Research status and progress of laboratory diagnostic tests for intraocular lymphoma_Chinese Journal of Ocular Fundus Diseases

Authors：

Qin Bixuan ,  Zhang Yanchun , Kang Ziwei

Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, Xi'an Ocular Fundus Disease Research Institute, Xi'an 710004, China;

Corresponding author：

Zhang Yanchun, Email: zhangyanchun1239@126.com

Keywords：

Intraocular lymphoma; Diagnosis; Ocular fluid; Ocular cytokine; MYD88; Metagenomic deep sequencing; Review

DOI：

10.3760/cma.j.cn511434-20210412-00190

Video：

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Intraocular lymphoma (IOL) is a rare lymphocytic malignancy. The gold standard for the definite diagnosis remains histopathologic examination of the ocular specimen. But cytologic confirmation of malignant lymphoma cells in vitreous or chorioretinal specimens is challenging and dependending on highly skilled cytopathologist, due to the sparse cellularity and specimen degeneration. Consequently, false-negative rates arecommon, which delays diagnosis and treatment seriously. Because of the limited diagnostic capacity of cytology, other adjunct diagnostic tools have been developed. Additional procedures that may support IOL diagnosis include flow cytometry, immunocytochemistry, cytokines study with identification of interleukin (IL)-10 and IL-6 level, and polymerase chain reaction amplification. And more recently, new techniques of mutational analysis have been validated for the diagnosis of vitreoretinal lymphoma (VRL) and may represent a helpful diagnostic tool for the detection of early cases. Metagenomic deep sequencing technology may provide an important basis for VRL diagnosis and personalized treatment. In the future, it is expected to deepen the understanding of IOL disease phenotypes at the molecular level, discover new target therapies, monitor response to treatment, and detect intraocular recurrences. These may offer insights into how we might create a tailored therapeutic approach for each patient's VRL in the future.

Citation： Qin Bixuan, Zhang Yanchun, Kang Ziwei. Research status and progress of laboratory diagnostic tests for intraocular lymphoma. Chinese Journal of Ocular Fundus Diseases, 2023, 39(1): 68-73. doi: 10.3760/cma.j.cn511434-20210412-00190 Copy

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3. Tang LJ, Gu CL, Zhang P. Intraocular lymphoma[J]. Int J Ophthalmol, 2017, 10(8): 1301-1307. DOI: 10.18240/ijo.2017.08.19.
4. Chan C-C, Shen D, Hackett JJ, et al. Expression of chemokine receptors, CXCR4 and CXCR5, and chemokines, BLC and SDF-1, in the eyes of patients with primary intraocular lymphoma[J]. Ophthalmology, 2003, 110(2): 421-426. DOI: 10.1016/S0161-6420(02)01737-2.
5. Takhar J, Doan T, Gonzales JA. Vitreoretinal lymphoma: a literature review and introduction of a new diagnostic method[J]. Asia-Pacific J Ophthalmol, 2021, 10(2): 93-98. DOI: 10.1097/APO.0000000000000365.
6. Fend F, Ferreri AJM, Coupland SE. How we diagnose and treat vitreoretinal lymphoma[J]. Br J Haematol, 2016, 173(5): 680-692. DOI: 10.1111/bjh.14025.
7. Chan C-C, Rubenstein JL, Coupland SE, et al. Primary vitreoretinal lymphoma: a report from an international primary central nervous system lymphoma collaborative group symposium[J]. Oncologist, 2011, 16(11): 1589-1599. DOI: 10.1634/theoncologist.2011-0210.
8. Gonzales JA, Chan C-C. Biopsy techniques and yields in diagnosing primary intraocular lymphoma[J]. Int Ophthalmol, 2007, 27(4): 241-250. DOI: 10.1007/s10792-007-9065-6.
9. Davis JL, Solomon D, Nussenblatt RB, et al. Immunocytochemical staining of vitreous cells. Indications, techniques, and results[J]. Ophthalmology, 1992, 99(2): 250-256. DOI: 10.1016/s0161-6420(92)31984-0.
10. Raparia K, Chang CC, Chevez-Barrios P. Intraocular lymphoma: diagnostic approach and immunophenotypic findings in vitrectomy specimens[J]. Arch Pathol Lab Med, 2009, 133(8): 1233-1237. DOI: 10.5858/133.8.1233.
11. Davis JL, Ruiz P Jr, Shah M, et al. Evaluation of the reactive T-cell infiltrate in uveitis and intraocular lymphoma with flow cytometry of vitreous fluid (an American Ophthalmological Society thesis)[J]. Trans Am Ophthalmol Soc, 2012, 110: 117-129.
12. Whitcup SM, Stark-Vancs V, Wittes RE, et al. Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma[J]. Arch Ophthalmol, 1997, 115(9): 1157-1160. DOI: 10.1001/archopht.1997.01100160327010.
13. Kimura K, Usui Y, Goto H, et al. Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma[J]. Jpn J Ophthalmol, 2012, 56(4): 383-389. DOI: 10.1007/s10384-012-0150-7.
14. Bonzheim I, Giese S, Deuter C, et al. High frequency of MYD88 mutations in vitreoretinal B-cell lymphoma: a valuable tool to improve diagnostic yield of vitreous aspirates. [J] Blood, 2015, 126(1): 76-79. DOI: 10.1182/blood-2015-01-620518.
15. Hoffman PM, McKelvie P, Hall AJ, et al. Intraocular lymphoma: a series of 14 patients with clinicopathological features and treatment outcomes[J]. Eye (Lond), 2003, 17(4): 513-521. DOI: 10.1038/sj.eye.6700378.
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18. Katoch D, Bansal R, Nijhawan R, et al. Primary intraocular central nervous system lymphoma masquerading as diffuse retinal vasculitis[J]. BMJ Case Rep, 2013, 2013: bcr2013009354. DOI: 10.1136/bcr-2013-009354.
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20. Damato B, Bever GJ, Kim DJ, et al. An audit of retinal lymphoma treatment at the University of California San Francisco[J]. Eye (Lond), 2020, 34(3): 515-522. DOI: 10.1038/s41433-019-0539-3.
21. AlQahtani A, Touitou V, Cassoux N, et al. More than a masquerade syndrome: atypical presentations of vitreoretinal lymphomas[J]. Ocul Immunol Inflamm, 2014, 22(3): 189-196. DOI: 10.3109/09273948.2013.835427.
22. Casady M, Faia L, Nazemzadeh M, et al. Fundus autofluorescence patterns in primary intraocular lymphoma[J]. Retina, 2014, 34(2): 366-372. DOI: 10.1097/IAE.0b013e31829977fa.
23. Ishida T, Ohno-Matsui K, Kaneko Y, et al. Fundus autofluorescence patterns in eyes with primary intraocular lymphoma[J]. Retina, 2010, 30(1): 23-32. DOI: 10.1097/IAE.0b013e3181b408a2.
24. Takhar JS, Doan TA, Gonzales JA. Primary vitreoretinal lymphoma: empowering our clinical suspicion[J]. Curr Opin Ophthalmol, 2019, 30(6): 491-499. DOI: 10.1097/ICU.0000000000000620.
25. Fardeau C, Lee CPL, Merle-Béral H, et al. Retinal fluorescein, indocyanine green angiography, and optic coherence tomography in non-Hodgkin primary intraocular lymphoma[J]. Am J Ophthalmol, 2009, 147(5): 886-894. DOI: 10.1016/j.ajo.2008.12.025.
26. Deák GG, Goldstein DA, Zhou M, et al. Vertical hyperreflective lesions on optical coherence tomography in vitreoretinal lymphoma[J]. JAMA Ophthalmol, 2019, 137(2): 194-198. DOI: 10.1001/jamaophthalmol.2018.5835.
27. Yang X, Dalvin LA, Mazloumi M, et al. Spectral domain optical coherence tomography features of vitreoretinal lymphoma in 55 eyes[J]. Retina, 2021, 41(2): 249-258. DOI: 10.1097/IAE.0000000000002819.
28. Lee WJ, Lee BR, Shin YU. Retromode imaging: review and perspectives[J]. Saudi J Ophthalmol, 2014, 28(2): 88-94. DOI: 10.1016/j.sjopt.2014.02.003.
29. Sen HN, Bodaghi B, Hoang P Le, et al. Primary intraocular lymphoma: diagnosis and differential diagnosis[J]. Ocul Immunol Inflamm, 2009, 17(3): 133-141. DOI: 10.1080/09273940903108544.
30. Margolis R. Diagnostic vitrectomy for the diagnosis and management of posterior uveitis of unknown etiology[J]. Curr Opin Ophthalmol, 2008, 19(3): 218-224. DOI: 10.1097/ICU.0b013e3282fc261d.
31. Cursiefen C, Holbach LM, Lafaut B, et al. Oculocerebral non-Hodgkin’s lymphoma with uveal involvement: development of an epibulbar tumor after vitrectomy[J]. Arch Ophthalmol, 2000, 118(10): 1437-1440. DOI: 10.1001/archopht.118.10.1437.
32. Karma A, von Willebrand EO, Tommila PV, et al. Primary intraocular lymphoma: improving the diagnostic procedure[J]. Ophthalmology, 2007, 114(7): 1372-1377. DOI: 10.1016/j.ophtha.2006.11.009.
33. Coupland SE, Bechrakis NE, Anastassiou G, et al. Evaluation of vitrectomy specimens and chorioretinal biopsies in the diagnosis of primary intraocular lymphoma in patients with masquerade syndrome[J]. Graefes Arch Clin Exp Ophthalmol, 2003, 241(10): 860-870. DOI: 10.1007/s00417-003-0749-y.
34. Mehta M, Rasheed RA, Duker J, et al. Vitreous evaluation: a diagnostic challenge[J]. Ophthalmology, 2015, 122(3): 531-537. DOI: 10.1016/j.ophtha.2014.09.016.
35. Kanno-Okada H, Takakuwa E, Tagawa Y, et al. Cytopathologic findings of cell block materials from the vitreous: diagnostic distinction between intraocular lymphoma and non-lymphomatous diseases[J]. Pathol Int, 2017, 67(7): 342-349. DOI: 10.1111/pin.12551.
36. Davis JL, Miller DM, Ruiz P. Diagnostic testing of vitrectomy specimens[J]. Am J Ophthalmol, 2005, 140(5): 822-829. DOI: 10.1016/j.ajo.2005.05.032.
37. Missotten T, Tielemans D, Bromberg JE, et al. Multicolor flowcytometric immunophenotyping is a valuable tool for detection of intraocular lymphoma[J]. Ophthalmology, 2013, 120(5): 991-996. DOI: 10.1016/j.ophtha.2012.11.007.
38. Lee J, Kim SW, Kim H, et al. Differential diagnosis for vitreoretinal lymphoma with vitreoretinal findings, immunoglobulin clonality tests, and interleukin levels. [J] Retina, 2019, 39(6): 1165-1176. DOI: 10.1097/IAE.0000000000002127.
39. Shen DF, Zhuang Z, LeHoang P, et al. Utility of microdissection and polymerase chain reaction for the detection of immunoglobulin gene rearrangement and translocation in primary intraocular lymphoma[J]. Ophthalmology, 1998, 105(9): 1664-1669. DOI: 10.1016/S0161-6420(98)99036-4.
40. Wallace DJ, Shen D, Reed GF, et al. Detection of the bcl-2 t(14;18) translocation and proto-oncogene expression in primary intraocular lymphoma[J]. Invest Ophthalmol Vis Sci, 2006, 47(7): 2750-2756. DOI: 10.1167/iovs.05-1312.
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