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  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    4 Ophthalmic Pathology and Intraocular Tumors

    Part I: Ophthalmic Pathology

    Chapter 5: Conjunctiva

    Neoplasia

    Lymphoid Lesions

    Both benign and malignant lymphoid proliferations can occur in the conjunctiva. Normal conjunctiva contains mucosa-associated lymphoid tissue (MALT), including a few small lymphoid follicles that are often visible clinically in the normal inferior fornix. However, lymphoid tissue may proliferate abnormally in the conjunctiva, often in the absence of inflammatory signs; this lymphoid hyperplasia may be benign (reactive) or malignant. Clinically, both benign and malignant lymphoid conjunctival lesions appear as soft, mobile, salmon-pink masses with a smooth surface, characteristically localized to the forniceal and bulbar conjunctivae (Fig 5-25A, B). The condition may be unilateral (more common) or bilateral. An orbital component may also be present.

    Benign lymphoid hyperplasia consists of a polyclonal proliferation of lymphocytes, often with a follicular pattern demonstrating germinal centers. Lymphoma, a malignant neoplasm derived from a monoclonal proliferation of B or T lymphocytes and, less frequently, natural killer cells (NK cells), is divided into 2 major groups: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). The NHLs, a large heterogeneous group of neoplasms, can be divided into those originating from B lymphocytes and those developing from their precursors, T cells, and NK cells. Non-Hodgkin B-cell lymphoma is the most common type of lymphoma observed in the ocular adnexa.

    Figure 5-25 Lymphoid proliferations of the conjunctiva. Clinical photographs show a salmon-pink mass in the inferior fornix (A) and in the bulbar conjunctiva (B). C, Histologic examination of benign lymphoid hyperplasia reveals normal follicular architecture with a well-defined germinal center (G) and corona (C). D, Histologic examination of lymphoma shows a monotonous sheet of lymphocytes infiltrating the stroma, without well-defined follicles. Note the conjunctival epithelium (arrowhead).

    (Part A courtesy of Anthony J. Lubniewski, MD; part B courtesy of Anjali K. Pathak, MD; parts C and D courtesy of George J. Harocopos, MD.)

    Conjunctival lymphoid lesions require biopsy in order to determine the nature of the neoplasm (ie, benign vs malignant). Because the pathologic evaluation of these lesions is limited by the size of the biopsy specimen obtained, communication with the pathologist regarding optimal specimen submission (including handling and fixation) is essential. Histologic examination and IHC are routinely used to evaluate conjunctival lymphoid lesions. IHC analysis includes staining for a variety of lymphocyte antigens. When the submitted tissue is sufficient for additional studies, flow cytometry and molecular genetic studies can also be performed. Flow cytometry can be especially useful in identifying clonality, which is typical of lymphoid malignancies (see Chapters 2 and 3).

    On routine hematoxylin-eosin sections, histologic features favoring a diagnosis of benign lymphoid hyperplasia include the presence of normal-appearing lymphoid follicles with distinct germinal centers and with small, mature coronal lymphocytes (Fig 5-25C). In contrast, lymphoma frequently demonstrates a diffuse monomorphic sheet of lymphocytes in the stroma, without well-defined follicles (Fig 5-25D). IHC stains typically show a predominance of B lymphocytes that are often kappa or lambda light chain restricted. The most common type of lymphoma involving the conjunctiva is extranodal marginal zone B-cell lymphoma (MALT type) (Fig 5-26).

    Figure 5-26 Histology of conjunctival extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. A, Clinical photograph of a salmon-patch conjunctival lesion. B, H&E-stained preparation demonstrates a diffuse proliferation of small lymphocytes with mildly irregular nuclear contours, inconspicuous nucleoli, and scant cytoplasm. C, IHC staining shows that nearly all lymphocytes are CD20+, indicating the presence of mainly B cells. D, Scattered reactive T cells are positive with CD3. E, The lymphocytes are cyclin-D1 negative, and (F) show diffuse expression of BCL-2, a regulator of the cell cycle.

    (Courtesy of Hans Grossniklaus, MD.)

    Of all ocular adnexal lymphomas, a conjunctival tumor has the most favorable prognosis, as approximately 70%–75% of these lymphomas are localized to the conjunctiva, with the remainder associated with systemic disease. When a conjunctival lymphoma is diagnosed, systemic evaluation is necessary in order to exclude other sites of involvement (tumor staging). See BCSC Section 8, External Disease and Cornea, and Section 7, Oculofacial Plastic and Orbital Surgery, for additional discussion.

    Figure 5-27 Oncocytoma. A, Clinical photograph of a mass in the caruncle. B, Histology shows cystadenomatous proliferation of large polygonal epithelial cells with abundant, deeply eosinophilic cytoplasm. Some of the cells surround protein-filled lumina (arrows).

    (Part A courtesy of Mark J. Mannis, MD; part B courtesy of George J. Harocopos, MD.)

    • Kirkegaard MM, Coupland SE, Prause JU, Heegaard S. Malignant lymphoma of the conjunctiva: a major review. Surv Ophthalmol. 2015;60(5):444–458.

    • Shields CL, Chien JL, Surakiatchanukul T, Sioufi K, Lally SE, Shields JA. Conjunctival tumors: review of clinical features, risks, biomarkers, and outcomes—the 2017 J. Donald M. Gass Lecture. Asia-Pac J Ophthalmol. 2017;6(2):109–120.

    • Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoieticand Lymphoid Tissues. 4th ed. International Agency for Research on Cancer (IARC); 2008.

    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.

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