Woman presents with forniceal lesions in left eye

There was also a mass under the left upper lid.

Issue: August 10, 2015

ByMichael B. Raizman, MD

ByErica Liu, MD

A 32-year-old woman was referred to the New England Eye Center by an optometrist for conjunctival cysts and concern for a possible neoplasm in the left eye.

History

The patient initially presented 1 month prior for a routine eye exam. She mentioned that she had noticed bumps in her left inferior fornix 1 year prior. Her only symptom at that time was itching of the left eye that had since resolved. She did not have any current ocular or systemic complaints. She had no ocular or medical history. Her surgical history consisted only of an appendectomy at the age of 24 years. She took no medications and did not have any known drug allergies. Social history was significant only for secondhand smoke exposure.

Examination

On examination, the patient’s uncorrected visual acuity was 20/20 in both eyes. Pupils were round, equal and reactive without afferent pupillary defect. IOP was 15 mm Hg in both eyes. Extraocular motility and confrontation visual fields were within normal limits. Examination of the conjunctiva of the right eye was unremarkable. The conjunctiva of the left eye, including the inferior fornix, initially appeared normal (Figure 1).

With further downward pressure, multiple conjunctival lesions deep within the fornix were revealed (Figure 2). Additionally, there was a mass under the left upper lid that was not previously noted. The remainder of the exam, including dilated funduscopic exam, was unremarkable.

Figure 1. External color photograph of the left eye and inferior fornix.

Figure 2. External color photograph of left inferior fornix with forceful downward pressure on the lower eyelid.

Figure 3. Photomicroscopy at 20× H&E (left) and CD20 stain (right) showing dense atypical lymphoid infiltrate with ill-defined follicular structures identified in the deeper portion and predominantly composed of small to medium-sized lymphoid cells with abundant cytoplasm. CD20 stain shows numerous B cells.

What is your diagnosis?

Forniceal lesions

The differential diagnosis for this patient with multiple forniceal masses includes neoplastic, inflammatory and infectious causes.

Neoplastic causes include lymphoma, squamous cell carcinoma, metastasis, amelanotic melanoma and amyloid. These are often difficult to discern from each other except by biopsy. Often these will present as fleshy pink or yellow masses.

Inflammatory causes include lymphoid hyperplasia, sarcoidosis, allergic response or granulomas. Sarcoidosis typically appears as small, tan, distinct granulomatous nodules on the palpebral surface of the conjunctiva.

Infections such as chronic follicular conjunctivitis may present similarly.

Diagnosis and management

One week after presentation, the upper eyelid lesion and one lower eyelid lesion were biopsied, and the pathologic diagnosis was extranodal lymphoma, mucosa-associated lymphoid tissue (MALT) type (Figure 3).

The patient was referred to oncology and radiation oncology for further work-up and management. MRI of the brain and orbits did not show spread of lymphoma. She also had a PET scan without abnormal uptake in the chest, abdomen, pelvis or bone. Bone marrow biopsy did not show evidence of B-cell lymphoproliferative disorder.

Four months after initial presentation, she underwent local radiation to the left eye. One month after completion of radiation treatment, she returned to our clinic and was found to have almost complete resolution of the lesions.

Discussion

Ocular adnexal lymphomas are considered rare; however, it is likely underdiagnosed because many are discovered on autopsy, and the incidence is rising at 6% per year. Risk factors include age, immunosuppression and female sex. They make up 55% of all orbital tumors and 1.5% of conjunctival tumors. Conjunctival lesions have a better prognosis, although 20% eventually result in disseminated disease. The majority are primary tumors; however, 10% to 30% are secondary to disseminated disease. The most common type (80%) is extranodal marginal zone B-cell lymphoma of MALT type, as in our case.

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Ocular adnexal lymphomas typically present with a slow, indolent course. These can be asymptomatic or cause irritation, proptosis and, in rare cases, diplopia. On exam, conjunctival lesions are classically described as “salmon patch” fleshy lesions. The etiology is unknown but is thought to be due to chronic inflammation. Although there is significant geographic variation, there is reported correlation with Helicobacter pylori and Chlamydia psittaci infection, as well as an association with autoimmune disorders including thyroid disease and Sjögren’s disease.

Diagnosis is made with biopsy of fresh tissue and standard formalin-fixed tissue. Fresh tissue is needed for flow cytometry, immunohistochemical stains (B-cell vs. T-cell) and gene rearrangement studies (to confirm clonality). Staging is complex and based primarily on anatomic and clinical features. Standard systemic work-up includes complete blood count, basic metabolic panel, lactate dehydrogenase (LDH), MRI and PET scan. Bone marrow biopsy is frequently performed but controversial due to low yield.

Management of ocular adnexal lymphoma is multidisciplinary, with the involvement of the primary care physician and radiation oncologist, and is dependent on staging and cytology. Radiation is the current standard of care for localized disease but has a high rate of side effects. It can cause an immediate conjunctival reaction, and 50% of patients will have either cataract formation or xerophthalmia. Rarely, doses greater than 36 Gy can cause radiation retinopathy, optic atrophy, corneal ulceration or neovascular glaucoma. Isolated use of chemotherapy has limited data, and recurrences are common. Immunotherapy such as interferon-alpha and rituximab are promising; however, there are limited case reports to date. Surgery is an option for encapsulated tumors, although micro-infiltration is common, so recurrence rates are high without adjuvant radiation/chemotherapy. Cryotherapy can also be done on small, localized lesions.

Prognosis is excellent, with more than 90% complete remission of MALT type ocular adnexal lymphoma. Recurrence locally or in other adnexal sites can occur. Poor prognostic factors include bilateral disease, deep orbital involvement, eyelid lesion (70% systemic involvement), high LDH levels, malignant histopathologic features and T-cell origin. Given the high recurrence rate, frequent follow-up is recommended every 3 months for 1 year after diagnosis and every 6 months thereafter.

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For more information:
Erica Liu, MD, and Michael B. Raizman, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.