A 66-year-old Caucasian woman presented with conjunctival redness and irritation of the right eye, as well as increased tear production of 6 months’ duration. Prior to seeing her ophthalmologist, she had noticed a palpable area in the upper inner quadrant of her right eye. An eye exam revealed a painless, pink, fleshy patch on the right eye, with a smooth surface in the superior aspect of the nasal bulbar conjunctiva. A mild ptosis on the right side was also noted.
There were no palpable preauricular, submandibular, or cervical lymph nodes. The physical examination was otherwise normal. Complete blood count, metabolic panel, serum lactate dehydrogenase levels, serum protein electrophoresis, and beta2-microglobulin levels were normal. MRI of the face and orbit (Top) revealed ill-defined, asymmetric soft tissue density and enhancement on the superior right orbit.
CT of the neck, chest, abdomen, and pelvis were negative. A conjunctival biopsy of the lesion was performed (Bottom). Histologic sections showed a monotonous population of predominantly small round lymphocytes with poorly defined, follicular-appearing dense areas extending into conjunctival epithelium. Immunophenotyping studies were positive for CD20, but negative for CD5, CD10, CD23, and CD3. Gene rearrangement analysis revealed rearrangement of the immunoglobulin gene with kappa light chain restriction.
D. Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue
Benign reactive lymphoid hyperplasia of the conjunctiva (Answer A) is a benign lymphoproliferative condition encompassing a wide spectrum of disorders. Before the advent of immunophenotyping and molecular diagnostic techniques, mucosa-associated lymphoid tissue (MALT) lymphomas were frequently misdiagnosed as reactive lymphoid hyperplasia or “pseudotumors” because of their cellular heterogeneity and presence of reactive germinal centers. Histologically, reactive lymphoid hyperplasia shows a dense infiltration of mature small lymphocytes with scattered histiocytes and plasma cells.
Chronic follicular conjunctivitis (Answer B) is the proliferation of lymphoid tissue on the bulbar surface of the third eyelid, often extending to the adjacent bulbar and palpebral conjunctiva in response to any chronic inflammation or stimulation such as dust, entropion, ectropion, distichiasis, or bacterial infection. The most common cause of chronic follicular conjunctivitis is Chlamydia trachomatis infection.
Mantle cell lymphoma of the conjunctiva (Answer C) is less common and presents with the same immunohistochemical markers as in nodal mantle cell lymphoma. The neoplastic B cells typically express CD19, CD20, CD22, CD5, FMC7, surface immunoglobulin (IgM and IgD), CD43, Bcl-2, and Bcl-1 (cyclin D1). It tends to be more commonly lambda-restricted than kappa-restricted. Although it is usually negative for CD23, it can weakly express CD23, CD11c, CD10, and Bcl-6.
Small lymphocytic lymphoma of the conjunctiva (Answer E) is less common and histologically a fairly monomorphic population of lymphoid cells, almost equal to or slightly larger than mature lymphocytes. Immunophenotypically, it is characterized by CD20 membranous positivity, while CD5- and CD3-negative.
The most common subtype of ocular adnexal lymphoma is marginal zone lymphoma of MALT (Answer D) accounting for 80% of all cases. It is immunophenotypically characterized by CD20-positive, CD10-negative, CD23-negative, Bcl-6–negative B-cell lymphocytic infiltrates, with few interspersed CD3-positive T lymphocytes. It is almost always (95%) negative for CD5, distinguishing this entity from mantle cell lymphoma and small lymphocytic lymphoma/chronic lymphocytic leukemia.