Saudi Journal of Ophthalmology (2013) 27, 61–63
Case Report
Primary bilateral small lymphocytic lymphoma of ocular adnexal origin: Imprint cytology suggests the intraoperative diagnosis Arghya Bandyopadhyay, MD a,⇑,1; Kaushik Majumdar, MD, DNB a; Mimi Gangopadhyay, MD a; Kalyan Khan, MD a; Subrata Chakraborty, MD a; Asim Kr. Ghosh, MS b
Abstract Ocular adnexal lymphomas (OAL) involve the peri-global soft tissues like orbit, eyelid, conjunctiva, lacrimal gland. We describe a rare case of primary bilateral OAL, histomorphologically small lymphocytic lymphoma, B cell phenotype of lacrimal gland origin. Rapid intraoperative diagnosis can be suggested on imprint cytology; subsequent histology and immunohistochemistry are helpful for confirmation and further line of management. Since no preformed lymphoid structures are expected within the orbit or lacrimal gland, any lymphoid mass here should be critically evaluated as a lymphoproliferative lesion. Keywords: Lymphoma, Lacrimal, Ocular adnexal, B cell, Bilateral, Imprint cytology Ó 2012 Saudi Ophthalmological Society, King Saud University. All rights reserved. http://dx.doi.org/10.1016/j.sjopt.2012.03.006
Introduction
Case report
The term ocular adnexal lymphoma (OAL) is used to designate lymphomas affecting the orbit, eyelid, conjunctiva and other ocular adnexal structures singly or in combination. It is estimated to account for nearly 2% of all Non-Hodgkin’s lymphomas (NHLs) and about 5–15% of NHLs at extra nodal site.2 Despite this, orbital lymphoma is the most frequent primary malignant orbital tumor of adults accounting for about 55% of all orbital tumors.5 It affects primarily the orbit (44%), lacrimal gland (26%), conjunctiva (21%) and eye lid (9%).7 In about 19% cases of primary orbital NHL there is bilateral lacrimal gland involvement.7 Herein we describe a case of primary bilateral small lymphocytic lymphoma of lacrimal gland, which had been initially suggested on imprint cytology.
A 55-year old lady presented with complaints of gradually enlarging fullness of bilateral upper eyelids, especially in the lateral aspects. The swelling of right eyelid was present for one and half years, while that of left eyelid developed subsequently (Fig. 1, above). As a result she developed bilateral pseudoptosis, more marked in the right. Ocular movement was slightly restricted in lateral gaze of each eye tested separately. No diplopia was present; intraocular tension and fundus were unremarkable. Visual acuities with her most recent correction were 6/6 for both eyes. On palpation, both the masses were nodular, nontender, freely mobile and rubbery in consistency. CT scan revealed bilateral enhancing lacrimal gland mass present behind both eyeballs (mass in the right side measuring 30 20 mm and that in left 22 11 mm),
Received 5 June 2011; received in revised form 14 February 2012; accepted 20 March 2012; available online 29 March 2012. a b
Dept. of Pathology, North Bengal Medical College, Darjeeling, India Dept. of Ophthalmology, North Bengal Medical College, Darjeeling, India
⇑ Corresponding author. Address: Dept. of Pathology, Institute, North Bengal Medical College, Sushrutanagar, Darjeeling, West Bengal, India. Mobile: +91 9433389946. e-mail address:
[email protected] (A. Bandyopadhyay). 1
Present address: Dept. of Pathology, G B Pant Hospital, New Delhi, India.
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Figure 1. Above: Bilateral swelling of upper eye lids, lateral aspect, below: Computed tomography shows space occupying lesion behind both eye balls involving bilateral lateral recti.
with the involvement of bilateral lateral recti (Fig. 1, below). Biopsy from the mass in the right side measured 2 cm in diameter, with multinodular, soft, gray white, fish flesh in appearance. The blood mixed fluid adhered to the specimen was soaked in a filter paper, and imprint cytology smears were made by touching freshly cut surface of the specimen on clean, grease free slides. The stained smears showed a fairly monomorphic population of lymphoid cells, almost equal to or slightly larger than a mature lymphocyte, with scanty blue cytoplasm, predominantly condensed chromatin and inconspicuous nucleoli (Fig. 2). Background showed few lymphoglandular bodies. A cytologic impression of low grade (small lymphocytic) lymphoma, along with a differential diagnosis of atypical lymphoid hyperplasia (ALH) was considered. Histological examination revealed lymphoid cells arranged in multinodular pattern replacing the orbital fat (Fig. 3), bearing similar morphology as seen in cytology smears (Fig. 3, inset). Immunohistochemistry for CD 20 showed membranous positivity (Fig. 4), while CD 3 was negative. The diagnosis of extranodal B-cell small lymphocytic lymphoma was offered. A thorough work up of the patient was done including complete clinical examination, peripheral blood film, bone marrow, chest X-ray, CT scan thorax and CT scan of abdomen, all of which did not reveal any other mass
A. Bandyopadhyay et al.
Figure 3. Low magnification photomicrograph showing multinodular architecture of lacrimal gland replaced by fairly monomorphic population of lymphoid cells (H & E stain, 40); inset: higher magnification showing monotonous diffuse proliferation of small lymphoid cells (H & E stain, 400).
Figure 4. CD 20 immunostain showing membranous positivity in the lymphoid cells (400).
lesion or secondary involvement. This patient was also euthyroid, and auto-antibodies against extractable nuclear and cytoplasmic antigen (Ro/SS-A,La/SS-B), Rheumatoid factor (RF) and anti-nuclear antibody (ANA) were all negative. Serum angiotensin converting enzyme (ACE) was also within the normal range. As no systemic disease was found, the patient was treated with local orbital external beam radiotherapy with shielding of the eyeballs. Periodic follow up with repeated workup every 6 months interval was recommended. The patient was doing well during her first two follow up visits.
Discussion
Figure 2. Imprint smear of the biopsy material showing lymphoid cells with scanty blue cytoplasm, slightly opened up chromatin, inconspicuous nucleoli, and occasional nuclear cleaving (Giemsa stain, 400).
The lymphoid lesions of orbital region have been described under various terms such as chronic nonspecific inflammation (inflammatory pseudotumor), reactive lymphoid hyperplasia (pseudolymphoma), atypical lymphoid hyperplasia (ALH), indeterminate cases and lymphoma.1 Many ocular adnexal neoplasms previously classified as ‘‘pseudolymphoma’’ or benign lymphoid hyperplasia may actually contain
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Primary bilateral small lymphocytic lymphoma of ocular adnexal clonal B-cell expansion and are presumably B-cell lymphoma. It is to be borne in mind that there are no preformed lymph nodes within the orbit or within lacrimal gland, therefore any lymphoid mass within orbit is abnormal.4 As in our case, orbital lymphoma is more common in women and most of them develop in 5th to 6th decade.4 Bilateral orbital lymphoma develops in about 20% patients and shows the same morphological, immunological and immunoglobin gene rearrangement in each eye suggesting origin from the same clone. As there is no lymphatic connection between the orbits this could be due to site specific homing.7 The presence of a preexisting inflammatory background due to infection or autoimmune reaction may have an etiopathogenetic role in orbital lymphoma. Some of the orbital lymphoma patients, especially those having MALT lymphoma type may have history of autoimmune disorders like thyrotoxicosis, sarcoidosis or Sjogren syndrome.6 However, extensive workup for this patient, including anti Ro/SS-A, La/SS-B, RF, ANA and ACE did not reveal any systemic illness or other mass lesion. On cytology, it may be difficult to distinguish low grade NHL from ALH or indeterminate lymphocytic lesion.1 In this case described, initial suggestion of a low grade NHL was offered through imprint cytology of the biopsy material. Subsequent histopathology confirmed the diagnosis. The commonest subtype of lymphoma originating in orbit is extra nodal marginal zone lymphoma; other low grade lymphomas which may arise in orbit are small B lymphocytic lymphoma, follicular lymphoma and rarely mantle cell lymphoma.7 In this case there was monomorphic nodular and diffuse proliferation of small lymphocytes consistent with small lymphocytic lymphoma, with immunohistochemical evidence of clonal B cell origin (CD 20 positive). As the patient had primary bilateral orbital lymphoma with no systemic involvement, we preferred orbital radiotherapy, which is viewed as the gold standard for primary extranodal lymphoma localized to the orbit. Other treatment strategies for OAL are ‘‘wait and watch’’ strategy after surgical resection or biopsy in patient with stage I disease, chemotherapy and immunotherapy.3 The role of chemotherapy has not yet been clearly defined and its role in the treatment of low grade localized disease is questionable.8 Rituximab is the
monoclonal antibody most commonly used for the treatment of CD 20 positive small lymphocytic lymphoma, and it can be used to obtain transient symptomatic benefit in OAL patients for whom other therapeutic strategies are contraindicated.3 Recent experiments do suggest that radioimmunotherapy with standard doses of 90Y ibritumomab tiuxetan is a safe and effective front line treatment for early stage extranodal indolent lymphoma of ocular adnexa.3 The major prognostic criteria for OAL include anatomic location, stage of disease at first presentation, lymphoma subtype, immunohistochemical markers for tumor growth rate and serum lactate dehydrogenase (LDH) level.8 To conclude, any lymphoid tissue in the orbital region is abnormal and should be evaluated with a suspicion of a lymphoproliferative lesion. Primary orbital NHL/OAL though rare, should come in differential diagnosis of bilateral orbital masses. Rapid intraoperative diagnosis can be suggested by imprint cytology; histology and immunohistochemistry are useful for confirmation. Orbital radiotherapy is the treatment of choice for localized disease, with increasing role of targeted immunotherapy in years to come.
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