Risk factors for failure of vitrectomy cell block technique in cytological diagnosis of vitreoretinal lymphoma

  • Takako Ito
  • Atsunobu TakedaEmail author
  • Kohta Fujiwara
  • Eiichi Hasegawa
  • Shintaro Nakao
  • Yoshihiro Ohishi
  • Yoshinao Oda
  • Hiroshi Yoshikawa
  • Koh-Hei Sonoda



To determine the factors that may affect the accuracy of vitrectomy cell block technique in detecting atypical lymphoid cells in patients with vitreoretinal lymphoma (VRL).


We retrospectively reviewed 43 eyes in 39 patients who underwent vitrectomy for definitive histological diagnosis of VRL with vitrectomy cell block technique and/or smear preparation at Kyushu University Hospital from January 2001 to March 2016. The association of detection of atypical lymphoid cells using vitrectomy cell block technique with the following factors was assessed using logistic regression analysis: age at diagnosis, sex, presence or absence of concurrent cataract surgery with vitrectomy, clinical grading of vitreous haze, presence or absence of subretinal tumor infiltration, interval between initial symptoms and vitrectomy, and presence or absence of systemic corticosteroid therapy before vitrectomy.


Atypical lymphoid cells were more significantly detected using vitrectomy cell block technique compared to that using smear preparation (p = 0.018). After adjusting for age and sex, concurrent cataract surgery (odds ratio [OR], 10.41; 95% confidence interval [CI], 1.42–76.41) and subretinal tumor infiltration (OR, 5.06; 95% CI, 1.06–24.32) were significantly associated with failure of histological analysis with vitrectomy cell blocks. In multivariable logistic regression analysis, similar results were obtained, although subretinal tumor infiltration was only marginally associated with the detective capability of the technique.


Vitrectomy cell block technique significantly improved the definitive diagnosis of VRL. Concurrent cataract surgery with vitrectomy and subretinal tumor infiltration were risk factors for failure in vitrectomy cell blocks.


Single-center study Vitreoretinal lymphoma Vitrectomy cell block technique Concurrent cataract surgery Subretinal tumor infiltration 



The atuhors thank Dr. Tatsuro Ishibashi for helpful suggestions.

Funding information

This study was supported by a grant from JSPS KAKENHI Grant Number 15K10896 and 18K09471 [grants C (A.T.)] from the Ministry of Education, Science, Sports and Culture, and Japan and the Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical’s Founder (A.T.), Novartis Pharma Research Grants (AT), and Alcon Pharma Research Grants (AT).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Kyushu University Institutional Review Board for Clinical Research. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed concent was obtained.


  1. 1.
    Coupland SE, Chan CC, Smith J (2009) Pathophysiology of retinal lymphoma. Ocul Immunol Inflamm 17:227–237. CrossRefGoogle Scholar
  2. 2.
    Faia LJ, Chan CC (2009) Primary intraocular lymphoma. Arch Pathol Lab Med 133:1228–1232. Google Scholar
  3. 3.
    Chan CC, Buggage RR, Nussenblatt RB (2002) Intraocular lymphoma. Curr Opin Ophthalmol 13:411–418CrossRefGoogle Scholar
  4. 4.
    Chan CC, Sen HN (2013) Current concepts in diagnosing and managing primary vitreoretinal (intraocular) lymphoma. Discov Med 15:93–100Google Scholar
  5. 5.
    Kimura K, Usui Y, Goto H (2012) Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma. Jpn J Ophthalmol 56:383–389. CrossRefGoogle Scholar
  6. 6.
    Akpek EK, Ahmed I, Hochberg FH, Soheilian M, Dryja TP, Jakobiec FA, Foster CS (1999) Intraocular-central nervous system lymphoma: clinical features, diagnosis, and outcomes. Ophthalmology 106:1805–1810. CrossRefGoogle Scholar
  7. 7.
    Coupland SE, Heimann H, Bechrakis NE (2004) Primary intraocular lymphoma: a review of the clinical, histopathological and molecular biological features. Graefes Arch Clin Exp Ophthalmol 242:901–913. CrossRefGoogle Scholar
  8. 8.
    Hashida N, Nakai K, Saitoh N, Nishida K (2014) Association between ocular findings and preventive therapy with onset of central nervous system involvement in patients with primary vitreoretinal lymphoma. Graefes Arch Clin Exp Ophthalmol 252:687–693. CrossRefGoogle Scholar
  9. 9.
    Fend F, Ferreri AJ, Coupland SE (2016) How we diagnose and treat vitreoretinal lymphoma. Br J Haematol 173:680–692. CrossRefGoogle Scholar
  10. 10.
    Ma WL, Hou HA, Hsu YJ, Chen YK, Tang JL, Tsay W, Yeh PT, Yang CM, Lin CP, Tien HF (2016) Clinical outcomes of primary intraocular lymphoma patients treated with front-line systemic high-dose methotrexate and intravitreal methotrexate injection. Ann Hematol 95:593–601. CrossRefGoogle Scholar
  11. 11.
    Akiyama H, Takase H, Kubo F, Miki T, Yamamoto M, Tomita M, Mochizuki M, Miura O, Arai A (2016) High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma. Cancer Sci 107:1458–1464. CrossRefGoogle Scholar
  12. 12.
    Kaburaki T, Taoka K, Matsuda J, Yamashita H, Matsuda I, Tsuji H, Tanaka R, Nakazaki K, Nakamura F, Kamiya K, Kurokawa M, Ohtomo K, Aihara M (2017) Combined intravitreal methotrexate and immunochemotherapy followed by reduced-dose whole-brain radiotherapy for newly diagnosed B-cell primary intraocular lymphoma. Br J Haematol 179:246–255. CrossRefGoogle Scholar
  13. 13.
    Kreher S, Strehlow F, Martus P, Roth P, Hertenstein B, Roth A, Birnbaum T, Griesinger F, Rauch M, Kanz L, Thiel E, Weller M, Korfel A (2015) Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial. Ann Hematol 94:409–414. CrossRefGoogle Scholar
  14. 14.
    Lee S, Kim MJ, Kim JS, Oh SY, Kim SJ, Kwon YH, Chung IY, Kang JH, Yang DH, Kang HJ, Yoon DH, Kim WS, Kim HJ, Suh C (2015) Intraocular lymphoma in Korea: the consortium for improving survival of lymphoma (CISL) study. Blood Res 50:242–247. CrossRefGoogle Scholar
  15. 15.
    Cheah CY, Milgrom S, Chihara D, Gombos DS, Pinnix CC, Dabaja BS, Fowler NH (2016) Intensive chemoimmunotherapy and bilateral globe irradiation as initial therapy for primary intraocular lymphoma. Neuro-Oncology 18:575–581. CrossRefGoogle Scholar
  16. 16.
    Davis JL, Miller DM, Ruiz P (2005) Diagnostic testing of vitrectomy specimens. Am J Ophthalmol 140:822–829. CrossRefGoogle Scholar
  17. 17.
    Margolis R, Brasil OF, Lowder CY, Singh RP, Kaiser PK, Smith SD, Perez VL, Sonnie C, Sears JE (2007) Vitrectomy for the diagnosis and management of uveitis of unknown cause. Ophthalmology 114:1893–1897. CrossRefGoogle Scholar
  18. 18.
    Oahalou A, Schellekens PA, de Groot-Mijnes JD, Rothova A (2014) Diagnostic pars plana vitrectomy and aqueous analyses in patients with uveitis of unknown cause. Retina 34:108–114. CrossRefGoogle Scholar
  19. 19.
    Whitcup SM, Stark-Vancs V, Wittes RE, Solomon D, Podgor MJ, Nussenblatt RB, Chan CC (1997) Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma. Arch Ophthalmol 115:1157–1160CrossRefGoogle Scholar
  20. 20.
    Baehring JM, Androudi S, Longtine JJ, Betensky RA, Sklar J, Foster CS, Hochberg FH (2005) Analysis of clonal immunoglobulin heavy chain rearrangements in ocular lymphoma. Cancer 104:591–597. CrossRefGoogle Scholar
  21. 21.
    Sugita S, Takase H, Sugamoto Y, Arai A, Miura O, Mochizuki M (2009) Diagnosis of intraocular lymphoma by polymerase chain reaction analysis and cytokine profiling of the vitreous fluid. Jpn J Ophthalmol 53:209–214. CrossRefGoogle Scholar
  22. 22.
    Davis JL, Viciana AL, Ruiz P (1997) Diagnosis of intraocular lymphoma by flow cytometry. Am J Ophthalmol 124:362–372CrossRefGoogle Scholar
  23. 23.
    Intzedy L, Teoh SC, Hogan A, Mangwana S, Mayer EJ, Dick AD, Pawade J (2008) Cytopathological analysis of vitreous in intraocular lymphoma. Eye (London) 22:289–293. CrossRefGoogle Scholar
  24. 24.
    Zaldivar RA, Martin DF, Holden JT, Grossniklaus HE (2004) Primary intraocular lymphoma: clinical, cytologic, and flow cytometric analysis. Ophthalmology 111:1762–1767. Google Scholar
  25. 25.
    Matsuo T, Ichimura K (2012) Immunocytochemical diagnosis as inflammation by vitrectomy cell blocks in patients with vitreous opacity. Ophthalmology 119:827–837. CrossRefGoogle Scholar
  26. 26.
    Kase S, Namba K, Iwata D, Mizuuchi K, Kitaichi N, Tagawa Y, Okada-Kanno H, Matsuno Y, Ishida S (2016) Diagnostic efficacy of cell block method for vitreoretinal lymphoma. Diagn Pathol 11:29. CrossRefGoogle Scholar
  27. 27.
    Feng H, Adelman RA (2014) Cataract formation following vitreoretinal procedures. Clin Ophthalmol 8:1957–1965. CrossRefGoogle Scholar
  28. 28.
    Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol 140:509–516CrossRefGoogle Scholar
  29. 29.
    Chan CC, Rubenstein JL, Coupland SE, Davis JL, Harbour JW, Johnston PB, Cassoux N, Touitou V, Smith JR, Batchelor TT, Pulido JS (2011) Primary vitreoretinal lymphoma: a report from an international primary central nervous system lymphoma collaborative group symposium. Oncologist 16:1589–1599. CrossRefGoogle Scholar
  30. 30.
    Taki R, Takeda A, Yoshikawa H, Fukuhara T, Arita R, Suehiro Y, Choi I, Kumano Y, Nakamura T, Ishibashi T (2017) Clinical features of systemic metastatic retinal lymphoma in Japanese patients. Ocul Immunol Inflamm 25:654–662. CrossRefGoogle Scholar
  31. 31.
    Takeda A, Yoshikawa H, Fukuhara T, Hikita S, Hijioka K, Otomo T, Arita R, Hisatomi T, Kimura K, Yoshida S, Kawano Y, Sonoda KH, Ishibashi T (2015) Distinct profiles of soluble cytokine receptors between B-cell vitreoretinal lymphoma and uveitis. Invest Ophthalmol Vis Sci 56:7516–7523. CrossRefGoogle Scholar
  32. 32.
    Wakefield D, Zierhut M (2009) Intraocular lymphoma: more questions than answers. Ocul Immunol Inflamm 17:6–10. CrossRefGoogle Scholar
  33. 33.
    Char DH, Ljung BM, Miller T, Phillips T (1988) Primary intraocular lymphoma (ocular reticulum cell sarcoma) diagnosis and management. Ophthalmology 95:625–630CrossRefGoogle Scholar
  34. 34.
    Mayall F, Chang B, Darlington A (1997) A review of 50 consecutive cytology cell block preparations in a large general hospital. J Clin Pathol 50:985–990CrossRefGoogle Scholar
  35. 35.
    Sakamoto T, Miyazaki M, Hisatomi T, Nakamura T, Ueno A, Itaya K, Ishibashi T (2002) Triamcinolone-assisted pars plana vitrectomy improves the surgical procedures and decreases the postoperative blood-ocular barrier breakdown. Graefes Arch Clin Exp Ophthalmol 240:423–429. CrossRefGoogle Scholar
  36. 36.
    Michael R, Bron AJ (2011) The ageing lens and cataract: a model of normal and pathological ageing. Philos Trans R Soc Lond Ser B Biol Sci 366:1278–1292. CrossRefGoogle Scholar
  37. 37.
    Davis JL, Ruiz P Jr, Shah M, Mandelcorn ED (2012) Evaluation of the reactive T-cell infiltrate in uveitis and intraocular lymphoma with flow cytometry of vitreous fluid (an American ophthalmological society thesis). Trans Am Ophthalmol Soc 110:117–129Google Scholar
  38. 38.
    Sagoo MS, Mehta H, Swampillai AJ, Cohen VM, Amin SZ, Plowman PN, Lightman S (2014) Primary intraocular lymphoma. Surv Ophthalmol 59:503–516. CrossRefGoogle Scholar
  39. 39.
    Bonzheim I, Giese S, Deuter C, Susskind D, Zierhut M, Waizel M, Szurman P, Federmann B, Schmidt J, Quintanilla-Martinez L, Coupland SE, Bartz-Schmidt KU, Fend F (2015) High frequency of MYD88 mutations in vitreoretinal B-cell lymphoma: a valuable tool to improve diagnostic yield of vitreous aspirates. Blood 126:76–79. CrossRefGoogle Scholar
  40. 40.
    Raja H, Salomao DR, Viswanatha DS, Pulido JS (2016) Prevalence of Myd88 L265p mutation in histologically proven, diffuse large B-cell vitreoretinal lymphoma. Retina 36:624–628. CrossRefGoogle Scholar
  41. 41.
    Cani AK, Hovelson DH, Demirci H, Johnson MW, Tomlins SA, Rao RC (2017) Next generation sequencing of vitreoretinal lymphomas from small-volume intraocular liquid biopsies: new routes to targeted therapies. Oncotarget 8:7989–7998. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Takako Ito
    • 1
  • Atsunobu Takeda
    • 1
    • 2
    Email author
  • Kohta Fujiwara
    • 1
    • 3
  • Eiichi Hasegawa
    • 1
  • Shintaro Nakao
    • 1
  • Yoshihiro Ohishi
    • 4
  • Yoshinao Oda
    • 4
  • Hiroshi Yoshikawa
    • 1
  • Koh-Hei Sonoda
    • 1
  1. 1.Department of Ophthalmology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Ophthalmology, Clinical Research Institute, National Hospital OrganizationKyushu Medical CenterFukuokaJapan
  3. 3.Department of OphthalmologyAkita University Graduate School of MedicineAkitaJapan
  4. 4.Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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