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Conjunctival Pediatric Follicular Lymphoma

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. Report of a Case 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. Comment 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. Back to top Article Information 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). Financial Disclosure: None reported. Funding/Support: Dr Perry is supported in part by the Heed Foundation. References 1. Sigelman J, Jakobiec FA. Lymphoid lesions of the conjunctiva: relation of histopathology to clinical outcome. Ophthalmology. 1978;85(8):818-843101924PubMedGoogle Scholar 2. Shields CL, Shields JA, Carvalho C, Rundle P, Smith AF. Conjunctival lymphoid tumors: clinical analysis of 117 cases and relationship to systemic lymphoma. Ophthalmology. 2001;108(5):979-98411320031PubMedGoogle ScholarCrossref 3. Ferry JA, Fung CY, Zukerberg L, et al. Lymphoma of the ocular adnexa: a study of 353 cases. Am J Surg Pathol. 2007;31(2):170-18417255761PubMedGoogle ScholarCrossref 4. Jaffe ES, ed, Harris NL, ed, Vardiman JW, ed, Campo E, ed, Arber DA, ed. Hematopathology. Philadelphia, PA: Elsevier; 2011 5. Lorsbach RB, Shay-Seymore D, Moore J, et al. Clinicopathologic analysis of follicular lymphoma occurring in children. Blood. 2002;99(6):1959-196411877266PubMedGoogle ScholarCrossref 6. Oschlies I, Salaverria I, Mahn F, et al. Pediatric follicular lymphoma: a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin's Lymphoma–Berlin-Frankfurt-Munster (NHL-BFM) multicenter trials. Haematologica. 2010;95(2):253-25919679882PubMedGoogle ScholarCrossref 7. Jakobiec FA. Ocular adnexal lymphoid tumors: progress in need of clarification. Am J Ophthalmol. 2008;145(6):941-95018405875PubMedGoogle ScholarCrossref 8. Stacy RC, Jakobiec FA, Schoenfield L, Singh AD. Unifocal and multifocal reactive lymphoid hyperplasia vs follicular lymphoma of the ocular adnexa. Am J Ophthalmol. 2010;150(3):412-426, e120599186PubMedGoogle ScholarCrossref 9. Gaffar M, Thebpatiphat N, Przygodzki R, Jacobs S, Miller MM. Primary follicular lymphoma of the conjunctiva in a 6-year-old child. J AAPOS. 2010;14(6):538-54021093330PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

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References (9)

Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archophthalmol.2011.2529
Publisher site
See Article on Publisher Site

Abstract

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. Report of a Case 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. Comment 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. Back to top Article Information 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). Financial Disclosure: None reported. Funding/Support: Dr Perry is supported in part by the Heed Foundation. References 1. Sigelman J, Jakobiec FA. Lymphoid lesions of the conjunctiva: relation of histopathology to clinical outcome. Ophthalmology. 1978;85(8):818-843101924PubMedGoogle Scholar 2. Shields CL, Shields JA, Carvalho C, Rundle P, Smith AF. Conjunctival lymphoid tumors: clinical analysis of 117 cases and relationship to systemic lymphoma. Ophthalmology. 2001;108(5):979-98411320031PubMedGoogle ScholarCrossref 3. Ferry JA, Fung CY, Zukerberg L, et al. Lymphoma of the ocular adnexa: a study of 353 cases. Am J Surg Pathol. 2007;31(2):170-18417255761PubMedGoogle ScholarCrossref 4. Jaffe ES, ed, Harris NL, ed, Vardiman JW, ed, Campo E, ed, Arber DA, ed. Hematopathology. Philadelphia, PA: Elsevier; 2011 5. Lorsbach RB, Shay-Seymore D, Moore J, et al. Clinicopathologic analysis of follicular lymphoma occurring in children. Blood. 2002;99(6):1959-196411877266PubMedGoogle ScholarCrossref 6. Oschlies I, Salaverria I, Mahn F, et al. Pediatric follicular lymphoma: a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin's Lymphoma–Berlin-Frankfurt-Munster (NHL-BFM) multicenter trials. Haematologica. 2010;95(2):253-25919679882PubMedGoogle ScholarCrossref 7. Jakobiec FA. Ocular adnexal lymphoid tumors: progress in need of clarification. Am J Ophthalmol. 2008;145(6):941-95018405875PubMedGoogle ScholarCrossref 8. Stacy RC, Jakobiec FA, Schoenfield L, Singh AD. Unifocal and multifocal reactive lymphoid hyperplasia vs follicular lymphoma of the ocular adnexa. Am J Ophthalmol. 2010;150(3):412-426, e120599186PubMedGoogle ScholarCrossref 9. Gaffar M, Thebpatiphat N, Przygodzki R, Jacobs S, Miller MM. Primary follicular lymphoma of the conjunctiva in a 6-year-old child. J AAPOS. 2010;14(6):538-54021093330PubMedGoogle ScholarCrossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Jul 1, 2012

Keywords: follicular lymphoma,pediatrics,conjunctiva

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