Ophthalmic Pearls EXTRA

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Diagnosis and Management of Orbital Lymphoma

by trisha sharma, mbbs, and m. manjunath kamath, mbbs, doms, ms edited by sharon fekrat, md, and ingrid u. scott, md, mph

rbital lymphoma is a type various pathogens has entered into the 1 of non-Hodgkin lymphoma debate. These include associations with (NHL) that originates in the Chlamydia psittaci and Helicobacter , lacrimal gland, pylori, as well as some viruses. soft tissues of the , or Oextraocular muscles; it is most com- Histology monly extraconal in location. Orbital Almost 80 percent of orbital and ad- lymphoma is said to be primary when nexal lymphomas are of low-grade it arises spontaneously from one of variety, with B-cell lymphomas and these locations, and secondary when extranodal marginal zone lymphoma it is associated with metastatic spread of the mucosa-associated lymphoid tis- from an extraorbital site. sue type (MALT lymphoma) being the most common histological diagnoses.4 Epidemiology MALT lymphomas comprise a distinct While lymphoma constitutes more set of tumors that exhibit the unique than half of all orbital malignancies property of “homing,” which permits RADIOLOGIC EVIDENCE. CT scan shows 1 (55 percent), the incidence of orbital lymphoma cells to adhere to other epi- lymphoma in the right superotemporal lymphoma has been reported to ac- thelial and mucosal sites, thus enabling quadrant. count for between 1 and 10 percent bilateral involvement. of NHL cases.2 Other subtypes have also been Lacrimal gland. The enlarged Orbital lymphoma may be unilat- reported, including follicular lympho- gland displaces the eyeball inferomedi- eral or bilateral. Although it has been mas, diffuse large B-cell lymphomas, ally. known to present in patients between and mantle cell lymphomas. . Swelling and prolapse may 15 and 70 years of age, most cases occur in the eyelid. cluster around the seventh decade. Clinical Presentation Historically, a female preponderance The clinical presentation is generally Diagnosis has been noted,3 but there have been nonspecific and depends on the loca- The differential diagnosis of orbital several conflicting reports regarding tion of the lymphoma. Vision is usu- lymphoma includes the following: gender predominance. Geographically, ally preserved, as infiltration of the • Pseudotumor the disease is most common in Asia or is rare. • Orbital metastases and Europe. Conjunctiva. Patients typically • Diffuse lymphangioma demonstrate a pink or red “salmon • Lacrimal adenoma Pathophysiology patch” of swollen conjunctiva or con- • Cavernous hemangioma Immunosuppression due to any cause junctival hyperemia. • Lymphoid lesions of the (be- —including AIDS, immunosuppres- Orbit. Orbital presentation is most nign reactive lymphoid hyperplasia, sive drugs, or increasing age—has long commonly observed as a painless atypical lymphoid hyperplasia) been established as the main factor palpable mass in the superolateral Diagnostic workup. The following contributing to the pathophysiology quadrant. It may lead to proptosis, evaluations form the basis of a good of orbital lymphoma. , , or abnormal ocular diagnostic workup, undertaken in con-

trisha sharma, mbbs sharma, trisha More recently, however, the role of movement. junction with the patient’s internist:

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• History and physical examination Grading and Staging the histology, grade and stage (see • Dilated fundus examination “Grading and Staging”), and treatment • Thorough examination of opposite GRADING modality employed, but the overall orbit as well as the oral cavity and oro- Grade describes the aggressiveness of five-year survival rate is approximately pharynx the disease. 60 percent. • Complete blood count, biochemis- • Low grade. Indolent or slow growth try profile rate Surgery • Fine-needle aspiration and biopsy • Intermediate grade. Moderate Surgery plays a dual role in the man- • Liver function tests, renal function growth rate agement of orbital lymphomas, being tests • High grade. Aggressive or rapid both diagnostic and therapeutic. How- • Chest x-ray growth rate ever, although biopsy is important for • Computed tomography (CT) and accurate diagnosis, surgery as the sole STAGING magnetic resonance imaging (MRI) of treatment modality often ends with a Orbital lymphomas are staged accord- orbit, abdomen, thorax, and pelvis much-dreaded relapse of disease. This ing to the Ann Arbor system. • Bone marrow aspiration is probably because the location of the • Stage I. Confined to the orbit tumor makes it difficult for the sur- • Stage II. Involvement of adjacent Imaging geon to achieve both complete excision structures such as the sinuses, tonsil, Computed tomography. The typical and preservation of ocular function and/or nose finding on CT scanning is a moder- and aesthetics. • Stage III. Abdominal nodal disease ately well-defined orbital mass, which below the diaphragm molds to the adjacent ocular structures Radiotherapy • Stage IV. Disseminated involvement without bony destruction (Fig. 1). It is Because most orbital lymphomas are of one or more extranodal sites, such usually homogeneous in density, either localized, radiotherapy is the most as liver or bone isodense or slightly hyperdense when common and preferred treatment compared with the density of the ex- SUFFIXES modality. The entire orbit must be traocular muscles. It may exhibit any The following letters are added to pro- encompassed in the radiation field, ir- of the following four patterns: retro- vide more specific information. respective of how much of the orbit is ocular, anterior preseptal, lacrimal • E. Used when there is local extrano- involved. This reduces the chance of dal extension (e.g., I , II , III , IV ). gland involvement, or extension of an E E E E recurrence in previously uninvolved adnexal lesion. • A. No symptoms areas. Lesions that are heterogeneous, • B. Fever (temperature higher than Doses of 25 to 35 Gy are considered with bony destruction, are indicative 38°C), drenching night sweats, and to be curative for low-grade tumors, of high-grade lymphomas, which are unexplained loss of more than 10 per- and 30 to 40 Gy for the high-grade usually accompanied by pain. cent of body weight within the preced- varieties. However, the higher doses, Magnetic resonance imaging. ing six months. especially greater than 35 Gy, are asso- Compared with the extraocular mus- ciated with significant complications. cles, the orbital mass appears isoin- enhancement. Lymphoma may display These include tense or hypointense on a T1-weighted decreased density on delayed images, • and dry eye, which MRI scan, but it appears isointense to thus differentiating it from orbital are the most common acute side effects. hyperintense on a T2-weighted scan. pseudotumor, which shows increasing • and corneal ulceration. Hypointense T2-weighted images are density on delayed images. (See Web • , which is the most fre- suggestive of high-grade lymphomas. Extra, “Orbital Lesions on Contrast- quent delayed consequence of radia- Contrast-enhanced imaging tech- Enhanced CT/MRI.”) tion to the orbit. shielding can niques. Contrast-enhanced CT/MRI Dynamic contrast-enhanced MRI. substantially reduce the incidence of scans reveal mild to moderate en- Dynamic contrast-enhanced MRI scans radiation-induced cataract and should hancement of the lesion, and when this may be performed to distinguish lym- be used in cases where it does not com- is seen in T1-weighted images, high phomas from other conditions. Studies promise complete coverage of tumor. cellularity of the lymphoma can be ex- of contrast index curves of orbital lym- • Radiation . pected. High cellularity in lymphoma phomas exhibit a characteristic steep Recurrences can be treated by either produces a lower apparent diffusion rise followed by a rapid decline. surgery or repeat radiation. coefficient (ADC) of <0.1 × 10-3. This differentiates it from other types of ex- Treatment and Prognosis pansive orbital lesions. There are four main treatment op- Chemotherapy has a limited role in the Spiral CT. Another radiological tions for orbital lymphoma: surgery, definitive treatment of orbital lympho- investigation that may be helpful is radiotherapy, chemotherapy, and im- mas. Currently, there is no indication spiral CT using dual-phase contrast munotherapy. Prognosis depends upon for use of chemotherapy in solitary

38 june 2015 Ophthalmic Pearls orbital lymphomas, except in diffuse sisting of rituximab and chlorambucil large B-cell lymphoma. It is usually re- has shown promising results in newly Coming in the next served for tumors categorized as stage diagnosed cases of orbital lymphoma. II or higher, especially advanced stages like IIIEA and IVEA. It may be adminis- Other Therapeutic Options tered either after surgery or in combi- Antibiotics. Oral doxycycline has been nation with radiation. Chemotherapy used for treatment in cases of orbital may be given as a single agent or as lymphoma that were positive for C. combination therapy. Consultation psittaci DNA. It shows a response rate Feature with an oncologist is necessary. of about 48 percent.7 Diabetic Monotherapy. Alkylating agents Radioimmunotherapy. In this Five experts discuss the such as cyclophosphamide are typi- modality, a monoclonal antibody is results of the recent DRCR.net cally used. administered with a radioactive ligand. Protocol T study—specifying Oral chlorambucil has been used as Although some antigen-negative tu- a monotherapy for MALT lymphoma, mor cells may be missed by immuno- how it will change their use at a mean total dose of 600 mg. A com- therapy, they are destroyed by the beta of aflibercept, ranibizumab, plete response of almost 80 percent particles emitted during radiation, al- and bevacizumab in clinical has been reported. It has minimal side lowing lysis of such cells by radioactive practice. effects and is well tolerated, even by cross-fire from neighboring antigen- elderly patients.5 However, recurrence positive antibody–coated cells. rates are high. Clinical Update Combination therapy. Regimens Follow-up Comprehensive An update on containing doxorubicin are preferred, Treated patients require lifelong fol- stem cell and gene therapy for such as CHOP (cyclophosphamide, low-up to monitor for complications eye diseases. doxorubicin, vincristine, and predni- and to detect recurrence and second- sone or prednisolone) and CVAD (cy- ary tumor formation. Visits may be Ultrawide-field imaging clophosphamide, vincristine, doxoru- scheduled once every three months for provides a look at the periphery bicin, and dexamethasone). Significant two years, then every six months for —and may reshape treatment side effects include myelosuppression the subsequent three years, and then of . and congestive heart failure. every year. Each visit should include a complete history, physical examina- Immunotherapy tion, and radiological investigations, if Pearls Phacoemulsification after pars Neoplastic cells of MALT lymphomas indicated. n have been shown to express the antigen plana vitrectomy. CD20 on their surfaces. Rituximab is 1 Margo CE, Mulla ZD. Ophthalmology. a chimeric monoclonal antibody that 1998;105(1):185-190. Savvy Coder is directed against CD20, ultimately 2 Eckardt AM et al. World J Surg Oncol. 2013; tips for ICD-10. leading to cell destruction by vari- 11:73. ous mechanisms including apoptosis, 3 Ahmed S et al. Am J Med Sci. 2006;331(2): Blink complement-mediated cytolysis, and 79-83. Take a guess at the next issue’s antibody-dependent cytotoxicity. 4 Fung CY et al. Int J Rad Oncol Biol Phys. mystery image. The major drawback of mono- 2003;57(5):1382-1391. therapy with rituximab is a high rate of 5 Ben Simon GJ et al. Ophthalmology. 2006; relapse.6 Initially, the standard induc- 113(7):1209-1213. tion therapy was four weekly cycles of 6 Ferreri AJ et al. Haematologica. 2005; For Your Convenience rituximab at doses of 375 mg/m2 ad- 90(11):1578-1579. These stories also will be ministered as intravenous infusion.7 7 Stefanovic A, Lossos IS. Blood. 2009; available online at However, to overcome the problem of 114(3):501-510. recurrence, an additional maintenance 8 Ardeshna KM et al. Lancet Oncol. 2014; www.eyenet.org. regimen of treatment every two months 15(4):424-435. for two years has been proposed.8 FOR ADVERTISING INFORMATION Reported side effects include nau- Dr. Sharma is a resident in ophthalmology, Mark Mrvica or Kelly Miller sea, fever, and pruritus; rarely, bron- and Dr. Kamath is professor of ophthalmology M. J. Mrvica Associates Inc. chospasm, anaphylaxis, and hypoten- at Kasturba Medical College, Mangalore, Kar- 856-768-9360 sion may occur. nataka, India. The authors report no financial [email protected] Recently, combination therapy con- interests.

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