Journal of Pediatric Ophthalmology and Strabismus

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Short Subjects 

Bilateral Benign Reactive Lymphoid Hyperplasia of the Conjunctiva in a Pediatric Patient

Andre Jastrzebski, MD; Bruce F. Burns, MD; David R. Jordan, MD; Kay Lam, MD; Seymour Brownstein, MD

Abstract

A 13-year-old boy presented with asymptomatic, bilateral, nasal bulbar conjunctival lesions. Excisional biopsy of the larger lesion showed a mature, mixed lymphocytic infiltrate with germinal centers, consistent with a diagnosis of benign reactive lymphoid hyperplasia, a rare condition in children.

Abstract

A 13-year-old boy presented with asymptomatic, bilateral, nasal bulbar conjunctival lesions. Excisional biopsy of the larger lesion showed a mature, mixed lymphocytic infiltrate with germinal centers, consistent with a diagnosis of benign reactive lymphoid hyperplasia, a rare condition in children.

Bilateral Benign Reactive Lymphoid Hyperplasia of the Conjunctiva in a Pediatric Patient

From the Departments of Ophthalmology (KL, SB, AJ, DRJ) and Pathology (KL, SB, AJ, BRB), University of Ottawa Eye Institute and The Ottawa Hospital, the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Seymour Brownstein, MD, University of Ottawa Eye Institute, 501 Smyth Road, Suite 6213, Ottawa, Ontario, Canada K1H 8L6. E-mail: sbrownstein@ohri.ca

Received: September 09, 2011
Accepted: November 10, 2011
Posted Online: December 13, 2011

Introduction

Benign reactive lymphoid hyperplasia (BRLH) of the conjunctiva is rare in children with only eight cases in the reviewed literature,1–5 two of which were documented with bilateral involvement.1,4 The clinical course and appropriate management of conjunctival BRLH in children is not well established.2 We describe a child with bilateral nasal bulbar conjunctival masses that demonstrated BRLH on histopathological examination of the larger lesion.

Case Report

A 13-year-old boy presented with a 5-month history of an asymptomatic left conjunctival mass that developed over a few days. It was not associated with any symptoms of pain or discharge. A similar, smaller lesion developed in the right eye a few weeks after the onset of the initial lesion, but neither lesion had shown much change during the following 3 months. The child was previously well, with no medications and no present or past systemic illnesses.

Examination revealed a salmon-colored nodule measuring 5 × 5 × 4 mm in the left bulbar conjunctiva abutting the plica semilunaris and a similar, smaller lesion on the right side (Fig. 1). This was clinically suspicious for a lymphoproliferative growth and an excisional biopsy of the left conjunctival lesion was performed. Histologically, the biopsy specimen showed a prominent submucosal mature lymphoid infiltrate with several well-defined germinal centers (Fig. 2). The germinal centers contained macrophages with scattered debris (tingible bodies) and were surrounded by a mantle of small mature lymphocytes. No evidence of cytologic atypia was present to suggest lymphoma.

Bilateral, asymmetric (right smaller than left), salmon-pink colored nodules involving the nasal bulbar conjunctiva at time of presentation.

Figure 1. Bilateral, asymmetric (right smaller than left), salmon-pink colored nodules involving the nasal bulbar conjunctiva at time of presentation.

The conjunctival biopsy specimen shows well-defined variably sized lymphoid follicles with irregular germinal centers in the substantia propia (hematoxylin-eosin, original magnification ×25).

Figure 2. The conjunctival biopsy specimen shows well-defined variably sized lymphoid follicles with irregular germinal centers in the substantia propia (hematoxylin-eosin, original magnification ×25).

Immunohistochemical studies revealed a mixed T-cell (CD3-positive) and B-cell (CD20-positive) infiltrate with a predominance of B-cells, especially within the follicles (Fig. 3). The lymphocytes surrounded irregularly shaped germinal centers (CD10- and BCL-6-positive). Oncoprotein BCL-2 staining was negative within the follicles. Staining for Epstein–Barr virus group was negative. The light microscopic and immunohistochemical findings were consistent with a benign reactive process and a diagnosis of BRLH was made.

Immunohistochemical stains show a mixed infiltrate of T-cells with CD3 (A), but a predominance of B-cells with CD20 (B). Positive staining with BCL-6 (C) and negative staining for BCL-2 (D) in the germinal centers show an inverse relationship of expression consistent with reactive secondary lymphoid follicles (original magnification ×31).

Figure 3. Immunohistochemical stains show a mixed infiltrate of T-cells with CD3 (A), but a predominance of B-cells with CD20 (B). Positive staining with BCL-6 (C) and negative staining for BCL-2 (D) in the germinal centers show an inverse relationship of expression consistent with reactive secondary lymphoid follicles (original magnification ×31).

Postoperatively, the patient was closely observed for signs of local or systemic disease. Six months later, only a small residual conjunctival lesion remained on the left eye. There was approximately 50% partial regression of the lesion on the right eye and the patient had no symptomatology.

Discussion

Lymphoproliferative lesions of the ocular adnexa cover a wide spectrum of entities ranging from BRLH to malignant lymphomas.5,6 BRLH is fairly common and constitutes approximately 10% of the patients with lymphoid proliferations of the ocular adnexa.6,7 However, this lesion is distinctly rare in children.8 Only eight case reports of conjunctival BRLH in pediatric patients were identified in the reviewed literature, thus the natural history of this entity in children is still unclear.1–5 Furthermore, there is no consensus regarding the appropriate investigations and management for these benign conjunctival lesions in children because of their low probability of malignant transformation and extraocular extension.2

The association of BRLH developing into systemic lymphoma has been reported, but it is rare. Coupland et al.6 reported 112 ocular adnexal lymphoproliferative lesions with none of the 12 patients with BRLH developing localized or systemic lymphoma. Shields et al.9 reported 117 adult patients with conjunctival lymphoid tumors in whom only 1 of 20 cases (5%) of BRLH developed systemic lymphoma. McKelvie et al.7 reported that 3 of their 6 adult patients with ocular adnexal BRLH later developed lymphoma, but all 6 of these lesions were located in the orbit and not in the conjunctiva. The relationship between prognosis and anatomic site of the lesion has been suggested, with lesions of the conjunctiva having the best prognosis with respect to the development of systemic disease compared with those of the orbit and eyelids.5,10,11 Thus, there appears to be a statistically favorable prospect for conjunctival BRLH.

Certain histopathologic and immunophenotypic features help to distinguish BRLH from follicular lymphoma. As in our case, light microscopy of BRLH typically exhibit clearly defined, irregularly shaped follicles of varying size with prominent mantle zones (Fig. 2). The follicles are composed of a polymorphic population of mature lymphocytes with tingible-body macrophages and mitoses are present. The follicles stain positively for the B-cell marker CD20 and T-cell marker CD3. BCL-6 staining is positive in the follicular centers, whereas the oncoprotein BCL-2 staining is negative in the same areas (Fig. 3).5 All of these findings are consistent with a benign reactive process leading to the diagnosis of BRLH.5,12 Thus, careful histopathologic evaluation, combined with the clinical findings, is a practical approach to distinguish BRLH from malignant lymphoma.5,11

In our patient, only the larger left conjunctival lesion was biopsied. Treatment for the smaller lesion on the right was deferred. At the 6-month follow-up, there was no local recurrence of the tumor on the left eye that had been treated with excisional biopsy, and the untreated lesion of the right eye showed partial regression. Other reported cases of pediatric BRLH were similarly successfully treated with surgical excision and no adjuvant therapies were indicated.1–3

Due to the rare but potential risk of the development of non-Hodgkin’s lymphoma in patients with conjunctival BRLH, systemic evaluation and regular follow-up have generally been advised. However, all of the reported cases indicate that excisional biopsy is curative in the pediatric population. No local recurrence or systemic dissemination was reported during the postoperative follow-up, ranging from 1 month to 3.5 years.1–5 Extensive investigations, including magnetic resonance imaging, computed tomography scans, and full-body gallium scans, to rule out local or systemic involvement have been conducted with no report of systemic abnormalities.1–3 This suggests that conjunctival lymphoid hyperplasia in children is a localized, benign disease and that these patients may require only careful monitoring rather than extensive investigations and potentially harmful treatments. Thus, we recommend that the clinical approach for a pediatric patient be excisional biopsy to prove the diagnosis of BRLH followed by close observation. Certainly, if there is evidence of local recurrence and especially if there are signs of systemic disease, evaluation by a pediatric oncologist and more extensive investigations are recommended, with appropriate treatment where indicated.

Our 13-year-old patient experienced isolated bilateral nasal bulbar conjunctival lesions with no evidence of local extension clinically. He was treated exclusively with excision in the larger lesion in the left eye with a histopathological diagnosis of BRLH. After 6 months of follow-up, there was no recurrent disease in the left eye, whereas the untreated right eye remained unchanged.

References

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  2. McLeod SD, Edward DP. Benign lymphoid hyperplasia of the conjunctiva in children. Arch Ophthalmol. 1999;117:832–835.
  3. Tang J, Rodgers IR, Basham KL, Goh J. Rare case of exuberant benign lymphoid hyperplasia involving the conjunctiva, caruncle, and plica in a child with tonsilar enlargement. J AAPOS. 2003;7:293–294. doi:10.1016/S1091-8531(03)00146-0 [CrossRef]
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  10. Knowles DM, Jakobiec FA, McNally L, Burke JS. Lymphoid hyperplasia and malignant lymphoma occurring in the ocular adnexa (orbit, conjunctiva and eyelids): a prospective multiparametric analysis of 108 cases during 1977 to 1987. Hum Pathol. 1990;21:959–973. doi:10.1016/0046-8177(90)90181-4 [CrossRef]
  11. Sigelman J, Jakobiec FA. Lymphoid lesions of the conjunctiva: relation of histopathology to clinical outcome. Ophthalmology. 1978:85:8818–8843.
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Authors

From the Departments of Ophthalmology (KL, SB, AJ, DRJ) and Pathology (KL, SB, AJ, BRB), University of Ottawa Eye Institute and The Ottawa Hospital, the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Seymour Brownstein, MD, University of Ottawa Eye Institute, 501 Smyth Road, Suite 6213, Ottawa, Ontario, Canada K1H 8L6. E-mail: sbrownstein@ohri.ca

10.3928/01913913-20111213-01

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