Abstract
Conjunctival lymphomas are rare entities and may present with non-specific ocular signs that resemble inflammation. They may mimic common ocular pathologies, leading to a delay in diagnosis and treatment. The treatment options of conjunctival lymphomas should be tailored to individuals due to their indolent nature compared to other adnexal lymphomas. Herein, the authors report a case of a primary follicular conjunctival lymphoma in a patient who presented with signs and symptoms of nodular anterior scleritis. The final histology of the conjunctiva lesion revealed primary follicular lymphoma. The patient was managed conservatively with active surveillance.
Non-Hodgkin lymphoma (NHL) is a malignant neoplasm derived from clonal proliferation of B or T-lymphocytes. Extra nodal NHL accounts for approximately 20% to 30% of reported cases of lymphoma.1 Of these, about 8% occur primarily in the ocular adnexa.1 Conjunctival lymphomas constitute approximately 28% of the adnexal lymphomas, with bilateral involvement 20% to 38% of the time.2 Females are more often affected, with an average age range from 60 to 68 years.2 The histological subtypes and clinical stage of conjunctival lymphomas remain the most crucial disease outcome predictors to determine the risk of systemic progression as well as the treatment modality.3 Long-term follow up is necessary, as systemic development may occur months or years after the initial diagnosis.
Case Report
A healthy female, aged 33 years, complained of bilateral eye redness with mild discomfort for the past 3 months. She denied blurring of vision, eye discharge, or preceding trauma. She was otherwise well systematically. Eye assessment revealed injected conjunctivae with pinkish nodular lesions on the upper bulbar conjunctivae (Figure 1). The lesions had an ill-defined margin, with peripheral tortuous vessels and were immobile with palpation. Both eyes did not blanch with phenylephrine 2.5% eye drops. Her visual acuity was 6/9 bilaterally, with no relative afferent pupillary defect. The extraocular muscle movements were normal, with no pain elicited on eye movement. There was no ptosis, and her intraocular pressure was normal. Fundus and systemic examinations were unremarkable. B-scan ultrasonography showed normal scleral thickness with no ‘T’ sign. Given the protracted symptoms and prolonged history, she was treated as nodular anterior scleritis with ibuprofen tablets and prednisolone acetate 1% eye drops.
Clinical photography of the right (panel A) and left (panel B) eye, revealing bilateral nodular lesions with surrounding tortuous vessel (arrows in blue) over the anterior segment of the supero-nasal bulbar conjunctivae.
Unfortunately, her symptoms failed to improve despite anti-inflammatory medications. An excisional biopsy of the conjunctival lesions was carried out, which revealed follicular B-cell NHL of grade I to II, evidenced by low proportion of centrocyte and centroblast (Figure 2). Laboratory studies included complete blood count, renal profile, liver function tests, serum lactate dehydrogenase, which were all normal. Computed tomography (CT) of the whole body did not reveal active tissue beyond the orbit. In view of the localized disease, she was kept on watchful observation. A surveillance CT scan after 6 months showed no sign of dissemination. The patient continued to be well 2 years after the initial diagnosis.
Hematoxylin and eosin (H&E) staining (panel A) revealed diffuse small atypical lymphoid cells with centroblast (arrows in black). The atypical lymphoid cells were diffusely positive for CD20 stain (panel B) and BCL 2 stain (panel C).
Discussion
Conjunctival lymphoma has been classically described as a painless, nodular lesion with salmon-pink or fleshy patches at the fornix or bulbar conjunctiva. It is slow-growing, and feeder vessels are not typically seen. Patients can be asymptomatic or can suffer ocular irritation with redness. Other clinical manifestations such as ptosis, diplopia, or palpable mass were rarely reported. Systemic involvement was observed in 20% to 31% of conjunctival cases.2 The relatively asymptomatic presentation and indolent course of the disease often result in clinical conundrum and delay in diagnosis. Similar to the presenting case, studies have reported conjunctival lymphomas masquerading as chronic follicular conjunctivitis and scleritis.4,5 Therefore, lymphoma should be considered in the case of an atypical presentation of conjunctivitis or scleritis that does not respond to antibiotic and anti-inflammatory therapy. In such cases, a conjunctival excisional biopsy should be performed.
The prognosis of ocular adnexal lymphoma is determined by the grade of histology, TNM stage, and age of the patient.3 Conjunctival lymphoma has a good prognosis, with a 66% 5-year progression-free survival and a 76% overall 5-year survival rate.3 The management of conjunctiva lymphoma should involve a multidisciplinary approach. After a confirmed diagnosis, expert opinion from a hematologist-oncologist should be sought, and a workup should be performed to rule out systemic involvement. Staging typically includes complete blood count with differentials, serum lactate dehydrogenase levels, serum protein electrophoresis, chest radiograph, CT, or magnetic resonance imaging (MRI) of the neck, thorax, abdomen and pelvis, MRI of the brain and orbit, and bone marrow biopsy.
The mainstay of treatment in localized high grade conjunctival disease is with external-beam radiotherapy (EBRT).6 A radiation dose of 30-40 Gy is advocated, and it is effective for all histological subtypes of conjunctival lymphomas.6 Complications of radiation include xeropthalmia, keratitis, cataract formation, and radiation retinopathy.6 Intralesional injections of interferon alpha-2b have been reported. However, its role is limited to low-grade lymphomas due to the risk of progression to systemic lymphoma after regression of conjunctival lesion.6 Alternatively, some studies demonstrated spontaneous regression of low-grade conjunctival lymphomas.7-9 Watchful waiting remains an option for these patients, as low-grade conjunctival lymphomas rarely metastasize.6 Chemotherapy is indicated with systemic involvement.9
Conclusion
Due to the rarity of this condition, conjunctival lymphoma is often overlooked or misdiagnosed. It is important to consider lymphoma as a differential diagnosis when ophthalmologists encounter an atypical case of nodular anterior scleritis. Conjunctival biopsy should be performed in the circumstance where the patient does not seem to respond to appropriate medical therapy.
Author Contributions
Hui Yin GOH was responsible for manuscript drafting, reviewing and editing.
Che Mahiran Binti CHE DAUD was responsible for manuscript reviewing and editing.
Both Chandramalar SANTHIRATHELAGAN and Shamala RETNASABAPATHY were responsible for supervising, manuscript reviewing and editing.
Footnotes
Disclosure: TThe authors have no potential conflicts of interest with respect to the research, authorship of this article and have no financial support related to this work to declare.
- Received March 14, 2021.
- Accepted January 3, 2022.
References
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