Ocular adnexal lymphoma: a review of clinicopathologic features and treatment options

Abstract

IntroductionLymphoproliferations of the eye, including intraocular and ocular adnexal non-Hodgkin lymphoma (NHL), constitute a heterogeneous group of neoplasms that represent less than 1% of all NHLs 1 and 5% to 15% of all extranodal sites. 2 First described in 1952, 3 they are the most frequent malignant tumors of the eye and ocular adnexae; in fact, in the Florida cancer registry, they represent up to 55% of all orbital tumors. 4 As for all NHLs, a marked increase of the incidence of ocular adnexal NHL has also been observed. 4 The clinical features and natural history of ocular adnexal lymphoma (OAL) is completely different from those of intraocular lymphoma, which emphasizes the need to distinguish between the therapeutic management of both. Intraocular lymphoma is a subset of primary central nervous system lymphoma, 5-7 and intraocular involvement is found in approximately 15% of affected patients. 8 The histologic subtype of intraocular lymphoma is almost always high grade 9,10 and it can occur in the context ofAIDS-related lymphoproliferations. In contrast, OALs-including lesions of the conjunctiva, lacrimal gland, orbit, and eyelids-are mainly low-grade tumors not associated with HIV infection. 11 Although combination chemotherapy with highdose methotrexate is the basis of treatment of primary central nervous system and intraocular lymphomas, 10,12 radiotherapy has been the standard treatment for low-grade ophthalmologic lymphomas. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] However, other treatment options, such as therapy with monoclonal anti-CD20 antibody, 31,32 may constitute a promising alternative to external beam irradiation and its potential toxicity. In addition, some reports have suggested a possible value of anti-Chlamydia psittaci antibiotic therapy. 33,34 In this review, which is exclusively focused on ophthalmologic lymphomas, we first present the pathologic, clinical, and prognostic factors of these lymphomas and then discuss all available treatment options in terms of safety and efficacy and their respective indications. Biology of ophthalmologic lymphomas Diagnosis of OALAs for all other forms of nodal and extranodal NHL, confirming a positive diagnosis of OAL is often long and difficult because the tumor is very small in most patients. Positive diagnosis must be based on histologic examination of a sufficient tumor sample obtained by surgical biopsy that is large enough to allow rigorous definition of lymphoproliferative disease according to the World Health Organization (WHO) classification. 35 Histopathologic examination consists of morphologic examination of cellular proliferation (cellular appearance and architectural pattern), usually combined with immunohistochemical analysis and molecular analysis.The exact modalities of biopsy depend on the anatomic site of the lesion and its relation to the eye: biopsy may be performed of the conjunctiva, an eyelid lesion, an orbital mass, or the lacrimal gland. However, sometimes patients have nodal involvement, an...

Role of Chlamydia in the Development of Ocular Adnexal Lymphoma

“…The strong association of C. psittaci with ocular adnexal lymphomas, observed by Ferreriwas not be confirmed by other groups, [10,19,24,31,[83][84][85] suggesting evidence for geographic heterogeneity.…”

“…have a prevalence below 10% [10,19,31,86,87]. In Kenya, where the underdeveloped conditions and the rather high plethora of infectious agents which could establish an excellent pabulum for the cancerous transformation and the development of the OAL, no association has been found between OAL and C. psittaci [88].…”

“…They can infiltrate every orbital and ocular adnexal tissue [19]. The slow evolution of symptoms, especially in conjunctival lymphomas explains the long median interval between onset of symptoms and time of diagnosis ranging from 1 month to 10 years (median, 7 months).…”

“…The most frequent site of origin is the orbit (40%), followed by conjunctiva [35% -40%], lachrymal gland (10% -15%), and eyelid (10%) [19,20]. Most patients with conjunctival lymphoma have visible, characteristic "salmon-pink patch" lesions reflecting tumour vascularity associated with swollen conjunctiva, redness and irritation (Figure 1).…”

“…Ideally, the opti-mal treatment should not be negatively counter balanced by side effects. In deciding of optimal therapy several factors must be taken into account and include: 1) histopathological type of lymphoma according to the WHO classification [103]; 2) extension of disease, within and outside the periocular region; 3) prognostic factors related to the patient [age, autoimmune disorders] and the disease; and 4) additionally consideration of the functional impact of the treatment on the eye [19,104].…”