Classification schemes for lymphoid neoplasms remain problematic, and classification of these lesions is a work in progress. Most classifications of lymphoid lesions have been based on lymph node architecture; such nodal classifications have therefore been difficult to apply to extranodal sites such as the ocular adnexa. Classification remains important with regard to selection of treatment protocols and prognostication. In general, diagnosis of lymphoma involves identifying a monoclonal population of lymphocytes. Because there are no lymph nodes in the orbit, it is problematic to classify these lesions according to the criteria used for lymph nodes.
Ocular adnexal lymphoproliferative lesions are traditionally divided into reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and ocular adnexal lymphoma (OAL). Many orbital lymphoid masses previously classified as reactive or atypical hyperplasia would now be considered neoplasia with newer, more specific diagnostic techniques such as IHC and flow cytometry, as well as with molecular testing. OAL is subtyped according to the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition.
Unlike patients with NSOI, those with orbital lymphoproliferative lesions present with gradual, painless progression of proptosis. Bilateral disease, which may occur, is suggestive of systemic disease. Staging of patients with orbital lymphoproliferative lesions should be done in collaboration with a medical oncologist. Studies may include positron emission tomography (PET) imaging and bone marrow biopsy.
When a biopsy of an orbital or conjunctival lymphoproliferative lesion is to be performed, the ophthalmologist should consult with the pathologist in advance to determine the optimal method for handling the tissue, including the type of fixative to use and the volume of tissue to obtain. It is very important that the tissue be handled gently; crush artifact can prevent the pathologist from rendering a diagnosis. Fresh (unfixed) tissue is required for touch preparations and flow cytometry. Exposure of the biopsy specimen to air for long periods should be avoided. Tissue samples may be wrapped in saline-moistened gauze or placed in tissue culture medium to slow autolysis. Gene rearrangement studies and IHC can be performed on fixed tissue. See Chapter 3, Table 3-1, for a checklist for requesting an ophthalmic pathology consultation.
Olsen TG, Heegaard S. Orbital lymphoma. Surv Ophthalmol. 2019;64(1):45–66.
Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoieticand Lymphoid Tissues. 4th ed. International Agency for Research on Cancer; 2008.
Reactive lymphoid hyperplasia (RLH) is characterized histologically by prominent lymphoid follicles with germinal centers (Fig 14-9), tingible body macrophages (containing apoptotic debris), and a polymorphous population of mature lymphocytes. Other inflammatory cells may be present in small numbers in the infiltrate. Atypical lymphoid hyperplasia (ALH) involves diffuse lymphoid proliferation, generally without reactive germinal centers. Histologically, it is characterized by an admixture of small, mature-appearing lymphocytes and larger lymphoid cells of unknown maturity. RLH and ALH are believed to represent one end of a continuum of lymphoproliferative lesions, with lymphoma at the other end.
Lymphomas of the orbit may be a presenting manifestation of systemic lymphoma or may be a localized orbital neoplasm. Orbital lymphomas are generally non-Hodgkin low-grade B-cell tumors with an excellent prognosis. Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is the most common type of lymphoma seen in the orbit. Other types of lymphoma, typically non-Hodgkin lymphomas such as follicular, large B-cell, and mantle cell, occur in the orbit but with a lower incidence. Each of these subtypes has a different prognosis for survival, and different treatment regimens tend to be used for each. Orbital lymphomas constitute one-half of the malignant tumors arising in the orbit and ocular adnexa.
Figure 14-9 Reactive lymphoid hyperplasia of the orbit. The photomicrograph shows a dense infiltrate of lymphoid cells with a follicular pattern and well-formed germinal centers (asterisks). A panel of immunohistochemical stains (not shown) demonstrated a polyclonal population of lymphocytes.
(Courtesy of Nasreen A. Syed, MD.)
Histologically, orbital lymphomas typically demonstrate a monomorphic sheet of lymphocytes and are composed of B-cells with immunopositivity for CD19 and CD20 (Fig 14-10). Immunophenotyping with different lymphocytic markers is used to further subclassify these tumors. T-cell lymphomas of the orbit are rare, more aggressive, and immunopositive for CD3, CD4, and CD8. The risk of secondary orbital involvement in systemic lymphoma is approximately 1%–2%; however, the risk of systemic lymphoma developing in a patient with orbital lymphoma is in the range of 30%–40%. The incidence of orbital lymphoma is increasing.
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.