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Original Investigation |

Conjunctival Lymphoma—An International Multicenter Retrospective Study

Marina M. Kirkegaard, MD1; Peter K. Rasmussen, MD, PhD1; Sarah E. Coupland, MBBS, PhD, FRCPath2; Bita Esmaeli, MD3; Paul T. Finger, MD4; Gerardo F. Graue, MD4; Hans E. Grossniklaus, MD, MBA5; Santosh G. Honavar, MD6,7; Jwu J. Khong, MBBS, Hons, MMed, FRANZCO8; Penny A. McKelvie, MD, PhD8; Kaustubh Mulay, DNB9,10; Jan U. Prause, MD, DMSc1; Elisabeth Ralfkiaer, MD, DMSc1; Lene D. Sjö, MD, PhD1; Peter B. Toft, MD, DMSc11; Geeta K. Vemuganti, MD12,13; Bradley A. Thuro, MD3; Jeremy Curtin, MD8; Steffen Heegaard, MD, DMSc1,11
[+] Author Affiliations
1Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
2Department of Cellular and Molecular Pathology, University of Liverpool, Liverpool, England
3Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston
4The New York Eye Cancer Center, New York, New York
5Section of Ocular Oncology, Emory Eye Center, Atlanta, Georgia
6Department of Ophthalmic and Facial Plastic Surgery, Orbit and Ocular Oncology, Centre for Sight, Hyderabad, India
7Department of Ocular Oncology and Oculoplastics, LV Prasad Eye Institute, Hyderabad, India
8Orbital, Plastic and Lacrimal Unit, The Royal Victorian Eye and Ear Hospital, Melbourne, Australia
9National Reporting Centre for Ophthalmic Pathology, Centre for Sight, Hyderabad, India
10Ocular Pathology, LV Prasad Eye Institute, Hyderabad, India
11Department of Ophthalmology, Rigshospitalet–Glostrup, University of Copenhagen, Copenhagen, Denmark
12Visiting Faculty, Ophthalmic Pathology Services, LV Prasad Eye Institute, Hyderabad, India
13Kallam Anji Reddy Campus, School of Medical Sciences, University of Hyderabad, Hyderabad, India
JAMA Ophthalmol. 2016;134(4):406-414. doi:10.1001/jamaophthalmol.2015.6122.
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Importance  To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort.

Objective  To characterize subtype-specific clinical features of CL and their effect on patient outcome.

Design, Setting, and Participants  A retrospective multicenter study was performed. Patient data were collected from January 1, 1980, through December 31, 2010. The dates of the analysis were May 15, 2015, to August 20, 2015. The median follow-up period was 43 months. Seven eye cancer centers were involved in the study. In total, 268 patients with CL were identified, 5 of whom were excluded because of missing clinical data.

Main Outcomes and Measures  Overall survival, disease-specific survival, and progression-free survival were the primary end points.

Results  Two hundred sixty-three patients with CL were included in the study. Their mean age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were frequently secondary diseases (41.7% [5 of 12] and 88.9% [16 of 18], respectively), with MCL showing a frequent occurrence of stage IVE lymphoma (61.1% [11 of 18]) and bilateral manifestation (77.8% [14 of 18]). Localized disease (stage IE or IIE) was commonly treated with external beam radiation therapy (EBRT) with or without chemotherapy, while widespread lymphoma (stage IIIE or IVE) and MCL of any stage were managed with chemotherapy with or without EBRT. Diffuse large B-cell lymphoma and MCL had a poor prognosis, with 5-year disease-specific survival of 55.0% and 9.0%, respectively, in contrast to EMZL (97.0%) and FL (82.0%). Further survival predictors included age (EMZL), sex (FL), and Ann Arbor staging classification (EMZL and FL). The American Joint Committee on Cancer TNM staging showed limited prognostic usefulness, only being able to predict survival for patients with DLBCL.

Conclusions and Relevance  Conjunctival lymphoma consists of mainly 4 subtypes of B-cell non-Hodgkin lymphoma: EMZL, FL, MCL, and DLBCL. Mantle cell lymphoma is characterized by a particularly high frequency of secondary disease of stage IVE and bilateral manifestation. The histological subtype is the main outcome predictor, with MCL and DLBCL having a markedly poorer prognosis than EMZL and FL.

Figures in this Article


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Figure 1.
Clinical and Histological Findings of EMZL

EMZL indicates extranodal marginal zone lymphoma.

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Figure 2.
Disease-Specific Survival Among Patients With Conjunctival Lymphoma

A, Disease-specific survival is associated with the subtype of conjunctival lymphoma. EMZL has the most favorable disease-specific survival, while MCL has the poorest disease-specific survival (P = <.001). B, Stage >IE is associated with lower disease-specific survival than stage IE for low-grade conjunctival lymphomas (P = .03). BL indicates Burkitt lymphoma; DLBCL, diffuse large B-cell lymphoma; EMZL, extranodal marginal zone lymphoma; FL, follicular lymphoma; LPL, lymphoplasmacytic lymphoma; MCL, mantle cell lymphoma; and PL, plasmacytoma.

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