Reactive lymphoid hyperplasia of the ocular surface: clinicopathologic features and search for infectious agents

Abstract

Editor, Reactive lymphoid hyperplasia (RLH) is a benign and reversible enlargement of lymphoid tissue composed of dense lymphocytic infiltrates with formation of well-defined reactive lymphoid follicles with germinal centres (Sigelman & Jakobiec 1978; Coupland et al. 1998). There is some evidence that infectious agents, in particular Chlamydia (C.) psittaci for ocular adnexal lymphoma (OAL) (Ferreri et al. 2004) and Epstein–Barr virus (EBV) for RLH (Feinberg et al. 2000), may contribute to the pathogenesis of lymphoid neoplasia. This study provides a detailed analysis of clinical features of RLH on the ocular surface and screening for infectious agents by polymerase chain reaction (PCR) and liquid hybridization. Clinical features of seven histologically proven RLHs of the ocular surface were analysed. DNA from paraffin-embedded formalin-fixed tissue of 6 RLHs and 8 conjunctival non-Hodgkin lymphomas was extracted and screened for Chlamydia species (C. trachomatis, C. pneumoniae, C. psittaci) and EBV. Particular PCR protocols were developed. The PCR product was visualized by agarose gel electrophoresis. To verify the amplification results, each PCR product underwent additional liquid hybridization testing. Specific probes were designed for the detection of each Chlamydia species and EBV. (Please contact the corresponding author for detailed information). In this case series, RLH occurred over a wide spectrum of ages (range: 8–77 years, median: 23 years) with a main incidence within the third decade (Fig. 1). The lesions were predominantly located nasally, except for one tumour occurring in the lower fornix. In two cases, the process was confined to the caruncle, and in one case, to the plica. The remainder developed in the nasal conjunctiva. All tumours were of salmon-coloured appearance. The clinical appearance varied between cyst-like (n = 2), nodular (n = 1) and pemphigoid-like (n = 1) lesions, as well as lesions mimicking the diffuse conjunctival thickening of a lymphoma (n = 3) were observed. In two patients, the tumour followed the manifestation of a conjunctival lymphoma in the fellow eye. Follow-up (1–11 years) was uneventful in all patients with no recurrence or transformation into a true lymphoma. Clinical picture illustrating different manifestations of reactive lymphoid hyperplasia (RLH). (A) Cystoid lesion in the left caruncle of a 22 years old female patient. (B) Plain and salmon-coloured lesion in the left conjunctiva (next to the plica) of an 11 years old male patient. (C) Nodule-like lesion in the left caruncle of a 23 years old male patient. (D) Salmon-coloured lesion in the right lower fornix of a 26 years old female patient. This lesion developed 1 month after the patient was diagnosed with a conjunctival non-Hodgkin lymphoma in the lower fornix of the fellow eye. In none of the investigated specimens either Chlamydia species or EBV were detected. In our cohort, RLH was presented as a mostly unilateral circumscribed lesion with varying clinical morphology and an apparent preference for the nasal conjunctiva/caruncle. Six of seven patients were younger than 31 years, which is different from the average age reported in the literature. RLH has – similar to malignant lymphoma – been reported to affect adults typically in the 5th through 7th decade (Sigelman & Jakobiec 1978; Coupland et al. 1998). The proposed aetiology of RLH as a reaction to antigen hyperstimulation (Sigelman & Jakobiec 1978), however, might account for a more likely occurrence in children and young adults, as well as for the nasal location. Two of our patients with a non-Hodgkin lymphoma and subsequent treatment with radiation therapy of the affected eye developed RLH in the fellow eye. Whether the occurrence of RLH is connected to radiation therapy or lymphoma remains unclear. There is still an ongoing debate on a possible association between OAL and C. psittaci (Ferreri et al. 2004; Decaudin et al. 2008). Differences in the prevalence of C. psittaci infection in various geographical regions and technical differences in the application of the assays have to be considered (Decaudin et al. 2008). However, from our results, we would not recommend a change in treatment strategy unless the association with an infectious agent can be unequivocally proven for single cases. Especially, in young adults and children, RLH should be considered in the differential diagnosis of salmon-coloured lesion of the ocular surface, even if cyst like and located at unusual sites such as the caruncle (Herwig et al. 2008).