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| ==Overview== | | ==Overview== |
| If left untreated, 50% of patients with uveal melanoma may progress to develop [[metastasis]]. Common complications of uveal melanoma include [[glaucoma]], [[vision loss]], and [[metastasis]]. Prognosis is generally good for patients with iris melanoma, and the 10 year-survival for iris melanoma is approximately 95 percent and for ciliochoroidal [[tumors]] is 77 percent respectively.<ref name="pmid23826405">{{cite journal| author=Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V| title=Ocular melanoma: an overview of the current status. | journal=Int J Clin Exp Pathol | year= 2013 | volume= 6 | issue= 7 | pages= 1230-44 | pmid=23826405 | doi= | pmc=PMC3693189 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23826405 }} </ref> | | If left untreated, 50% of patients with uveal melanoma may progress to develop [[metastasis]]. Common [[complications]] of uveal melanoma include [[glaucoma]], [[vision loss]], and [[metastasis]]. [[Prognosis]] is generally good for [[Patient|patients]] with [[iris]] [[melanoma]], and the 10 year-survival for iris melanoma is approximately 95 percent and for ciliochoroidal [[tumors]] is 77 percent respectively. |
| ==Natural History==
| | ==Natural History, Complications, and Prognosis== |
| The clinical course is unpredictable and metastatic disease can develop very late after a long disease-free interval. Uveal melanoma metastasizes haematogenously, predominantly to the [[liver]].<ref name="pmid10661768">{{cite journal| author=Wöll E, Bedikian A, Legha SS| title=Uveal melanoma: natural history and treatment options for metastatic disease. | journal=Melanoma Res | year= 1999 | volume= 9 | issue= 6 | pages= 575-81 | pmid=10661768 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10661768 }} </ref> Less than 4% of patients with uveal melanoma have detectable metastatic disease, at the time of diagnosis. However in further course about half of patients will develop metastases. When metastatic disease appears it unavoidably leads to death because of lack of effective systemic treatment.<ref name="pmid23826405">{{cite journal| author=Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V| title=Ocular melanoma: an overview of the current status. | journal=Int J Clin Exp Pathol | year= 2013 | volume= 6 | issue= 7 | pages= 1230-44 | pmid=23826405 | doi= | pmc=PMC3693189 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23826405 }} </ref> | | |
| ==Complications== | | === Natural history === |
| Complications of eye melanoma includes the following:<ref>Singh, Arun D., and Bertil Damato. Clinical ophthalmic oncology : uveal tumors. Heidelberg: Springer, 2014. Print.</ref> | | |
| | * The clinical course is unpredictable and [[metastatic]] [[disease]] can develop very late after a long [[disease]]-free interval. <ref name="pmid10661768">{{cite journal| author=Wöll E, Bedikian A, Legha SS| title=Uveal melanoma: natural history and treatment options for metastatic disease. | journal=Melanoma Res | year= 1999 | volume= 9 | issue= 6 | pages= 575-81 | pmid=10661768 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10661768 }} </ref><ref name="pmid23826405">{{cite journal| author=Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V| title=Ocular melanoma: an overview of the current status. | journal=Int J Clin Exp Pathol | year= 2013 | volume= 6 | issue= 7 | pages= 1230-44 | pmid=23826405 | doi= | pmc=PMC3693189 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23826405 }} </ref> |
| | *[[Uvea (anatomy)|Uveal]] melanoma [[Metastasis|metastasizes]] haematogenously, predominantly to the [[liver]]. |
| | * Less than 4% of [[Patient|patients]] with uveal melanoma have detectable [[metastatic]] [[disease]], at the time of [[diagnosis]]. |
| | * However in further course about half of [[Patient|patients]] will develop [[Metastasis|metastases]]. |
| | * When [[metastatic]] disease appears it unavoidably leads to death because of lack of effective systemic treatment. |
| | ===Complications=== |
| | [[Complications]] of eye [[melanoma]] include the following:<ref>Singh, Arun D., and Bertil Damato. Clinical ophthalmic oncology : uveal tumors. Heidelberg: Springer, 2014. Print.</ref> |
| | |
| *[[Glaucoma]] | | *[[Glaucoma]] |
| *[[Cataract]] | | *[[Cataract]] |
| *[[Anterior chamber]] [[hemorrhage]] | | *[[Anterior chamber]] [[hemorrhage]] |
| *[[Corneal]] decompensation wth [[edema]] and band [[keratopathy]] | | *[[Corneal]] decompensation with [[edema]] and band [[keratopathy]] |
| *[[Metastasis]] | | *[[Metastasis]] |
| | **Eye melanoma can spread outside of the [[Eye-eating amoebas|eye]] and to distant areas of the [[body]], including the [[liver]], [[lungs]] and [[bones]]. |
| *[[Vision loss]] | | *[[Vision loss]] |
| :Eye melanomas that are large often cause vision loss in the affected eye and may cause complications, such as [[retinal detachment]], that also cause [[vision loss]]. If small eye melanomas occur in critical parts of the eye they may cause some vision loss. There may be difficulty seeing in the center of the vision or on the side. Advanced eye melanomas can cause complete vision loss. | | |
| Eye melanoma can spread outside of the eye and to distant areas of the body, including the [[liver]], [[lungs]] and [[bones]].
| | :* Eye melanomas that are large often cause [[vision loss]] in the affected [[Acanthamoeba|eye]] and may cause [[complications]], such as [[retinal detachment]], that also cause [[vision loss]]. |
| | :* If small [[eye]] melanomas occur in critical parts of the eye they may cause some [[vision loss]]. |
| | :* There may be difficulty seeing in the center of the [[vision]] or on the side. |
| | :* Advanced eye melanomas can cause complete [[vision loss]]. |
| ===Complications of therapy of uveal melanoma=== | | ===Complications of therapy of uveal melanoma=== |
| *Complications of radiotherapy include the following: | | *[[Complications]] of [[radiotherapy]] include the following:<ref name="SummanenImmonen1996">{{cite journal|last1=Summanen|first1=P|last2=Immonen|first2=I|last3=Kivela|first3=T|last4=Tommila|first4=P|last5=Heikkonen|first5=J|last6=Tarkkanen|first6=A|title=Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma.|journal=British Journal of Ophthalmology|volume=80|issue=8|year=1996|pages=732–739|issn=0007-1161|doi=10.1136/bjo.80.8.732}}</ref> |
| **[[Radiation]] [[retinopathy]] | | **[[Radiation]] [[retinopathy]] |
| **[[Radiation]] [[maculopathy]] | | **[[Radiation]] [[maculopathy]] |
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| **[[Neovascular glaucoma]] | | **[[Neovascular glaucoma]] |
| **[[Vitreous]] [[haemorrhage]] | | **[[Vitreous]] [[haemorrhage]] |
| **[[Retinal detachment]] and dryness | | **[[Retinal detachment]] and dryness |
| **Radiation retinopathy, opticopathy and neovascular glaucoma are responsible for the majority of secondary visual loss and secondary enucleations after therapy. | | **[[Radiation therapy|Radiation]] [[retinopathy]], opticopathy and neovascular [[glaucoma]] are responsible for the majority of secondary [[Vision loss|visual loss]] and secondary enucleations after therapy. |
| ==Prognosis== | | |
| Poor prognostic factors for systemic disease include the follwing:
| | ===Prognosis=== |
| *Older age: >60 years of age<ref name="pmid2208011">{{cite journal| author=Augsburger JJ, Gamel JW| title=Clinical prognostic factors in patients with posterior uveal malignant melanoma. | journal=Cancer | year= 1990 | volume= 66 | issue= 7 | pages= 1596-600 | pmid=2208011 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2208011 }} </ref> | | |
| *Larger tumor size<ref name="pmid12470140">{{cite journal| author=Gragoudas E, Li W, Goitein M, Lane AM, Munzenrider JE, Egan KM| title=Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. | journal=Arch Ophthalmol | year= 2002 | volume= 120 | issue= 12 | pages= 1665-71 | pmid=12470140 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12470140 }} </ref><ref name="pmid16344433">{{cite journal| author=Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD et al.| title=Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. | journal=Arch Ophthalmol | year= 2005 | volume= 123 | issue= 12 | pages= 1639-43 | pmid=16344433 | doi=10.1001/archopht.123.12.1639 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16344433 }} </ref><ref name="pmid23664467">{{cite journal| author=Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA| title=American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients. | journal=Ophthalmology | year= 2013 | volume= 120 | issue= 10 | pages= 2066-71 | pmid=23664467 | doi=10.1016/j.ophtha.2013.03.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23664467 }} </ref><ref name="pmid23816968">{{cite journal| author=Kujala E, Damato B, Coupland SE, Desjardins L, Bechrakis NE, Grange JD et al.| title=Staging of ciliary body and choroidal melanomas based on anatomic extent. | journal=J Clin Oncol | year= 2013 | volume= 31 | issue= 22 | pages= 2825-31 | pmid=23816968 | doi=10.1200/JCO.2012.45.2771 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23816968 }} </ref><ref name="pmid25555246">{{cite journal| author=AJCC Ophthalmic Oncology Task Force| title=International Validation of the American Joint Committee on Cancer's 7th Edition Classification of Uveal Melanoma. | journal=JAMA Ophthalmol | year= 2015 | volume= 133 | issue= 4 | pages= 376-83 | pmid=25555246 | doi=10.1001/jamaophthalmol.2014.5395 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25555246 }} </ref>
| | *The 5-year [[mortality rate]] associated with [[metastasis]] from [[ciliary body]] or choroidal melanoma is approximately 30%, compared with a rate of 2% to 3% for [[iris]] [[Melanoma|melanomas]].<ref name="ShieldsMellen2013">{{cite journal|last1=Shields|first1=CarolL|last2=Mellen|first2=PhoebeL|last3=Morton|first3=SpenserJ|title=American joint committee on cancer staging of uveal melanoma|journal=Oman Journal of Ophthalmology|volume=6|issue=2|year=2013|pages=116|issn=0974-620X|doi=10.4103/0974-620X.116652}}</ref><ref name="pmid23664467">{{cite journal| author=Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA| title=American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients. | journal=Ophthalmology | year= 2013 | volume= 120 | issue= 10 | pages= 2066-71 | pmid=23664467 | doi=10.1016/j.ophtha.2013.03.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23664467 }} </ref> |
| :The mortality rate for small (< 2 - 3 mm apical height), medium (3 - 8 mm apical height) and large (> 8 mm apical height) melanoma is 16%, 32% and 53% in 5 years, respectively.<ref name="vanKoopmans2013">{{cite journal|last1=van|first1=J.G.M.|last2=Koopmans|first2=A.E.|last3=Verdijk|first3=R.M.|last4=Naus|first4=N.C.|last5=de|first5=A.|last6=Kilic|first6=E.|title=Diagnosis, Histopathologic and Genetic Classification of Uveal Melanoma|year=2013|doi=10.5772/53631}}</ref>
| | *Overall [[Survival rate|survival]] depends on [[tumor]] size, extraocular spread, and [[metastases]]. Even small (<10 mm diameter, <3 mm thickness) [[tumors]] still carry a 10-15% 5-year [[Mortality rate|mortality]]. |
| *[[Choroidal]] [[nevi]] are considered benign if there diameter and thickness are approximately ≤5 mm and ≤ 1 mm respectively. The mortality risk from such a [[lesion]] is essentially zero.<ref name="pmid8140689">{{cite journal| author=Augsburger JJ| title=Is observation really appropriate for small choroidal melanomas. | journal=Trans Am Ophthalmol Soc | year= 1993 | volume= 91 | issue= | pages= 147-68; discussion 169-75 | pmid=8140689 | doi= | pmc=PMC1298464 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8140689 }} </ref>
| | *The 10 year-[[Survival rate|survival]] for [[iris]] [[melanoma]] is approximately 95 percent and for ciliochoroidal tumors is 77 percent respectively. |
| *[[Ciliary body]] involvement<ref name="pmid10922199">{{cite journal| author=Li W, Gragoudas ES, Egan KM| title=Metastatic melanoma death rates by anatomic site after proton beam irradiation for uveal melanoma. | journal=Arch Ophthalmol | year= 2000 | volume= 118 | issue= 8 | pages= 1066-70 | pmid=10922199 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10922199 }} </ref>
| | *The [[tumor]] node [[metastasis]] (TNM) staging system of the American Joint Committee on Cancer takes into account the key factors involved which are known to be of [[Prognosis|prognostic]] significance. |
| *Presence of orange pigment overlying the tumor<ref name="pmid12470140">{{cite journal| author=Gragoudas E, Li W, Goitein M, Lane AM, Munzenrider JE, Egan KM| title=Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. | journal=Arch Ophthalmol | year= 2002 | volume= 120 | issue= 12 | pages= 1665-71 | pmid=12470140 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12470140 }} </ref> | | *The [[prognosis]] is usually poor when local control is not achieved with the initial treatment.<ref name="pmid12605964">{{cite journal| author=Egger E, Zografos L, Schalenbourg A, Beati D, Böhringer T, Chamot L et al.| title=Eye retention after proton beam radiotherapy for uveal melanoma. | journal=Int J Radiat Oncol Biol Phys | year= 2003 | volume= 55 | issue= 4 | pages= 867-80 | pmid=12605964 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12605964 }} </ref><ref name="pmid9514491">{{cite journal| author=Egan KM, Ryan LM, Gragoudas ES| title=Survival implications of enucleation after definitive radiotherapy for choroidal melanoma: an example of regression on time-dependent covariates. | journal=Arch Ophthalmol | year= 1998 | volume= 116 | issue= 3 | pages= 366-70 | pmid=9514491 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9514491 }} </ref> |
| *Extrascleral extension<ref name="pmid3014416">{{cite journal| author=Gragoudas ES, Seddon JM, Egan KM, Polivogianis L, Hsieh CC, Goitein M et al.| title=Prognostic factors for metastasis following proton beam irradiation of uveal melanomas. | journal=Ophthalmology | year= 1986 | volume= 93 | issue= 5 | pages= 675-80 | pmid=3014416 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3014416 }} </ref><ref name="pmid15519510">{{cite journal| author=Schmittel A, Bechrakis NE, Martus P, Mutlu D, Scheibenbogen C, Bornfeld N et al.| title=Independent prognostic factors for distant metastases and survival in patients with primary uveal melanoma. | journal=Eur J Cancer | year= 2004 | volume= 40 | issue= 16 | pages= 2389-95 | pmid=15519510 | doi=10.1016/j.ejca.2004.06.028 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15519510 }} </ref><ref name="pmid8248556">{{cite journal| author=Kleineidam M, Guthoff R, Bentzen SM| title=Rates of local control, metastasis, and overall survival in patients with posterior uveal melanomas treated with ruthenium-106 plaques. | journal=Radiother Oncol | year= 1993 | volume= 28 | issue= 2 | pages= 148-56 | pmid=8248556 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8248556 }} </ref><ref name="pmid7436829">{{cite journal| author=Affeldt JC, Minckler DS, Azen SP, Yeh L| title=Prognosis in uveal melanoma with extrascleral extension. | journal=Arch Ophthalmol | year= 1980 | volume= 98 | issue= 11 | pages= 1975-9 | pmid=7436829 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7436829 }} </ref>
| | *Detection of circulating [[tumor]] cells at the time of [[diagnosis]] is an independent [[risk factor]] for relapse and shortened survival in patients at high-risk based upon clinical parameters.<ref name="pmid17317826">{{cite journal| author=Schuster R, Bechrakis NE, Stroux A, Busse A, Schmittel A, Scheibenbogen C et al.| title=Circulating tumor cells as prognostic factor for distant metastases and survival in patients with primary uveal melanoma. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 4 | pages= 1171-8 | pmid=17317826 | doi=10.1158/1078-0432.CCR-06-2329 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17317826 }} </ref><ref name="pmid16314735">{{cite journal| author=Boldin I, Langmann G, Richtig E, Schwantzer G, Ardjomand N, Wegscheider B et al.| title=Five-year results of prognostic value of tyrosinase in peripheral blood of uveal melanoma patients. | journal=Melanoma Res | year= 2005 | volume= 15 | issue= 6 | pages= 503-7 | pmid=16314735 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16314735 }} </ref> |
| *Histological and cytological factors associated with higher risk of [[metastasis]] includes the following:
| | *The [[prognosis]] for any patient with recurring or relapsing disease is poor, regardless of [[cell type]] or stage. |
| **Presence and extent of [[cells]] with epitheliod morphology
| | |
| **Presence of looping [[extracellular matrix]] patterns
| | {| style="border: 0px; font-size: 90%; margin: 8px; width: 800px" align="center" |
| **Increased infiltration of immune cells<ref>Robbins, Stanley L., Vinay Kumar, and Ramzi S. Cotran. Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Saunders/Elsevier, 2010. Print.</ref>
| | | valign="top" | |
| **Staining with several immunohistochemical markers<ref name="pmid17425462">{{cite journal| author=Pardo M, Dwek RA, Zitzmann N| title=Proteomics in uveal melanoma research: opportunities and challenges in biomarker discovery. | journal=Expert Rev Proteomics | year= 2007 | volume= 4 | issue= 2 | pages= 273-86 | pmid=17425462 | doi=10.1586/14789450.4.2.273 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17425462 }} </ref>
| | |+ |
| *[[Cell]] type
| | == References == |
| :Cell type is the most commonly used predictor of outcome following [[enucleation]], with spindle-A cell melanomas carrying the best prognosis and epithelioid cell melanomas carrying the least favorable prognosis. Nevertheless, most tumors have an admixture of cell types, and there is no clear consensus regarding the proportion of epithelioid cells that constitutes designation of a tumor as mixed or epithelioid.
| |
| *Several additional microscopic features can affect the prognosis of intraocular melanoma, including:<ref name="NIH"> Uveal melanoma. National Cancer Institute(2015) http://www.cancer.gov/types/eye/hp/intraocular-melanoma-treatment-pdq#link/_304_toc Accessed on October 23, 2015</ref>
| |
| **Mitotic activity.
| |
| **[[Lymphocytic]] infiltration.
| |
| **Fibrovascular loops
| |
| **Extraocular extension, recurrence, and metastasis are associated with an extremely poor prognosis, and long-term survival cannot be expected. Systemic [[metastases]] may be wide spread, with the [[liver]] > [[lung]] > [[bone]] > [[kidney]] > [[brain]] being a common sites for tumor deposits.
| |
| **Uveal melanoma disseminates hematogenously, with a high propensity for liver, which is the most common (93%) site of metastasizing, followed by [[lung]] (24%) and [[bones]] (16%). It can also metastasize in brain and skin, or any other site in the body. The majority of patients with metastatic disease have metastases in multiple sites of body. Patients without liver metastases or with liver being not the first site of metastases have better prognosis.
| |
| **Patients with iris melanoma have better prognosis. In patients with iris melanoma at 5 and 10 years of follow up metastases were found in 4.1%, and 6.9%, respectively, compared to 15% and 25%, respectively, for [[choroidal]] [[melanomas]]. [[Ciliary body melanoma]] carries worse prognosis with metastases found at 5 and 10 years follow up in 19% and 33%, respectively.
| |
| **Uveal melanoma does not spread to regional [[lymph nodes]], due to lack of lymphatic drainage in [[uvea]] except in rare cases of direct invasion of [[conjunctiva]] and then through conjunctival lymphatics to regional lymph nodes. Five-year survival rates for uveal melanoma ranges from 69% to 81.6% and ten-year survival rates from 57% to 62%. After detection of metastases 80% of patients die within 1 year, and 92% within 2 year. Long term survivals are rare in patients with uveal melanoma, and mean survival is only few months.<ref name="pmid23826405">{{cite journal| author=Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V| title=Ocular melanoma: an overview of the current status. | journal=Int J Clin Exp Pathol | year= 2013 | volume= 6 | issue= 7 | pages= 1230-44 | pmid=23826405 | doi= | pmc=PMC3693189 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23826405 }} </ref>
| |
| *The 5-year mortality rate associated with metastasis from [[ciliary body]] or choroidal melanoma is approximately 30%, compared with a rate of 2% to 3% for iris melanomas.
| |
| *Overall survival depends on tumour size, extraocular spread, and [[metastases]]. Even small (<10 mm diameter, <3 mm thickness) tumors still carry a 10-15% 5-year mortality.
| |
| *The 10 year-survival for iris melanoma is approximately 95 percent and for ciliochoroidal tumors is 77 percent respectively.
| |
| *The most important genetic alteration associated with poor prognosis in uveal melanoma is inactivation of ''BAP1'', which most often occurs through [[mutation]] of one [[allele]] and subsequent loss of an entire copy of [[chromosome 3]] ([[monosomy 3]] ) to unmask the mutant copy.<ref name="pmid21051595">{{cite journal| author=Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA et al.| title=Frequent mutation of BAP1 in metastasizing uveal melanomas. | journal=Science | year= 2010 | volume= 330 | issue= 6009 | pages= 1410-3 | pmid=21051595 | doi=10.1126/science.1194472 | pmc=PMC3087380 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21051595 }} </ref> Because of this function in inactivation of ''BAP1'', monosomy 3 correlates strongly with metastatic spread.<ref name="pmid8622452">{{cite journal| author=Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jöckel KH, Becher R| title=Prognostic implications of monosomy 3 in uveal melanoma. | journal=Lancet | year= 1996 | volume= 347 | issue= 9010 | pages= 1222-5 | pmid=8622452 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8622452 }} </ref>
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| *Where ''BAP1'' [[mutation]] status is not available, gains on [[chromosomes 6]] and 8 can be used to refine the predictive value of the [[monosomy 3]] screen, with gain of 6p indicating a better prognosis and gain of 8q indicating a worse prognosis in [[disomy]] 3 [[tumors]].<ref name="pmid19182252">{{cite journal| author=Damato B, Dopierala J, Klaasen A, van Dijk M, Sibbring J, Coupland SE| title=Multiplex ligation-dependent probe amplification of uveal melanoma: correlation with metastatic death. | journal=Invest Ophthalmol Vis Sci | year= 2009 | volume= 50 | issue= 7 | pages= 3048-55 | pmid=19182252 | doi=10.1167/iovs.08-3165 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19182252 }} </ref>
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| *In rare instances, [[monosomy 3]] [[tumors]] may duplicate the ''BAP1''-mutant copy of the [[chromosome]] to return to a [[disomic]] state referred to as isodisomy. Thus, [[isodisomy 3]] is prognostically equivalent to [[monosomy 3]], and both can be detected by tests for chromosome 3 [[loss of heterozygosity]].<ref name="pmid17504992">{{cite journal| author=Onken MD, Worley LA, Person E, Char DH, Bowcock AM, Harbour JW| title=Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 10 | pages= 2923-7 | pmid=17504992 | doi=10.1158/1078-0432.CCR-06-2383 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17504992 }} </ref>
| |
| *Monosomy 3, along with other chromosomal gains, losses, amplifications, and LOH, can be detected in fresh or paraffin embedded samples by virtual [[karyotyping]].
| |
| *The most accurate prognostic factor is molecular classification by gene expression profiling of uveal melanomas. This analysis has been used to identify two subclasses of uveal melanomas:<ref name="pmid12750282">{{cite journal| author=Tschentscher F, Hüsing J, Hölter T, Kruse E, Dresen IG, Jöckel KH et al.| title=Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. | journal=Cancer Res | year= 2003 | volume= 63 | issue= 10 | pages= 2578-84 | pmid=12750282 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12750282 }} </ref> <ref name="pmid15492234">{{cite journal| author=Onken MD, Worley LA, Ehlers JP, Harbour JW| title=Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. | journal=Cancer Res | year= 2004 | volume= 64 | issue= 20 | pages= 7205-9 | pmid=15492234 | doi=10.1158/0008-5472.CAN-04-1750 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15492234 }} </ref>
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| **Class 1 tumors that have a very low risk of [[metastasis]].
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| **Class 2 tumors that have a very high risk of metastasis.
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| ::Gene expression profiling outperforms all of the above-mentioned factors at predicting metastatic spread of the primary tumor, including monosomy 3.<ref name="pmid17384575">{{cite journal| author=Petrausch U, Martus P, Tönnies H, Bechrakis NE, Lenze D, Wansel S et al.| title=Significance of gene expression analysis in uveal melanoma in comparison to standard risk factors for risk assessment of subsequent metastases. | journal=Eye (Lond) | year= 2008 | volume= 22 | issue= 8 | pages= 997-1007 | pmid=17384575 | doi=10.1038/sj.eye.6702779 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17384575 }} </ref><ref name="pmid18552379">{{cite journal| author=van Gils W, Lodder EM, Mensink HW, Kiliç E, Naus NC, Brüggenwirth HT et al.| title=Gene expression profiling in uveal melanoma: two regions on 3p related to prognosis. | journal=Invest Ophthalmol Vis Sci | year= 2008 | volume= 49 | issue= 10 | pages= 4254-62 | pmid=18552379 | doi=10.1167/iovs.08-2033 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18552379 }} </ref><ref name="pmid17332290">{{cite journal| author=Worley LA, Onken MD, Person E, Robirds D, Branson J, Char DH et al.| title=Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 5 | pages= 1466-71 | pmid=17332290 | doi=10.1158/1078-0432.CCR-06-2401 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17332290 }} </ref>
| |
| :The [[tumor]] [[node]] [[metastasis]] (TNM) staging system of the American Joint Committee on Cancer takes into account the key factors involved which are known to be of prognostic significance.<ref name="ShieldsMellen2013">{{cite journal|last1=Shields|first1=CarolL|last2=Mellen|first2=PhoebeL|last3=Morton|first3=SpenserJ|title=American joint committee on cancer staging of uveal melanoma|journal=Oman Journal of Ophthalmology|volume=6|issue=2|year=2013|pages=116|issn=0974-620X|doi=10.4103/0974-620X.116652}}</ref><ref name="pmid23664467">{{cite journal| author=Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA| title=American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients. | journal=Ophthalmology | year= 2013 | volume= 120 | issue= 10 | pages= 2066-71 | pmid=23664467 | doi=10.1016/j.ophtha.2013.03.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23664467 }} </ref>
| |
| *The prognosis is usually poor when local control is not achieved with the initial treatment.<ref name="pmid12605964">{{cite journal| author=Egger E, Zografos L, Schalenbourg A, Beati D, Böhringer T, Chamot L et al.| title=Eye retention after proton beam radiotherapy for uveal melanoma. | journal=Int J Radiat Oncol Biol Phys | year= 2003 | volume= 55 | issue= 4 | pages= 867-80 | pmid=12605964 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12605964 }} </ref> <ref name="pmid9514491">{{cite journal| author=Egan KM, Ryan LM, Gragoudas ES| title=Survival implications of enucleation after definitive radiotherapy for choroidal melanoma: an example of regression on time-dependent covariates. | journal=Arch Ophthalmol | year= 1998 | volume= 116 | issue= 3 | pages= 366-70 | pmid=9514491 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9514491 }} </ref>
| |
| :Detection of circulating tumor cells at the time of diagnosis is an independent risk factor for relapse and shortened survival in patients at high-risk based upon clinical parameters.<ref name="pmid17317826">{{cite journal| author=Schuster R, Bechrakis NE, Stroux A, Busse A, Schmittel A, Scheibenbogen C et al.| title=Circulating tumor cells as prognostic factor for distant metastases and survival in patients with primary uveal melanoma. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 4 | pages= 1171-8 | pmid=17317826 | doi=10.1158/1078-0432.CCR-06-2329 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17317826 }} </ref><ref name="pmid16314735">{{cite journal| author=Boldin I, Langmann G, Richtig E, Schwantzer G, Ardjomand N, Wegscheider B et al.| title=Five-year results of prognostic value of tyrosinase in peripheral blood of uveal melanoma patients. | journal=Melanoma Res | year= 2005 | volume= 15 | issue= 6 | pages= 503-7 | pmid=16314735 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16314735 }} </ref>
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| *The prognosis for any patient with recurring or relapsing disease is poor, regardless of cell type or stage.
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| ==References==
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| [[Category:Disease]]
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| [[Category:Ophthalmology]]
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