The diagnosis of metastatic uveal melanoma. What has changed during 10 years?

Cover Page


Cite item

Full Text

Abstract

Uveal melanoma is the most common intraocular malignancy. Despite significant progress in the treatment of the primary tumor, uveal melanoma continues to be the most aggressive tumor due to its high potential for hematogenous metastatic spread. Uveal melanoma metastases are located mostly in the liver. Overall survival of patients with liver metastases is 4 to 15 months. There is no adjuvant systemic therapy to prevent metastases of uveal melanoma. In this paper, we aim to analyze achievement in diagnosis of metastatic uveal melanoma made during the last 10 years and to show advantages and disadvantages of the main diagnostic methods. The last years showed the emergence of understanding the differences between skin and uveal melanoma based on different molecular genetic abnormalities and different signaling pathways of these tumors. The success of target treatments for skin melanoma is not applicable to uveal melanoma. Skin and uveal melanoma responds differently to immune checkpoint inhibitors. Insufficient efficacy of systemic chemotherapy, immune and target therapy has made it necessary to develop techniques of local chemoembolization and radioembolization of uveal melanoma metastases. At present, there are no available assessment algorithms for the management of patients with uveal melanoma and suspected metastases. Ultrasonography, if seen as available techniques for radiology diagnostics, should be enhanced either by the intravenous contrast, or by qualifying computed tomography. The use of positron emission tomography / computed tomography has not demonstrated the maximal diagnostic value in identification of liver metastases, and, taken into account its high costs, low availability, and large radiation dose, it cannot be considered as a  feasible method for every 6  months' application. The most effective diagnostic method is magnetic resonance imaging with the liver-specific contrast agents, due to the possibility to detect metastases of less than 1  cm in diameter. However, this technique has not been widely accepted clinically due to high costs, contraindications and a big proportion of false positive results. Current armamentarium of radiation techniques that could be potentially applicable for visualization of hepatic focal abnormalities is rather impressive and is being continuously updated; however, the problem of the metastatic uveal melanoma diagnosis remains unsolved.

About the authors

E. E. Grishina

Moscow Regional Research and Clinical Institute (MONIKI);

Author for correspondence.
Email: eyelena@mail.ru
ORCID iD: 0000-0003-2668-9136

Elena E. Grishina – MD, PhD, Professor, Chief Research Fellow, Department of Oncology

61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Russian Federation

E. A. Stepanova

Moscow Regional Research and Clinical Institute (MONIKI);

Email: fake@neicon.ru
ORCID iD: 0000-0002-9037-0034

Elena A. Stepanova – MD, PhD, Leading Research Fellow, Department of Diagnostics

61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Russian Federation

A. M. Bogatyrev

Moscow Regional Research and Clinical Institute (MONIKI);

Email: fake@neicon.ru
ORCID iD: 0000-0002-6877-0023

Aleksandr M. Bogatyrev – MD, Resident Physician, Department of Ophthalmology

61/2 Shchepkina ul., Moscow, 129110, Russian Federation

Russian Federation

References

  1. Бровкина АФ, ред. Офтальмоонкология. М.: Медицина; 2002. 424 с.
  2. McLaughlin CC, Wu XC, Jemal A, Martin HJ, Roche LM, Chen VW. Incidence of noncutaneous melanomas in the U.S. Cancer. 2005;103(5): 1000–7. doi: 10.1002/cncr.20866.
  3. Singh AD, Topham A. Incidence of uveal melanoma in the United States: 1973–1997. Ophthalmology. 2003;110(5):956–61. doi: 10.1016/S0161-6420(03)00078-2.
  4. Зиангирова ГГ, Лихванцева ВГ. Опухоли сосудистого тракта глаза. М.: Последнее слово; 2003. 455 с.
  5. Park SJ, Oh CM, Kim BW, Woo SJ, Cho H, Park KH. Nationwide Incidence of Ocular Melanoma in South Korea by Using the National Cancer Registry Database (1999–2011). Invest Ophthalmol Vis Sci. 2015;56(8):4719–24. doi: 10.1167/iovs.15-16532.
  6. Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A, Crocetti E, Lutz JM, Paci E; EUROCARE Working Group. Incidence of uveal melanoma in Europe. Ophthalmology. 2007;114(12): 2309–15. doi: 10.1016/j.ophtha.2007.01.032.
  7. Shields CL, Kels JG, Shields JA. Melanoma of the eye: revealing hidden secrets, one at a time. Clin Dermatol. 2015;33(2):183–96. doi: 10.1016/j.clindermatol.2014.10.010.
  8. Гришина ЕЕ, Лернер МЮ, Гемджян ЭГ. Эпидемиология увеальной меланомы в г. Москве. Альманах клинической медицины. 2017;45(4):321–5. doi: 10.18786/2072-0505-2017-45-4-321-325.
  9. Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118(9):1881–5. doi: 10.1016/j.ophtha.2011.01.040.
  10. Triozzi PL, Singh AD. Adjuvant Therapy of Uveal Melanoma: Current Status. Ocul Oncol Pathol. 2014;1(1):54–62. doi: 10.1159/000367715.
  11. Collaborative Ocular Melanoma Study Group. 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. 2001;119(5):670–6. doi: 10.1001/archopht.119.5.670.
  12. Cerbone L, Van Ginderdeuren R, Van den Oord J, Fieuws S, Spileers W, Van Eenoo L, Wozniak A, Sternberg CN, Schöffski P. Clinical presentation, pathological features and natural course of metastatic uveal melanoma, an orphan and commonly fatal disease. Oncology. 2014;86(3):185–9. doi: 10.1159/000358729.
  13. Саакян СВ, Пантелеева ОГ, Ширина ТВ. Оценка выживаемости больных с увеальной меланомой после органосохранного лечения и энуклеации. Российский офтальмологический журнал. 2011;4(1):67–70.
  14. Саакян СВ, Амирян АГ, Цыганков АЮ, Склярова НВ, Залетаев ДВ. Клинические, патоморфологические и молекулярно-генетические особенности увеальной меланомы с высоким риском метастазирования. Российский офтальмологический журнал. 2015;8(2):47–52.
  15. Бровкина АФ, Вальский ВВ, Гусев ГА, Пантелеева ОГ, Юровская НН. Риск метастазирования меланом хориоидеи после брахитерапии. Вестник офтальмологии. 2003;119(2): 26–28.
  16. Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Green DL, Hawkins BS, Hayman J, Jaiyesimi I, Kirkwood JM, Koh WJ, Robertson DM, Shaw JM, Thoma J; Collaborative Ocular Melanoma Study Group Report 23. Screening for metastasis from choroidal melanoma: the Collaborative Ocular Melanoma Study Group Report 23. J Clin Oncol. 2004;22(12):2438–44. doi: 10.1200/JCO.2004.08.194.
  17. Grossniklaus HE. Progression of ocular melanoma metastasis to the liver: the 2012 Zimmerman lecture. JAMA Ophthalmol. 2013;131(4):462–9. doi: 10.1001/jamaophthalmol.2013.2547.
  18. Grossniklaus HE, Zhang Q, You S, McCarthy C, Heegaard S, Coupland SE. Metastatic ocular melanoma to the liver exhibits infiltrative and nodular growth patterns. Hum Pathol. 2016;57:165–75. doi: 10.1016/j.humpath.2016.07.012.
  19. Dayani PN, Gould JE, Brown DB, Sharma KV, Linette GP, Harbour JW. Hepatic metastasis from uveal melanoma: angiographic pattern predictive of survival after hepatic arterial chemoembolization. Arch Ophthalmol. 2009;127(5):628–32. doi: 10.1001/archophthalmol.2009.45.
  20. Halenda KM, Kudchadkar RR, Lawson DH, Kies DD, Zhelnin KE, Krasinskas AM, Grossniklaus HE. Reduction of Nodular Growth Pattern of Metastatic Uveal Melanoma after Radioembolization of Hepatic Metastases. Ocul Oncol Pathol. 2016;2(3):160–5. doi: 10.1159/000442950.
  21. Postow MA, Kuk D, Bogatch K, Carvajal RD. Assessment of overall survival from time of metastastasis in mucosal, uveal, and cutaneous melanoma. J Clin Oncol. 2014;32(15 Suppl):9074. doi: 10.1200/jco.2014.32.15_suppl.9074.
  22. Назарова ВВ, Орлова КВ, Утяшев ИА, Мазуренко НН, Демидов ЛВ. Современные тенденции в терапии увеальной меланомы: обзор проблемы. Злокачественные опухоли. 2014;4(11):54–61. doi: 10.18027/2224-5057-2014-4-54-61.
  23. Авакян КВ, Саакян СВ, Амирян АГ, Асланиди ИП, Мухортова ОВ Роль современных методов исследования в ранней диагностике метастазов у пациентов с увеальной меланомой. REJR. 2016;6(4):8–18. doi: 10.21569/2222-7415-2016-6-4-8-18.
  24. Казимирова ЕГ, Гришина ЕЕ. Ранняя диагностика метастатической увеальной меланомы: современные возможности и перспективы развития (обзор литературы). Современная онкология 2008;(1):37–41.
  25. van der Kooij MK, Speetjens FM, van der Burg SH, Kapiteijn E. Uveal Versus Cutaneous Melanoma; Same Origin, Very Distinct Tumor Types. Cancers (Basel). 2019;11(6). pii: E845. doi: 10.3390/cancers11060845.
  26. Ny L, Nyakas M, Hernberg M, Koivunen J, Oddershede L, Yoon M-R, Wang X, Guyot P, Geisler J. BRAF mutation as a prognostic marker for survival in malignant melanoma: A systematic review and meta-analysis. J Clin Oncol. 2018;36(15 Suppl):e21566. doi: 10.1200/JCO.2018.36.15_suppl.e21566.
  27. Spathis A, Katoulis AC, Damaskou V, Liakou AI, Kottaridi C, Leventakou D, Sgouros D, Mamantopoulos A, Rigopoulos D, Karakitsos P, Panayiotides IG. BRAF Mutation Status in Primary, Recurrent, and Metastatic Malignant Melanoma and Its Relation to Histopathological Parameters. Dermatol Pract Concept. 2019;9(1):54–62. doi: 10.5826/dpc.0901a13.
  28. Heppt MV, Siepmann T, Engel J, Schubert-Fritschle G, Eckel R, Mirlach L, Kirchner T, Jung A, Gesierich A, Ruzicka T, Flaig MJ, Berking C. Prognostic significance of BRAF and NRAS mutations in melanoma: a German study from routine care. BMC Cancer. 2017;17(1):536. doi: 10.1186/s12885-017-3529-5.
  29. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, Simpson EM, Barsh GS, Bastian BC. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009;457(7229):599–602. doi: 10.1038/nature07586.
  30. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010;363(23): 2191–9. doi: 10.1056/NEJMoa1000584.
  31. Bauer J, Kilic E, Vaarwater J, Bastian BC, Garbe C, de Klein A. Oncogenic GNAQ mutations are not correlated with disease-free survival in uveal melanoma. Br J Cancer. 2009;101(5): 813–5. doi: 10.1038/sj.bjc.6605226.
  32. Koopmans AE, Vaarwater J, Paridaens D, Naus NC, Kilic E, de Klein A; Rotterdam Ocular Melanoma Study group. Patient survival in uveal melanoma is not affected by oncogenic mutations in GNAQ and GNA11. Br J Cancer. 2013;109(2):493–6. doi: 10.1038/bjc.2013.299.
  33. Staby KM, Gravdal K, Mørk SJ, Heegaard S, Vintermyr OK, Krohn J. Prognostic impact of chromosomal aberrations and GNAQ, GNA11 and BAP1 mutations in uveal melanoma. Acta Ophthalmol. 2018;96(1):31–8. doi: 10.1111/aos.13452.
  34. Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, Council ML, Matatall KA, Helms C, Bowcock AM. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330(6009):1410–3. doi: 10.1126/science.1194472.
  35. Yavuzyigitoglu S, Mensink HW, Smit KN, Vaarwater J, Verdijk RM, Beverloo B, Brüggenwirth HT, van Marion R, Dubbink HJ, Paridaens D, Naus NC, de Klein A, Kiliç E; Rotterdam Ocular Melanoma Study Group (ROMS). Metastatic Disease in Polyploid Uveal Melanoma Patients Is Associated With BAP1 Mutations. Invest Ophthalmol Vis Sci. 2016;57(4):2232–9. doi: 10.1167/iovs.15-18608.
  36. Sato T, Eschelman DJ, Gonsalves CF, Terai M, Chervoneva I, McCue PA, Shields JA, Shields CL, Yamamoto A, Berd D, Mastrangelo MJ, Sullivan KL. Immunoembolization of malignant liver tumors, including uveal melanoma, using granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2008;26(33):5436–42. doi: 10.1200/JCO.2008.16.0705.
  37. Klingenstein A, Haug AR, Zech CJ, Schaller UC. Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients. Cardiovasc Intervent Radiol. 2013;36(1): 158–65. doi: 10.1007/s00270-012-0373-5.
  38. Abbott AM, Doepker MP, Kim Y, Perez MC, Gandle C, Thomas KL, Choi J, Shridhar R, Zager JS. Hepatic Progression-free and Overall Survival After Regional Therapy to the Liver for Metastatic Melanoma. Am J Clin Oncol. 2018;41(8): 747–53. doi: 10.1097/COC.0000000000000356.
  39. Shibayama Y, Namikawa K, Sone M, Takahashi A, Tsutsumida A, Sugawara S, Arai Y, Aihara Y, Suzuki S, Nakayama J, Imafuku S, Yamazaki N. Efficacy and toxicity of transarterial chemoembolization therapy using cisplatin and gelatin sponge in patients with liver metastases from uveal melanoma in an Asian population. Int J Clin Oncol. 2017;22(3):577–84. doi: 10.1007/s10147-017-1095-0.
  40. de Leede EM, Burgmans MC, Kapiteijn E, Luyten GP, Jager MJ, Tijl FG, Hartgrink HH, Grünhagen DJ, Rothbarth J, van de Velde CJ, Verhoef C, Vahrmeijer AL. Isolated (hypoxic) hepatic perfusion with high-dose chemotherapy in patients with unresectable liver metastases of uveal melanoma: results from two experienced centres. Melanoma Res. 2016;26(6):588–94. doi: 10.1097/CMR.0000000000000286.
  41. Frenkel S, Nir I, Hendler K, Lotem M, Eid A, Jurim O, Pe'er J. Long-term survival of uveal melanoma patients after surgery for liver metastases. Br J Ophthalmol. 2009;93(8):1042–6. doi: 10.1136/bjo.2008.153684.
  42. Akyuz M, Yazici P, Dural C, Yigitbas H, Okoh A, Bucak E, McNamara M, Singh A, Berber E. Laparoscopic management of liver metastases from uveal melanoma. Surg Endosc. 2016;30(6): 2567–71. doi: 10.1007/s00464-015-4527-9.
  43. Gomez D, Wetherill C, Cheong J, Jones L, Marshall E, Damato B, Coupland SE, Ghaneh P, Poston GJ, Malik HZ, Fenwick SW. The Liverpool uveal melanoma liver metastases pathway: outcome following liver resection. J Surg Oncol. 2014;109(6):542–7. doi: 10.1002/jso.23535.
  44. Ripley RT, Davis JL, Klapper JA, Mathur A, Kammula U, Royal RE, Yang JC, Sherry RM, Hughes MS, Libutti SK, White DE, Steinberg SM, Dudley ME, Rosenberg SA, Avital I. Liver resection for metastatic melanoma with postoperative tumor-infiltrating lymphocyte therapy. Ann Surg Oncol. 2010;17(1):163–70. doi: 10.1245/s10434-009-0677-0.
  45. Mariani P, Piperno-Neumann S, Servois V, Berry MG, Dorval T, Plancher C, Couturier J, Levy-Gabriel C, Lumbroso-Le Rouic L, Desjardins L, Salmon RJ. Surgical management of liver metastases from uveal melanoma: 16 years' experience at the Institut Curie. Eur J Surg Oncol. 2009;35(11):1192–7. doi: 10.1016/j.ejso.2009.02.016.
  46. Choudhary MM, Gupta A, Bena J, Emch T, Singh AD. Hepatic Ultrasonography for Surveillance in Patients With Uveal Melanoma. JAMA Ophthalmol. 2016;134(2):174–80. doi: 10.1001/jamaophthalmol.2015.4810.
  47. Eso Y, Takai A, Takeda H, Matsumoto T, Lee M, Inuzuka T, Takahashi K, Ueda Y, Marusawa H, Seno H. Sonazoid-enhanced ultrasonography guidance improves the quality of pathological diagnosis in the biopsy of focal hepatic lesions. Eur J Gastroenterol Hepatol. 2016;28(12):1462–7. doi: 10.1097/MEG.0000000000000745.
  48. Mishima M, Toh U, Iwakuma N, Takenaka M, Furukawa M, Akagi Y. Evaluation of contrast Sonazoid-enhanced ultrasonography for the detection of hepatic metastases in breast cancer. Breast Cancer. 2016;23(2):231–41. doi: 10.1007/s12282-014-0560-0.
  49. Patel M, Winston CB, Marr BP, Carvajal RD, Schwartz GK, Wolchok J, Busam K, Abramson DH. Characterization of computed tomography scan abnormalities in patients with biopsy-proven hepatic metastases from uveal melanoma. Arch Ophthalmol. 2011;129(12):1576–82. doi: 10.1001/archophthalmol.2011.263.
  50. Feinstein EG, Marr BP, Winston CB, Abramson DH. Hepatic abnormalities identified on abdominal computed tomography at diagnosis of uveal melanoma. Arch Ophthalmol. 2010;128(3):319–23. doi: 10.1001/archophthalmol.2009.401.
  51. Altenbernd J, Wetter A, Forsting M, Umutlu L. Dual-energy CT of liver metastases in patients with uveal melanoma. Eur J Radiol Open. 2016;3:254–8. doi: 10.1016/j.ejro.2016.10.003.
  52. Авакян КВ, Мухортова ОВ, Амирян АГ, Асланиди ИП, Саакян СВ. ПЭТ/КТ в диагностике метастатической увеальной меланомы. Эффективная фармакотерапия. 2016;(39):60–3.
  53. Rodríguez-Marco NA, Caicedo-Zamudio C, Solanas-Álava S, Gil-Arnaiz I, Córdoba-Iturriagagoitia A, Andonegui-Navarro J. Whole body PET/CT imaging for detection of metastatic choroidal melanoma. An Sist Sanit Navar. 2014;37(2):293–8. Spanish.
  54. Eldredge-Hindy H, Ohri N, Anne PR, Eschelman D, Gonsalves C, Intenzo C, Bar-Ad V, Dicker A, Doyle L, Li J, Sato T. Yttrium-90 Microsphere Brachytherapy for Liver Metastases From Uveal Melanoma: Clinical Outcomes and the Predictive Value of Fluorodeoxyglucose Positron Emission Tomography. Am J Clin Oncol. 2016;39(2):189–95. doi: 10.1097/COC.0000000000000033.
  55. Авакян КВ, Саакян СВ, Амирян АГ, Асланиди ИП, Мухортова ОВ. Полинеоплазии у больных увеальной меланомой по данным позитронно-эмиссионной томографии, совмещенной с компьютерной томографией (два клинических случая). Альманах клинической медицины. 2017;45(4):348–51. doi: 10.18786/2072-0505-2017-45-4-348-351.
  56. Cohen VML, Pavlidou E, DaCosta J, Arora AK, Szyszko T, Sagoo MS, Szlosarek P. Staging Uveal Melanoma with Whole-Body Positron-Emission Tomography /Computed Tomography and Abdominal Ultrasound: Low Incidence of Metastatic Disease, High Incidence of Second Primary Cancers. Middle East Afr J Ophthalmol. 2018;25(2):91–5. doi: 10.4103/meajo.MEAJO_96_18.
  57. Strobel K, Bode B, Dummer R, Veit-Haibach P, Fischer DR, Imhof L, Goldinger S, Steinert HC, von Schulthess GK. Limited value of 18F-FDG PET/CT and S-100B tumour marker in the detection of liver metastases from uveal melanoma compared to liver metastases from cutaneous melanoma. Eur J Nucl Med Mol Imaging. 2009;36(11):1774–82. doi: 10.1007/s00259-009-1175-0.
  58. Orcurto V, Denys A, Voelter V, Schalenbourg A, Schnyder P, Zografos L, Leyvraz S, Delaloye AB, Prior JO. (18)F-fluorodeoxyglucose positron emission tomography / computed tomography and magnetic resonance imaging in patients with liver metastases from uveal melanoma: results from a pilot study. Melanoma Res. 2012;22(1):63–9. doi: 10.1097/CMR.0b013e32834d3dcb.
  59. Marshall E, Romaniuk C, Ghaneh P, Wong H, McKay M, Chopra M, Coupland SE, Damato BE. MRI in the detection of hepatic metastases from high-risk uveal melanoma: a prospective study in 188 patients. Br J Ophthalmol. 2013;97(2):159–63. doi: 10.1136/bjophthalmol-2012-302323.
  60. Piperno-Neumann S, Servois V, Mariani P, Plancher C, Lévy-Gabriel C, Lumbroso-Le Rouic L, Couturier J, Asselain B, Desjardins L, Cassoux N. Prospective study of surveillance testing for metastasis in 100 high-risk uveal melanoma patients. J Fr Ophtalmol. 2015;38(6): 526–34. doi: 10.1016/j.jfo.2015.04.005.
  61. Bellerive C, Ouellet E, Kamaya A, Singh AD. Liver Imaging Techniques: Recognition of Uveal Melanoma Metastases. Ocul Oncol Pathol. 2018;4(4):254–60. doi: 10.1159/000485424.
  62. Xue S, Yang H, Qiao J, Pu F, Jiang J, Hubbard K, Hekmatyar K, Langley J, Salarian M, Long RC, Bryant RG, Hu XP, Grossniklaus HE, Liu ZR, Yang JJ. Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging. Proc Natl Acad Sci U S A. 2015;112(21):6607–12. doi: 10.1073/pnas.1423021112.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2019 Grishina E.E., Stepanova E.A., Bogatyrev A.M.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies