Eye
Uvea (iris, choroid and ciliary body), limbus and sclera
Melanoma-uvea
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Last author update: 1 August 2018
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PubMed Search: Uveal melanoma review pathology
Table of Contents
Definition / general | Essential features | Epidemiology | Pathophysiology | Clinical features | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Whole mount images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Tretter EM, Schoenfield LR. Melanoma-uvea. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/eyeuveamelanoma.html. Accessed April 24th, 2024.
Definition / general
- Malignant neoplasm of melanocytes within uveal tract, including iris, ciliary body and choroid
Essential features
- Tumor center located in iris, ciliary body or choroid (Methods Mol Biol 2014;1102:397)
- Approximately half metastasize, almost exclusively to liver (Methods Mol Biol 2014;1102:397)
- Tumor size, location and cell type are the most important histopathologic prognostic factors but molecular testing plays an increasing clinical role in prognostication
Epidemiology
- Most common primary intraocular malignancy in adults (PDQ Cancer Information Summaries: Intraocular (Uveal) Melanoma Treatment [Accessed 7 August 2018])
- Incidence is 5.1 new cases per million people in United States, which is low compared to other countries (Ophthalmol Clin North Am 2005;18:75)
- Mean age at diagnosis is 61 years (Br J Ophthalmol 2015;99:1550)
- Risk factors include light skin, Caucasian race, light eye color, inability to tan; weak association with sunlight exposure (Cancer Causes Control 2003;14:251, Ophthalmol Clin North Am 2005;18:75)
Pathophysiology
- May arise from preexisting uveal nevi or de novo (Arch Ophthalmol 2009;127:981)
Clinical features
- Half of cases are asymptomatic and discovered on exam; half present with visual disturbance
- Melanoma of iris: presents as elevated mass with variable pigmentation, often with distortion of pupil and prominent vessels
- Melanoma of choroid: irregular, slate gray, solid, choroidal tumor that may extend through Bruch membrane into retina and vitreous producing retinal detachment, macular edema, choroidal hemorrhage; occasionally spreads along scleral canals into orbit, rarely invades optic nerve
- Melanoma of ciliary body: may interfere with accommodation or cause localized cataract
- Tends to spread through scleral emissary canal
- Up to half of cases metastasize
- Distant metastases nearly exclusively to liver (95%), sometimes to lung and bone (Methods Mol Biol 2014;1102:397)
- Lymphatic spread uncommon due to lack of lymphatic channels in eye
Radiology images
Contributed by Arun Singh, M.D.
B scan
Prognostic factors
- Size of tumor
- Ciliary body involvement
- Extension outside of orbit, metastasis and recurrence have very poor prognosis (Ophthalmology 1991;98:383)
- Cytogenetic abnormalities, particularly monosomy 3 and gain of 8q (Cancer Control 2016;23:93)
- Gene expression profiling (class 1A, 1B and 2) (Ophthalmology 2012;119:1596, Clin Cancer Res 2007;13:1466, Ophthalmology 2014;121:1281, JAMA Ophthalmol 2016;134:734)
- Histologic features: mitoses, cell type (spindle B versus epithelioid), extravascular matrix loops, tumor infiltrating lymphocytes and macrophages (PDQ Cancer Information Summaries: Intraocular (Uveal) Melanoma Treatment [Accessed 7 August 2018])
Case reports
- 19 year old man with melanoma of anterior chamber presenting as pigmentary glaucoma (Surv Ophthalmol 2017;62:670)
- 60 year old woman with sudden ocular pain (Indian J Ophthalmol 2018;66:1059)
- 63 year old woman with extension of choroidal melanoma after brachytherapy (Ophthalmology 2017;124:1503)
- 74 year old man with metastases treated with ipilimumab and nivolumab (Pigment Cell Melanoma Res 2017;30:558)
Treatment
- Episcleral brachytherapy utilizing radioactive seeds is the mainstay of eye sparing treatment and yields equivalent survival rates to enucleation (Arch Ophthalmol 2001;119:969, Clin Ophthalmol 2018;12:925)
- Location and size of tumor affect ability to use this mode of treatment (Brachytherapy 2014;13:1)
- Local resection for select tumors of the iris and ciliary body
- Enucleation reserved for large tumors (PDQ Cancer Information Summaries: Intraocular (Uveal) Melanoma Treatment [Accessed 7 August 2018])
- Rarely evisceration is necessary
Clinical images
Contributed by Lynn R. Schoenfield, M.D. and AFIP images
Fundoscopy
Ciliary body tumor
Orange pigment
Vessels over tumor are out of focus
Gross description
- Small uveal melanomas may be difficult to distinguish from a nevus clinically; size criteria are used
- Gross findings suspicious for melanoma include:
- Orange pigment
- Subretinal fluid
- Tumor thickness > 2 mm
- Low internal reflectivity on ultrasound examination
Gross images
Contributed by Lynn R. Schoenfield, M.D. and AFIP images
Uveal melanoma
Heavily pigmented choroidal tumor
Large transillumination defect
Ruptured Bruch membrane
Subretinal hemorrhage and total retinal detachment
Partially organized hemorrhage
Amelanotic tumor with retinal detachment
Extraocular extension
Iridocyclectomy
Tumor of ciliary body
Subluxation of lens
Extraocular extension
Vortex vein invasion
Whole mount images
AFIP images
Tightly packed melanoma cells
Tumor with exudative retinal detachment
Uveal tract diffuse tumor
Choroidal tumor with extraocular extension
Microscopic (histologic) description
- There are 2 distinct cell types and most tumors contain a combination of the 2:
- Spindle B cells: spindle shaped cells with large oval nuclei and distinct nucleoli
- Epithelioid cells: large polygonal cells with atypical nuclei, 1 or more prominent nucleoli and sometimes intranuclear pseudoinclusions
- Note that spindle A cells also exist, which are spindle shaped cells with slender nuclei that lack visible nucleoli; these are typically benign and are the melanocytes of uveal nevi
Microscopic (histologic) images
Contributed by Lynn R. Schoenfield, M.D.
Dome shaped melanoma
Epithelioid cells
Spindle B cells
PAS
HMB45+
MelanA+
MITF+
Positive stains
- HMB45: specific and sensitive
- S100: sensitive
- Vimentin, MelanA, MITF1 (Arch Pathol Lab Med 1996;120:497, Invest Ophthalmol Vis Sci 2002;43:2533, Methods Mol Biol 2014;1102:397)
- SOX10: highly sensitive for melanocytic proliferation
- Ki67 and pHH3: used to estimate proliferation rate but not for clinical management
Negative stains
- Cytokeratin markers should be negative but may sometimes stain focally
Molecular / cytogenetics description
- Monosomy 3, 8q gain and expression profiling (Invest Ophthalmol Vis Sci 2001;42:313, Clin Cancer Res 2007;13:1466)
Differential diagnosis
- Metastatic carcinoma (especially if amelanotic):
- Nevi:
- Small uveal melanomas may be difficult to distinguish from a nevus clinically; size criteria are used
- Clinical findings suspicious for melanoma include:
- Orange pigment
- Subretinal fluid
- Tumor thickness > 2 mm
- Low internal reflectivity on ultrasound examination
Board review style question #1
Which feature is suspicious for uveal melanoma as opposed to choroidal nevus?
- High internal reflectivity on ultrasound examination
- Lack of subretinal fluid
- Orange pigment
- Tumor thickness of 1.5 mm
Board review style answer #1
Board review style question #2
Large polygonal cells with 1 or more prominent nucleoli describe which cell type of uveal melanoma?
- Epithelioid cells
- Intermediate cells
- Spindle A cells
- Spindle B cells
Board review style answer #2
