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�D^^�^^^^^@@�^^^�^^^^��������������������������������������������������������������������� ^^^^^^^^^�	�:	Title:
Choroidal Melanoma Of Left Eye With Very Early Liver Metastasis � A Case Report

Abstract
Uveal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid (collectively referred to as the uvea). The liver is a frequent site for metastasis in patients with uveal melanoma. The interval between the diagnosis of the uveal melanoma and the diagnosis of the metastatic lesion can vary. Despite therapy, the median survival of those with liver metastasis is five to seven months.
We report here a case of choriodal melanoma in a 45 year old male smoker presented with liver metastasis within just eight months after completion of initial treatments consists of enucleation of eye and Three Dimensional �conformal radiation therapy (3D-CRT). The metastasis is an incidental finding on imaging after having some vague symptoms. This very early metastasis after completing initial treatment is very rare and proves the aggressiveness of the disease.
Key words: uveal melanoma, liver metastasis, metastasis,
Key Messages: Metastasis should be zealously sought following treatment of a primary leison



Introduction:
Uveal melanoma is a cancer of the eye involving the iris, ciliary body, or choroid. Tumors arise from the pigment cells (melanocytes) that reside within the uvea giving color to the eye. These melanocytes are distinct from the retinal pigment epithelium cells underlying the retina that do not form melanomas
Melanomas are the most common primary intraocular malignancy in adults 1 .They represent 5% of all melanomas 1 but, because of the high rate of metastases and poor response to treatment, they account for about 13% of melanoma deaths 2.
In the COMS (The Collaborative Ocular Melanoma Study) the liver was the most common site (89% in patients with metastasis); the death rate following the report of melanoma metastasis was 80% at 1 year and 92% at 2 years 3, 4. Fifty percent of patients develop metastases within minimum five years to 24 years after treatment of the primary tumor, and the liver is involved 90% of the time5.
This report describes a rare case of a patient of choriodal melanoma left eye who developed very early liver metastasis within just eight months even after completion of initial treatment of the primary tumor consists of enucleation and 3 dimensional conformal radiation therapy (3D-CRT). Hence, Metastasis should be zealously sought following treatment of a primary lesion.

Case Report:
A 45 year old male smoker presented with gradual blurring of vision for last one month without any other significant abnormality in the month of October�13. After consulting physicians and ophthalmologists, he underwent USG (Ultrasonography) B scan (16/11/2013) of left eye which showed choriodal mass (14.5mmx10.25mm) overlying the disc showing sound attenuation, with retinal detachment and choroidal excavation s/o choriodal melanoma (FIGURE.1).Computed Tomography (CT) scan brain (18/11/13) showed hyperdense mass located on posterior segment of left eyeball, confined within left eyeball and no obvious orbital extension, other segment of brain showing no abnormality (FIGURE.2). Then he underwent enucleation of left eye with an implant placement on 6/12/2013.The chest X-ray, USG of whole abdomen and Liver Function Test before the operation were within normal limit.
The histopathology of the enucleated specimen showed spindle cell type of choroidal melanoma of left eye ball (PT2C NX).Tumor size-10.0x8.0mm; involvement of sclera and retina present; extra scleral extension present (less than 5.0 mm) but without ciliary body involvement; cut end of optic nerve-free from malignancy. Slides examination revealed histopathological features of a tumor mass composed of cells arranged in nests. The cells are highly pleomorphic and have large atypical irregular hyperchromatic nuclei, prominent eosinophilic nucleoli and scanty cytoplasm. Melanin pigments are present in between the cells and also within cytoplasm of some cells (FIGURE.3) & Immunohistochemistry(IHC) showed the cells were reactive to Cytokeratin(CK),HMB45,S100(FIGURE.4,5,6).
He underwent 3Dimentional-Conformal Radiation Therapy (3D-CRT) at our hospital from 10/01/2014 to 14/02/2014 of total dose 45Gray and 25 fractions to his left eye. No brachytherapy or boost or concurrent chemo radiations were used (FIGURE.7).
He was on follow up. Around 8 months later, he had developed some vague symptoms like loss of appetite and weakness. USG of whole abdomen (31/10/2014) reported as multiple small hypoechoic lesions spread throughout liver and then CECT scan of abdomen (04/11/2014) documented it (FIGURE.8) as secondary deposits in liver. FNAC from the liver lesions proved metastatic choriodal melanoma (FIGURE.9). On abdominal examination liver is found to be enlarged around 3cm from below the lower costal margin, sharp regular margin, smooth surface, mild tenderness of right hypochondrium. According to the decision of the medical board, now the patient is receiving chemotherapy.


Discussion:
Choriodal melanoma is a very aggressive type of tumor.� If you are newly diagnosed with a primary choroidal "intraocular" melanoma, you are likely to have no signs or symptoms of metastatic melanoma. Even with total body PET/CT imaging, less than 4% of patients are found to have their melanomas spread to other parts of their body at the time of diagnosis of their eye tumor. But, many more will be found to have metastasis over the following years. This is because there is no test that can find microscopic metastatic tumors� 6.
Here, we present a case of very early metastasis (within eight months of completion of initial treatment) from choroidal melanoma. There are some studies which showed metastasis developed after a short and long disease free interval 7, 8 . Again, a 1986 study (Gragoudas et al )9 showed a 20% cumulative risk of developing metastasis 5 years after irradiation, based on 128 patients followed for a median of 5.4 years. 780 eyes (which included many of the 128 noted above) followed for a median of 2.2 years, 8% of that study population actually developed metastases, the median time to detection being 2.1 years10.
Sixty-five of the 237 patients died of confirmed or suspected metastatic melanoma during the follow-up interval, with 55 of these deaths occurring during the first 5 posttreatment years. The cumulative actuarial survival of this group of patients with posterior uveal melanoma was 75.7% (standard error [SE] = 2.9%) at 5 years and 68.5% (SE = 3.5%) at 8 years posttreatment.11
The cumulative rates of metastases in the Collaborative Ocular Melanoma Study (COMS) at 5 and 10 years after treatment were 25% and 34%, respectively. Common sites of metastases include liver (90%), lung (24%), and bone (16%) 12, 13
The median time from diagnosis of choroidal melanoma to diagnosis of metastasis was 44.8 months (3.7 years). Ten of the 13 patients with metastasis (76.9%) were diagnosed within the first 5 years after treatment (irradiation).14. Previous case studies have shown intervals of 10, 15, and even 24 years.15, 16, 17
Prognosis after metastatic disease remains poor. Once liver is involved the median survival of patients after diagnosis of liver metastasis ranges from 2 to 9 months 18,19.
No studies are found in supporting very early liver metastasis within eight months after completion of the initial treatment of primary choroidal melanoma of eye.
Acknowledegments:
We thank the Department of Pathology at the SGCCRI, Kolkata, for providing us enormous support.

Reference:
Singh AD, Bergman L, Seregard S. Uveal melanoma: epidemiological aspects. Ophthalmol Clin North Am 2005;18:75.
Albert DM, Ryan LM, Borden EC. Metastatic ocular and cutaneous melanoma: a comparison of patient characteristics and prognosis. Arch Ophthalmol 1996;114:107.3.
Diener-West M, Reynolds SM, Agugliaro DJ, et al. Collaborative Ocular Melanoma Study Group. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: COMS report no. 26. Arch Ophthalmol 2005;123:1639.
4.  Agarwala SS, Panikkar R, Kirkwood JM. Phase I/II randomized trial of intrahepatic arterial infusion chemotherapy with cisplatin and chemoembolization with cisplatin and polyvinyl sponge in patients with ocular melanoma metastatic to the liver. Melanoma Res 2004;14:217.
5.   Spagnolo, Francesco; Graziano Caltabiano; Paola Queirolo (January 2012). "Uveal melanoma".Cancer Treatment Reviews, Volume 38, Issue 5, Pages 549�553, August 2012

6.    HYPERLINK "http://www.eyecancer.com/conditions/30/metastatic-choroidal-melanoma"http://www.eyecancer.com/conditions/30/metastatic-choroidal-melanoma
7.   Teruya Komatsu, Terumasa Sowa et al. A case of solitary pulmonary metastasis of        choroidal melanoma with an exceptionally long disease-free period. Int J Surg Case Rep. 2013; 4(10):849�851 .
8.    Gragoudas et al. Long-term risk of local failure after proton therapy for choroidal/ciliary body melanoma. Trans Am Ophthalmol Soc. 2002; 100: 43�49.
9.      Gragoudas ES, Seddon Jm et.al. Long-term results of proton beam irradiated uveal melanomas.Ophthalmology. 1987 Apr; 94(4):349-53.
10.    Gragoudas ES, Seddon JM, Egan KM, et al. Metastasis from uveal melanoma after proton beam irradiation. Ophthalmology. 1988;95:992�9.
11.    James J. Augsburger, MD et al. Clinical Prognostic Factors in Patients With Posterior Uveal Malignant Melanoma. Cancer , Volume 66, Issue 7, Article first published online: 29 JUN 2006.
12.   Diener-West M., Reynolds S.M., Agugliaro D.J. Screening for metastasis from choroidal melanoma: the collaborative ocular melanoma study group report 23. Journal of Clinical Oncology. 2004;22(12):2438�2444.
13.     Group COMS 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. Archives of Ophthalmology. 2001;119(5):670�676.
14. Chryssanthi Koutsandrea, Marilita M Moschos et. Al. Metastasis rates and sites after treatment for choroidal melanoma by proton beam irradiation or by enucleation. Clin Ophthalmol. Dec 2008; 2(4): 989�995.
15.     Slattery E, O�Donoghue D. Metastatic melanoma presenting 24 years after surgical resection: a case report and review of the literature. Cases J. 2009; 2:189.
16.   Grosjean J, Penel N, Gauthier H, Vanseymortier L. [Ultra-late metastasis of ocular melanoma: about two cases]. Rev Med Interne. 2004;25:147-149.
17.  B Brasiuniene, V Sokolovas et.al. Combined treatment of uveal melanoma liver metastases. European Journal of Medical Research�2011,�16:71-75
18.   Feldman ED, Pingpank JF and Alexander HR Jr: Regional treatment options for patients with ocular melanoma metastatic to liver. Ann Surg Oncol 11: 290-297, 2004.
19.  Kath R, Hayungs J et.al. Prognosis and treatment of disseminated uveal melanoma. Cancer. 1993 Oct 1;72(7):2219
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