What ophthalmologists need to know about ocular cancer

Ophthalmologists may be first to make a diagnosis of eye cancer in patients who present with ocular tumors and should be aware of the various forms and types of disease.

By Liz Meszaros; Reviewed by Mary E. Aronow, MD

Bethesda, MD-Though cancers of the eye present rarely, it is vital for clinicians to familiarize themselves with the various forms and presentations of ocular cancer.

“Eye cancer is a rare disease,” said Mary E. Aronow, MD, a clinical fellow at the National Eye Institute, National Institutes of Health, Bethesda, MD.

The American Cancer Society projects that in 2014 in the United States, there will be about 2,730 new cases of eye cancer.¹

“It is important to take a good medical history and to perform a thorough ophthalmic examination in all patients who present with ocular tumors,” she said. “It is also important to remember the associations with various syndromes and masquerading conditions.”

Dr. Aronow reviewed some of the types of intraocular tumors comprehensive ophthalmologists should be aware of, including uveal melanoma, vascular tumors, retinoblastoma, and intraocular lymphomas.

Ancillary imaging studies-such as ultrasonography and angiography-are also helpful in distinguishing the various forms of intraocular tumors.

Uveal melanoma

Uveal melanoma is the most common primary intraocular malignancy in adults. The age-adjusted incidence in the United States is 5.1 per million.²

Though these tumors are frequently pigmented, they may also be amelanotic. Uveal melanoma is most commonly “collar-button,” dome, or lobulated in shape. Rarely, these tumors can present in a diffuse pattern or as a ring lesion. Clinical features-such as overlying orange pigmentation, subretinal fluid, or significant recent growth-can help to differentiate malignant melanoma from benign lesions, such as choroidal nevi.

On ultrasonography, uveal melanoma typically demonstrates regular structure, low internal reflectivity, and moderate-to-marked intrinsic vascularity. This is in contrast to other intraocular tumors, such as choroidal hemangioma or choroidal metastases, which commonly demonstrate high internal reflectivity on ultrasonography.

Vascular tumors

Several of the main vascular tumors of the retina include retinal capillary hemangioma, retinal cavernous hemangioma, and retinal vasoproliferative tumor.

“It is important to remember the association between retinal capillary hemangioma and von Hippel-Lindau (VHL) disease,” Dr. Aronow said.

Ophthalmologists may be first to make the diagnosis in these individuals. For this reason, genetic testing for VHL in patients with retinal capillary hemangioma is generally recommended. Vascular tumors of the choroid include circumscribed hemangioma, which occurs in the absence of systemic disease, and diffuse choroidal hemangioma, which is associated with Sturge-Weber Syndrome.

It is important to remember that individuals with Sturge-Weber Syndrome should also be monitored for glaucoma.

Retinoblastoma

Retinoblastoma is the most common intraocular malignancy of childhood. This disease results from mutation in the retinoblastoma gene, which is a tumor suppressor gene located on the long arm of chromosome 13 at region 14. The incidence of retinoblastoma is about 1 in 14,000 to 20,000 live births. In the United States, this translates to 250 to 300 new cases each year.³

About 60% of retinoblastoma cases are due to somatic, non-heritable mutations. Most of these mutations result in unilateral, solitary tumors. The remaining 40% of cases result from germline (heritable) mutations. There is a pre-existing familial germline mutation in 10% of cases, while the remaining 30% result from new germline mutations.³

The typical inheritance pattern is autosomal dominant.

“It’s very important to remember that even in unilateral retinoblastoma, 15% of cases result from germline mutations,” Dr. Aronow said. “This underscores the importance of genetic testing in these children.”

The presenting signs are somewhat different, depending on the age of the child, she added. Leukocoria is the most common presenting symptom, but in younger children, strabismus is also common.

In older children, symptoms including pain, decreased vision, and floaters may be present. The differential diagnosis of leukocoria is broad and includes cataract, Coats’ disease, persistent fetal vasculature, retinopathy of prematurity, toxocariasis, retinal detachment, familial exudative vitreoretinopathy, physiologic leukocoria, and retinoblastoma.

“A good clinical examination and ancillary imaging is important in helping to differentiate between these entities,” Dr. Aronow said.

A calcified mass within the globe of a child is highly suggestive of retinoblastoma. This can be seen with B-scan ultrasonography, or computed tomography scan of the orbits. Currently, most children undergo magnetic resonance imaging (with contrast) of the brain and orbits, which avoids radiation exposure, and can detect extraocular extension and exclude trilateral retinoblastoma (pinealoblastoma) in patients with germline mutations.

Intraocular lymphomas

Intraocular lymphomas can be divided into primary vitreoretinal lymphoma (PVRL), primary uveal lymphoma, and secondary intraocular manifestations of systemic lymphomas, Dr. Aronow continued.

PVRL is a variant primary central nervous system lymphoma. This is a very aggressive malignancy that is typically of diffuse large B-cell origin. The hallmark clinical features include vitreous cells and subretinal infiltrates.

“Despite treatment, the majority of patients with PVRL eventually develop CNS disease and have a poor prognosis,” Dr. Aronow said.

In contrast, primary uveal lymphoma is most frequently an extranodal marginal zone lymphoma that follows an indolent clinical course.

Though most patients may not die from this disease, there is a significant amount of morbidity and vision loss associated with this type of lymphoma, Dr. Aronow said. She added that these tumors are very rare, with only about 70 to 80 case reports in the literature.⁴

References

• The American Cancer Society: Cancer Facts & Figures 2014. Available at: http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014

• Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011;118:1881-1885.

• Singh AD, Damato BE, Pe’er J, Murphree AL, Perry JD, eds. Clinical Ophthalmic Oncology. Philadelphia, PA: Saunders-Elsevier; 2007.

• Aronow ME, Portell CA, Sweetenham JW, Singh AD. Uveal lymphoma: clinical features, diagnostic studies, treatment selection, and outcomes. Ophthalmology. 2014;121:334-431.

Mary E. Aronow, MD

P: 301/451-7362

E: marybeth.aronow@nih.gov

This article is adapted from Dr. Aronow’s presentation at the annual Current Concepts in Ophthalmology meeting at the Wilmer Eye Institute/Johns Hopkins University. Dr. Aronow has no financial disclosures.

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