Ocular adnexal Lymphomas comprise approximately 1% to 2% of non-Hodgkin lymphomas (NHLs) and 8% of extranodal lymphomas. The most common subtype, accounting for up to 80% of cases of primary ocular adnexal lymphoma (POAL), is marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type. Chlamydia psittaci is associated with the pathogenesis of ocular adnexal lymphomas in some parts of the world.
DISEASE SITE
It commonly arises from conjunctiva and can be localized to conjunctiva only. Conjunctival lesions typically present as pink infiltrates in the substantia propria (“salmon-pink patch”), causing conjunctival swelling (fleshy appearance), redness, and irritation. (See image below)
Most frequent site of origin is the orbit (∼ 40%), followed by conjunctiva (35%-40%), lacrimal gland (10%-15%), and eyelid (∼ 10%).
Orbital lymphoid proliferations presents with progressive proptosis, decreased visual acuity and diplopia. Lacrimal gland lymphomas arise from superior anterior orbit and hence present as inferior and nasal displacement of the globe. Lymphomatous lesions of the eyelids may cause ptosis.
IMAGING METHODS FOR DIAGNOSIS AND STAGING
Imaging methods are important establishing diagnosis of PAOL as well as for accurate staging and therapy planning. Important perspective is see whether there is any intraocular spread (e.g. Uveal involvement) or spread beyond orbit to
adjacent structures such as bone (including periosteum) and brain. Infiltration into the globe or bony erosions are unusual features of MALT lymphoma and should raise suspicion for high-grade transformation with aggressive clinical behavior.
| CT or MRI | PET-CT* |
| CT and magnetic resonance tomography (MRI) with contrast enhancement are initial imaging of choice for evaluation of ocular adnexal proliferations.
Assessment of location, size, and degree of infiltration can be made by these imaging methods. |
Several studies have indicated that PET has a higher sensitivity than CT scan in the detection of extent of local spread as well as presence of distant disease and hence the addition of PET imaging to CT and MRI lead to “upstaging” and change in patient management |
*Important to note that the overall FDG uptake is reported in only 50% of cases of MALT lymphomas and those showing FDG uptake has usually low SUVmax ( i.e. <5)
Below is an example of EMZL arising from conjunctiva localized to ocular adnexa without any infiltration into the globe or bony erosions.
| 65 year old male with 1 year history of gradually progressive swelling arising from lateral aspect of eye. The CT and corresponding PET images (lesion SUVmax 3.6) are shown below. No uptake elsewhere. No hepatosplenomegaly. What is your most likely clinical diagnosis? What will be your management approach ?  |
MANAGEMENT OF OCULAR ADNEXAL MZL
Roughly two-thirds of ocular adnexal lymphomas are stage 1E (localized extra nodal tumors) using the Ann Arbor system. Proposed TNM stage may appear more useful but it does not yet predict rate of relapse or survival.
1st STEP is to determine whether patient needs treatment or observation alone may be of help.
| Observation Alone* | Therapeutic intervention |
| Watchful waiting might be an acceptable option in select patients with unilateral extranodal marginal zone B-cell lymphoma of the ocular adnexa. | Surgical resection, radiotherapy, single-agent or combination chemotherapy, and immunotherapy are valid approach in management. |
*Generally reserved for frail elderly patients with asymptomatic disease or in the setting of severe comorbidities that preclude an therapeutic approach.
RADIOTHERAPY
Radiation therapy is the treatment of choice for the majority of patients with localized POAL. Typically, radiotherapy results in a high rate of local control that ranges from 85% to 100%.
- Dose: 30 Gy is considered to be the optimal radiation dose for local disease control in patients with POAL. Radiation doses of more than or equal to 36 Gy may result in ischemic retinopathy, optic atrophy, corneal ulceration, and neovascular glaucoma, associated with significant vision loss.
- Toxicity: Immediate toxicity can lead to conjunctival reactions. Long-term complications are observed in up to 50% of patients which includes cataract formation (30%-50%) and xerophthalmia (20%-40%).
- Note: Reirradiation in the setting of relapsed disease exceeds the maximum tolerable dose of the eye and should be avoided.
OTHER APPROCHES
Chemotherapy (CVP, R-CVP, R-Benda, Single Agent R, Chlorambucil): There are limited data on chemotherapy for patients with POAL and hence it is very difficult to draw conclusions and make practical recommendations based on the published data. Local recurrence is the predominant cause of treatment failure, occurring in up to 29% of patients and responses with single agent is short lived.
The is no comparative data for chemotherapy vs radiotherapy however the local disease control is superior with RT and hence RT should be preferred approach in tumor localized to orbit. If the disease has spread outside orbit then chemotherapy should be ideal approach.
- CNS prophylaxis in patients with POAL is unnecessary.
OUTCOME AND PROGNOSIS
The prognosis of patients with OAML is generally favorable, with a high proportion of localized disease, indolent clinical course, prolonged disease-free intervals, and low lymphoma-related mortality rates. Non conjunctival primary site, advanced disease stage and nodal involvement are poor prognostic markers. In general, conjunctival primaries are associated with the lowest (∼20%), orbital with intermediate (∼ 35%), and eyelid with the highest (∼ 65%) risk of disseminated disease.
References:-
- Sassone, Marianna; Ponzoni, Maurilio; Ferreri, Andrés J.M. (2017). Ocular adnexal marginal zone lymphoma: Clinical presentation, pathogenesis, diagnosis, prognosis, and treatment. Best Practice & Research Clinical Haematology, 30(1-2), 118–130. doi:10.1016/j.beha.2016.11.00
- Stefanovic A, Lossos IS. Extranodal marginal zone lymphoma of the ocular adnexa. Blood. 2009;114(3):501-510. doi:10.1182/blood-2008-12-195453