Older woman referred for unilateral eye redness
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An 81-year-old retired teacher presented to the cornea clinic for right eye redness and irritation that started 2 months prior.
At an outside ophthalmology practice, she was prescribed Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) and prednisolone. She had noticed slight improvement, but the redness remained. She was told to stop the prednisolone and was referred to us for further management.
Her ocular history was notable for cataracts in both eyes and dry eye syndrome. She had no history of ocular surgeries. Her family history was negative for ocular diseases. Her medical history included hypertension, hyperlipidemia, migraine, Helicobacter pylori infection and recurrent urinary tract infections. Her medications included aspirin, lisinopril, atorvastatin and famotidine. She also took erenumab and ubrogepant for migraine. She drank alcohol occasionally, never smoked and denied recreational drug use. She denied recent fevers, chills, myalgias, arthralgias, unintended weight loss or night sweats.
Examination
On examination, visual acuity with correction was 20/30 in the right eye and 20/25 in the left eye. Both pupils were reactive with no afferent pupillary defect. Extraocular motility and confrontation visual fields were full. IOP by iCare tonometer was measured as 14 mm Hg in the right eye and 16 mm Hg in the left eye.
External examination was notable for mild right upper lid ptosis. Slit lamp examination of the right eye showed a dome-shaped pink subconjunctival lesion superonasally that extended to the superonasal limbus (Figure 1). There was mild elevation of the lesion. There was no subconjunctival hemorrhage or tenderness to palpation. The conjunctiva of the left eye was white and quiet, and both eyes had clear and compact corneas, deep and quiet anterior chambers, normal irides and trace nuclear sclerosis. Dilated examination demonstrated clear vitreous, pink and healthy optic nerves with a cup-to-disc ratio of 0.2, flat maculae, normal vessels and a flat attached retinal periphery bilaterally. Anterior segment OCT of the right eye revealed a subepithelial hyporeflective homogenous lesion with smooth borders (Figure 2).
Source: Teresa P. Horan, MD, and Naveen K. Rao, MD
Source: Teresa P. Horan, MD, and Naveen K. Rao, MD
What is your diagnosis?
See answer below.
Pink subconjunctival lesion
The differential diagnosis for an older woman with a pink subconjunctival lesion includes conjunctival lymphoma, reactive lymphoid hyperplasia, amyloid deposition, squamous cell carcinoma, amelanotic melanoma, leukemic conjunctival tumor or inflammatory granulomas (tuberculosis or sarcoid).
Of the conjunctival malignant neoplasms, lymphoma is the most likely given the salmon-colored subepithelial mass seen on examination. While squamous cell carcinoma of the conjunctiva is the most common primary conjunctival malignant neoplasm, our patient’s lesion did not appear hypervascularized. Conjunctival lymphoma and reactive lymphoid hyperplasia may present similarly. Reactive lymphoid hyperplasia is more common in younger patients, and our patient is 81 years old, making lymphoma more concerning. As with amyloid deposition, the entities lymphoma and reactive lymphoid hyperplasia require a tissue biopsy to differentiate the disease process. Inflammatory granulomas of the conjunctiva from tuberculoma, sarcoid granuloma or foreign body can mimic malignant lymphoma; however, the history did not indicate previous trauma or foreign body or a history of tuberculosis or sarcoidosis.
Workup and management
The patient underwent incisional biopsy in the operating room, and samples were sent fresh in formalin and in tissue recovery media for pathology. Review of the conjunctival specimens revealed monomorphous sheets of small lymphocytes with slightly irregular nuclei. No germinal centers were noted. Immunohistochemistry showed an abnormal CD20 pattern, normal CD3 and CD5 patterns, and negative CD10 staining (Figure 3). The Ki-67 proliferation index was low. Flow cytometry of fresh tissue was positive for CD20, negative for CD5 and CD10, and showed a predominance of lambda light chain. Based on the pathology results, she was diagnosed with extranodal low-grade B-cell lymphoma of mucosal-associated lymphoid tissue.
Source: Majd Jawad, MD,Lahey Hospital Department of Pathology
Upon diagnosis of conjunctival lymphoma, the patient underwent further imaging for staging. MRI of the brain and orbits with contrast showed an enlarged and enhancing right superior rectus muscle with involvement of the distal tendinous insertion. There was otherwise no evidence of orbital disease. She was referred to the hematology-oncology service, which recommended PET imaging that showed minimal increased uptake in the superior rectus only. There was no evidence of metastatic disease. She met with radiation oncology, which is currently planning for definitive fractionated radiation (24 Gy) after discussing the options of 24 Gy vs. 4 Gy therapy.
Discussion
Conjunctival lymphoma typically occurs in older patients and appears as a pink, salmon-colored, smooth-surfaced subconjunctival mass. It represents 9% of conjunctival tumors. It can be unilateral or bilateral and is typically located in the fornix or mid-bulbar region. Pathology reveals a monoclonal collection of atypical lymphoid cells, typically of B-cell lineage and CD20 positive.
There are four types of conjunctival lymphoma: extranodal marginal zone lymphoma (ENMZL; 68% of cases), follicular lymphoma (FL; 16% of cases), mantle cell lymphoma (MCL; 7% of cases) and diffuse large B-cell lymphoma (DLBCL; 5% of cases). ENMZL and FL are considered low grade with 97% and 82% 5-year survival rates, respectively. DLBCL and MCL are high grade and have a worse prognosis with 55% and 9% 5-year survival rates, respectively. Predisposing factors may include autoimmune conditions, H. pylori infection and Chlamydia psittaci infection. Most cases are primary lymphomas; however, 10% to 30% arise from a secondary lymphoma, usually DLBCL or MCL. The risk for developing systemic lymphoma in 30 years is 15% in cases of unilateral conjunctival lymphoma and 50% in bilateral cases.
Workup of these conjunctival masses can include anterior segment OCT, which demonstrates a hyporeflective, homogenous subepithelial mass with monomorphic, stippled, hyporeflective dots. Still, surgical biopsy is required for diagnosis. The most common treatment of localized conjunctival lymphoma involving the conjunctiva and orbit is low-dose fractionated external beam radiation therapy (EBRT) with shielding of the cornea and lens. Usually patients receive 20 Gy to 50 Gy, fractionated over 15 sessions; however, more recently, studies have shown success with much lower doses. A recent retrospective study of patients who underwent ultra-low-dose EBRT with 4 Gy over two sessions resulted in 100% response 3 months after treatment and 75% local control after 2 years. Surgical resection or local immunotherapy with interferon alpha or rituximab can also be considered for these patients. For systemic lymphoma, chemotherapy and rituximab can be used.
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- For more information:
- Teresa P. Horan, MD, and Naveen K. Rao, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Allison V. Coombs, DO, MS, and Nisha S. Dhawlikar, MD, MPH. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.