Ocular Adnexal Marginal Zone Lymphoma: Retrospective Analysis and Clinical-Pathological Features

Öz

Objective: Ocular adnexal lymphomas are rare malignancies, accounting for approximately 1–2% of all non-Hodgkin lymphomas and 8–10% of extranodal lymphomas. Among these, ocular adnexal marginal zone lymphoma (OA-MZL) represents the predominant histologic subtype, comprising 55–80% of all orbital/ocular adnexal lymphomas. The aim of this study is to retrospectively evaluate the clinical and histopathological features of cases diagnosed with ocular adnexal marginal zone lymphoma (OA-MZL) and to compare the findings with the current literature. Methods: A total of 10 OA-MZL cases diagnosed between 2010 and 2025 in the archives of the Department of Pathology, Celal Bayar University, Manisa, with conjunctival and/or lacrimal gland involvement were included in this study. The slides of all cases were retrieved from the archives and re-evaluated under a microscope. Previously prepared hematoxylin–eosin sections and immunohistochemical slides were re-evaluated to confirm the diagnosis. The patients' clinical data, treatment protocols, and follow-up results were obtained from the hospital information system. Clinicopathological parameters were documented, and a descriptive statistical analysis was conducted and the data obtained were compared with the literature. Results: The mean age of the cases was 65.9 (39-82), and the female/male ratio was 3/7. The most common presenting symptom was orbital swelling. Histopathological examination revealed diffuse monomorphic small lymphoid cell infiltration, and the immunohistochemical panel applied showed tumor cells to be CD20 and BCL2 positive, CD3, CD5, CD21, CD23, Bcl-6, CD10, and Cyclin D1 negative. The mean Ki-67 index was 13.3%. Plasmacytic differentiation was observed in 2 cases. Three patients received definitive radiotherapy, whereas six patients were monitored with active surveillance due to indolent disease behavior. The mean follow-up period was 50 months, and recurrence was detected in 1 case. Conclusion: Ocular adnexal marginal zone lymphomas are neoplastic proliferations that are clinically indolent but require careful histopathological differential diagnosis. This study aims to contribute by presenting and evaluating the clinical and pathological findings of these rare localizations in the context of the literature.

Anahtar Kelimeler

• Ocular adnexal marginal
• zone lymphomas
• immunohistochemical stains

Etik Beyan

Ethical approval fort he study was granted by The Celal Bayar Univercity Ethics Committee (Approval No: 20.478.486/3341, dated July 30, 2025).

Oküler Adneksiyal Marjinal Zon Lenfoma : Retrospektif Analizi ve klinikopatolojik özellikleri

Öz

Amaç: Oküler adneksiyel lenfomalar, tüm non-Hodgkin lenfomaların yaklaşık %1–2’sini ve tüm ekstranodal lenfomaların %8–10’unu oluşturan nadir malignitelerdir. Bu anatomik bölgede en sık görülen histolojik tip ekstranodal marginal zon lenfoma olup, olguların %55–80’ini kapsamaktadır. Bu çalışmanın amacı, oküler adneksiyal marjinal zon lenfoma (OA-MZL) tanısı almış olguların klinik ve histopatolojik özelliklerini retrospektif olarak değerlendirmek ve elde edilen bulguları güncel literatür ile karşılaştırmaktır. Yöntemler: 2010–2025 yılları arasında Manisa Celal Bayar Üniversitesi Patoloji Anabilim Dalı arşivinde tanısı konmuş, konjonktiva ve/veya lakrimal gland yerleşimli toplam 10 OA-MZL olgusu bu çalışmaya dahil edildi. Tüm olgulara ait lamlar arşivden çıkarılarak tekrar değerlendirildi. Tanıların doğrulaması amacıyla mevcut hematoksilen-eozin kesitleri ve immünohistokimyasal boyalı lamlar yeniden gözden geçirildi. Hastaların klinik verileri, tedavi protokolleri ve takip sonuçları hastane bilgi sisteminden elde edildi. Klinikopatolojik bulgular dökumante edilip tanımlayıcı istatiksel analiz uygulandı ve elde edilen veriler literatür ile karşılaştırıldı. Bulgular: Olguların yaş ortalaması 65.9 (39-82) olup, kadın/erkek oranı 3/7 idi. En sık başvuru bulgusu orbitada şişlik olarak kaydedildi. Histopatolojik incelemede diffüz monomorfik küçük lenfoid hücre infiltrasyonu gözlenmiş olup uygulanan immunohistokimyasal panelde tümör hücreleri CD20 ve BCL2 pozitif, CD3, CD5, CD21, CD23, Bcl-6, CD10 ve Siklin D1 negatif olarak değerlendirildi. Ortalama Ki-67 indeksi %13.3 idi. Plazmasitik diferansiasyon 2 olguda izlendi. Üç hastaya yalnızca radyoterapi uygulanırken, hastalığın indolent seyri nedeniyle altı hasta aktif izlem ile takip edildi. Ortalama takip süresi 50 ay olup, 1 olguda nüks saptandı. Sonuç: Oküler adneksiyal marjinal zon lenfomalar, klinik olarak yavaş seyirli ancak histopatolojik olarak dikkatli ayırıcı tanı gerektiren neoplastik proliferasyonlardır. Bu çalışma, nadir görülen bu lokalizasyonlara ait klinik ve patolojik bulguları ortaya koyup literatür eşliğinde değerlendirerek katkı sağlamayı hedeflemektedir

Anahtar Kelimeler

• oküler adneksiyal marjinal
• zon lenfoma
• immunohistokimyasal panel.

Kaynakça

1. 1.Kirkegaard MK. Ocular adnexal lymphoma:Subtype-specific clinical and genetic features. ActaOphthalmol. 2022;100(Suppl 270):3-37.doi:10.1111/aos.15248
2. 2.Johansson P, Eckstein A, Küppers R. The biology of ocular adnexal marginal zone lymphomas. Cancers(Basel). 2022;14(5):1264.doi:10.3390/cancers14051264
3. 3.Choi S, Seo M, Park SH, et al. Clinicopathologiccharacteristics associated with prognosis in ocularextranodal marginal zone B-cell lymphoma.Medicina (Kaunas). 2022;58(6):818.doi:10.3390/medicina5806081
4. 4.Chung HU, Son JH. Ocular adnexal mucosa-associated lymphoid tissue lymphoma: A narrative review. J Yeungnam Med Sci. 2022;39(1):3-11. doi:10.12701/yujm.2021.01263
5. 5.Desai A, Joag MG, Lekakis L, et al. Long-termcourse of patients with primary ocular adnexalMALT lymphoma: A large single-institution cohortstudy. Blood. 2017;129(3):324-32.doi:10.1182/blood-2016-05-714584
6. 6.Coupland SE, White VA, Rootman J, Damato B,Finger PT. A TNM-based clinical staging system ofocular adnexal lymphomas. Arch Pathol Lab Med.2009;133(8):1262-7. doi:10.5858/133.8.1262
7. 7. Collina F, De Chiara A, De Renzo A, et al. Chlamydiapsittaci in ocular adnexa MALT lymphoma: Apossible role in lymphomagenesis and a differentgeographical distribution. Infect Agent Cancer.2012;7:8. doi:10.1186/1750-9378-7-8
8. 8.Sassone M, Ponzoni M, Ferreri AJ. Ocular adnexalmarginal zone lymphoma: Clinical presentation,pathogenesis, diagnosis, prognosis, and treatment.Best Pract Res Clin Haematol. 2017;30:118-30.

9. 9.Travaglino A, Pace M, Varricchio S, et al.Involvement of Helicobacter pylori in ocular adnexalymphoma. Pathol Oncol Res. 2020;26:2075-81.
10. 10.Coupland SE, Hellmich M, Auw-Haedrich C, LeeWR, Stein H. Prognostic value of cell-cycle markersin ocular adnexal lymphoma: An assessment of 230cases. Graefes Arch Clin Exp Ophthalmol.2004;242(2):130-45. doi:10.1007/s00417-003-0831-5
11. 11.Takahashi H, Usui Y, Ueda S, et al. Genome-wideanalysis of ocular adnexal lymphoproliferativedisorders using high-resolution single nucleotidepolymorphism array. Invest Ophthalmol Vis Sci.2015;56:4156-65. doi:10.1167/iovs.15-16382
12. 12.Hsu CR, Chen YY, Yao M, et al. Orbital and ocularadnexal lymphoma: A review of epidemiology andprognostic factors in Taiwan. Eye (Lond).2021;35:1946-53. doi:10.1038/s41433-020-01198-y
13. 13.Goto H, Asakage M, Niidime E, et al.Demographics, clinical features and prognosis ofpatients with primary malignant conjunctivaltumors at a tertiary hospital in Japan. Jpn JOphthalmol. 2025;69(2):316-25.doi:10.1007/s10384-025-01165-8
14. 14.Kaya M, Öner FH, Lebe B, et al. İntraokülerlenfoma tanısındaki zorluklar. Turk J Ophthalmol.2021;51(5):317-25.doi:10.4274/tjo.galenos.2021.50607
15. 15.Teles LPM, Lima JCDO, Schmidt LPB, Andrade EP.Orbital mucosa-associated lymphoid tissuelymphoma. Pan-Am J Ophthalmol. 2023;5(1):49.doi:10.4103/pajo.pajo_58_23
16. 16.Gao LR, X. Li, X. Wang, et al. Treatment andsurvival in patients with localized primary ocularadnexal MALT lymphoma: A large bicentric cohortstudy. Ann Oncol. 2023;34(Suppl):S544.
17. 17.Oktariana TP, Andriana A, Nugroho RS. Theoutcome of radiation therapy as a primarytreatment in orbital lymphoma: A systematicreview. Rep Pract Oncol Radiother. 2022;27(4):724-33.doi:10.5603/RPOR.a2022.0065
18. 18.Lo AC, Holloway CL, Savage KJ, et al.Radioimmunotherapy for orbital marginal zonelymphoma: A retrospective review. LeukLymphoma. 2022;63(5):1242-5.
19. 19.Liang Y, Fu RY, Liu XL, et al. Long-term survivaloutcomes of patients with primary ocular adnexalMALT lymphoma: A large single-center cohortstudy. Cancer Med. 2023;12(3):2514-23.
20. 20.Saul EE, Alderuccio JP, Reis IM, et al. Long-termoutcomes of patients with conjunctival extranodalmarginal zone lymphoma. Am J Hematol.2023;98(1):148-58. doi:10.1002/ajh.26591