Conjunctival Pediatric Follicular Lymphoma

Conjunctival lymphomas constitute 30% of adnexal lymphomas, affect women slightly more than men with median ages of 55 and 63 years in 2 series (<1% occurring in the first 2 decades), and carry a favorable prognosis.^1-3 Among childhood systemic lymphomas, only 1% to 2% are pediatric-type follicular lymphomas (PFLs); these lesions are also rarely seen in young adults.^4,5 Pediatric-type follicular lymphomas occur predominantly in boys, are frequently localized (36%-79%), have isolated lymphadenopathy and stage I disease, and are most commonly found in the head and neck region.^5,6 We describe a dramatic epibulbar, globoid, well-circumscribed conjunctival PFL that was considered clinically to be a pyogenic granuloma in a young man. The distinguishing clinical and immunohistochemical features of adult follicular lymphoma and PFL are described.

A 21-year-old man had a 5-month history of a slowly growing epibulbar lesion in the left eye. His medical history was otherwise unremarkable. Visual acuity was 20/50 OS. The external examination findings were notable for a mobile, 7-mm–elevated, salmon-colored, globoid medial conjunctival mass bordering the plica (Figure 1A). An excisional biopsy was performed. Histopathologically, there was a lymphoproliferation with ill-defined follicular regions (Figure 1B and C). Expression of CD20 (B lymphocytes) was heavily positive in lymphoid follicles; thin rims of CD3-positive T lymphocytes further accentuated the follicular architecture. Staining was positive for CD10 and negative for BCL-2 in the follicular centers (Figure 2). Immunostaining for Ki-67 disclosed 75% positivity. A loose scaffolding of CD23-positive dendritic cells was noted in the follicles, and small BCL-2–positive lymphocytes were present at the base of the excision. The lesion was characterized as grade 3A (>15 centroblasts/high-power field with admixed centrocytes). Polymerase chain reaction for immunoglobulin gene rearrangement revealed a clonal population. Findings on the systemic workup with total-body computed tomographic scanning and hematologic studies were unremarkable. Postoperatively, the operative site healed well; the patient declined any further local or systemic treatment. No evidence of recurrence has developed after 8 months of follow-up.

Pediatric-type follicular lymphoma is composed of a mixture of round centroblasts and, to a lesser extent, smaller cleaved centrocytes in the germinal center.^5,7 Clinical aggressiveness of PFL is directly correlated with increasing numbers of centroblasts and the intensity of Ki-67 nuclear staining for cells in S-phase. It predominantly manifests high-grade, level 3 cytological findings with more than 15 centroblasts/high-power field. It must be differentiated from reactive lymphoid hyperplasia because both lack BCL-2 expression in the follicular centers.⁸ Reactive lymphoid hyperplasia demonstrates large interfollicular zones, whereas this feature is drastically diminished in follicular lymphoma.⁸

Expression of BCL-2, an antiapoptotic gene product not expressed in normal B cells in the follicular center, occurs in most adult follicular lymphomas and is thought to play a role in pathogenesis. In approximately 80% of adult follicular lymphomas, a chromosomal translocation involving BCL-2 [t(14;18)(q32;q21)] is detected. In contrast, BCL-2 expression in PFL is highly variable, with 30% to 55% of tumors showing expression of BCL-2 by immunohistochemistry; most PFLs that are positive for BCL-2 by immunohistochemistry are negative for the typical adult translocation.⁶ Lesions in very young patients are more uniformly negative for BCL-2.^6,9 Pediatric patients with BCL-2–positive tumors usually have advanced disease that is more refractory to treatment.^7,9

The prognosis for patients with PFL is excellent. Of 23 patients in one study, all but 1 achieved complete clinical remission with a mean follow-up period of 11.4 years; 1 patient died of disease 8 years after initial diagnosis.⁵ In a second study of 25 patients, only 1 had a relapse; the 5-year event-free survival was 96%.⁶ Conservative management is acceptable when surgical resection appears to be curative.^7,9 In the only fully documented prior case of conjunctival PFL to our knowledge, a 6-year-old boy with a small placoid epibulbar lesion underwent local excision without ancillary chemotherapy or radiotherapy. Three years later, he was disease free as verified by a repeated systemic workup.⁹ Despite lymphocytic tissue identified at the base of the excision, which may have been benign, and in the absence of any clinical evidence of residual or recurrent disease, we have elected to defer adjunctive local therapy and will be following up with the patient closely.

Correspondence: Dr Jakobiec, David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts Eye and Ear Infirmary, 243 Charles St, Ste 321, Boston, MA 02114 (fred_jakobiec@meei.harvard.edu).

Funding/Support: Dr Perry is supported in part by the Heed Foundation.