Primary Uveal Lymphoma
Many cases of uveal lymphoid infiltration, formerly known as reactive lymphoid hyperplasia, are now recognized as low-grade B-cell marginal zone mucosa-associated lymphoid tissue (MALT) lymphomas of the uveal tract. Primary uveal lymphoma, though also a form of intraocular lymphoma, is distinct from PIOL, discussed earlier in the chapter. These lesions, which typically present in patients in the sixth decade of life, can occur in any part of the uveal tract (Fig 20-12). There is an overlap between uveal lymphoma and similar lymphoid proliferations in the conjunctiva and orbit, termed ocular adnexal lymphoma. For information on the pathology of ocular adnexal lymphoma, see Chapter 5 for conjunctival lymphoma and Chapter 14 for orbital lymphoma.
Figure 20-12 Uveal lymphoma, with concomitant ocular adnexal involvement. A, Slit-lamp photograph of a raised pink-orange “salmon patch” conjunctival lesion (asterisk) showing B-cell lymphoma. B, Multifocal creamy-yellow amelanotic choroidal lesions are seen ophthalmoscopically (arrows).C, Anterior segment optical coherence tomography (OCT) of the conjunctival lesion demonstrates a homogenous subepithelial mass (asterisk). D, OCT through the macula shows a diffusely thickened and irregular choroid (asterisk). E, B-scan ultrasonography shows a diffusely thickened choroid (yellow arrow) and crescentic, extrascleral lucencies (red arrows) that are pathognomonic for uveal lymphoma and represent extraocular collections of lymphoid cells. F, Histologic examination of the conjunctival biopsy specimen demonstrates a monomorphic sheet of small lymphocytes consistent with extranodal marginal zone B-cell lymphoma, as determined with additional special pathologic studies.
(Courtesy of Jesse L. Berry, MD.)
Patients with uveal lymphoma typically notice painless, progressive vision loss. Ophthalmoscopically, the presence of multifocal creamy-yellow amelanotic choroidal lesions tends to be most helpful in establishing the diagnosis (see Fig 20-12B); similar lesions may be seen in PIOL, although those lesions are located between the RPE and Bruch membrane and not in the choroid. Associated subretinal fluid is seen in some eyes, and diffuse uveal thickening is common. Secondary glaucoma may be present. Frequently, the delay between the onset of symptoms and diagnostic intervention is significant.
This rare disorder is characterized pathologically by localized or diffuse infiltration of the uveal tract by relatively mature lymphoid cells. Clinically, this condition can simulate posterior uveal melanoma, metastatic uveal carcinoma, sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, and posterior scleritis. Proptosis of the affected eye may occur in a small proportion of patients who develop simultaneous episcleral orbital infiltration. Of note, the component on the external surface of the sclera can be a polyclonal “reactive” lymphoid infiltrate.
Aronow ME, Portell CA, Sweetenham JW, Singh AD. Uveal lymphoma: clinical features, diagnostic studies, treatment selection, and outcomes. Ophthalmology. 2014;121(1): 334–341.
Fluorescein angiography depicts variable findings in patients with uveal lymphoma involving the choroid; ICG angiography provides superior characterization. Classically, multiple scattered hypocyanescent lesions are present, which correspond to the area of choroidal infiltration by the lymphoma. OCT, specifically EDI-OCT, reveals placoid or irregular lesions and thickening of the inner choroid, often associated with subretinal fluid (see Fig 20-12D). B-scan ultrasonography, the modality of choice for evaluation of choroidal lymphoma, typically reveals diffuse, homogenous choroidal thickening with associated secondary retinal detachment. A pathognomonic feature of uveal lymphoma is crescent-shaped areas of acoustically hollow extrascleral extension (see Fig 20-12E).
Biopsy confirmation should be targeted to the most accessible tissue. When extraocular involvement is present, biopsy of the involved conjunctiva or orbit may be considered. For isolated uveal involvement, FNAB or pars plana vitrectomy with biopsy may be indicated. Dense lymphoid infiltrates are seen on histologic evaluation. Coordination with the ophthalmic pathologist is crucial, as it increases the likelihood of diagnosis with appropriate specimen handling and cell marker studies.
Historically, eyes with uveal lymphoid infiltration were generally managed by enucleation. Current management emphasizes globe-conserving therapy aimed at vision preservation. Early intervention with low-dose ocular and orbital fractionated external beam radiotherapy may definitively manage the disease.
The prognosis for survival is excellent for patients with uveal lymphomas, as these are typically low-grade lymphomas, unlike PIOL. Preservation of visual function appears related to primary tumor location and secondary sequelae, including exudative retinal detachment or dysfunction from chronic tissue infiltration. Early intervention appears to improve the chances of visual preservation.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.