Possibilities for Identifying the Malignant Vasculature of Choroidal Melanoma

Choroidal melanoma is the most common and life-threatening intraocular malignant neoplasm affecting the eye choroid in about 90 % of cases. The incidence varies from 0.7 to 1.1 per 100,000 of the population. This category of malignant neoplasms is highly aggressive in terms of local distribution, the occurrence of loco-regional and distant metastases. According to various authors, the frequency of metastasis reaches up to 50 %, the risks of metastatic disease depend on the size of the tumor, the duration of observation, clinical and pathomorphological characteristics of the choroidal melanoma and genetic factors. This article provides a detailed literature review on the developmental aspects and growth dynamics of choroidal melanoma from the point of view of neoangiogenesis and the phenomenon of vasculogenic mimicry, and the possibilities of instrumental diagnostics for determining the malignant vasculature of a tumor. The relevance of studying this issue is determined by the peculiarities of the origin of choroidal melanoma, which can occur both de novo and due to malignant transformation from nevus cells and the critical point for it is a tumor thickness of more than 2 mm, at in which the the process of neoangiogenesis starts. This review details the role of various methods of instrumental diagnostics, such as doppler ultrasound imaging to determine the presence or absence of blood flow in the tumor and its blood flow characteristics, angiography using contrasts: fluorescein and indocyanine green angiography, and optical coherent tomography—angiography to identify the malignant vasculature and evaluation of tumor angioarchitectonics. It has been shown that in the diagnosis of especially small choroid melanomas, which are of significant diagnostic complexity, a multimodal approach using the above research methods is important. There is no doubt that these instrumental technologies aimed to identify the malignant vasculature of choroidal melanoma play a large role not only in diagnosis, but also are of considerable practical interest in planning treatment, in assessing its effectiveness, and also in predicting the risks of metastatic process development.

1. Важенин А.В., Панова И.Е. Избранные вопросы офтальмоонкологии. М.: Изд-во РАМН; 2006. [Vazhenin A.V., Panova I.E. Selected issues of ophthalmology. Moscow: Publishing house of RAMS; 2006 (In Russ.)].

2. Бровкина А.Ф. Офтальмоонкология. М.: Медицина; 2002. [Brovkina A.F. Ophthalmic oncology. Moscow: Medicine; 2002 (In Russ.)].

3. Shields C.L., Kaliki S., Furuta M., Mashayekhi A. et al. Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases. Retina. 2012;32(7):1363–1372. DOI: 10.1097/IAE.0b013e31824d09a8

4. Бровкина А.Ф., Панова И.Е., Саакян С.В. Офтальмоонкология: новое за последние два десятилетия. Вестник офтальмологии.2014;130(6):13–19. [Brovkina A.F., Panova I.E., Saakyan S.V. Ophthalmooncology: new over the past two decades. Annales of Ophthalmology = Vestnik oftal’mologii. 2014;130(6):13–9 (In Russ.)].

5. Саакян С.В., Ширина Т.В. Анализ метастазирования и выживаемости больных увеальной меланомой. Опухоли головы и шеи. 2012;2:53–56. [Saakyan S.V., Shirina T.V. Analysis of metastasis and survival of patients with uveal melanoma. Tumors of the head and neck = Opukholi golovy i shei. 2012;2:53–56 (In Russ.)].

6. Damato B., Eleuteri A., Taktak A.F., Coupland S.E. Estimating prognosis for survival after treatment of choroidal melanoma. Progress in retinal and eye research. 2011;30(5):285–295. DOI: 10.1016/j.preteyeres.2011.05.003

7. Зиангирова Г. Г., Лихванцева В. Г. Опухоли сосудистого тракта глаза. М.: Последнее слово; 2003. [Ziangirova G.G., Likhvantseva V.G. Tumors of the vascular tract of the eye. Moscow: Last word; 2003 (In Russ.)].

8. Пальцев М.А., Аничков Н.М. Атлас патологии опухолей человека. М.: Медицина; 2005. [Pal’tsev M.A., Anichkov N.M. Atlas of the pathology of human tumors. Moscow: Medicine; 2005 (In Russ.)].

9. Folberg R., Hendrix M.J.C., Maniotis A.J. Vasculogenic mimicry and tumor angiogenesis. The American journal of pathology.2000;156(2):361–381. DOI: 10.1016/ S0002-9440(10)64739-6

10. Зербино Д.Д., Дмитрук И.М. Внутриопухолевая пролиферация сосудов. Архив патологии.1983;45(4):80–83. [Zerbino D.D., Dmitruk I.M. Intratumoral proliferation of blood vessels. Pathology Archive = Arhiv patologii. 1983;45(4):80–83 (In Russ.)].

11. Карамышева А.Ф. Ангиогенез опухоли: механизмы, новые подходы к терапии. Канцерогенез. Под ред. Д.Г. Заридзе. М.; 2000:298–309 [Karamysheva A.F. Tumor angiogenesis: mechanisms, new approaches to therapy. Carcinogenesis. Ed. D.G. Zaridze. Moscow; 2000:298–309 (In Russ.)].

12. Лихтенштейн А.В., Шапот В.С. Опухолевый рост: ткани, клетки, молекулы. Патологическая физиология.1998;3:25–44. [Lichtenstein A.V., Shapot V.S. Tumor growth: tissues, cells, molecules. Pathological physiology = Patologicheskaja fiziologija. 1998;3:25–44 (In Russ.)].

13. Копнин Б.П. Неопластическая клетка: основные свойства и механизмы их возникновения. Практическая онкология. 2002;3(4):229–235. [Kopnin B.P. Neoplastic cell: basic properties and mechanisms of their occurrence. Practical oncology = Prakticheskaja onkologija. 2002;3(4):229–235 (In Russ.)].

14. Степанова Е.В., Барышников А.Ю., Личиницер М.Р. Оценка ангиогенеза опухолей человека. Успехи современной биологии. 2000;120(6):599. [Stepanova E.V., Baryshnikov A.Yu., Lichinitser M.R. Evaluation of the angiogenesis of human tumors. Advances in Modern Biology = Uspehi sovremennoj biologii. 2000;120(6):599 (In Russ.)].

15. Folkman J. Tumor angiogenesis. Advances in cancer research. Academic Press. 1974;(19):331–358. DOI: 10.1016/S0065-230X(08)60058-5

16. Folkman J. Angiogenesis inhibitors generated by tumors. Molecular medicine. 1995;1(2):120–122. DOI: 10.1007/BF03401559

17. Folkman J. Tumors Are Angiogenesis Dependent? Journal of the National Cancer Institute: JNCI. 1990;82(1):4.

18. Владимирская Е.Б. Биологические основы противоопухолевой терапии. М.: Агат-Мед; 2001:1. [Vladimirskaya E.B. Biological basis of antitumor therapy. Moscow: Agat-Med; 2001:1 (In Russ.)].

19. Мертвецов Н.П., Стефанович Л.Е. Ангиогенин и механизм ангиогенеза. Новосибирск: Наука; 1997:78. [Mertvetsov N.P., Stefanovich L.E. Angiogenin and the mechanism of angiogenesis. Novosibirsk: Nauka; 1997:78 (In Russ.)].

20. Folkman J., Haudenschild C. Angiogenesis in vitro. Nature. 1980;288(551):6. DOI: 10.1038/288551a0

21. Thompson W.D., Shiach K.J., Fraser R.A., Mcintosh L.C., et al. Tumors acquire their vasculature by vessel incorporation, not vessel ingrowth. J. Pathol. 1987;(151):323–332. DOI: 10.1002/path.1711510413

22. Shubik P., Warren B.A. Additional literature on ‘vasculogenic mimicry’ not cited. Am. J. Pathol. 2000;156:736. DOI: 10.1016/S0002-9440(10)64778-5

23. Hendrix M.J., Seftor E.A., Meltzer P.S., et al. Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry. Proc. Natl. Acad. Sci. U. S. A. 2001;98:8018–8023. DOI: 10.1073/pnas.131209798

24. McDonald D.M., Lance Munn, Rakesh K.J. Vasculogenic Mimicry: How Convincing, How Novel, and How Significant? American Journal of Pathology. 2000;156(2):383–388. DOI: 10.1016/S0002-9440(10)64740-2

25. Mueller A.J., Bartsch D.U., Folberg R., et al. Imaging the microvasculature of choroidal melanomas with confocal indocyanine green scanning laser ophthalmoscopy. Arch Ophthalmol. 1998;116:31–33. DOI: 10.1001/archopht.116.1.31

26. Mueller A.J., Freeman W.R., Folberg R., et al. Evaluation of microvascularization pattern visibility in human choroidal melanomas: comparison of confocal fluorescein with indocyanine green angiography. Graefes Arch Clin Exp Ophthalmol. 1999;237:448–456. DOI: 10.1007/s004170050260

27. Schneider U., Gelisken F., Inhoffen W., Kreissig I. Indocyanine-green videoangiography of malignant melanomas of the choroid using the scanning laser ophthalmoscope. Ger J Ophthalmol. 1996;5:6–11.

28. Alitalo K., Carmeliet P. Molecular mechanisms of lymphangiogenesis in health and disease.Cancer Cell. 2002;l:219–227. DOI: 10.1016/S1535-6108(02)00051-X

29. Самкович Е.В., Мелихова М.В., Панова И.Е. Комплексная инструментальная диагностика «малых» новообразований хориоидеи. Современные технологии в офтальмологии. 2019;6(31):104–107. [Samkovich E.V., Melikhova M.V., Panova I.E. Complex instrumental diagnostics of “small” neoplasms of the choroid. Modern technologies in ophthalmology = Sovremennye tehnologii v oftal’mologii. 2019;6(31):104–107 (In Russ.)].

30. Амирян А.Г., Бровкина А.Ф., Лелюк В.Г. Ангиоархитектоника увеальных меланом. Офтальмология. 2005;2(1):37–40. [Amiryan A.G., Brovkina A.F., Lelyuk V.G. Angioarchitectonics of uveal melanomas. Ophthalmology = Oftal’mologija. 2005;2(1):37–40 (In Russ.)].

31. Катькова Е.А. Диагностический ультразвук. Офтальмология: практическое руководство. М.: ООО «Фирма СТРОМ»: 2002:122. [Katkova E.A. Diagnostic ultrasound. Ophthalmology: a practical guide. Moscow: LLC “Firm STROM”; 2002:122 (In Russ.)].

32. Лелюк В.Г., Бровкина А.Ф., Амирян А.Г. Комплексное ультразвуковое исследование при увеальной меланоме. Эхография. 2004;5(2):166. [Lelyuk V.G., Brovkina A.F., Amiryan A.G. Integrated ultrasound examination for uveal melanoma. Sonography = Jehografija. 2004;5(2):166 (In Russ.)].

33. Яровой А.А., Линник Л.Ф., Семикова Т.С., Булгакова Е.С. Малые меланомы хориоидеи: особенности клиники и выбора метода лечения. Новое в офтальмологии. 2004;2:28–37. [Yarovoy A.A., Linnik L.F., Semikova T.S., Bulgakova E.S. Small melanomas of the choroidal: clinical features and the choice of treatment method. New in ophthalmology = Novoe v oftal’mologii. 2004;2:28–37 (In Russ.)].

34. Wang Z.Y., Yang W.L., Li D.J., Chen W., et al. Ultrasound diagnosis and differential diagnosis of medium and small choroidal melanomas. Chinese journal of ophthalmology. 2018;54(11):843–848. DOI: 10.3760/cma.j.issn.0412-4081.2018.11.009

35. Wolff‐Korman P.G., Kormann B.A., Hasenfratz G.C., et al. Duplex and color Doppler ultrasound in the differential diagnosis of choroidal tumors. Acta Ophthalmologica. 1992;70(204):66–70. DOI: 10.1111/j.1755-3768.1992.tb04928.x

36. Самкович Е.В., Мелихова М.В., Панова И.Е. Возможности идентификации сосудистой сети пигментированных новообразований хориоидеи. Современные технологии в офтальмологии. 2019;4(29):223–227. [Samkovich E.V., Melikhova M.V., Panova I.E. Possibilities of identification of the vasculature of pigmented neoplasms of the choroid. Modern technologies in ophthalmology = Sovremennye tehnologii v oftal’mologii. 2019;4(29):223–227 (In Russ.)]. DOI: 10.25276/2312-4911-2019-4-223-227

37. Нероев В.В., Киселева Т.Н. Ультразвуковые исследования в офтальмологии: Руководство для врачей. 1-е изд. М: ИКАР; 2019:324. [Neroev V.V., Kiseleva T.N. Ultrasound Research in Ophthalmology: A Guide for Physicians. 1st ed. Moscow: IKAR; 2019:324 (In Russ.)].

38. Рыкун В.С., Катькова Е.А. Особенности сосудистой сети меланомы хориоидеи по результатам триплексного ультразвукового исследования. Вестник офтальмологии. 2001;2:17–18. [Rykun V.S., Katkova E.A. Features of the vascular network of choroid melanoma according to the results of triplex ultrasound. Annales of Ophthalmology = Vestnik oftal’mologii. 2001;2:17–18 (In Russ.)].

39. Lassau N. New hemodynamic approach to angiogenesis: color and pulsed Doppler ultrasonography. Invest. Radiol. 1999;34(3):194–198.

40. Proniewska-Skretek E. An application of color Doppler ultrasonography in evaluate of brachytherapy in patients with uveal melanoma. Klin. Oczna. 2007;109(4–6):187–190. DOI: 10.1080/02713683.2017.1341534

41. Shields C.L., Shields J.A., De Potter P. Patterns of indocyanine green videoangiography of choroidal tumours. British journal of ophthalmology. 1995;79(3):237–245. DOI: 10.1136/bjo.79.3.237

42. Atmaca L.S., Batioğlu F., Atmaca P. Fluorescein and indocyanine green videoangiography of choroidal melanomas. Japanese journal of ophthalmology. 1999;43(1):25–30. DOI: 10.1016/S0021-5155(98)00059-8

43. Andersen M.V., Scherfig E., Prause J.U. Differential diagnosis of choroidal melanomas and naevi using scanner laser ophthalmoscopical indocyanine green angiography. Acta Ophthalmologica Scandinavica. 1995;73(5):453–456. DOI: 10.1111/j.1600-0420.1995.tb00308.x

44. Kubicka-Trzaska A., Starzycka M., Romanowska-Dixon B. Indocyanine green angiography in the diagnosis of small choroidal tumours. Ophthalmologica. 2002;216(5):316–319. DOI: 10.1159/000066177

45. Shiraki K., Moriwaki M., Yanagihara N., Kohno T. Indocyanine green angiograms of choroidal nevi: Comparison between confocal and nonconfocal scanning ophthalmoscope and fundus video camera. Japanese journal of ophthalmology. 2001;45(4):368–374. DOI: 10.1016/S0021-5155(01)00362-8

46. Yannuzzi L. Lawrence A. Indocyanine green angiography: a perspective on use in the clinical setting. American journal of ophthalmology. 2011;151(5):745–751. DOI: 10.1016/j.ajo.2011.01.043

47. Frenkel S., Barzel I., Levy J., Lin A.Y. Demonstrating circulation in vasculogenic mimicry patterns of uveal melanoma by confocal indocyanine green angiography. Eye. 2008;22(7):948. DOI: 10.1038/sj.eye.6702783

48. Shields C.L., Furuta M., Berman E.L., Zahler J.D. Choroidal nevus transformation into melanoma. Analysis of 2514 consecutive cases. Archives of Ophthalmology. 2009;127(8):981–987. DOI: :10.1001/archophthalmol.2009.151

49. Sallet G., Amoaku W.M.K., Lafaut B.A., Brabant P., De Laey J.J. Indocyanine green angiography of choroidal tumors. Graefes Arch Clin Exp Ophthalmol. 1995;233:677–689. DOI: 10.1007/BF00164669

50. Свирин А.В., Кийко Ю.И., Обруч Б.В., Богомолов А.В. Спектральная оптическая когерентная томография: принципы и возможности метода. РМЖ. Клиническая офтальмология. 2009;2:50–53. [Svirin A.V., Kiiko Yu.I., Obruch B.V., Bogomolov A.V. Spectral optic coherent tomography: principles and possibilities (Literary review). Russian Medical Journal. Clinical Ophthalmology = Rossijskij medicinskij zhurnal. Klinicheskaya oftal’mologiya. 2009;2:50–53 (In Russ.)].

51. Duker J.S., Waheed N.K., Goldman D.R. Handbook of retinal OCT: optical coherence tomography. Philadelphia: WB Saunders; 2014.

52. Jia Y., Tan O., Tokayer J. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express. 2012;20(4):4710. DOI: 10.1364/oe.20.004710

53. Chalam K. V., Sambhav K. Optical coherence tomography angiography in retinal diseases. Journal of ophthalmic & vision research. 2016;11(1):84. DOI: 10.4103/2008-322X.180709

54. Jia Y., Bailey S.T., Hwang T.S., McClintic S.M. Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye. Proc Natl Acad Sci USA. 2015;112(18):2395–2402. DOI: 10.1073/pnas.1500185112

55. Coscas G., Lupidi M., Coscas F. Heidelberg Spectralis Optical Coherence Tomography Angiography: Technical Aspects. Dev Ophthalmol. 2016;56:1–5. DOI: 10.1159/000442768

56. Shields C.L., Sioufi K., Fuller T., Higgins T. Which tumor, what imaging modality. Retina Today.2016;08:57–64.

57. Shields C.L., Say E.A., Samara W.A., Khoo C.T. Optical coherence tomography angiography of the macula after plaque radiotherapy of choroidal melanoma: Comparison of irradiated versus nonirradiated eyes in 65 patients. Retina. 2016;36(8):1493– 1505. DOI: 10.1097/IAE.0000000000001021

58. Lumbroso B., Huang D., Jia Y., Fujimoto J.A., Rispoli M. Clinical guide to Angio-OCT. Jaypee; 2014.

59. Valverde-Megías A., Say E.A., Ferenczy S.R., Shields C.L. Differential macular features on optical coherence tomography angiography in eyes with choroidal nevus and melanoma. Retina. 2017 Apr;37(4):731-740. doi: 10.1097/IAE.0000000000001233

60. Нероев В. В., Саакян, С. В., Мякошина, Е. Б. Оптическая когерентная томография-ангиография в диагностике начальной меланомы и отграниченной гемангиомы хориоидеи. Вестник офтальмологии. 2018;134(3):4–18. [Neroev V.V., Sahakyan, S.V., Myakoshina, E. B. Optical coherence tomography-angiography in the diagnosis of initial melanoma and delimited choroid hemangioma. Annales of Ophthalmology = Vestnik oftal’mologii. 2018;134(3):4–18 (In Russ.)]. DOI: 10.17116/oftalma201813434

61. Ghassemi F., Mirshahi R., Fadakar K., Sabour S. Optical coherence tomography angiography in choroidal melanoma and nevus. Clinical ophthalmology (Auckland, NZ). 2018;12:207. DOI: 10.2147/OPTH.S148897

62. Pellegrini M., Corvi F., Invernizzi A., Ravera V. Swept-source optical coherence tomography angiography in choroidal melanoma: an analysis of 22 consecutive cases. Retina. 2019;39(8):1510–1519. DOI: 10.1097/IAE.0000000000002205