Intraocular Lymphoma

Primary neoplastic involvement of the vitreous is uncommon because of the relatively acellular nature of the vitreous. However, the vitreous can be the site of primary involvement in cases of large cell lymphoma, which has been referred to as primary intraocular lymphoma (PIOL) and vitreoretinal lymphoma. Immunohistochemical and molecular genetic studies have confirmed that this entity is typically a B-cell lymphoma; however, T-cell lymphomas may occur in rare instances.

Clinically, PIOL presents most commonly as a vitritis. Some patients have sub-RPE infiltrates with a characteristic speckled pigmentation overlying tumor detachments of the RPE (Fig 10-14). Evidence suggests that the lymphoma cells may be attracted to the RPE by B-cell chemokines and subsequently migrate from the sub-RPE space into the vitreous. In more than half of patients presenting with ocular findings, the central nervous system is or will become involved. Neuroimaging of the brain is essential in the workup of patients with PIOL (Fig 10-15). See Chapter 20 for more information on the clinical aspects of PIOL.

The diagnosis of PIOL can be challenging and relies primarily on cytologic analysis of vitreous and/or subretinal specimens. Cytologically, the vitreous infiltrate in PIOL is heterogeneous. The atypical cells are large lymphoid cells, frequently with a convoluted nuclear membrane and multiple, conspicuous nucleoli. An accompanying infiltrate of small lymphocytes is almost always present, and the normal cells may obscure the neoplastic cell population. These small round lymphocytes are mostly reactive T cells. Necrotic cells are usually present, and this feature is very suggestive of a diagnosis of intraocular lymphoma (Fig 10-16). Immunohistochemically, the viable tumor cells typically label with B-cell markers. Flow cytometry may be helpful in demonstrating a monoclonal population. Other laboratory tests that may be useful in the diagnosis of intraocular lymphoma include a panel of immunohistochemical markers (if the amount of tissue is sufficient) and molecular studies for lymphocyte gene rearrangement and translocation, as well as for MYD88 mutations (found in 69% of cases of PIOL). An interleukin-10 to interleukin-6 ratio that is greater than 1.0 may be useful if this testing is available in the pathology laboratory.

Figure 10-14 Sub-RPE infiltrates in a patient with primary intraocular lymphoma (PIOL). A, Note the characteristic speckled pigmentation over the tumor detachments of the RPE. B, OCT image shows disruption of the RPE cell layer and tumor cells on top of the RPE cells (arrows).

(Part A courtesy of Robert H. Rosa Jr, MD; part B courtesy of Steffen Heegaard, MD.)

Figure 10-15 Axial computed tomography (CT) scan of the brain showing lymphomatous infiltrates (arrows).

(Courtesy of Steffen Heegaard, MD.)

Figure 10-16 Cytologic appearance of PIOL (vitreoretinal lymphoma). Note the atypical cells with hyperchromatic nuclei, prominent nucleoli, and scant cytoplasm (arrowhead). Numerous necrotic, smudgy cells (arrows) are present. Inset: Atypical lymphoid cells with irregular nuclear contours are shown.

(Courtesy of Robert H. Rosa Jr, MD.)

The diagnosis of PIOL relies on good communication between the vitreoretinal surgeon and the pathologist prior to scheduling a biopsy. Each pathology laboratory has its own preferred methods for how a specimen is collected and submitted for pathologic analysis. Also, the amount of tissue in the specimen is usually small, which can be a limiting factor when a diagnosis is being made. To avoid performing multiple biopsies for a definitive diagnosis, the clinician should ensure that the pathologist is experienced with handling and diagnosing PIOL.

The subretinal/sub-RPE infiltrates are composed of neoplastic lymphoid cells. With or without treatment, the subretinal infiltrates may resolve, leaving a focal area of RPE atrophy. Optic nerve and retinal infiltration may also be present. Infiltrates in these locations tend to be perivascular and may lead to ischemic retinal or optic nerve damage. The choroid is typically free of lymphoma cells; however, a secondary reactive population of chronic inflammatory cells may be present in the choroid (Fig 10-17). In the setting of systemic lymphoma with ocular involvement, the choroid (rather than the vitreous, retina, or subretinal space) is usually the primary site of involvement. See Chapter 12 for more information on choroidal lymphoma.

Figure 10-17 Histologic section through retina and choroid showing PIOL. Note the detachment of the RPE by tumor (arrows), the overlying retinal gliosis (asterisk), and the intact Bruch membrane (arrowhead). Secondary chronic inflammation is present in the under lying choroid.

(Courtesy of Robert H. Rosa Jr, MD.)

• Chan CC, Rubenstein JL, Coupland SE, et al. Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium. Oncologist. 2011;16(11):1589–1599.

• Coupland SE. Molecular pathology of lymphoma. Eye (Lond). 2013;27(2):180–189.

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.