Primary choroidal melanoma followed by two metachronous ipsilateral ocular metastases

Purpose. To describe two ipsilateral, metachronous, ocular choroidal melanoma metastases.
Material and methods. A 64-year-old choroidal melanoma patient was initially treated with palladium-103 ophthalmic plaque brachytherapy which induced local control of the primary cancer. Seven years later, ophthalmic findings of a second, ipsilateral, discrete choroidal melanoma prompted restaging which revealed new hepatic and nodal metastases. Systemic immunotherapy (ipilimumab 3 mg/kg with nivolumab 1 mg/kg IV every 3 weeks 4 doses) resulted in intraocular tumor regression and was followed by maintenance nivolumab 480 mg IV every 4 weeks with follow-up ophthalmic examinations.
Results. Three years after initiation of systemic immunotherapy, the patient was found to have a second ipsilateral local recurrence of choroidal melanoma. It presented with retinal detachment, uveitis, and optic neuritis. Then, due to its anterior uveal location, extrascleral tumor extension was amenable to a diagnostic biopsy. Overall, 3 years after onset of metastatic uveal melanoma and 2 months after her second ocular metastasis, the patient died. This was 10 years after the initial diagnosis of choroidal melanoma.
Conclusions. Metastatic choroidal melanoma can present twice in the same eye as the primary tumor. Ophthalmic and systemic examinations allowed for immunotherapy to affect initial systemic regression, vision sparing, and globe salvage.

1. Finger P.T., Pavlick A.C. Intraocular melanoma. In: Devita V.T. Jr., Lawrence T.S., Rosenberg S.A., eds. Devita, Hellman, and Rosenberg’s cancer: Principles practice of oncology. 11th ed. Philadelphia: Wolters and Kluwer; 2019: 1899–909.

2. Shammas H.F., Watzke R.C. Bilateral choroidal melanomas. Arch. Ophthalmol. 1977; 95 (4): 617–23. doi:10.1001/archopht.1977.04450040083012

3. Sabates F.N., Yamashita T. Congenital melanosis oculi. Arch. Ophthalmol. 1967; 77 (6): 801–3. doi:10.1001/archopht.1967.00980020803018

4. Glaser T., Thomas A.S., Materin M.A. Successive uveal melanomas with different gene expression profiles in an eye with ocular melanocytosis. Ocular Oncology and Pathology. 2018; 4 (4): 236–9. doi:10.1159/000484937

5. Milman T., Hu D.N., McCormick S.A., et al. Expression of neurotrophin receptors by retinoinvasive uveal melanoma. Melanoma Res. 2012; 22 (2): 164–8. doi: 10.1097/CMR.0b013e32835175ec

6. Pavlick A.C., Finger P.T. Systemic evaluation and management of patients with metastatic uveal melanoma. In: Ryan’s Retina. 6th edn. Elsevier, 2018: 2608–12.

7. 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

8. Freton A., Chin K.J., Raut R., et al. Initial PET/CT staging for choroidal melanoma: AJCC correlation and second nonocular primaries in 333 patients. Eur. J. Ophthalmol. 2012; 22 (2): 236–43. doi: 10.5301/ejo.5000049

9. Garg G., Finger P.T., Kivel T.T., et al. Patients presenting with metastases: stage IV uveal melanoma, an international study. Br. J. Ophthalmol. 2021 Jan 15: bjophthalmol-2020-317949. doi: 10.1136/bjophthalmol-2020-317949

10. Kivela T., Simpson E.R., Grossniklaus H.E., et al. Uveal melanoma. In: Amin M.B., Edge S.B., Greene F.L., et al., eds. AJCC cancer staging manual. 8th ed. New York: Springer; 2016: 805–13.

11. AJCC Ophthalmic Oncology Task Force. International Validation of the American Joint Committee on Cancer's 7th Edition Classification of Uveal Melanoma. JAMA Ophthalmol. 2015; 133 (4): 376–83. doi: 10.1001/jamaophthalmol.2014.5395

12. Morkos M., Jain P., Pavlick A.C., Finger P.T. Ipsilateral metastatic choroidal melanoma responds to systemic immunotherapy. Eur. J. Ophthalmol. 2019; 30 (5): 69–73. doi:10.1177/1120672119839925

13. Condon R.A., Mullaney J. Multiple malignant melanoma of the uveal tract in one eye. Br. J. Ophthalmol. 1967; 51 (10): 707–11. doi:10.1136/bjo.51.10.707

14. Holck D.E., Dutton J.J., Pendergast S.D., Klintworth G.K. Double choroidal malignant melanoma in an eye with apparent clinical regression. Surv. Ophthalmol. 1998; 42 (5): 441–8. doi:10.1016/s0039-6257(97)00136-7

15. Blumenthal E.Z, Pe'er J. Multifocal choroidal malignant melanoma: at least 3 melanomas in one eye. Arch. Ophthalmol. 1999; 117 (2): 255–8. doi:10.1001/archopht.117.2.255

16. Dithmar S., V lcker H.E., Grossniklaus H.E. Multifocal intraocular malignant melanoma. Ophthalmology. 1999; 106 (7): 1345–8. doi:10.1016/s0161-6420(99)00722-8

17. Prager A.J., Habib L.A., Busam K.J., Marr B.P. Two uveal melanomas in one eye: a choroidal nevus giving rise to a melanoma in an eye with a separate large choroidal melanoma. Ocular Oncology and Pathology. 2018; 4 (6): 355–8.doi:10.1159/000486682

18. Finger P.T., Kurli M. Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy. Br. J. Ophthalmol. 2005; 89 (6): 730–8. doi: 10.1136/bjo.2004.052159

19. Pelster M.S., Gruschkus S.K., Bassett R., et al. Nivolumab and Ipilimumab in metastatic uveal melanoma: results from a Single-Arm Phase II Study. J. Clin. Oncol. 2021; 39 (6): 599–607. doi: 10.1200/JCO.20.00605

20. Maheshwari A., Finger P.T. Regression patterns of choroidal melanoma: After palladium-103 (103Pd) plaque brachytherapy. Eur. J. Ophthalmol. 2018; 28 (6): 722–30. doi: 10.1177/1120672118776146

21. Finger P., Maheshwari A., Malpani A., et al. Doctor reported outcomes: Realworld data from a tertiary eye cancer center. Indian Journal of Ophthalmology. 2021; 69 (1): 135–9. doi:10.4103/ijo.ijo_257_20

22. Chang M.Y., McCannel T.A. Local treatment failure after globe-conserving therapy for choroidal melanoma. Br. J. Ophthalmol. 2013; 97: 804–11. doi: 10.1136/bjophthalmol-2012-302490

23. Ophthalmic Oncology Task Force. Local recurrence significantly increases the risk of metastatic uveal melanoma. Ophthalmology. 2016; 123 (1): 86–91. doi: 10.1016/j.ophtha.2015.09.014

24. Schank T.E., Hassel J.C. Immunotherapies for the treatment of uveal melanoma – history and future. Cancers. 2019; 11 (8): 1048. doi:10.3390/cancers11081048

25. Raamsdonk C.D.V., Bezrookove V., Green G., et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2008; 457 (7229): 599–602. doi:10.1038/nature07586

26. Van Raamsdonk C.D., Griewank K.G., Crosby M.B., et al. Mutations in GNA11 in uveal melanoma. The New England Journal of Medicine. 2010; 363 (23): 2191–9. doi:10.1056/NEJMoa1000584

27. Wong C.W., Fan Y.S., Chan T.L., et al. BRAF and NRAS mutations are uncommon in melanomas arising in diverse internal organs. J. Clin. Pathol. 2005; 58 (6): 640–4. doi:10.1136/jcp.2004.022509