Uveal melanoma overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

Uveal melanoma is a cancer of the eye involving the iris, ciliary body, or choroid. Uveal melanoma arise from melanocytes in the uvea. Uveal melanoma is a rare disease, but the most common primary intraocular malignancy. Iris melanomas are less common than choroidal melanomas. Uveal melanoma may be classified into several subtypes based on their location, based on ophthalmoscopic examination and based on the cell type. According to the Callender classification, there are four subtypes of uveal melanoma based on the cell type. Genes involved in the pathogenesis of uveal melanoma include GNAQ, GNA11, and BAP1. Uveal melanoma is caused by a mutation in the DNA. The incidence of uveal melanoma in the United States is approximately 0.43 per 100,000 individuals. The majority of uveal melanoma cases are reported in Europe and United States. The incidence of uveal melanoma increases with age; the median age at diagnosis is 60 years. Males are more commonly affected with uveal melanoma than females. Uveal melanoma commonly affects individuals older than twenty years of age. Caucasians are more commonly affected with uveal melanoma than Africans. Common risk factors in the development of uveal melanoma are cutaneous and iris nevi, host pigmentation factors, ultraviolet light exposure, caucasian race, and certain inherited skin disorders such as dysplastic nevus syndrome and ocular melanocytosis. 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. Symptoms of uveal melanoma include eye pain, eye redness, loss of peripheral vision, poor or blurry vision in one eye, a dark spot on the iris, flashing lights, floaters, and symptoms of glaucoma. The optimal therapy for uveal melanoma depends on the size of the tumor. The various treatment modalities for uveal melanoma include enucleation, plaque brachytherapy, external beam proton therapy, transupillary thermotherapy, Gamma Knife stereotactic radiosurgery, and resection of the tumor.

Classification

Uveal melanoma may be classified according to cell type into 5 subtypes: Spindle A, spindle B, epitheliolid, mixed, and necrotic. Uveal melanoma may also be classified according to its location into 2 types, anterior uveal melanoma which contain iris melanoma, and posterior uveal melanoma which contains ciliary body melanoma and chroidal melanoma.

Pathophysiology

It is understood that uveal melanoma is the result of genetic mutations. Activating mutations in GNAQ or GNA11, genes encoding for G protein alpha subunits. These mutations lead to activation of downstream signaling pathways including the MAPK pathway in uveal melanoma. Inactivating somatic mutations are present in the gene encoding BRCA1-associated protein 1 (BAP1) on chromosome 3p21.1. The mutations in the gene BAP1 are strongly linked to metastatic spread and patient survival. Conditions associated with uveal melanoma include ocular nevi, impaired immune system, pregnancy, and trauma. On microscopic histopathological analysis, we have 5 subtypes according to cell type into: Spindle A, spindle B, epitheliolid, mixed, and necrotic.

Causes

Uveal melanoma is caused by a mutation in the DNA.

Differential Diagnosis

Uveal melanoma must be differentiated from pigmented nevi, congenital hypertrophy of the retinal pigment epithelium, optic disc melanocytoma, hypertrophy of the retinal pigment epithelium, hyperplasia of retinal pigment epithelium, choroidal hemangioma, choroidal metastasis, choroidal osteoma, peripheral exudative hemorrhagic chorioretinopathy, choroidal hemorrhage, hemorrhagic detachment of retina and retinal pigment epithelium, posterior nodular scleritis, intraocular leiomyoma, adenoma of retinal pigment epithelium, retinoblastoma, uveal metastasis, choroidal detachment, choroidal hemangioma, choroidal cyst, uveal neurofibroma, and uveal schwannoma.

Epidemiology and Demographics

The incidence of uveal melanoma in the United States is approximately 0.43 per 100, 000 individuals. The incidence of uveal melanoma is approximately .53 to 1.09 cases per 100, 000 individuals worldwide. The incidence of uveal melanoma increases with age; the median age at diagnosis is 70 years. Males are more commonly affected with uveal melanoma than females. The incidence of uveal melanoma in males and females is approximately 0.49 and 0.37 per 100,000 individuals respectively. Uveal melanoma usually affects individuals of the caucasians race.

Risk Factors

Common risk factors in the development of uveal melanoma include advanced age, male gender, white race, genetic, ocular nevi, pregnancy, impaired immune system, light colored irides, sunlight exposure, and trauma.

Screening

According to the United States Preventive Services Task Force, screening for uveal melanoma is not recommended.

Natural History, Complications and Prognosis

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.

Staging

According to the American Joint Committee on Cancer, there are four stages of uveal melanoma based on the tumor size, spread to nearby lymph nodes, and metastasis. Each stage is assigned a number 0 through 4 that indicate increasing severity and letters T, N, and M that designate the tumor size, spread to nearby lymph nodes, and metastasis respectively.

History and Symptoms

Symptoms of uveal melanoma include eye pain, eye redness, loss of peripheral vision, poor or blurry vision in one eye, a dark spot on the iris, flashing lights, floaters, and symptoms of glaucoma.

Physical Examination

Common physical examination findings of uveal melanoma include presence of dark spot on the iris, anisicoria, loss of peripheral vision, decreased visual acuity and photopsia.

Laboratory Tests

Some patients with uveal melanoma may have elevated concentration of complete and differential blood counts and elevated liver enzyme levels, which is usually suggestive of metastasis of uveal melanoma to the liver.

Chest X Ray

Chest x-rays may be performed to detect metastases of uveal melanoma to the lungs.

CT Scan

On head and neck CT scan, uveal melanoma is characterized by elevated, hyperdense sharply marginated lenticular or mushroom shaped lesions that enhance with administration of contrast.

MRI scan

Head and neck MRI scan is diagnostic of uveal melanoma. On head and neck MRI, uveal melanoma is characterized by isointense to hypointense mass on T1-weighted MRI and hyperintense mass on T2-weighted MRI.

Ultrasound

On ultrasound, uveal melanoma is characterized by internal vascularity, collar button shape, and solid low to medium echotexture.

Other Imaging Studies

Other imaging studies of uveal melanoma include PET scan, ultrasound biomicroscopy, optical coherence tomography, color fundus photography, fluorescein angiography, indocyanine green angiography, transillumination, and photography.

Other Diagnostic Tests

Other diagnostic studies for uveal melanoma include biopsy.

Medical therapy

The optimal therapy for uveal melanoma depends on the size of the tumor. The various treatment modalities for uveal melanoma include enucleation, plaque brachytherapy, external beam proton therapy, transupillary thermotherapy, Gamma Knife stereotactic radiosurgery, and rection of the tumor.

Surgical therapy

Surgery is the mainstay of treatment for uveal melanoma.

Primary Prevention

There is no established method for prevention of uveal melanoma.

Secondary Prevention

Secondary prevention strategies following uveal melanoma include dilated fundus examination, liver function tests, abdominal MRI and abdominal ultrasound.