Uveal melanoma overview

Uveal melanoma Microchapters
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Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Uveal melanoma from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
Echocardiography and Ultrasound
CT
MRI
Other Imaging Findings
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Medical Therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D., Simrat Sarai, M.D. [2]

Overview

Uveal melanoma is a rare cancer arising from melanocytes of the eye involving the iris, ciliary body, or choroid. Iris melanomas are less common than choroidal melanomas. 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.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. 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. 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 iris, sunlight exposure, and trauma.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. A positive history of pre-existing iris nevus which increased in size, eye pain, visual loss, blurred vision, floaters, age between 50_70 years old, male gender, white race, pregnancy, impaired immune system, light colored-irides, sunlight exposure, trauma, and fluorescent lighting exposure is suggestive of uveal melanoma. The most common symptoms of uveal melanoma include ,eye pain, blurred vision, eye redness, loss of peripheral vision, poor or blurry vision in one eye, a dark spot on the iris, seeing flashing lights, and floaters. The optimal therapy for uveal melanoma depends on the size of the tumor. Surgery is the mainstay of treatment for uveal melanoma. The following types of surgery may be used resection, enucleation, and exenteration. Pharmacologic medical therapy is recommended among patients with metastatic disease and include chemotherapy, immunotherapy, and targeted therapy.

Historical Perspective

Uveal melanoma was first discovered by two Scottish surgeons, Allan Burns (1781–1813) and James Wardrop (1782–1869). Allan Burns described the first patients with uveal melanoma, Mrs Scot who had painless blindness in one eye and an opacity behind the lens.

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 retinoblastoma, coats disease, persistent fetal vasculature, astrocytic hamartoma, retinopathy of prematurity, ocular toxocariasis, familial exudative vitreoretinopathy, norrie’s disease, and coloboma.

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 iris, 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.

Diagnostic Study of Choice

There is no single diagnostic study of choice for the diagnosis of uveal melanoma, but uveal melanoma can be diagnosed based on ophthalmologic examination and imaging.

History and Symptoms

A positive history of pre-existing iris nevus which increased in size, eye pain, visual loss, blurred vision, floaters, age between 50_70 years old, male gender, white race, pregnancy, impaired immune system, light colored-irides, sunlight exposure, trauma, and fluorescent lighting exposure is suggestive of uveal melanoma. The most common symptoms of uveal melanoma include ,eye pain, blurred vision, eye redness, loss of peripheral vision, poor or blurry vision in one eye, a dark spot on the iris, seeing flashing lights, and floaters.

Physical Examination

Patients with uveal melanoma usually appear normal. Physical examination of patients with uveal melanoma is usually remarkable for ophthalmologic findings of melanoma.

Laboratory Tests

Some patients with uveal melanoma may have elevated liver enzyme level, which is usually suggestive of metastasis.

Electrocardiogram

There are no ECG findings associated with uveal melanoma.

X Ray

There are no x-ray findings associated with uveal melanoma.

Ultrasound

Ultrasound may be helpful in the diagnosis of uveal melanoma. Findings on an ultrasound suggestive of uveal melanoma include low reflectivity, vascularity inside the tumor, and acoustic hollowing. it can differentiate ciliary body cyst from tumor in lesions larger than 3 mm.

CT Scan

CT scan may be helpful in the diagnosis of uveal. Findings on CT scan suggestive of uveal melanoma include elevated mushroom shaped lesions, hyper-dense, and contrastenhancement.

MRI scan

MRI may be helpful in the diagnosis of uveal melanoma. Findings on MRI suggestive of uveal melanoma include high intensity mass lesion (due to melanin and hemorrhage) on T1, and low intensity mass lesion on T2. The lesion enhances with gadolinium.

Other Imaging Studies

PET scan, ultrasound biomicroscopy, optical coherence tomography, color fundus photography, fluorescein angiography, indocyanine green angiography, transillumination, and photography may be helpful in the diagnosis of uveal melanoma.

Other Diagnostic Tests

Biopsy may be helpful in the diagnosis of uveal melanoma.

Medical therapy

Pharmacologic medical therapy is recommended among patients with metastatic disease and include chemotherapy, immunotherapy, and targeted therapy.

Surgical therapy

Surgery is the mainstay of treatment for uveal melanoma. The following types of surgery may be used resection, enucleation, and exenteration.

Primary Prevention

There is no established method for prevention of uveal melanoma.

Secondary Prevention

There are no established measures for the secondary prevention of uveal melanoma.