A 64-Year-Old Man Presenting With Diplopia and Right Orbital Swelling Due to Mucosa-Associated Lymphoid Tissue Lymphoma

Introduction

Lymphoma stands out as the most prevalent primary cancerous tumor located in the orbit [1]. Primary orbital lymphoma constitutes 35–55% of malignant orbital tumors, yet it represents only about 1% of all non-Hodgkin lymphomas [2]. Over 95% of orbital lymphomas are B-cell types, with extranodal marginal lymphoma of mucosa-associated lymphoid tissue (MALT) being the most frequent subtype in primary orbital lymphoma cases [1,3]. Chronic antigen stimulation may contribute to ocular adnexal MALT lymphoma development, with associated factors including Chlamydia psittaci infection, chronic conjunctivitis, autoimmune disorders, and hepatitis C virus in specific groups [1].

Its rarity poses significant diagnostic challenges, as it often mimics more common conditions like orbital pseudotumor or infections [4]. MALT-type extranodal marginal-zone B-cell lymphomas account for most non-Hodgkin’s lymphomas of the orbit and orbital adnexa [5]. Typical presenting signs and symptoms include proptosis, diplopia, and less frequently, vision changes [3]. Diagnosis is commonly established through imaging studies, followed by confirmatory histopathological examination of biopsy specimens [1]. Radiotherapy remains the primary treatment for localized orbital malignancies [6]. Localized orbital MALT lymphoma is very sensitive to radiation, with local control rates over 90%, while systemic therapy is saved for widespread or resistant cases [7]. This report focuses on a 64-year-old man with diplopia and right orbital swelling caused by MALT lymphoma and treated with surgery and radiotherapy.

Case Report

A 64-year-old man presented with progressive right orbital swelling that had been gradually enlarging over 7 years (Figure 1). One year before seeking medical attention, he began experiencing worsening symptoms, including gaze-directed diplopia, particularly in vertical and right-sided gaze. Five years ago, he injured his right eyebrow while gardening by accidentally hitting himself with a shovel. He described the swelling as painless with only mild discomfort. He denied any history of ocular disease, prior ocular surgeries, or decreased vision. He also reported no systemic symptoms such as fever, weight loss, night sweats, or loss of appetite, and no lymphadenopathy was noted on examination.

His past medical history included dyslipidemia managed with a daily statin (20 mg). There was no history of surgeries, and his father had died of an unspecified cancer. The patient had no history of eye infections, including conjunctivitis, and the examination showed no chronic inflammation. There was also no history of hepatitis C, and no signs of liver disease were found.

On examination, a hard mass was identified in the superonasal orbital area, leading to fullness in the upper eyelid. This led to orbital dystopia and a mild right upper eyelid ptosis (2 mm). Visual acuity was 20/25 in the right eye and 20/20 in the left. Upward movement of the right eye was slightly limited, but the rest of the neurological exam was normal.

A computed tomography (CT) scan of the orbits revealed an abnormal soft-tissue lesion measuring 2.1×0.45 cm in the right orbit, which was infiltrating the posterior aspect of the superior rectus muscle (Figure 2). There was no bony reaction or extension into the brain, and the other ocular structures appeared unremarkable. A retention cyst was observed in the left maxillary sinus, but the other paranasal sinuses were clear.

To further evaluate the lesion, an orbital biopsy was performed. After a skin incision with a No. 15 blade, dissection with Wescott scissors was carried out between the orbicularis muscle and the orbital septum. Upon opening the septum, dissection proceeded until a rubbery, pinkish mass was encountered, from which a biopsy was obtained, and the mass was then excised.

Histopathological examination of the biopsy revealed a proliferation of small to medium-sized lymphoid cells arranged in a vaguely nodular architecture (Figure 3). The lymphoid cells exhibited irregular nuclei and mature chromatin. Immunohistochemical staining showed that the lymphoma cells were positive for cluster of differentiation (CD)20, CD43 (weak and in a subset), and B-cell lymphoma 2 (BCL-2) (Figure 4), while being negative for CD10, BCL6, CD5, multiple myeloma oncogene 1 (MUM-1), and Cyclin D1 (Figure 5). Background T cells were highlighted by CD3. The proliferation index marker Ki-67 was low, ranging from 5-10%, leading to the conclusion of low-grade B-cell lymphoma.

Further imaging studies, including a CT scan of the neck, chest, abdomen, and pelvis, did not reveal any lymphadenopathy or visceromegaly. A subsequent positron emission tomography (PET)-CT confirmed mildly avid soft-tissue thickening in the right eye globe, consistent with the biopsy findings of lymphoma, and indicated no signs of metastatic disease elsewhere (Figure 2). A bone marrow examination yielded negative results.

Based on clinical, histopathological, and imaging data, a diagnosis of right orbital mass lymphoma was established. The patient was then referred to the radiation oncology department, where he received a radiation therapy regimen consisting of 2400 centigrays (cGy) in 12 fractions, along with a simultaneous integrated boost of 3000 cGy delivered in 15 fractions to the right orbital mass. Post-radiation therapy images show marked interval regression of the previously noted right orbital superomedial extracoronal soft-tissue mass with minimal residual soft-tissue thickening. At the 3-month follow-up, the patient reported substantial improvement, although mild diplopia during right gaze persisted.

Discussion

This case highlights key lessons in diagnosing and managing orbital MALT lymphoma. It shows that the disease can develop slowly over years, with symptoms that mimic benign conditions, causing delays in recognition. It also emphasizes the importance of targeted imaging and histopathological analysis, including immunohistochemistry, to differentiate MALT lymphoma from other orbital masses. Additionally, the case demonstrates that localized orbital MALT lymphoma is highly sensitive to radiation, leading to positive outcomes with proper radiotherapy dosing. Overall, it underscores the need for vigilance regarding chronic orbital swelling and the importance of early tissue diagnosis for effective treatment.

Orbital lymphomas are the most common malignant tumors of the ocular adnexa, comprising up to 55% of all orbital tumors, yet they account for only about 1% of all non-Hodgkin lymphomas [2]. The vast majority – over 95% – are of B-cell origin, with approximately 80% being low-grade lymphomas [3]. The most prevalent subtype of primary orbital lymphoma, found in 35% to 80% of cases, is extranodal marginal-zone lymphoma of MALT type [1]. Other less common subtypes are diffuse large B-cell lymphoma (8%), follicular lymphoma (20%), and, more rarely, lymphoplasmacytic lymphoma, small lymphocytic lymphoma, and mantle cell lymphoma [1]. Orbital lymphoma is considered primary when a patient has no additional simultaneous systemic lymphoma or previous history of lymphoma [1]. It is typically seen in people over the age of 50 with a slight female predominance [1].

The most common signs of orbital lymphoma, such as a periorbital tumor mass and proptosis, are often insidious and indolent, resulting in delayed diagnosis [3]. Although both motility difficulties and visual restrictions are typically later findings in the disease, ocular pain itself is less common [3]. This gradual progression emphasizes the need for careful observation in patients with nonspecific ocular symptoms [3]. Tumors most commonly localize to the superior lateral quadrant, and the extraocular muscle most frequently involved is the superior rectus muscle, as was the case for our patient [8]. Staging is done using the 2 most commonly used staging systems: the Ann Arbor staging system and the tumor, node, metastasis (TNM) staging system developed by the American Joint Committee on Cancer (AJCC) [1]. According to the Ann Arbor system, any single extranodal site such as the orbit is categorized as stage IE disease [1].

Several previously published case reports closely parallel the presentation and evolution observed in our patient. Jung et al described a case of orbital lymphoma that presented with isolated inferior rectus palsy and diplopia. Their case showed how lymphoma affecting the extraocular muscles can mimic benign motility disorders and that this can delay diagnosis [9]. Guo et al reported a rare case of extranodal marginal-zone lymphoma that developed within the extraocular muscles after years of presumed chronic myositis. This underscores the slow progression and diagnostic challenges inherent in this type of tumor, similar to our case [10]. Another case by Chaurasiya et al revealed orbital lymphoma that was initially misdiagnosed as orbital cellulitis due to its nonspecific clinical appearance. This highlights how early presentations may be mistaken for inflammatory disease [11]. These individual case reports are in accordance with the characteristic slow progression, extraocular muscle involvement, and excellent response to radiotherapy seen in our patient.

Treatment options include surgery, radiotherapy, and chemotherapy. The role of surgery is primarily limited to biopsy, as surgical intervention alone tends to have a high rate of relapse [12]. Radiotherapy alone has shown excellent local control and survival in patients with localized MALT lymphoma with doses of 25 to 35 Gy, while chemotherapy is reserved for more aggressive systemic disease [3,6].

Overall prognosis for low-grade tumors is good, with local control rates over 90% following radiotherapy alone. In a multivariate analysis, younger age, favorable response, conjunctival localization, and complete staging were strongly correlated with better disease-free survival and lower risk of treatment failure [7].

Conclusions

Orbital MALT lymphoma can develop slowly and mimic benign conditions, making early detection challenging. Accurate diagnosis requires proper imaging and histopathological evaluation. Localized cases respond well to radiotherapy, highlighting the need for early diagnosis and tailored treatment for optimal outcomes.