Grand Rounds Conference Brett Mueller, D.O., Ph.D. 6/3/2016 University of Louisville Department of Ophthalmology and Visual Sciences

Patient Presentation CC: Blurry vision right eye HPI: 62 yo WF presents w/ progressive blurry vision OD for the past 11 months. She also mentions having monocular diplopia.

History POHx: Cataracts-NVS OU PMHx: 1) Hypertension w/ blood pressure being 141/81 in the ER. FAMHx: none ROS: none MEDS: none ALLERGIES: none

Exam 3--2 13 VA P T 14 EOM: full OU CVF: full OU No APD EOM: full OU CVF: full OU

Exam OD OS LIDS/LASHES WNL WNL CONJ WNL WNL CORNEA WNL WNL IRIS WNL WNL LENS 1-2+NS 1-2+NS

Fundus Photos OD Color fundus photos: Orange bigmen is lipofuscin. Retinal precipitates Color fundus photos: OD: 0.3 C/D, Large Macular elevation w/ inferior retinal precipitates and nasal RPE hyperplasia OS: 0.3 C/D, M, V, and P WNL

Ocular Ultrasound B scan hollowness, and low interreflecticity Elevated choroidal macular lesion measuring 12mm X 8mm X 5mm

Autofluorescence

OCT Retina Edge of lfuid there and all on that side

Summary DDx: Amelanotic Choroidal Melanoma Metastasis 62 y/o WF an elevated choroidal lesion in her right eye measuring 12mm X 10mm X 5mm DDx: Amelanotic Choroidal Melanoma Metastasis PLAN: Obtain FNA and place plaque for treatment. Melanoma systemic testing is

FNA of Choroidal Mass H&E Stain Sox10 S100 (Sample) Pleomorphic polyhedral cells with eosinophilic cytoplasm and a larger, rounder nucleus than spindle cells. SOX10 is a nuclear transcription factor that plays an important role in melanocytic cell differentiation The S100 family of proteins is a member of the calcium-binding EF-hand superfamily http://pathinfo.wikia.com/wiki/S100_Protein

Choroidal Melanoma Risk Factors To Find Small Ocular Melanoma Using Helpful Hints Daily Thickness > 2mm Subretinal fluid Symptoms Orange Pigment Margin w/in 3mm of the optic disc Ultrasonographic hollowness Absence of halo Absence of drusen Melanoma metastasis at 10 years was 10% for small melanoma (<3-mm thickness), 23% for medium-sized melanoma (3.1- to 8-mm thickness), and 52% for large melanoma (>8-mm thickness). More specifically, metastasis (per millimeter of thickness) at 10 years was found in 7% (0-1 mm), 13% (1-2 mm), 10% (2-3 mm), 16% (3-4 mm), 24% (4-5 mm), 27% (5-6 mm), 27% (6-7 mm), 39% (7-8 mm), 49% (8-9 mm), 53% (9-10 mm), and 58% (>10 mm) of cases. It is thus evident from these studies that tumor size strongly correlates with patient prognosis. Early detection of uveal melanoma at a time when the malignancy is small is critical in improving patients' survival. A halo refers to a pigmented choroidal nevus surrounded by a circular band of depigmentation.) istogenesis of cutaneous halo nevus involves damage to the nevus cells with vacuolization of cells and reduction in melanosomes in the halo. Invading macrophages display large aggregates of melanosomes. In the halo, the vacuolated melanocytes show coagulation of cytoplasm and autophagocytosis of melanosomes Shields CL, Furuta M, Berman EL, Zahler JD, Hoberman DM, Dinh DH, Mashayekhi A, Shields JA. Choroidal nevus transformation into melanoma: analysis of 2514 consecutive cases. Arch Ophthalmol. 2009 Aug;127(8):981-7. doi: 10.1001/archophthalmol.2009.151. PubMed PMID: 19667334.

Choroidal Melanoma Risk Factors Rishi P, Koundanya VV, Shields CL. Using risk factors for detection and prognostication of uveal melanoma. Indian J Ophthalmol. 2015 Feb;63(2):110-6. doi: 10.4103/0301-4738.154373. PubMed PMID: 25827540; PubMed Central PMCID: PMC4399118 Shields CL, CaterJ, Shields JA, Singh AD, Santos MC, Carvalho C. Combination of clinical factors predictive of growth of small choroidal melanocytic tumors. Arch Ophthalmol 2000;118:360‑4. Shields CL, Furuta M, Berman EL, Zahler JD, Hoberman DM, Dinh DH, et al. Choroidal nevus transformation into melanoma: Analysis of 2514 consecutive cases. Arch Ophthalmol 2009;127:981‑7.

Choroidal Melanoma Most common primary intraocular malignancy Age normally around 60 Histopathologically: spindle and epithelioid cell type Orbital spread through scleral channels and vortex veins Metastasis commonly found in the liver, and only 1-2 % of pts have detectable metastases at the time of presentation Mortality at 10 years is 50% CM is 80% of all uveal melanoma but is relaitly uncommon.

Amelanotic Choroidal Masses Differential Diagnosis Epidemiology Signs Symptoms Amelanotic Melanoma 50s and 60s White, blue-eyed blondes Orange pigment, serous retinal detachment, low internal reflectivity Asymptomatic  blurring of visionocular pain proptosis Choroidal Metastasis Males: lung (40%), GI (9%), kidney (8%) Females: Breast (68%), lung (12%) Yellow in color, subretinal fluid, high internal reflectivity Visual symptoms 90%: burred vision, flashes/floaters, and pain Choroidal hemangioma Rare, likely congenital, Caucasians Amelanotic, high internal reflectivity No symptoms until adulthood, Can get blurred vision 2ndary to RD http://www.slideshare.net/mtodman/choroidal-melanoma 88% of metastases are to the choroid, then iris and CB Choroidal can be bilateral and multifocal and have a lot of subretinal fluid if the mets are active. Very rarely metasis can be hollow FA and ICG for chroidal hemangioma http://www.eyerounds.org/cases/65-Choroidal-Hemangioma-Photodynamic-Therapy.htm http://atlasgeneticsoncology.org/Tumors/EyeTumOverviewID5272.html Differential Diagnosis Epidemiology Signs Symptoms Amelanotic Melanoma 50s and 60s White, blue-eyed blondes Orange pigment, serous retinal detachment, low internal reflectivity Asymptomatic  blurring of visionocular pain proptosis Choroidal Metastasis Males: lung (40%), GI (9%), kidney (8%) Females: Breast (68%), lung (12%) Yellow in color, subretinal fluid, high internal reflectivity Visual symptoms 90%: burred vision, flashes/floaters, and pain Choroidal hemangioma Rare, likely congenital, Caucasians Amelanotic, high internal reflectivity No symptoms until adulthood, Can get blurred vision 2ndary to RD

Conclusion Differentiate between choroidal nevus and choroidal melanoma To Find Small Ocular Melanoma Using Helpful Hints Daily Differential diagnosis of amelanotic choroidal masses Distinguish between amelanotic choroidal melanoma and metastasis to the choroid Sai chavala

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References Shields CL, Furuta M, Berman EL, Zahler JD, Hoberman DM, Dinh DH, Mashayekhi A, Shields JA. Choroidal nevus transformation into melanoma: analysis of 2514 consecutive cases. Arch Ophthalmol. 2009 Aug;127(8):981-7. doi: 10.1001/archophthalmol.2009.151. PubMed PMID: 19667334. Shields CL, CarterJ, Shields JA, Singh AD, Santos MC, Carvalho C. Combination of clinical factors predictive of growth of small choroidal melanocytic tumours. Arch Ophthalmol. 2000;188:360-4 Rishi P, Koundanya VV, Shields CL. Using risk factors for detection and prognostication of uveal melanoma. Indian J Ophthalmol. 2015 Feb;63(2):110-6. doi: 10.4103/0301-4738.154373. PubMed PMID: 25827540; PubMed Central PMCID: PMC4399118 Kanski’s Clinical Ophthalmology A systemic Approach, Eighth Edition. Brad Bowling Ophthalmic Pathology and Intraocular tumors, BSCS www.eyerounds.org  Phelps, P. O., et al. "Metastatic mixed germ-cell neoplasm presenting as retinal detachment." Journal of clinical oncology: official journal of the American Society of Clinical Oncology 30.13 (2012): e133 http://atlasgeneticsoncology.org/Tumors/EyeTumOverviewID5272.html http://www.eyerounds.org/cases/case12.htm Intraocular Tumors: An Atlas and Textbook By Jerry A. Shields, Carol L. Shields Gunduz K, Shields CL, Shields JA, et al. Presumed Choroidal granuloma with VH resembling choroidal melanoma Regillo C. Shields CL, Shields JA, et al. Ocular TB. JAMA 1991; 266; 1490 Demirci H, Shields CL, Shields JA, et al. Ocular TB masquerading as ocular tumors. Surv Ophthalmol 2004;49:78-89. Angioi K, Terrada C, Locatelli A, Hoang PL, Béné MC, Bodaghi B. Ocular Manifestations of X-linked Chronic Granulomatous Disease: About Two Atypical Case Reports. Ocul Immunol Inflamm. 2015 Dec;23(6):457-60. doi: 10.3109/09273948.2014.891753. Epub 2014 Mar 28. PubMed PMID: 24678791. http://eyewiki.aao.org/Primary_Vitreoretinal_Lymphoma