INTRAOCULAR LYMPHOMA

Intraocular lymphoma can be part of a primary, multicentric central nervous system-ocular lymphoma or it can occur as a metastatic uveal deposit associated with visceral lymphoma. In the older ophthalmic literature, primary ocular lymphoma has been called “reticulum cell sarcoma.” Intraocular lymphoma is more common in older and immunocompromised individuals. Diagnosis may be difficult to establish and is often delayed. Primary intraocular lymphoma is considered one of the “masquerade syndromes” because the clinical presentation can mimic those of other ocular conditions. Intraocular lymphoma should be considered in older patients with uveitis that is refractory to medical therapy.

Symptoms

Blurred vision and floaters may occur as a result of lymphomatous infiltration of the vitreous and other intraocular structures.

Clinical Features

Central nervous system-ocular lymphoma typically presents with a cellular vitreous infiltration with or without the presence of creamy deposits involving the retina, subretinal space, and retinal pigment epithelium (RPE). When present, the RPE detachments are the hallmark of ocular lymphoma. Intraocular lymphoma may mimic multifocal choroiditis with vitreous cells and multiple yellowish white RPE infiltrates. Uveal metastasis from a visceral lymphoma usually appears as an elevated, amelanotic choroidal mass. Most of these patients will have a previous diagnosis of systemic lymphoma. In some patients, there is overlap between these two presentations.

Ancillary Testing

Ultrasonography of the uveal mass can be helpful in ruling out melanoma. In the absence of known systemic lymphoma, definitive diagnosis usually requires a tissue biopsy. When vitreous cells are present, a core vitrectomy is often sufficient to obtain a specimen that can be diagnosed by cytopathology, immunohistochemistry, and flow cytometry. Occasionally, a retinal or choroidal biopsy is required.

Pathology/Pathogenesis

Most intraocular lymphomas are large cell lymphomas of B-cell lineage. These cells may infiltrate the vitreous, retina, subretinal space, sub-RPE space, and choroid. Rarely, T-cell lymphomas can involve the eye, and these cells are usually more aggressive.

Treatment/Prognosis

Central nervous system-ocular lymphoma is usually treated with external beam radiotherapy. Controversy exists as to whether the brain should be irradiated prophylactically or only if intracranial disease is present. Some centers also use adjunctival intrathecal chemotherapy. Uveal metastatic lymphoma can also be treated with external beam radiation if it does not respond to systemic therapy for the primary tumor. Prognosis is generally poor.

Systemic Evaluation

Systemic workup should include tests such as cranial magnetic resonance imaging, chest and abdominal computed tomography, bone marrow biopsy, and lumbar puncture to evaluate other potential sites of lymphoma. Lymphoma can be associated with immune deficiency, such as acquired immunodeficiency syndrome and immunosuppression following organ transplantation.

Fundus photograph of a 78-year-old woman with subretinal infiltrates. She was diagnosed with intraocular lymphoma.

This 58-year-old man had abrupt onset of floaters and blurred vision. He was originally diagnosed with

multifocal choroiditis but diagnostic vitrectomy revealed lymphoma cells.

Fundus photograph of a patient with intraocular lymphoma. Prominent vitreous cells reduce the quality of the photograph. Subretinal infiltrates were found in the peripapillary and superior fundus.

Midperipheral photograph of the same patient demonstrates the multifocal lesions at the level of the retinal pigment epithelium mimicking multifocal choroiditis.

MELANOCYTOMA

Melanocytoma is a special form of benign melanocytic uveal neoplasm that has a distinctive clinical and pathologic appearance. It can present in all age groups and races.

Symptoms

Melanocytoma is usually asymptomatic. Occasionally, a scotoma is noted due to nerve fiber layer damage.

Clinical Features

Melanocytomas commonly occur adjacent to or within the optic nerve, but they can arise anywhere in the uveal tract. Juxtapapillary tumors can cause nerve fiber layer defects or an afferent pupillary defect. Central retinal vascular obstruction has been described with melanocytoma of the optic nerve. Melanocytomas are a distinctive dark brown to black, with feathery margins. They are usually slightly elevated. Orange lipofuscin pigment and subretinal fluid are not often found. The vast majority of these tumors remain stable or grow only slightly over time, but there have been case reports of malignant degeneration.

Ancillary Testing

Baseline fundus photography is important for future monitoring. Visual field testing may identify visual field defects.

Pathology/Pathogenesis

Melanocytomas are composed of large, plump magnocellular nevus cells that are heavily pigmented. Bleaching of the specimen to remove the pigment reveals bland, regular, small nuclei consistent with a benign tumor.

Treatment/Prognosis

No treatment is usually recommended except in the rare instances of malignant degeneration, in which case the tumor is treated as a choroidal melanoma. The prognosis for survival is excellent except when malignant degeneration occurs. Vision may be affected by nerve fiber layer defects but usually remains stable.

Systemic Evaluation

No systemic evaluation is necessary.

Fundus photograph of a small melanocytoma. Melanocytomas usually occur adjacent to or within the optic disc.

Fundus photograph of a melanocytoma of the optic disc. Note the dark pigmentation. Importantly, there is no optic disc edema or hemorrhages that may indicate optic nerve invasion by a malignant tumor.

Juxtapapillary choroidal melanoma with optic nerve invasion. Note that this tumor has orange lipofuscin pigment over its surface, more consistent with melanoma than melanocytoma.

Fluorescein angiogram of a melanocytoma demonstrates hypofluorescence as a result of the darkly pigmented tumor.