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Characteristics of orbital lymphoproliferative disorders: a retrospective study of 84 cases

Eye volume 39, pages 2096–2103 (2025)Cite this article

Subjects

Abstract

Objective

To investigate the variations in clinical presentation, imaging characteristics, and immunohistochemical features between benign and malignant orbital lymphoproliferative disorders (OLPDs).

Methods

At the Eye Center of the First Affiliated Hospital, Zhejiang University School of Medicine, a retrospective analysis was performed on the clinical records of all patients diagnosed with OLPDs from 2014 to 2022. This study included a comparative analysis between patients diagnosed with benign and malignant OLPDs.

Results

A total of 84 patients were included in this research, with a mean age of 62.24 ± 14.52 years and male-to-female ratio of 43:41. The pathological types comprised benign orbital lymphoproliferative tumours (26/84, 31%, mean age 59.31 ± 10.4 years, male-to-female ratio of 16:10) and malignant orbital lymphomas (58/84, 69%, mean age 63.55 ± 15.93 years, male-to-female ratio of 27:31). The most common symptoms in benign and malignant OLPDs were palpable mass and eyelid swelling. Typically, malignant orbital lymphoma masses exhibited low signal intensity on T1-weighted imaging (T1WI), whereas benign lymphoproliferative tumours commonly demonstrated iso-intensity on T1WI. Notably, the expression of cluster of differentiation 3, 5, 10, 23, 43, and human immunoglobulin light chain lambda demonstrated statistically significant differences between the benign and malignant OLPD groups.

Conclusion

Benign and malignant OLPDs exhibit similar clinical presentations and imaging characteristics. Currently, distinguishing between benign and malignant OLPDs still requires pathological biopsy. Research on specialized imaging techniques and specific biomarkers for malignant orbital lymphomas is underway, showing potential for enhancing the accuracy of non-invasive diagnoses for benign and malignant OLPDs.

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Fig. 1: The differences between groups are represented by letters in this figure.

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Data availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.

References

  1. Hu H, Xu X-Q, Liu H, Hong X-N, Shi H-B, Wu F-Y. Orbital benign and malignant lymphoproliferative disorders: Differentiation using semi-quantitative and quantitative analysis of dynamic contrast-enhanced magnetic resonance imaging. Eur J Radiol. 2017;88:88–94.

    Article  PubMed  Google Scholar 

  2. Haradome K, Haradome H, Usui Y, Ueda S, Kwee TC, Saito K, et al. Orbital lymphoproliferative disorders (OLPDs): value of MR imaging for differentiating orbital lymphoma from benign OPLDs. AJNR Am J Neuroradiol. 2014;35:1976–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shields JA, Shields Cl Fau - Scartozzi R, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions: The 2002 Montgomery Lecture, part 1. Ophthalmology. 2004;111:997–1008.

    Article  PubMed  Google Scholar 

  4. Shinder R, Al-Zubidi N, Fau - Esmaeli B, Esmaeli B. Survey of orbital tumors at a comprehensive cancer center in the United States. Head Neck J Sci Spec. 2011;33:610–4.

    Article  Google Scholar 

  5. Ohtsuka K, Hashimoto M, Fau -, Suzuki Y, Suzuki Y. A review of 244 orbital tumors in Japanese patients during a 21-year period: origins and locations. Jpn J Ophthalmol. 2005;49:49–55.

    Article  PubMed  Google Scholar 

  6. Ohtsuka K, Hashimoto M, Fau -, Suzuki Y, Suzuki Y. High incidence of orbital malignant lymphoma in Japanese patients. Am J Ophthalmol. 2004;138:881–2.

    Article  PubMed  Google Scholar 

  7. Olsen TG, Holm F, Mikkelsen LH, Rasmussen PK, Coupland SE, Esmaeli B, et al. Orbital lymphoma-an International multicenter retrospective study. Am J Ophthalmol. 2019;199:44–57.

    Article  PubMed  Google Scholar 

  8. Ueda S, Usui Y, Nagai T, Diaz-Aguilar D, Nagao T, Goto H. Immunophenotypic profiles for distinguishing orbital mucosa-associated lymphoid tissue lymphoma from benign lymphoproliferative tumors. Jpn J Ophthalmol. 2017;61:354–60.

    Article  CAS  PubMed  Google Scholar 

  9. Briscoe D, Safieh C, Ton Y, Shapiro H, Assia EI, Kidron D. Characteristics of orbital lymphoma: a clinicopathological study of 26 cases. Int Ophthalmol. 2018;38:271–7.

    PubMed  Google Scholar 

  10. Ahmed OA-O, Ma AK, Ahmed TM, Pointdujour-Lim R. Epidemiology, outcomes, and prognostic factors of orbital lymphoma in the United States. Orbit. 2020;39:397–402.

    Article  PubMed  Google Scholar 

  11. Hunt SA-O, Pereni I, Ford RA-O, Garrott H. Lymphoma and inflammatory disorders presenting in the orbit- a comparison of characteristics from a 10-year series in a tertiary hospital. Orbit. 2022;41:315–20.

    Article  PubMed  Google Scholar 

  12. Demirci H, Shields Cl Fau -, Karatza EC, Karatza Ec Fau - Shields JA, Shields JA. Orbital lymphoproliferative tumors: analysis of clinical features and systemic involvement in 160 cases. Ophthalmology. 2008;115:1626–31.

    Article  PubMed  Google Scholar 

  13. Alaggio RA-O, Amador CA-O, Anagnostopoulos IA-O, Attygalle AA-O, Araujo IBO, Berti EA-O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36:1720–48.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Olsen TG, Heegaard S. Orbital lymphoma. Surv Ophthalmol. 2019;64:45–66.

    Article  PubMed  Google Scholar 

  15. Hsu CR, Chen YY, Yao M, Wei YH, Hsieh YT, Liao SA-O. Orbital and ocular adnexal lymphoma: a review of epidemiology and prognostic factors in Taiwan. Eye. 2021;35:1946–53.

    Article  PubMed  Google Scholar 

  16. Sagiv O, Thakar SD, Manning JT, Kandl TJ, Fayad LE, Fowler N, et al. Prevalence of a histologic change of ocular adnexal lymphoma in patients with a history of lymphoma. Ophthalmic Plast Reconstr Surg. 2019;35:243–6.

    Article  PubMed  Google Scholar 

  17. Xu XQ, Hu H, Liu H, Wu JF, Cao P, Shi HB, et al. Benign and malignant orbital lymphoproliferative disorders: Differentiating using multiparametric MRI at 3.0T. J Magn Reson Imaging. 2017;45:167–76.

    Article  PubMed  Google Scholar 

  18. Priego G, Majos C, Fau -, Climent F, Climent F, Fau, et al. Orbital lymphoma: imaging features and differential diagnosis. Insights Imaging. 2012;3:337–44.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ren J, Yuan Y, Wu Y, Tao XA-O. Differentiation of orbital lymphoma and idiopathic orbital inflammatory pseudotumor: combined diagnostic value of conventional MRI and histogram analysis of ADC maps. BMC Med Imaging. 2018;18:6.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Akansel G, Hendrix L, Fau - Erickson BA, Erickson Ba Fau - Demirci A, Demirci A, Fau - Papke A, et al. MRI patterns in orbital malignant lymphoma and atypical lymphocytic infiltrates. Eur J Radio. 2005;53:175–81.

    Article  Google Scholar 

  21. Sullivan TJ, Valenzuela AA. Imaging features of ocular adnexal lymphoproliferative disease. Eye. 2006;20:1189–95.

    Article  CAS  PubMed  Google Scholar 

  22. Yeo Jh Fau - Jakobiec FA, Jakobiec Fa Fau - Abbott GF, Abbott Gf Fau - Trokel SL, Trokel SL. Combined clinical and computed tomographic diagnosis of orbital lymphoid tumors. Am J Ophthalmol. 1982;94:235–45.

    Article  Google Scholar 

  23. Polito E, Galieni P, Fau -, Leccisotti A, Leccisotti A. Clinical and radiological presentation of 95 orbital lymphoid tumors. Graefes Arch Clin Exp Ophthalmol. 1996;234:504–9.

    Article  CAS  PubMed  Google Scholar 

  24. Tunlayadechanont P, Panyaping T, Kaewkerd B. Role of quantitative spectral CT analysis for differentiation of orbital lymphoma and other orbital lymphoproliferative disease. Eur J Radio. 2020;133:109372.

    Article  Google Scholar 

  25. Xu XQ, Qian W, Hu H, Su GY, Liu H, Shi HA-O, et al. Histogram analysis of dynamic contrast-enhanced magnetic resonance imaging for differentiating malignant from benign orbital lymphproliferative disorders. Acta Radio. 2019;60:239–46.

    Article  Google Scholar 

  26. Cameron CA, Tong JY, Juniat V, Patel S, Selva D. Diagnostic utility of diffusion-weighted imaging and apparent diffusion coefficient for common orbital lesions: a review. Ophthalmic Plast Reconstr Surg. 2022;38:515–21.

    Article  PubMed  Google Scholar 

  27. Xie X, Yang L, Zhao FA-O, Wang D, Zhang H, He X, et al. A deep learning model combining multimodal radiomics, clinical and imaging features for differentiating ocular adnexal lymphoma from idiopathic orbital inflammation. Eur Radio. 2022;32:6922–32.

    Article  CAS  Google Scholar 

  28. Yang L, Zhang H, Xie X, Jiang S, Zhang H, Cao X, et al. MRI-based radiomics nomogram for preoperative differentiation between ocular adnexal lymphoma and idiopathic orbital inflammation. J Magn Reson Imaging. 2023;57:1594–604.

    Article  PubMed  Google Scholar 

  29. Shimizu H, Usui Y, Wakita R, Aita Y, Tomita A, Tsubota K, et al. Differential Tissue Metabolic Signatures in IgG4-related ophthalmic disease and orbital mucosa-associated lymphoid tissue lymphoma. Invest Ophthalmol Vis Sci. 2021;62:15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nezu N, Usui YA-O, Asakage M, Shimizu H, Tsubota KA-O, Narimatsu A, et al. Distinctive tissue and serum MicroRNA profile of IgG4-related ophthalmic disease and MALT Lymphoma. J Clin Med. 2020;9. https://doi.org/10.3390/jcm9082530 LID–2530.

  31. Shi J, Zhu T, Lin H, Liu Z, Zhou M, Yu Z, et al. Proteotranscriptomics of ocular adnexal B-cell lymphoma reveals an oncogenic role of alternative splicing and identifies a diagnostic marker. J Exp Clin Cancer Res. 2022;41:234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank TopEdit (www.topeditsci.com) for its linguistic assistance during the preparation of this manuscript.

Funding

The work was supported by the Key R&D Program of Zhejiang Province of China (2021C03032), the TCM Innovation Talent Support Program (2023ZR106), and the Special Fund for the Construction of Nursing Discipline of the First Affiliated Hospital of Zhejiang University School of Medicine (2023ZYHL05).

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  1. These authors contributed equally: Xiawei Wang, Menghui Zhang.

Authors and Affiliations

  1. Department of Ophthalmology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Xiawei Wang, Menghui Zhang, Ying Chen, Xinyun Wang & Hongguang Cui

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  1. Xiawei Wang
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Contributions

Xiawei Wang and Hongguang Cui were responsible for designing and writing the protocol. Menghui Zhang, Ying Chen, and Xinyun Wang obtained and analyzed the data. Xiawei Wang and Menghui Zhang drafted the manuscript. Hongguang Cui modified the manuscript for academic content.

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Correspondence to Hongguang Cui.

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Wang, X., Zhang, M., Chen, Y. et al. Characteristics of orbital lymphoproliferative disorders: a retrospective study of 84 cases. Eye 39, 2096–2103 (2025). https://doi.org/10.1038/s41433-025-03816-z

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