A case of palpebral conjunctival MALT lymphoma misdiagnosed as giant papillary conjunctivitis


 Background

Although conjunctival lymphoma is generally easy to diagnose, misdiagnosis of this condition has been repeatedly reported. This article presents a rare case of lymphoma arising from the palpebral conjunctiva in a very young woman whose disease was initially misdiagnosed as giant papillary conjunctivitis.

Case presentation

A 20-year-old young woman with a history of chronic rhinitis presented with bilateral, salmon-pink, multiple-nodular patches in both the superior and inferior palpebral conjunctivae. The patient did not respond to hormone (glucocorticoids) and other anti-inflammatory medications. Therefore, she underwent surgical resection combined with cryosurgery and achieved complete remission. According to histopathology and immunohistochemistry examinations, a diagnosis of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) was made. Two months post-treatment, she received additional radiation therapy because a sign of recurrence was apparent. From then, she had no recurrence, vision loss, or cataract during a follow-up of six months.

Conclusions

Although the diagnosis of conjunctival MALT lymphoma is straightforward in most cases due to its characteristic salmon-like appearance, misdiagnosis of this condition can occur. When conventional antibiotic and anti-inflammatory treatments are not effective, conjunctival lymphoma should be considered and biopsy for histological and immunohistochemical analyses is warranted. The combination of excision, cryosurgery and radiation therapy is an effective approach to achieve complete remission.

multiple-nodular patches in both the superior and inferior palpebral conjunctivae. The patient did not respond to hormone (glucocorticoids) and other anti-inflammatory medications. Therefore, she underwent surgical resection combined with cryosurgery and achieved complete remission. According to histopathology and immunohistochemistry examinations, a diagnosis of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) was made. Two months post-treatment, she received additional radiation therapy because a sign of recurrence was apparent. From then, she had no recurrence, vision loss, or cataract during a follow-up of six months.

Conclusions
Although the diagnosis of conjunctival MALT lymphoma is straightforward in most cases due to its characteristic salmon-like appearance, misdiagnosis of this condition can occur. When conventional antibiotic and anti-inflammatory treatments are not effective, conjunctival lymphoma should be considered and biopsy for histological and immunohistochemical analyses is warranted. The combination of excision, cryosurgery and radiation therapy is an effective approach to achieve complete remission.

Background
The conjunctiva consists of bulbar and palpebral membranes, which are connected at the conjunctival fornix. Lymphomas localized in the conjunctivae (conjunctival lymphoma) account for 25-40% of all ocular adnexal lymphomas [1][2][3]. Notably, most conjunctival lymphomas (35-80%) belong to the extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-type 3 lymphoma) subtype, followed by follicular and diffuse large B-cell lymphoma [1][2][3]. Clinically, conjunctival MALT lymphoma has a slight female predilection, and the patients, who generally present with salmon-pink nodular patches, are mostly in their fifth to seventh decade of life at the time of diagnosis, with a median age of about 60 years [1][2][3]. The lesions typically affect the bulbar conjunctiva and the fornix. Various clinical symptoms include conjunctival redness, irritation, foreign body sensation, and excessive tear production [1]. Most of these lesions, about 70-90%, are primary tumors. In addition, most patients have lesions (80%) localized in the conjunctiva; unfortunately, 20% of patients may eventually advance to disseminated disease [2][3]. In general, conjunctival MALT lymphoma presents as characteristic salmon-pink nodular patches; thus, its diagnosis is straightforward. However, there have been reports of its misdiagnosis as allergic conjunctivitis [4], chronic conjunctivitis [5][6][7], and Sjögren's syndrome [8].
In the present report, we document a rare case of conjunctival MALT lymphoma, which was initially misdiagnosed as giant papillary conjunctivitis. The female patient was very young at only 20 years.
Moreover, bilateral lesions affected the palpebral conjunctivae, which is extremely rare.

Case Report
A 20-year-old female noticed large palpebral tumor masses in both of her eyes in the mirror. She then visited several large hospitals and failed to receive effective treatments for the condition. Three months after she initially noticed the condition, she was referred to our clinic; she was initially diagnosed with bilateral giant papillary conjunctivitis based on macroscopic appearance and her medical history of chronic rhinitis. Thus, she was treated with topical hormones (Tobramycin and Dexamethasone Eye Drops) and other anti-inflammatory eye drops (Olopatadine Hydrochloride Eye Drops); however, none of the treatments were effective. Therefore, the patient was hospitalized to undergo comprehensive ophthalmological examinations and a complete physical exam. Before surgery, as shown in slit lamp images ( Figure 1A-D), the hyperplastic lesions were bilateral and occurred at both upper and lower conjunctivae; the masses were multinodular and salmon-pink. Her visual acuity without and with correction was 0.8 /0. 6 and 1.0/1.0, respectively. Meanwhile, the anterior segments and fundus in both eyes were normal, with an intraocular pressure of 14/16 mmHg.
She was subjected to a whole body examination and there was no surgical contraindications. She signed the written form consent and underwent the surgical resection. After she underwent surgical resection of the masses, she additionally received cryosurgery, which was performed 3 seconds per site, which was repeated for three times. The histopathological examination of the surgical samples confirmed the diagnosis of MALT lymphoma. Hematoxylin and eosin staining showed that monocytelike lymphocytes, with weakly stained cytoplasm, were distributed in patches, with some cells demonstrating plasmacyte-like differentiation (Figure 2A). Immunohistochemical exams revealed that the lesions were positive for CD20 ( Figure 2B)

Discussion And Conclusions
We report here a rare case of conjunctival MALT lymphoma in a young female. The bilateral, widespread lesions were localized in the palpebral conjunctivae, which is extremely rare since this condition is classically localized in the conjunctival fornix [1][2][3]. Conjunctival MALT lymphoma is typically easy to diagnose because of its characteristic appearance: salmon-like nodular patches.
However, several reports have documented the misdiagnosis of this disease. For example, it has been repeatedly misdiagnosed as chronic conjunctivitis [5][6][7]. In general, conjunctival MALT lymphoma occurs in elderly people ranging in age from 50-70 years. The patient in this study was only 20 years old at the time of diagnosis, and it is very rare for people this young to be affected by this disease.
Conjunctival MALT lymphomas classically arise from the conjunctival fornix and bulbar membrane [1][2][3]. The lesions in the present case covered a large area over both the superior and inferior palpebral conjunctivae, which is very rare. An increased incidence of systemic involvement has been reported 5 for patients with bilateral lesions and a higher number of conjunctival lesions [1][2][3]. However, the patient in this case, although she had bilateral lesions and a high number of lesions, did not show signs of systemic involvement.
The conventional and currently standard treatment for conjunctival MALT lymphoma is external beam radiation therapy, which achieves complete remission exceeding 90% [3,9]. Other treatments, including excision only, excision and topical chemotherapy, and intralesional chemotherapy, have also been reported to achieve complete remission [10][11]. In the present case, we chose surgical resection of the lesions combined with cryosurgery. The patient was further treated with standard radiation therapy after a follow-up exam showed signs of recurrence of the condition. After that, no recurrence was detected during a period of six months of follow-up.
The diagnosis of conjunctival MALT lymphoma is usually straightforward; however, misdiagnosis can occur. If conjunctivitis-like conditions do not respond to conventional antibiotic and anti-inflammatory treatments, conjunctival lymphoma should be considered, and biopsy for histological and immunohistochemical analyses is warranted. The combination of excision, cryosurgery and radiation therapy is an effective approach to achieve complete remission of this condition. Ethics approval and consent to participate Not applicable.

Consent for publication
Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor of BMC Ophthalmology.

Competing interests
The authors declare that they have no competing interests.

Supplementary Files
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