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Primary intraocular lymphoma: a review of the clinical, histopathological and molecular biological features

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Abstract

Introduction

Primary intraocular lymphoma (PIOL) is a rare non-Hodgkin lymphoma which arises in the retina or the vitreous. It can occur either together with or independently of primary cerebral nervous system lymphoma (PCNSL); the incidence of the latter has significantly increased over the past three decades. PIOL remains one of the most difficult diagnoses to establish, particularly due to its ability to mimic other diseases in the eye and to the limited material which is often available for examination.

Methods

The article reviews the clinical, histopathological, molecular biological and biochemical approaches to the diagnosis of PIOL. The differential diagnoses, including other lymphomatous manifestations in the eye, e.g. primary uveal lymphoma, as well as non-neoplastic uveal diseases are addressed. Furthermore, the treatment strategies for PIOL are summarised.

Results

Diagnostic progress has been made in various fields, including flow cytometry and immunocytology, cytokine analysis, and as well as molecular biological analysis of the immunoglobulin heavy and light chains using polymerase chain reaction on both fixed and non-fixed material. The optimal therapy of PIOL remains to be determined: the current trends suggest that combined radiotherapy and chemotherapy, as well as intravitreal chemotherapy, are of value. Novel therapies which may have a role in the future include oral trofosfamide.

Conclusion

Our understanding of the pathogenesis of PIOL/PCNSL remains far from complete. Intensified efforts must be made to determine the cell of origin of PIOL, as well as to establish “molecular signatures”, which could be used to decrease diagnostic delay. Further studies, possibly prospective ones, are required to establish the optimal therapy for initial and recurrent disease.

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References

  1. Abrey LE, DeAngelis LM, Yahalom J (1998) Long-term survival in primary CNS lymphoma. J Clin Oncol 16:859–863

    CAS  PubMed  Google Scholar 

  2. Akpek EK, Ahmed I, Hochberg FH et al (1999) Intraocular-central nervous system lymphoma: clinical features, diagnosis, and outcomes. Ophthalmology 106:1805–1810

    Article  CAS  PubMed  Google Scholar 

  3. Anagnostopoulos I, Stein H (2000) Large B-cell lymphomas: variants and entities. Pathologe 21:178–189

    Article  CAS  PubMed  Google Scholar 

  4. Appen RE (1975) Posterior uveitis and primary cerebral reticulum cell sarcoma. Arch Ophthalmol 93:123–124

    CAS  PubMed  Google Scholar 

  5. Barr CC, Green WR, Payne JW et al (1975) Intraocular reticulum-cell sarcoma: clinico-pathologic study of four cases and review of the literature. Surv Ophthalmol 19:224–239

    CAS  PubMed  Google Scholar 

  6. Basso U, Brandes AA (2002) Diagnostic advances and new trends for the treatment of primary central nervous system lymphoma. Eur J Cancer 38:1298–1312

    Article  CAS  PubMed  Google Scholar 

  7. Batchelor TT, Kolak G, Ciordia R et al (2003) High-dose methotrexate for intraocular lymphoma. Clin Cancer Res 9:711–715

    CAS  PubMed  Google Scholar 

  8. Baumann MA, Ritch PS, Hande KR et al (1986) Treatment of intraocular lymphoma with high-dose Ara-C. Cancer 57:1273–1275

    CAS  PubMed  Google Scholar 

  9. Beasley H (1961) Lymphosarcoma of the choroid. Am J Ophthalmol 51:1294–1296

    CAS  PubMed  Google Scholar 

  10. Bechrakis NE, Foerster MH, Bornfeld N (2002) Biopsy in indeterminate intraocular tumors. Ophthalmology 109:235–242

    Article  PubMed  Google Scholar 

  11. Ben-Ezra D, Sahel JA, Harris NL et al (1989) Uveal lymphoid infiltrates: immunohistochemical evidence for a lymphoid neoplasia. Br J Ophthalmol 73:846–851

    CAS  PubMed  Google Scholar 

  12. Brown SM, Jampol LM, Cantrill HL (1994) Intraocular lymphoma presenting as retinal vasculitis. Surv Ophthalmol 39:133–140

    Article  CAS  PubMed  Google Scholar 

  13. Buggage RR, Chan CC, Nussenblatt RB (2001) Ocular manifestations of central nervous system lymphoma. Curr Opin Oncol 13:137–142

    Article  CAS  PubMed  Google Scholar 

  14. Cassoux N, Merle-Beral H, Leblond V et al (2000) Ocular and central nervous system lymphoma: clinical features and diagnosis. Ocul Immunol Inflamm 8:243–250

    Article  CAS  PubMed  Google Scholar 

  15. Chan CC, Buggage RR, Nussenblatt RB (2002) Intraocular lymphoma. Curr Opin Ophthalmol 13:411–418

    Article  PubMed  Google Scholar 

  16. Chan CC, Whitcup SM, Solomon D, Nussenblatt RB (1995) Interleukin-10 in the vitreous of patients with primary intraocular lymphoma. Am J Ophthalmol 120:671–673

    CAS  PubMed  Google Scholar 

  17. Chang TS, Byrne SF, Gass JD et al (1996) Echographic findings in benign reactive lymphoid hyperplasia of the choroid. Arch Ophthalmol 114:669–675

    CAS  PubMed  Google Scholar 

  18. Char DH, Ljung BM, Deschenes J, Miller TR (1988) Intraocular lymphoma: immunological and cytological analysis. Br J Ophthalmol 72:905–911

    CAS  PubMed  Google Scholar 

  19. Char DH, Ljung BM, Miller T, Phillips T (1988) Primary intraocular lymphoma (ocular reticulum cell sarcoma) diagnosis and management. Ophthalmology 95:625–630

    CAS  PubMed  Google Scholar 

  20. Char DH, Margolis L, Newman AB (1981) Ocular reticulum cell sarcoma. Am J Ophthalmol 91:480–483

    CAS  PubMed  Google Scholar 

  21. Cheung MK, Martin DF, Chan CC et al (1994) Diagnosis of reactive lymphoid hyperplasia by chorioretinal biopsy. Am J Ophthalmol 118:457–462

    CAS  PubMed  Google Scholar 

  22. Ciricillo SF, Rosenblum ML (1990) Use of CT and MR imaging to distinguish intracranial lesions and to define the need for biopsy in AIDS patients. J Neurosurg 73:720–724

    Google Scholar 

  23. Ciulla TA, Bains RA, Jakobiec FA et al (1997) Uveal lymphoid neoplasia: a clinical-pathologic correlation and review of the early form. Surv Ophthalmol 41:467–476

    Article  CAS  PubMed  Google Scholar 

  24. Ciulla TA, Pesavento RD, Yoo S (1997) Subretinal aspiration biopsy of ocular lymphoma. Am J Ophthalmol 123:420–422

    CAS  PubMed  Google Scholar 

  25. Cochereau I, Hannouche D, Geoffray C et al (1996) Ocular involvement in Epstein–Barr virus-associated T-cell lymphoma. Am J Ophthalmol 121:322–324

    CAS  PubMed  Google Scholar 

  26. Cockerham GC, Hidayat AA, Bijwaard KE, Sheng ZM (2000) Re-evaluation of “reactive lymphoid hyperplasia of the uvea”: an immunohistochemical and molecular analysis of 10 cases. Ophthalmology 107:151–158

    Article  CAS  PubMed  Google Scholar 

  27. Cook C (1954) Uveal lymphosarcoma. Br J Ophthalmol 38:182–185

    CAS  PubMed  Google Scholar 

  28. Cooper EL, Riker JL (1951) Malignant lymphoma of the uveal tract. Am J Ophthalmol 34:1153–1158

    CAS  PubMed  Google Scholar 

  29. Corn BW, Donahue BR, Rosenstock JG et al (1997) Performance status and age as independent predictors of survival among AIDS patients with primary CNS lymphoma: a multivariate analysis of a multi-institutional experience. Cancer J Sci Am 3:52–56

    CAS  PubMed  Google Scholar 

  30. Corriveau C, Easterbrook M, Payne D (1986) Lymphoma simulating uveitis (masquerade syndrome). Can J Ophthalmol 21:144–149

    CAS  PubMed  Google Scholar 

  31. Coupland SE, Anastassiou G, Hummel M, Stein H Primary intraocular lymphoma of T-cell type: report of a case and review of the literature. Graefe’s Arch Clin Exp Ophthalm DOI 10.1007/s00417-004-0890-2 (in press)

  32. Coupland SE, Bechrakis NE, Anastassiou G et al (2003) Evaluation of vitrectomy specimens and chorioretinal biopsies in the diagnosis of primary intraocular lymphoma in patients with Masquerade syndrome. Graefes Arch Clin Exp Ophthalmol 10:860–870

    Article  Google Scholar 

  33. Coupland SE, Foss HD, Assaf C et al (1999) T-cell and T/natural killer-cell lymphomas involving ocular and ocular adnexal tissues: a clinicopathologic, immunohistochemical, and molecular study of seven cases. Ophthalmology 106:2109–2120

    Article  CAS  PubMed  Google Scholar 

  34. Coupland SE, Foss HD, Bechrakis NE et al (2001) Secondary ocular involvement in systemic “memory” B-cell lymphocytic leukemia. Ophthalmology 108:1289–1295

    Article  CAS  PubMed  Google Scholar 

  35. Coupland SE, Foss HD, Hidayat AA et al (2002) Extranodal marginal zone B cell lymphomas of the uvea: an analysis of 13 cases. J Pathol 197:333–340

    Article  PubMed  Google Scholar 

  36. Coupland SE, Willerding G, Jahnke K, Stoltenburg-Didinger G, Hummel M, Stein H (2004) Demonstration of identical clonal derivation in a case of “oculocerebral” lymphoma. Br J Ophthamol (in press)

  37. Crookes GP, Mullaney J (1967) Lymphoid hyperplasia of the uveal tract simulating malignant lymphoma. Am J Ophthalmol 63:962–967

    CAS  PubMed  Google Scholar 

  38. Davis JL, Solomon D, Nussenblatt RB et al (1992) Immunocytochemical staining of vitreous cells. Indications, techniques, and results. Ophthalmology 99:250–256

    CAS  PubMed  Google Scholar 

  39. Davis JL, Viciana AL, Ruiz P (1997) Diagnosis of intraocular lymphoma by flow cytometry. Am J Ophthalmol 124:362–372

    CAS  PubMed  Google Scholar 

  40. Dean JM, Novak MA, Chan CC, Green WR (1996) Tumor detachments of the retinal pigment epithelium in ocular/ central nervous system lymphoma. Retina 16:47–56

    CAS  PubMed  Google Scholar 

  41. DeAngelis LM (1994) Primary central nervous system lymphoma. Recent Results Cancer Res 135:155–169

    CAS  PubMed  Google Scholar 

  42. DeAngelis LM (1999) Primary central nervous system lymphoma. Curr Opin Neurol 12:687–691

    Article  CAS  PubMed  Google Scholar 

  43. DeAngelis LM (2001) Primary central nervous system lymphomas. Curr Treat Options Oncol 2:309–318

    CAS  PubMed  Google Scholar 

  44. DeAngelis LM, Seiferheld W, Schold SC et al (2002) Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 20:4643–4648

    Article  PubMed  Google Scholar 

  45. DeAngelis LM, Yahalom J, Thaler HT, Kher U (1992) Combined modality therapy for primary CNS lymphoma. J Clin Oncol 10:635–643

    CAS  PubMed  Google Scholar 

  46. Desroches G, Abrams GW, Gass JD (1983) Reactive lymphoid hyperplasia of the uvea. A case with ultrasonographic and computed tomographic studies. Arch Ophthalmol 101:725–728

    CAS  PubMed  Google Scholar 

  47. van Dongen JJ, Langerak AW, Bruggemann M et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17:2257–2317

    Article  PubMed  Google Scholar 

  48. Duker JS, Shields JA, Eagle RC, Jr (1989) Ocular lymphoid hyperplasia. Arch Ophthalmol 107:446–447

    CAS  PubMed  Google Scholar 

  49. Duker JS, Shields JA, Ross M (1987) Intraocular large cell lymphoma presenting as massive thickening of the uveal tract. Retina 7:41–455

    CAS  PubMed  Google Scholar 

  50. Eby NL, Grufferman S, Flannelly CM et al (1988) Increasing incidence of primary brain lymphoma in the US. Cancer 62:2461–2465

    CAS  PubMed  Google Scholar 

  51. Engel HM, Green WR, Michels RG et al (1981) Diagnostic vitrectomy. Retina 1:121–149

    CAS  PubMed  Google Scholar 

  52. Erny BC, Egbert PR, Peat IM et al (1991) Intraocular involvement with subretinal pigment epithelium infiltrates by mycosis fungoides. Br J Ophthalmol 75:698–701 (Erratum 76(2):128)

    CAS  PubMed  Google Scholar 

  53. Escoffery RF, Bobrow JC, Smith ME (1985) Exudative retinal detachment secondary to orbital and intraocular benign lymphoid hyperplasia. Retina 5:91–93

    CAS  PubMed  Google Scholar 

  54. Falini B, Fizzotti M, Pucciarini A et al (2000) A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood 95:2084–2092

    CAS  PubMed  Google Scholar 

  55. Faulborn J, Daicker B, Bowald S (1983) Clinical signs and histopathology of so-called reticulum cell sarcoma of the eye. Klin Monatsbl Augenheilkd 183:120–121

    CAS  PubMed  Google Scholar 

  56. Feiden W, Milutinovic S (2002) Primary CNS lymphomas morphology and diagnosis. Pathologe 23:284–291

    Article  CAS  PubMed  Google Scholar 

  57. Ferreri AJ, Blay JY, Reni M (2002) Relevance of intraocular involvement in the management of primary central nervous system lymphomas. Ann Oncol 13:531–538

    Article  CAS  PubMed  Google Scholar 

  58. Feugier P, Virion JM, Tilly H et al (2004) Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab. Ann Oncol 15:129–133

    Article  CAS  PubMed  Google Scholar 

  59. Fine HA, Mayer RJ (1993) Primary central nervous system lymphoma. Ann Intern Med 119:1093–1104

    CAS  PubMed  Google Scholar 

  60. Fishburne BC, Wilson DJ, Rosenbaum JT, Neuwelt EA (1997) Intravitreal methotrexate as an adjunctive treatment of intraocular lymphoma. Arch Ophthalmol 115:1152–1156

    CAS  PubMed  Google Scholar 

  61. Foerster H (1960) Mycosis fungoides with intraocular involvement. Trans Am Acad Ophthalmol Otolaryngol 64:308–314

    CAS  PubMed  Google Scholar 

  62. Fredrick DR, Char DH, Ljung BM, Brinton DA (1989) Solitary intraocular lymphoma as an initial presentation of widespread disease. Arch Ophthalmol 107:395–397

    CAS  PubMed  Google Scholar 

  63. Freeman LN, Schachat AP, Knox DL et al (1987) Clinical features, laboratory investigations, and survival in ocular reticulum cell sarcoma. Ophthalmology 94:1631–1639

    CAS  PubMed  Google Scholar 

  64. Freilich RJ, DeAngelis LM (1995) Primary central nervous system lymphoma. Neurol Clin 13:901–914

    CAS  PubMed  Google Scholar 

  65. Freilich RJ, Delattre JY, Monjour A, DeAngelis LM (1996) Chemotherapy without radiation therapy as initial treatment for primary CNS lymphoma in older patients. Neurology 46:435–439

    CAS  PubMed  Google Scholar 

  66. Gärtner J (1989) Mycosis fungoides mit Beteiligung der Aderhaut. Klin Monatsbl Augenheilkd 131:61–69

    Google Scholar 

  67. Gass JD (1967) Retinal detachment and narrow-angle glaucoma secondary to inflammatory pseudotumor of the uveal tract. Am J Ophthalmol 64(Suppl):612–621

    PubMed  Google Scholar 

  68. Gass JD, Sever RJ, Grizzard WS et al (1984) Multifocal pigment epithelial detachments by reticulum cell sarcoma. A characteristic funduscopic picture. Retina 4:135–143

    CAS  PubMed  Google Scholar 

  69. Gass JD, Trattler HL (1991) Retinal artery obstruction and atheromas associated with non-Hodgkin’s large cell lymphoma (reticulum cell sarcoma). Arch Ophthalmol 109:1134–1139

    CAS  PubMed  Google Scholar 

  70. Gill MK, Jampol LM (2001) Variations in the presentation of primary intraocular lymphoma: case reports and a review. Surv Ophthalmol 45:463–471

    Article  CAS  PubMed  Google Scholar 

  71. Goeminne JC, Brouillard A, Jaumain P et al (1999) Bilateral granulomatous panuveitis as initial presentation of diffuse systemic T cell lymphoma. Ophthalmologica 213:323–326

    Article  CAS  PubMed  Google Scholar 

  72. Goldey SH, Stern GA, Oblon DJ et al (1989) Immunophenotypic characterization of an unusual T-cell lymphoma presenting as anterior uveitis. A clinicopathologic case report. Arch Ophthalmol 107:1349–1353

    CAS  PubMed  Google Scholar 

  73. Gorochov G, Parizot C, Bodaghi B et al (2003) Characterization of vitreous B-cell infiltrates in patients with primary ocular lymphoma, using CDR3 size polymorphism analysis of antibody transcripts. Invest Ophthalmol Vis Sci 44:5235–5241

    Article  PubMed  Google Scholar 

  74. Grossniklaus HE, Martin DF, Avery R et al (1998) Uveal lymphoid infiltration. Report of four cases and clinicopathologic review. Ophthalmology 105:1265–1273

    Article  CAS  PubMed  Google Scholar 

  75. Helbig H, Cerny T, De Smet MD (2003) Intravitreal chemotherapy for intraocular lymphoma. Ophthalmologe 100:145–149

    Article  CAS  PubMed  Google Scholar 

  76. Henry JM, Heffner RR Jr, Dillard SH et al (1974) Primary malignant lymphomas of the central nervous system. Cancer 34:1293–1302

    CAS  PubMed  Google Scholar 

  77. Herrlinger U, Schabet M, Bitzer M et al (1999) Primary central nervous system lymphoma: from clinical presentation to diagnosis. J Neurooncol 43:219–226

    Google Scholar 

  78. Hochberg FH, Miller DC (1988) Primary central nervous system lymphoma. J Neurosurg 68:835–853

    Google Scholar 

  79. Hoffman PM, McKelvie P, Hall AJ et al (2003) Intraocular lymphoma: a series of 14 patients with clinicopathological features and treatment outcomes. Eye 17:513–521

    Article  CAS  PubMed  Google Scholar 

  80. Holz FG, Boehmer HV, Mechtersheimer G et al (1999) Uveal non-Hodgkin’s lymphoma with epibulbar extension simulating choroidal effusion syndrome. Retina 19:343–346

    CAS  PubMed  Google Scholar 

  81. Jaffe ES, Harris NL, Stein H, Vardiman JW (2001) World Health Organization classification of tumours. Tumours of haematopoietic and lymphoid tissues. Pathology and genetics. IARC, Lyon

    Google Scholar 

  82. Jahnke K, Bechrakis NE, Coupland SE, et al (2004) Trofosfamide for relapsed intraocular lymphoma: case report and review of the literature. Graefes Arch Clin Exp Ophthalmol 242:771–776

    Article  Google Scholar 

  83. Jakobiec FA, Sacks E, Kronish JW et al (1987) Multifocal static creamy choroidal infiltrates. An early sign of lymphoid neoplasia. Ophthalmology 94:397–406

    CAS  PubMed  Google Scholar 

  84. Jensen OA, Johansen S, Kiss K (1994) Intraocular T-cell lymphoma mimicking a ring melanoma. First manifestation of systemic disease. Report of a case and survey of the literature. Graefes Arch Clin Exp Ophthalmol 232:148–152

    Article  CAS  PubMed  Google Scholar 

  85. Kaplan HJ, Meredith TA, Aaberg TM, Keller RH (1980) Reclassification of intraocular reticulum cell sarcoma (histiocytic lymphoma). Immunologic characterization of vitreous cells. Arch Ophthalmol 98:707–710

    CAS  PubMed  Google Scholar 

  86. Katai N, Kuroiwa S, Fujimori K, Yoshimura N (1997) Diagnosis of intraocular lymphoma by polymerase chain reaction. Graefes Arch Clin Exp Ophthalmol 235:431–436

    CAS  PubMed  Google Scholar 

  87. Kawai Y, Kawai R, Nakayama T et al (1999) Successful treatment of cytomegalovirus retinitis in a patient with malignant lymphoma: a case report and review of the literature. Int J Hematol 69:256–259

    CAS  PubMed  Google Scholar 

  88. Keltner JL, Fritsch E, Cykiert RC, Albert DM (1977) Mycosis fungoides. Intraocular and central nervous system involvement. Arch Ophthalmol 95:645–650

    CAS  PubMed  Google Scholar 

  89. Kincaid ME, Green WR (1983) Ocular and orbital involvement in leukemia. Surv Ophthalmol 27:211–232

    Article  CAS  PubMed  Google Scholar 

  90. Kirmani MH, Thomas EL, Rao NA, Laborde RP (1987) Intraocular reticulum cell sarcoma: diagnosis by choroidal biopsy. Br J Ophthalmol 71:748–752

    CAS  PubMed  Google Scholar 

  91. Klingele TG, Hogan MJ (1975) Ocular reticulum cell sarcoma. Am J Ophthalmol 79:39–47

    CAS  PubMed  Google Scholar 

  92. Kohno T, Uchida H, Inomata H et al (1993) Ocular manifestations of adult T-cell leukemia/lymphoma. A clinicopathologic study. Ophthalmology 100:1794–1799

    CAS  PubMed  Google Scholar 

  93. Kuker W, Herrlinger U, Gronewaller E et al (2002) Ocular manifestation of primary nervous system lymphoma: what can be expected from imaging? J Neurol 249:1713–1716

    Google Scholar 

  94. Kumar SR, Gill PS, Wagner DG et al (1994) Human T-cell lymphotropic virus type I-associated retinal lymphoma. A clinicopathologic report. Arch Ophthalmol 112:954–959

    CAS  PubMed  Google Scholar 

  95. Lafaut BA, Hanssens M, Verbraeken H, De Laey JJ (1994) Chorioretinal biopsy in the diagnosis of intraocular lymphoma: a case report. Bull Soc Belge Ophtalmol 252:67–73

    CAS  PubMed  Google Scholar 

  96. Leitch RJ, Rennie IG, Parsons MA (1993) Ocular involvement in mycosis fungoides. Br J Ophthalmol 77:126–127

    CAS  PubMed  Google Scholar 

  97. Levy-Clarke GA, Byrnes GA, Buggage RR et al (2001) Primary intraocular lymphoma diagnosed by fine needle aspiration biopsy of a subretinal lesion. Retina 21:281–284

    Article  CAS  PubMed  Google Scholar 

  98. Ljung BM, Char D, Miller TR, Deschenes J (1988) Intraocular lymphoma. Cytologic diagnosis and the role of immunologic markers. Acta Cytol 32:840–847

    CAS  PubMed  Google Scholar 

  99. Lobo A, Larkin G, Clark BJ et al (2003) Pseudo-hypopyon as the presenting feature in B-cell and T-cell intraocular lymphoma. Clin Exp Ophthalmol 31:155–158

    Article  Google Scholar 

  100. Lobo A, Lightman S (2003) Vitreous aspiration needle tap in the diagnosis of intraocular inflammation. Ophthalmology 110:595–599

    Article  PubMed  Google Scholar 

  101. Lois N, Hiscott PS, Nash J, Wong D (2000) Immunophenotypic shift in a case of mycosis fungoides with vitreous invasion. Arch Ophthalmol 118:1692–1694

    CAS  PubMed  Google Scholar 

  102. Margolis L, Fraser R, Lichter A, Char DH (1980) The role of radiation therapy in the management of ocular reticulum cell sarcoma. Cancer 45:688–692

    CAS  PubMed  Google Scholar 

  103. Martin DF, Chan CC, de Smet MD et al (1993) The role of chorioretinal biopsy in the management of posterior uveitis. Ophthalmology 100:705–714

    CAS  PubMed  Google Scholar 

  104. Mason JO, Fischer DH (2003) Intrathecal chemotherapy for recurrent central nervous system intraocular lymphoma. Ophthalmology 110:1241–1244

    Article  PubMed  Google Scholar 

  105. McGavic JS (1943) Lymphomatoid diseases involving the eye and its adnexa. Arch Ophthalmol 30:179–193

    Google Scholar 

  106. Merchant A, Foster CS (1997) Primary intraocular lymphoma. Int Ophthalmol Clin 37:101–115

    CAS  PubMed  Google Scholar 

  107. Merle-Beral H, Davi F, Cassoux N et al (2004) Biological diagnosis of primary intraocular lymphoma. Br J Haematol 124:469–473

    PubMed  Google Scholar 

  108. Michels RG, Knox DL, Erozan YS, Green WR (1975) Intraocular reticulum cell sarcoma. Diagnosis by pars plana vitrectomy. Arch Ophthalmol 93:1331–1335

    CAS  PubMed  Google Scholar 

  109. Nathwani BN, Kim H, Rappaport H et al (1978) Non-Hodgkin’s lymphomas: a clinicopathologic study comparing two classifications. Cancer 41:303–325

    CAS  PubMed  Google Scholar 

  110. Nelson DF, Martz KL, Bonner H et al (1992) Non-Hodgkin’s lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys 23:9–17

    CAS  PubMed  Google Scholar 

  111. Palexas GN, Green WR, Goldberg MF, Ding Y (1995) Diagnostic pars plana vitrectomy report of a 21-year retrospective study. Trans Am Ophthalmol Soc 93:281–308 (Discussion 308–314)

    CAS  PubMed  Google Scholar 

  112. Parver LM, Font RL (1979) Malignant lymphoma of the retina and brain. Initial diagnosis by cytologic examination of vitreous aspirate. Arch Ophthalmol 97:1505–1507

    Google Scholar 

  113. Pavan PR, Oteiza EE, Margo CE (1995) Ocular lymphoma diagnosed by internal subretinal pigment epithelium biopsy. Arch Ophthalmol 113:1233–1234

    CAS  PubMed  Google Scholar 

  114. Pels H, Schmidt-Wolf IG, Glasmacher A et al (2003) Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol 21:4489–4495 (e-pub 3 Nov 2003)

    Article  PubMed  Google Scholar 

  115. Peterson K, Gordon KB, Heinemann MH, DeAngelis LM (1993) The clinical spectrum of ocular lymphoma. Cancer 72:843–849

    CAS  PubMed  Google Scholar 

  116. Plowman PN, Montefiore DS, Lightman S (1993) Multiagent chemotherapy in the salvage cure of ocular lymphoma relapsing after radiotherapy. Clin Oncol R Coll Radiol 5:315–316

    CAS  PubMed  Google Scholar 

  117. Qualman SJ, Mendelsohn G, Mann RB, Green WR (1983) Intraocular lymphomas. Natural history based on a clinicopathologic study of eight cases and review of the literature. Cancer 52:878–886

    CAS  PubMed  Google Scholar 

  118. Read RW, Zamir E, Rao NA (2002) Neoplastic masquerade syndromes. Surv Ophthalmol 47:81–124

    Article  PubMed  Google Scholar 

  119. Reim H, Dieler R, Wessing A (1990) Non-Hodgkin’s lymphoma simulating chorioretinitis. Fortschr Ophthalmol 87:557–559

    CAS  PubMed  Google Scholar 

  120. Ridley ME, McDonald HR, Sternberg P Jr et al (1992) Retinal manifestations of ocular lymphoma (reticulum cell sarcoma). Ophthalmology 99:1153–1160 (Discussion 1160–1161)

    CAS  PubMed  Google Scholar 

  121. Rosenthal AR (1983) Ocular manifestations of leukemia. Ophthalmology 90:899–905

    CAS  PubMed  Google Scholar 

  122. Rothova A, Ooijman F, Kerkhoff F et al (2001) Uveitis masquerade syndromes. Ophthalmology 108:386–399

    Article  CAS  PubMed  Google Scholar 

  123. Rubenstein JL, Combs D, Rosenberg J et al (2003) Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood 101:466–468 (e-pub 5 Sep 2002)

    Article  CAS  PubMed  Google Scholar 

  124. Ryan SJ Jr, Frank RN, Green WR (1971) Bilateral inflammatory pseudotumors of the ciliary body. Am J Ophthalmol 72:586–591

    PubMed  Google Scholar 

  125. Ryan SJ, Zimmerman LE, King FM (1972) Reactive lymphoid hyperplasia. An unusual form of intraocular pseudotumor. Trans Am Acad Ophthalmol Otolaryngol 76:652–671

    CAS  PubMed  Google Scholar 

  126. Saga T, Ohno S, Matsuda H et al (1984) Ocular involvement by a peripheral T-cell lymphoma. Arch Ophthalmol 102:399–402

    CAS  PubMed  Google Scholar 

  127. Schachat AP, Markowitz JA, Guyer DR et al (1989) Ophthalmic manifestations of leukemia. Arch Ophthalmol 107:697–700

    CAS  PubMed  Google Scholar 

  128. Scroggs MW, Johnston WW, Klintworth GK (1990) Intraocular tumors. A cytopathologic study. Acta Cytol 34:401–408

    CAS  PubMed  Google Scholar 

  129. Shen DF, Zhuang Z, LeHoang P et al (1998) Utility of microdissection and polymerase chain reaction for the detection of immunoglobulin gene rearrangement and translocation in primary intraocular lymphoma. Ophthalmology 105:1664–1669

    Article  CAS  PubMed  Google Scholar 

  130. Shields JA, Augsburger JJ, Gonder JR, MacLeod D (1981) Localized benign lymphoid tumor of the iris. Arch Ophthalmol 99:2147–2148

    CAS  PubMed  Google Scholar 

  131. Shields JA, McDonald PR (1974) Improvements in the diagnosis of posterior uveal melanomas. Arch Ophthalmol 91:259–264

    CAS  PubMed  Google Scholar 

  132. de Smet MD, Nussenblatt RB, Davis JL, Palestine AG (1990) Large cell lymphoma masquerading as a viral retinitis. Int Ophthalmol 14:413–417

    Google Scholar 

  133. Soussain C, Merle-Beral H, Reux I et al (1996) A single-center study of 11 patients with intraocular lymphoma treated with conventional chemotherapy followed by high-dose chemotherapy and autologous bone marrow transplantation in 5 cases. Leuk Lymphoma 23:339–345

    CAS  PubMed  Google Scholar 

  134. Soussain C, Suzan F, Hoang-Xuan K et al (2001) Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol 19:742–749

    CAS  PubMed  Google Scholar 

  135. Stenson S, Ramsay DL (1981) Ocular findings in mycosis fungoides. Arch Ophthalmol 99:272–277

    CAS  PubMed  Google Scholar 

  136. Strauchen JA, Dalton J, Friedman AH (1989) Chemotherapy in the management of intraocular lymphoma. Cancer 63:1918–1921

    CAS  PubMed  Google Scholar 

  137. Triebenstein O (1920) Ein Beitrag zur Frage der aleukämischen Augenveränderungen. Klin Monatsbl Augenheilkd 64:825–836

    Google Scholar 

  138. Umland O, Ulmer AJ, Vollmer E, Goldmann T (2003) HOPE fixation of cytospin preparations of human cells for in situ hybridization and immunocytochemistry. J Histochem Cytochem 51:977–980

    CAS  PubMed  Google Scholar 

  139. Ursea R, Heinemann MH, Silverman RH et al (1997) Ophthalmic, ultrasonographic findings in primary central nervous system lymphoma with ocular involvement. Retina 17:118–123

    CAS  PubMed  Google Scholar 

  140. Valluri S, Moorthy RS, Khan A, Rao NA (1995) Combination treatment of intraocular lymphoma. Retina 15:125–129

    CAS  PubMed  Google Scholar 

  141. Velez G, Chan CC, Csaky KG (2002) Fluorescein angiographic findings in primary intraocular lymphoma. Retina 22:37–43

    PubMed  Google Scholar 

  142. Velez G, de Smet MD, Whitcup SM et al (2000) Iris involvement in primary intraocular lymphoma: report of two cases and review of the literature. Surv Ophthalmol 44:518–526

    Article  CAS  PubMed  Google Scholar 

  143. Verbraeken HE, Hanssens M, Priem H et al (1997) Ocular non-Hodgkin’s lymphoma: a clinical study of nine cases. Br J Ophthalmol 81:31–36

    CAS  PubMed  Google Scholar 

  144. Wender A, Adar A, Maor E, Yassur Y (1994) Primary B-cell lymphoma of the eyes and brain in a 3-year-old boy. Arch Ophthalmol 112:450–451

    CAS  PubMed  Google Scholar 

  145. Whitcup SM, de Smet MD, Rubin BI et al (1993) Intraocular lymphoma. Clinical and histopathologic diagnosis. Ophthalmology 100:1399–1406

    CAS  PubMed  Google Scholar 

  146. Whitcup SM, Stark-Vancs V, Wittes RE et al (1997) Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma. Arch Ophthalmol 115:1157–1160

    CAS  PubMed  Google Scholar 

  147. White VA, Gascoyne RD, Paton KE (1999) Use of the polymerase chain reaction to detect B- and T-cell gene rearrangements in vitreous specimens from patients with intraocular lymphoma. Arch Ophthalmol 117:761–765

    CAS  PubMed  Google Scholar 

  148. Williams GC, Holz E, Lee AG, Font RL (2000) T-cell lymphoproliferative disorder of vitreous associated with mycosis fungoides. Arch Ophthalmol 118:278–280

    CAS  PubMed  Google Scholar 

  149. Wolter J, Leenhouts T, Hendrix R (1963) Corneal involvement in mycosis fungoides. Am J Ophthalmol 55:315–322

    Google Scholar 

  150. Wylen EL, Williams RB, Nanda A (1998) Cutaneous T-cell lymphoma with intracerebral and bilateral intraocular spread. Neurol Res 20:307–312

    CAS  PubMed  Google Scholar 

  151. Yahalom C, Cohen Y, Averbukh E et al (2002) Bilateral iridociliary T-cell lymphoma. Arch Ophthalmol 120:204–207

    PubMed  Google Scholar 

  152. Yamada K, Hirata A, Kimura A, Tanihara H (2003) A case of primary B-cell type non-Hodgkin lymphoma originating in the iris. Am J Ophthalmol 136:380–382

    Article  PubMed  Google Scholar 

  153. Young TL, Himelstein BP, Rebsamen SL et al (1996) Intraocular Ki-1 lymphoma in a 2-year-old boy. J Pediatr Ophthalmol Strabismus 33:268–270

    CAS  PubMed  Google Scholar 

  154. Yunis JJ, Oken MM, Kaplan ME et al (1982) Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin’s lymphoma. N Engl J Med 307:1231–1236

    CAS  Google Scholar 

  155. Zauberman H, Freund M (1971) Pseudolymphoma of the choroid in a patient with senile disciform macular degeneration. Ophthalmologica 163:65–72

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Mrs Eva Seibt, Mrs Petra Nowak and Mr Henning Müller for their technical assistance in the preparation of the vitreous specimens examined in our referral centre. The authors would also like to thank Dr K. Jahnke (Department of Haematology, University Medicine Berlin, Campus Benjamin Franklin) for his discussions on the various treatment options of PIOL patients.

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Authors and Affiliations

  1. Department of Pathology, Charité—University Medicine, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, 12200, Germany

    Sarah E. Coupland, Heinrich Heimann & Nikolaos E. Bechrakis

  2. Department of Ophthalmology, Charité—University Medicine, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, 12200, Germany

    Sarah E. Coupland, Heinrich Heimann & Nikolaos E. Bechrakis

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  1. Sarah E. Coupland
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  2. Heinrich Heimann
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Correspondence to Sarah E. Coupland.

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Coupland, S.E., Heimann, H. & Bechrakis, N.E. Primary intraocular lymphoma: a review of the clinical, histopathological and molecular biological features. Graefe's Arch Clin Exp Ophthalmol 242, 901–913 (2004). https://doi.org/10.1007/s00417-004-0973-0

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  • DOI: https://doi.org/10.1007/s00417-004-0973-0

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