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Editor,—Primary ocular non-Hodgkin's lymphoma (NHL) may be found in the conjunctiva, eyelids, and lacrimal glands, but the majority occur in the orbit.1 Most primary ocular NHL are of B cell origin, either of the follicular, diffuse small, or mixed cell type.1
According to the Revised European American classification of lymphoid neoplasms (REAL classification)2 the most common ocular NHL, arising from mucosa associated lymphoid tissue (MALT) and the marginal zone of lymph follicles, is included in the group of extranodal peripheral B cell lymphomas.1 Histopathological features of marginal zone lymphoma (MZL) of the MALT type consists of a diffuse and parafollicular growth pattern and the presence of lymphoepithelial lesions.2 The tumour cells express monotypic surface Ig (sIg) and sometimes cytoplasmic Ig (cIg) (usually IgM), moreover the pan B cell antigens CD19, CD20, CD22, and CD79a.2 Typically, they are negative for CD5, CD10, and CD23.2
Characteristically, MZL of the MALT type affects older patients and may remain localised for years,2 while disseminated disease involving bone marrow and peripheral blood is rare.2Localised tumours may be cured with local irradiation, whereas disseminated stages of the disease are not curable and transformation into a large cell NHL may occur.2
We report a case of conjunctival MZL of the MALT type with an unusual clinical appearance, an CD5+ immunophenotype, and a history of idiopathic non-specific anterior uveitis.
A 79 year old man was referred to our hospital with a 3 month history of right eye discomfort and an epibulbar mass below the upper eyelid. Ophthalmological examination of the right eye revealed a reddish palpable tumour, 1.5 cm in diameter, located in the upper conjunctiva (Fig 1C). The extraocular movements were normal. Cornea and anterior chamber appeared clear; however, cortical and nuclear opacities were noted in the crystalline lens. Posterior segment examinations showed areas of confluent drusen and retinal pigment epithelium atrophy, with a normal optic disc. The patient's left eye had suffered from a severe anterior uveitis 30 years earlier and some recurrences, resulting in subsequent phthisis bulbi. Slit lamp examination revealed a low flare without cells in the anterior chamber, an indication of persisting vascular damage, moreover posterior synechiae. Lens opacification and age related macular degeneration were similar to the right eye. Because of the age related macular degeneration and the cataract visual acuity was “only” 20/100 for the right eye, for the phthisic left eye counting fingers/1 metre. The intraocular pressure was normal for the right eye (17 mm Hg), but hypotonic for the left eye (7 mm Hg). Because the uveitis was not due to any systemic or ocular disorder (characterised by blood chemistry tests and anterior chamber tap) it has to be diagnosed as idiopathic non-specific uveitis.
Orbital magnetic resonance imaging (MRI) showed a supraequatorial lesion that surrounded the right eyeball (Fig 1A and B). Computed tomography (CT) scans demonstrated an intact bone structure of the orbit and no abnormalities were seen in the remaining skull, body or abdomen. As extensive as possible the anterior, visible part of the epibulbar lesion was surgically resected (Fig 1C and D), formalin fixed and paraffin embedded sent to the pathology department of Justus-Liebig-University Giessen, Germany, for immunohistological studies (Fig 2). Immunohistochemistry was done on the routinely formalin-fixed, paraffin embedded biopsy specimen after microwave pretreatment of the prepared 3–4 μm tissue sections. In the absence of analysable epithelium or mucosal glands, lymphoepithelial lesions were not assessed. However, general expression of CD20 and CD79a revealed the B cell nature of the tumour infiltrate, but it was interesting that CD5 expression in about 50% of tumour cells was positive (Fig 2D), while only few intermingled reactive T lymphocytes were observed (Fig 2C). Hints for a plasma cellular differentiation were not detected by VS38c and reactivity for CD10, CD23, and CD30 was negative.
General physical examination of the patient showed no abnormality. There were no lymphadenopathy or hepatosplenomegaly. Peripheral blood smears as well as bone marrow aspiration biopsy showed no signs for a disseminating lymphoma. All haematological and biochemical parameters were within the normal range with the exception of slightly elevated thymidine kinase (8 U/l) and β2-microglobulin levels (2.9 μg/l) suggestive for intensified cell growth. In conclusion, the final diagnosis of a low malignant conjunctival MLZ of the MALT type was established and confirmed by the German reference centre (Prof M-L Hansmann, University of Frankfurt). The patient underwent radiotherapy (40 Gy) of the right orbit (fractionated to 5 × 2 Gy/week). After radiotherapy, the lesion decreased markedly. No recurrence of the orbital lesion or any systemic involvement was noted during the follow up period of 18 months.
The immunophenotypic profiles of low grade B cell NHL are complex and still under investigation. Especially the T cell antigen CD5 is used to subclassify this group of B cell lymphomas. Since CD5+ B cells were found in normal liver, spleen, and lymph node, CD5+ B cell NHL are considered to be a malignant clonal proliferation of a specific stage of B cell differentiation.3 The T cell antigen CD5 has been reported in B cell NHL between 3% and 40%.145In extranodal MZL the presence of CD5 is described in one of 35 cases, in two of 63 cases, respectively in one of nine cases.6-8 Only three cases were disclosed which affected the eye.910
Since increased numbers of CD5+ B cells are found in blood of patients with autoimmune diseases,11 CD5+ B cells are thought to exert an immunoregulatory function. Whether CD5 expression is relevant to the prognosis of patients with MALT lymphoma is controversial.6910
The association of MALT lymphomas with diverse autoimmune disorders, especially Sjögren's syndrome and Hashimoto's thyroiditis is well known.1213 Until now, the pathogenetic link of this relation is not clear, but an influence of a long standing inflammation and a lack of a regulatory lymphocytic subset are discussed to promote the development of MALT lymphoma.14 Perhaps there is also a (autoimmune) correlation of anterior uveitis (of the contralateral eye) and MALT lymphoma as demonstrated here, but it cannot be proved and is perhaps incidental.
The differential diagnoses of our patient are MZL, bearing the unusual CD5+ phenotype, chronic lymphocytic B cell leukaemia (B-CLL), and mantle cell lymphoma (MCL). The last were excluded because of different morphological and phenotypic features.2 Furthermore, B-CLL and MCL are usually widespread at diagnosis showing diffuse lymphadenopathy, substantial lymphocytosis, and bone marrow involvement. Both diseases are more aggressive than MALT lymphoma and usually not curable.2 Although there was an extended growth from the epibulbar conjunctiva towards the deep orbit, our patient showed a localised stage of the disease, an indolent clinical course, and a favourable response to radiotherapy. Thus, we demonstrated an exceptional case of a conjunctival MZL of the MALT type with unusual CD5+ phenotype.
We thank Drs Irina Fenic, Joachim Woenckhaus, Karsten Münstedt, and Christian Vorwerk for critical reading the manuscript. Furthermore, we thank all colleagues from the Medical School Bad Hersfeld and the Institute of Pathology, University Giessen, who were involved in the diagnosis and treatment of our patient.