Extranodal presentations of a marginal zone B-cell lymphoma is an entity well described in association with the gastrointestinal tract, salivary gland, thyroid gland, lung, breast, skin, and orbit. 1–5 These are more frequently referred to as mucosa-associated lymphoid tissue (MALT) lymphomas. Primary orbital lymphomas account for 5% to 14% of all extranodal lymphomas. 4,6 Within the orbit, the most commonly involved tissues are conjunctiva, eyelid, or retrobulbar tissues, 7,8 whereas lacrimal gland involvement is rare. Among a series of 121 patients with lacrimal masses from which biopsy specimens were taken at an eye institute, only 3% proved to be malignant lymphoma. 9 There are only a few reports in the literature depicting lymphoma involving exclusively lacrimal gland 10 or its collecting system. 11,12 Thus, it is apparent that MALT lymphoma of the lacrimal gland is a rare entity with little information available with respect to presentation, treatment, and follow-up. We report herein a patient who had a MALT lymphoma of the lacrimal gland, treated successfully with radiation therapy.
A 63-year-old woman was referred to the Princess Margaret Hospital after a biopsy of an anterior orbital mass demonstrating a MALT lymphoma. She initially was examined for a tightening of her left lateral canthus and a lump in the area of the lacrimal gland. She denied any anhidrosis, irritation of the eye, or xerostomia, and had been asymptomatic otherwise. A biopsy was done of the left lacrimal tumor, which showed MALT lymphoma. Examination revealed a 1.5-cm healing incision in the lateral aspect of the left upper eyelid with a small (1 cm) mass in this area. The mass effect produced mild ptosis of the upper eyelid. There was no palpable cervical lymphadenopathy. The right eye was completely normal. Investigations showed normal abdominal ultrasound and chest radiograph results. Laboratory evaluation revealed a normal complete blood count, normal liver and renal function, and a normal bone marrow aspirate and biopsy. Gallium scan showed a solitary focus of abnormal uptake corresponding to the region of the left lacrimal gland. Magnetic resonance imaging confirmed a 2.5-cm mass occupying the left lacrimal gland (Fig. 1). She therefore has localized, clinical stage IAE disease according to the Ann Arbor classification for malignant lymphomas. 13
Autoimmune antibody screen results were negative for antiextractable nuclear antigens and double-stranded DNA, and the antinuclear antibody (ANA) titer was positive at 1:80 with a homogenous pattern.
The patient received radiation therapy; the entire left bony orbit was treated using an anterior telecobalt field (6.5 × 5 cm) to a dose of 25 Gy in 15 fractions during 3 weeks. The anterior chamber of the eye, lens, and macula were protected by shielding with a pencil-shaped eye bar suspended just above the cornea, throughout the course of treatment. By the end of the course of radiation therapy, the palpable mass disappeared and ptosis was no longer present. She had minimal eye dryness, and a repeat magnetic resonance scan 6 months after treatment showed resolution of the tumor (Fig. 1). She remained in complete clinical remission of disease 3 years after treatment (December 2000).
The biopsy specimen of the left lacrimal gland tumor measured 1.2 × 0.7 × 0.5 cm. Microscopic examination revealed a dense infiltrate of lymphocytes with destruction of the normal glandular architecture. The cells were composed predominately of small lymphocytes, centrocyte-like cells, monocytoid cells, and occasional transformed lymphocytes. Some lymphoepithelial lesions were noted. No granulomas were seen. Stains for immunoglobulin kappa and lambda chains showed an excess of plasma cells staining for kappa light chains. Stains for cytokeratin accentuated the lymphoepithelial lesions. Immunophenotypic studies were performed on paraffin sections and demonstrated that the majority of cells were B lymphocytes (CD45 positive, CD20 positive). These cells were negative for CD5, CD10, and cyclin D1. These findings were diagnostic of MALT lymphoma involving an extranodal site. 14
MALT lymphoma, also known as extranodal marginal zone B-cell lymphoma, is a distinctive type of malignant B-cell lymphoma first described in 1983 by Isaacson et al. 2 Since that time, it has been increasingly recognized as a distinct clinical–pathologic entity and recently has been incorporated in the revised European-American Classification of Lymphoid Neoplasms, 15 and the World Health Organization Classification. 16 MALT lymphomas have morphologic evidence of centrocyte-like cells, monocytoid B cells, small lymphocytes, and lymphoepithelial lesions. 1–3,10,14,15,17 All of these features were apparent in the microscopic examination of our patient’s tumor. MALT lymphomas show a tendency to remain localized; thus, they are potentially curable with local therapy. These lymphomas are usually indolent in behavior, although some can transform into histologically aggressive large-cell lymphomas. Molecular studies have confirmed MALT lymphomas to have a monoclonal origin. 3,10,15,18 Characteristic genetic abnormalities can include trisomy 3, and chromosomal translocations t(11;18)(q21;q21), t(1,14)(p22;q32). 18
Orbital lymphomas are more commonly seen in the elderly, 17 with a mean age in the sixth decade. There is a tendency to bilateral involvement, particularly for conjunctival presentations. 19 Treatment is directed at cure and preservation of vision and integrity of the orbit; therefore, extensive surgery should be avoided. 19,20 Jeffrey et al. 10 describe six cases of lacrimal gland lymphoma, of which only four would fit in the current criteria of MALT-type lymphoma. All four patients were treated with biopsy or subtotal excision and postoperative radiation (unspecified doses). On follow-up after 9 months, no recurrences were observed. Patients with Sjögren syndrome are at risk of developing lymphomas of the salivary glands and lacrimal gland. 21 Our patient did not have symptoms or serologic findings of Sjögren syndrome.
The rationale for our treatment approach for this patient was based on the available literature for ocular adnexal lymphomas. Many series included patients treated in an era before the recognition of MALT lymphoma as a distinctive entity. 6–8,11,22,23 Other histopathologic types of lymphoma, such as follicular lymphomas, small lymphocytic lymphomas, and diffuse large-cell lymphomas, were variably included. 17,24 These tumors have different immunohistologic, genetic, and clinical characteristics compared with MALT lymphomas. 15,17 Despite this, investigators who applied radiation therapy to indolent or “low grade” lesions (termed pseudolymphoma by some authors) reported excellent local control rates of 95% to 100%. 6–8,20,22,25 Recurrence at distant sites can occur in 10% to 25% of patients. 6,17,20,22,23 The consensus, to date, is that radiotherapy is the optimal treatment for indolent orbital lymphomas. Fitzpatrick and Macko 7 reported on 42 patients with orbital lymphomas of various histopathologic types, and concluded that doses of 25 Gy to 35 Gy in 10 to 15 fractions delivered in 2 or 3 weeks was effective treatment. Smitt and Donaldson 23 reviewed 25 patients with lymphoma of the orbit and suggested radiotherapy with lens shielding as definitive treatment. The curative doses used (25–30 Gy) by most investigators were generally lower than for the treatment of epithelial cancers or other histologically aggressive lymphomas. 6,17,20 Chao et al. 22 agreed with this recommendation, and stated that 30 Gy in 15 fractions appeared to be a sufficient dose for local control of these low grade lymphomas. The use of low-dose radiation, together with the capability of shielding the lens and macula, results in a well-tolerated treatment with very low risk of morbidity for the eye. With shielding, the dose to the lens can be lowered to ≤10 Gy, reducing the risk of cataract formation to approximately 10% to 15%. 6,26
There are a few recent reports on treatment results specifically for MALT lymphomas of the orbit. White et al. 17 described 16 cases of MALT lymphoma in the ocular adnexa, of which 3 (19%) had involvement of the lacrimal gland. Of the 16 patients, 11 had radiation alone and 9 of these went into complete remission, with the other 2 in partial remission. The patients who had lacrimal gland involvement were not separately identified. Galieni et al. 27 reported on 15 patient with orbital MALT lymphoma (8 with involved lacrimal gland), treated variably with chemotherapy or local radiation, and they reported long-term disease control in 12 patients. Bailey et al. 1 described cases of MALT lymphoma of skin and subcutaneous tissue, of which only 1 of 15 had involvement of the lacrimal gland and after a course of radiation therapy has been in complete remission for 24 months. Cahill et al. 24 described 10 cases recently and reported excellent local control with local therapy.
MALT lymphomas of other extranodal organs also have a tendency to be localized at diagnosis, and the disease responds well to local treatment. 4 In a series of pseudolymphomas diagnosed from the stomach at the Armed Forces Institute of Pathology (years 1970–1997, 97 cases), a review of the pathology with modern techniques showed that 79% were malignant lymphomas and two thirds of the lymphomas (n = 51) were of MALT histology. Recent reports indicated excellent local control rate with radiotherapy for gastric MALT lymphomas, 28 and for other nongastric extranodal sites, 4 although occasional late relapses in distant sites do occur, typically in other MALT locations, particularly for nongastric presentations. 4
We have reported a rare case of a localized malignant lymphoma of MALT type presenting in the lacrimal gland. Low-dose radiation (25 Gy) was successful in eradicating the lymphoma with minimal morbidity. Based on previous reports of patients with orbital lymphomas (low grade) and pseudolymphomas, of which many will now be recognized as MALT lymphomas, radiotherapy has an excellent local control rate and is the treatment of choice. Further follow-up on a large number of treated patients is required to determine the long-term outcome, because some patients relapse at distant sites.
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