LE, Shalin SC, Tackett AJ. Current state of melanoma diagnosis and treatment. Cancer Biol Ther. 2019;20(11):1366-1379.
Tazi K, Hathaway A, Chiuzan C, Shirai K. Survival of melanoma patients with brain metastases treated with ipilimumab and stereotactic radiosurgery. Cancer Med. 2015;4(1):1–6. [18] Reed RJ, Martin P. Variants of melanoma. Semin Cutan Med Surg. 1997 Jun;16(2):137-58. [19] Perera E, Gnaneswaran N, Jennens R, et al. Malignant Melanoma. Healthcare (Basel). 2013 Dec 20;2(1):1-19.
Long GV, Swetter SM, Menzies AM, et al. Cutaneous melanoma. Lancet. 2023 Aug 5;402(10400):485-502.
Lopes J, Rodrigues CMP, Gaspar MM, et al. Melanoma Management: From Epidemiology to Treatment and Latest Advances. Cancers (Basel). 2022 Sep 24;14(19):4652.
Rastrelli M, Tropea S, Rossi CR, et al. Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In Vivo. 2014 Nov-Dec;28(6):1005-11.
Chang AE, Karnell LH, Menck HR . The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998; 83 (8): 1664–1678.
Hu DN, Savage HE, Roberts JE. Uveal melanocytes, ocular pigment epithelium, and Müller cells in culture: in vitro toxicology. Int J Toxicol. 2002 Nov-Dec;21(6):465-72.
Banou L, Tsani Z, Arvanitogiannis K, et al. Radiotherapy in Uveal Melanoma: A Review of Ocular Complications. Curr Oncol. 2023 Jul 3;30(7):6374-6396.
Miller PE. Uvea. Slatter's Fundamentals of Veterinary Ophthalmology. 2008:203–29.
Branisteanu DC, Bogdanici CM, Branisteanu DE, et al. Uveal melanoma diagnosis and current treatment options (Review). Exp Ther Med. 2021 Dec;22(6):1428.
Maheshwari A, Finger PT. Cancers of the eye. Cancer Metastasis Rev. 2018 Dec;37(4):677-690.
Bai H, Bosch JJ, Heindl LM. Current management of uveal melanoma: A review. Clin Exp Ophthalmol. 2023 Jul;51(5):484-494.[30] Kaliki, S., Shields, C. Uveal melanoma: relatively rare but deadly cancer. Eye. 2017;31: 241–257.
Bai H, Bosch JJ, Heindl LM. Current management of uveal melanoma: A review. Clin Exp Ophthalmol. 2023 Jul;51(5):484-494.
Kaliki S, Shields CL, Shields JA. Uveal melanoma: estimating prognosis. Indian J Ophthalmol. 2015 Feb;63(2):93-102.
Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A et al, EUROCARE Working Group. Incidence of uveal melanoma in Europe. Ophthalmology 2007; 114: 2309–2315.
Kivelä T . The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Ophthalmol 2009; 93 (9): 1129–1131.
Kaliki, S., Shields, C. Uveal melanoma: relatively rare but deadly cancer. Eye 31, 241–257 (2017).
Singh AD, Turell ME, Topham AK . Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology 2011; 118 (9): 1881–1885.
Banou L, Tsani Z, Arvanitogiannis K, Pavlaki M, Dastiridou A, Androudi S. Radiotherapy in Uveal Melanoma: A Review of Ocular Complications. Curr Oncol. 2023 Jul 3;30(7):6374-6396.
Sturm RA, Larsson M. Genetics of human iris colour and patterns. Pigment Cell Melanoma Res. 2009 Oct;22(5):544-62.
Davis-Silberman N, Ashery-Padan R. Iris development in vertebrates; genetic and molecular considerations. Brain Res. 2008 Feb 4;1192:17-28.
Freddo TF. Ultrastructure of the iris. Microsc Res Tech. 1996 Apr 1;33(5):369-89.
Soh ZD, Thakur S, Majithia S, Nongpiur ME, Cheng CY. Iris and its relevance to angle closure disease: a review. Br J Ophthalmol. 2021 Jan;105(1):3-8.
Demirci H, Shields CL, Shields JA, Eagle Jr RC, Honavar SG . Diffuse iris melanoma: a report of 25 cases. Ophthalmology 2002; 109 (8): 1553–1560.
Bianciotto CG, Shields CL, Romanelli M, Romanelli-Gobbi M, Mazzuca Jr D, Green WR et al. Assessment of anterior segment tumors with ultrasound biomicroscopy versus anterior segment optical coherence tomography in 200 cases. Ophthalmology 2011; 118 (7): 1297–1302.
Li B, Xie T, Nawy S, Shen Y. The development and the genetic diseases of the ciliary body. Cell Insight. 2024 Mar 15;3(3):100162.
Tamm ER, Lütjen-Drecoll E. Ciliary body. Microsc Res Tech. 1996 Apr 1;33(5):390-439.
Delamere NA. Ciliary Body and Ciliary Epithelium. Adv Organ Biol. 2005 Jan 1;10:127-148.
Fernández-Vigo JI, Kudsieh B, Shi H, De-Pablo-Gómez-de-Liaño L, Fernández-Vigo JÁ, García-Feijóo J. Diagnostic imaging of the ciliary body: Technologies, outcomes, and future perspectives. Eur J Ophthalmol. 2022 Jan;32(1):75-88.
Fisher RF. The ciliary body in accommodation. Trans Ophthalmol Soc U K (1962). 1986;105 ( Pt 2):208-19.
Retinoinvasive amelanotic ring melanoma of the ciliary body
Lemaître, Stéphanie et al. Canadian Journal of Ophthalmology, Volume 58, Issue 5, e218 - e219.
Tigari B, Saini M, Manchanda S, Vankdoth S. Large ciliary body melanoma. BMJ Case Rep. 2021 Nov 11;14(11):e246386.
Zhang W, Kaser-Eichberger A, Fan W, et al. The structure and function of the human choroid. Ann Anat. 2024 Jun;254:152239.
Huynh E, Chandrasekera E, Bukowska D, et al. Past, Present, and Future Concepts of the Choroidal Scleral Interface Morphology on Optical Coherence Tomography. Asia Pac J Ophthalmol (Phila). 2017 Jan-Feb;6(1):94-103.
Sezer T, Altınışık M, Koytak İA, et al. The Choroid and Optical Coherence Tomography. Turk J Ophthalmol. 2016 Jan;46(1):30-37.
Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res. 2010 Mar;29(2):144-68.
Reiner A, Fitzgerald MEC, Del Mar N, et al. Neural control of choroidal blood flow. Prog Retin Eye Res. 2018 May;64:96-130.
Spaide RF. Age-related choroidal atrophy. Am J Ophthalmol. 2009 May;147(5):801-10.
Sharma D, Hamilton J. Choroidal Melanoma in an Asymptomatic Patient. CRO Journal. Published online February 10, 2023.
Soliman N, Mamdouh D, Elkordi A. Choroidal Melanoma: A Mini Review. Medicines (Basel). 2023 Jan 5;10(1):11.
Maheshwari A, Finger PT. Laser treatment for choroidal melanoma: Current concepts. Surv Ophthalmol. 2023 Mar-Apr;68(2):211-224.
Singh P, Singh A. Choroidal melanoma. Oman J Ophthalmol. 2012 Jan;5(1):3-9.
Shields CL, Kaliki S, Furuta M, et al. Diffuse versus nondiffuse small (≤ 3 MM thickness) choroidal melanoma: comparative analysis in 1,751 cases. The 2012 F. Phinizy Calhoun lecture. Retina. 2013 Oct;33(9):1763-76.
Shields CL, Manalac J, Das C, et al. Choroidal melanoma: clinical features, classification, and top 10 pseudomelanomas. Curr Opin Ophthalmol. 2014 May;25(3):177-85.
Shields CL, Shields JA, De Potter P, et al. Diffuse choroidal melanoma. Clinical features predictive of metastasis. Arch Ophthalmol. 1996 Aug;114(8):956-63.
Chao AN, Rose K, Racher H, et al. Cytogenetic Abnormalities for Predicting the Risk of Metastases in Choroidal and Ciliary Body Melanoma. Invest Ophthalmol Vis Sci. 2023 Jan 3;64(1):15.
Mishra KK, Daftari IK. Proton therapy for the management of uveal melanoma and other ocular tumors. Chin Clin Oncol. 2016 Aug;5(4):50.
Shields CL, Shields JA, Cater J et al. Plaque Radiotherapy for Uveal Melanoma: Long-term Visual Outcome in 1106 Consecutive Patients. Arch Ophthalmol. 2000 Sep;118(9):1219–1228.
Dogrusöz M, Jager MJ, Damato B. Uveal Melanoma Treatment and Prognostication. Asia Pac J Ophthalmol (Phila). 2017 Mar-Apr;6(2):186-196. doi: 10.22608/APO.201734. Erratum in: Asia Pac J Ophthalmol (Phila). 2017 May-Jun;6(3):305.
Shah SU, Shields CL, Bianciotto CG, et al. Intravitreal bevacizumab at 4-month intervals for prevention of macular edema after plaque radiotherapy of uveal melanoma. Ophthalmology 2014; 121: 269–275.
Shields CL, Kaliki S, Furuta M, et al. Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases. Retina 2012, 32, 1363–1372.
Mazzini C, Pieretti G, Vicini G, et al. Clinical Outcomes and Secondary Glaucoma after Gamma-Knife Radiosurgery and Ruthenium-106 Brachytherapy for Uveal Melanoma: A Single Institution Experience. Melanoma Res. 2021, 31, 38–48.
Violanti SS, Bononi I, Gallenga CE, et al. New Insights into Molecular Oncogenesis and Therapy of Uveal Melanoma. Cancers (Basel). 2019 May 19;11(5):694.
Kaliki S, Shields CL, Rojanaporn, D, et al Scleral Necrosis after Plaque Radiotherapy of Uveal Melanoma: A Case-Control Study. Ophthalmology 2013, 120, 1004–1011.
Perez BA, Mettu P, Vajzovic L, et al. Uveal melanoma treated with iodine-125 episcleral plaque: an analysis of dose on disease control and visual outcomes. Int J Radiat Oncol Biol Phys 2014;89:127-36.
Wang JZ, Lin V, Toumi E, et al. Development of new therapeutic options for the treatment of uveal melanoma. FEBS J. 2021 Nov;288(21):6226-6249.
Shoushtari AN, Carvajal RD. Treatment of Uveal Melanoma. Cancer Treat Res. 2016;167:281-93.
Rusňák Š, Hecová L, Kasl Z, Sobotová M, Hauer L. Therapy of uveal melanoma A Review. Cesk Slov Oftalmol. 2020 Fall;77(1):1-13. English.
Kivelä T, Suciu S, Hansson J, et al. Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma. Eur J Cancer. 2003 May;39(8):1115-20.
Koch EAT, Heppt MV, Berking C. The Current State of Systemic Therapy of Metastatic Uveal Melanoma. Am J Clin Dermatol. 2024 Sep;25(5):691-700.
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