Primary intraocular lymphoma of T-cell type: report of a case and review of the literature

  • Sarah E. Coupland
  • Gerasimos Anastassiou
  • Norbert Bornfeld
  • Michael Hummel
  • Harald Stein
Review Article

Abstract

Purpose

Primary intraocular lymphoma (PIOL) is an uncommon non-Hodgkin lymphoma and is usually of B-cell type. Intraocular T-cell or T/NK-cell lymphomas are extremely rare and mostly represent a secondary manifestation of either a cutaneous or a systemic lymphoma. The aim of the current paper is to report the clinical, histopathological and molecular biological findings of a PIOL of T-cell type.

Methods

Conventional cytological and immunocytological examination of vitrectomy specimens. Conventional histology, immunohistochemistry and polymerase chain reaction (PCR) for the detection of immunoglobulin heavy chain (IgH) and T-cell-receptor gamma (TCR-γ) gene rearrangement, GeneScan analysis, and DNA sequencing were performed on the chorioretinal biopsy.

Results

Cytology of the right vitreous aspirate revealed a moderate cellular infiltrate consisting of medium-sized T-cells with pleomorphic nuclei. Similar atypical lymphocytes were seen in the partially necrotic chorioretinal biopsy. These lymphocytes expressed CD3, CD4, βF1 and CD30, with a growth fraction of 90%. TCR-γ-PCR, GeneScan analysis and DNA sequencing demonstrated a monoclonal amplification product within the expected range. In contrast, IgH-PCR revealed oligoclonal amplificates. The patient was treated with low-dose radiotherapy (total 45 Gy), and was in complete remission at final follow-up.

Conclusion

A rare PIOL of T-cell type was diagnosed on the basis of vitreous aspiration and chorioretinal biopsy. In addition to conventional cytology and immunocytology, the utilisation of gene rearrangement studies on vitreous or chorioretinal biopsies increases the chances of diagnosing or excluding a PIOL of either B-cell or T-cell type. Despite its rarity, ophthalmic pathologists should always consider the diagnosis of T-PIOL when reviewing vitreous samples.

References

  1. 1.
    Abrey LE, DeAngelis LM, Yahalom J (1998) Long-term survival in primary CNS lymphoma. J Clin Oncol 16:859–863PubMedGoogle Scholar
  2. 2.
    Appen RE (1975) Posterior uveitis and primary cerebral reticulum cell sarcoma. Arch Ophthalmol 93:123–124PubMedGoogle Scholar
  3. 3.
    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 19:224–239PubMedGoogle Scholar
  4. 4.
    Ben-Ezra D, Sahel JA, Harris NL et al (1989) Uveal lymphoid infiltrates: immunohistochemical evidence for a lymphoid neoplasia. Br J Ophthalmol 73:846–851PubMedGoogle Scholar
  5. 5.
    Blumenkranz MS, Ward T, Murphy S et al (1992) Applications and limitations of vitreoretinal biopsy techniques in intraocular large cell lymphoma. Retina 12:S64–S70PubMedGoogle Scholar
  6. 6.
    Brown SM, Jampol LM, Cantrill HL (1994) Intraocular lymphoma presenting as retinal vasculitis. Surv Ophthalmol 39:133–140CrossRefPubMedGoogle Scholar
  7. 7.
    Cassoux N, Merle-Beral H, Leblond V et al (2000) Ocular and central nervous system lymphoma: clinical features and diagnosis. Ocul Immunol Inflamm 8:243–250CrossRefPubMedGoogle Scholar
  8. 8.
    Cassoux N, Charlotte F, Rao NA et al (2004) Endoretinal biopsy in establishing the diagnosis of uveitis entities: clinicopathological report of three cases. Ocul Immunol Inflamm (in press)Google Scholar
  9. 9.
    Chan CC, Whitcup SM, Solomon D, Nussenblatt RB (1995) Interleukin-10 in the vitreous of patients with primary intraocular lymphoma. Am J Ophthalmol 120:671–673PubMedGoogle Scholar
  10. 10.
    Char DH, Ljung BM, Deschenes J, Miller TR (1988) Intraocular lymphoma: immunological and cytological analysis. Br J Ophthalmol 72:905–911PubMedGoogle Scholar
  11. 11.
    Char DH, Ljung BM, Miller T, Phillips T (1988) Primary intraocular lymphoma (ocular reticulum cell sarcoma) diagnosis and management. Ophthalmology 95:625–630PubMedGoogle Scholar
  12. 12.
    Ciulla TA, Bains RA, Jakobiec FA et al (1997) Uveal lymphoid neoplasia: a clinical-pathologic correlation and review of the early form. Surv Ophthalmol 41:467–476CrossRefPubMedGoogle Scholar
  13. 13.
    Ciulla TA, Pesavento RD, Yoo S (1997) Subretinal aspiration biopsy of ocular lymphoma. Am J Ophthalmol 123:420–422PubMedGoogle Scholar
  14. 14.
    Cochereau I, Hannouche D, Geoffray C et al (1996) Ocular involvement in Epstein-Barr virus-associated T-cell lymphoma. Am J Ophthalmol 121:322–324PubMedGoogle Scholar
  15. 15.
    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 107:151–158CrossRefPubMedGoogle Scholar
  16. 16.
    Cooper EL, Riker JL (1951) Malignant lymphoma of the uveal tract. Am J Ophthalmol 34:1153–1158PubMedGoogle Scholar
  17. 17.
    Cordell JL, Falini B, Erber WN et al (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229PubMedGoogle Scholar
  18. 18.
    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 106:2109–2120CrossRefPubMedGoogle Scholar
  19. 19.
    Coupland SE, Foss HD, Bechrakis NE et al (2001) Secondary ocular involvement in systemic “memory” B-cell lymphocytic leukemia. Ophthalmology 108:1289–1295CrossRefPubMedGoogle Scholar
  20. 20.
    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 197:333–340CrossRefPubMedGoogle Scholar
  21. 21.
    Coupland SE, Bechrakis NE, Anastassiou G et al (2003) Evaluation of vitrectomy specimens in the diagnosis of primary intraocular lymphoma. Graefes Arch Clin Exp Ophthalmol 241(10):860–870CrossRefPubMedGoogle Scholar
  22. 22.
    Davis JL, Viciana AL, Ruiz P (1997) Diagnosis of intraocular lymphoma by flow cytometry. Am J Ophthalmol 124:362–372PubMedGoogle Scholar
  23. 23.
    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 (published erratum appears in Br J Ophthalmol Feb;76(2):128)PubMedGoogle Scholar
  24. 24.
    Fine HA, Mayer RJ (1993) Primary central nervous system lymphoma. Ann Intern Med 119:1093–1104PubMedGoogle Scholar
  25. 25.
    Foerster H (1960) Mycosis fungoides with intraocular involvement. Trans Am Acad Ophthalmol Otolaryngol 64:308–314PubMedGoogle Scholar
  26. 26.
    Freeman LN, Schachat AP, Knox DL et al (1987) Clinical features, laboratory investigations, and survival in ocular reticulum cell sarcoma. Ophthalmology 94:1631–1639PubMedGoogle Scholar
  27. 27.
    Gärtner J (1989) Mycosis fungoides mit Beteiligung der Aderhaut. Klin Monatsbl Augenheilkd 131:61–69Google Scholar
  28. 28.
    Gass JD, Trattler HL (1991) Retinal artery obstruction and atheromas associated with non-Hodgkin’s large cell lymphoma (reticulum cell sarcoma). Arch Ophthalmol 109:1134–1139PubMedGoogle Scholar
  29. 29.
    Gass JD, Sever RJ, Grizzard WS et al (1984) Multifocal pigment epithelial detachments by reticulum cell sarcoma. A characteristic funduscopic picture. Retina 4:135–143PubMedGoogle Scholar
  30. 30.
    Gass JD, Weleber RG, Johnson DR (1987) Non-Hodgkin’s lymphoma causing fundus picture simulating fundus flavimaculatus. Retina 7:209–214PubMedGoogle Scholar
  31. 31.
    Gill MK, Jampol LM (2001) Variations in the presentation of primary intraocular lymphoma: case reports and a review. Surv Ophthalmol 45:463–471CrossRefPubMedGoogle Scholar
  32. 32.
    Goeminne JC, Brouillard A, Jaumain P et al (1999) Bilateral granulomatous panuveitis as initial presentation of diffuse systemic T cell lymphoma. Ophthalmologica 213:323–326CrossRefPubMedGoogle Scholar
  33. 33.
    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 107:1349–1353PubMedGoogle Scholar
  34. 34.
    Grossniklaus HE, Martin DF, Avery R et al (1998) Uveal lymphoid infiltration. Report of four cases and clinicopathologic review. Ophthalmology 105:1265–1273CrossRefPubMedGoogle Scholar
  35. 35.
    Hoffman PM, McKelvie P, Hall AJ et al (2003) Intraocular lymphoma: a series of 14 patients with clinicopathological features and treatment outcomes. Eye 17:513–521CrossRefPubMedGoogle Scholar
  36. 36.
    Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580PubMedGoogle Scholar
  37. 37.
    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, LyonGoogle Scholar
  38. 38.
    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 232:148–152CrossRefPubMedGoogle Scholar
  39. 39.
    Kaplan HJ, Meredith TA, Aaberg TM, Keller RH (1980) Reclassification of intraocular reticulum cell sarcoma (histiocytic lymphoma). Immunologic characterization of vitreous cells. Arch Ophthalmol 98:707–710PubMedGoogle Scholar
  40. 40.
    Katai N, Kuroiwa S, Fujimori K, Yoshimura N (1997) Diagnosis of intraocular lymphoma by polymerase chain reaction. Graefes Arch Clin Exp Ophthalmol 235:431–436PubMedGoogle Scholar
  41. 41.
    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 69:256–259PubMedGoogle Scholar
  42. 42.
    Keltner JL, Fritsch E, Cykiert RC, Albert DM (1977) Mycosis fungoides. Intraocular and central nervous system involvement. Arch Ophthalmol 95:645–650PubMedGoogle Scholar
  43. 43.
    Kincaid ME, Green WR (1983) Ocular and orbital involvement in leukemia. Surv Ophthalmol 27:211–232CrossRefPubMedGoogle Scholar
  44. 44.
    Kohno T, Uchida H, Inomata H et al (1993) Ocular manifestations of adult T-cell leukemia/lymphoma. A clinicopathologic study. Ophthalmology 100:1794–1799PubMedGoogle Scholar
  45. 45.
    Kumar SR, Gill PS, Wagner DG et al (1994) Human T-cell lymphotropic virus type I-associated retinal lymphoma. A clinicopathologic report. Arch Ophthalmol 112:954–959PubMedGoogle Scholar
  46. 46.
    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 252:67–73PubMedGoogle Scholar
  47. 47.
    Leitch RJ, Rennie IG, Parsons MA (1993) Ocular involvement in mycosis fungoides. Br J Ophthalmol 77:126–127PubMedGoogle Scholar
  48. 48.
    Lobo A, Larkin G, Clark BJ et al (2003) Pseudo-hypopyon as the presenting feature in B-cell and T-cell intraocular lymphoma. Clin Experiment Ophthalmol 31:155–158CrossRefPubMedGoogle Scholar
  49. 49.
    Lois N, Hiscott PS, Nash J, Wong D (2000) Immunophenotypic shift in a case of mycosis fungoides with vitreous invasion. Arch Ophthalmol 118:1692–1694PubMedGoogle Scholar
  50. 50.
    Martin DF, Chan CC, de Smet MD et al (1993) The role of chorioretinal biopsy in the management of posterior uveitis. Ophthalmology 100:705–714PubMedGoogle Scholar
  51. 51.
    Merle-Beral H, Davi F, Cassoux N et al (2004) Biological diagnosis of primary intraocular lymphoma. Br J Haematol 124:469–473PubMedGoogle Scholar
  52. 52.
    Norton AJ, Jordan S, Yeomans P (1994) Brief, high-temperature heat denaturation (pressure cooking): a simple and effective method of antigen retrieval for routinely processed tissues. J Pathol 173:371–379PubMedGoogle Scholar
  53. 53.
    Pavan PR, Oteiza EE, Margo CE (1995) Ocular lymphoma diagnosed by internal subretinal pigment epithelium biopsy. Arch Ophthalmol 113:1233–1234PubMedGoogle Scholar
  54. 54.
    Peterson K, Gordon KB, Heinemann MH, DeAngelis LM (1993) The clinical spectrum of ocular lymphoma. Cancer 72:843–849PubMedGoogle Scholar
  55. 55.
    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 52:878–886PubMedGoogle Scholar
  56. 56.
    Read RW, Zamir E, Rao NA (2002) Neoplastic masquerade syndromes. Surv Ophthalmol 47:81–124CrossRefPubMedGoogle Scholar
  57. 57.
    Reim H, Dieler R, Wessing A (1990) Non-Hodgkin’s lymphoma simulating chorioretinitis. Fortschr Ophthalmol 87:557–559PubMedGoogle Scholar
  58. 58.
    Ridley ME, McDonald HR, Sternberg P Jr et al (1992) Retinal manifestations of ocular lymphoma (reticulum cell sarcoma). Ophthalmology 99:1153–1160PubMedGoogle Scholar
  59. 59.
    Rockwood EJ, Zakov ZN, Bay JW (1984) Combined malignant lymphoma of the eye and CNS (reticulum-cell sarcoma). Report of three cases. J Neurosurg 61:369–374PubMedGoogle Scholar
  60. 60.
    Rothova A, Ooijman F, Kerkhoff F et al (2001) Uveitis masquerade syndromes. Ophthalmology 108:386–399CrossRefPubMedGoogle Scholar
  61. 61.
    Saga T, Ohno S, Matsuda H et al (1984) Ocular involvement by a peripheral T-cell lymphoma. Arch Ophthalmol 102:399–402PubMedGoogle Scholar
  62. 62.
    de Smet MD, Nussenblatt RB, Davis JL, Palestine AG (1990) Large cell lymphoma masquerading as a viral retinitis. Int Ophthalmol 14:413–417PubMedGoogle Scholar
  63. 63.
    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 19:742–749PubMedGoogle Scholar
  64. 64.
    Stenson S, Ramsay DL (1981) Ocular findings in mycosis fungoides. Arch Ophthalmol 99:272–277PubMedGoogle Scholar
  65. 65.
    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 112:450–451PubMedGoogle Scholar
  66. 66.
    Whitcup SM, de Smet MD, Rubin BI et al (1993) Intraocular lymphoma. Clinical and histopathologic diagnosis. Ophthalmology 100:1399–1406PubMedGoogle Scholar
  67. 67.
    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 115:1157–1160PubMedGoogle Scholar
  68. 68.
    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 117:761–765PubMedGoogle Scholar
  69. 69.
    Williams GC, Holz E, Lee AG, Font RL (2000) T-cell lymphoproliferative disorder of vitreous associated with mycosis fungoides. Arch Ophthalmol 118:278–280PubMedGoogle Scholar
  70. 70.
    Wolter J, Leenhouts T, Hendrix R (1963) Corneal involvement in mycosis fungoides. Am J Ophthalmol 55:315–322Google Scholar
  71. 71.
    Wylen EL, Williams RB, Nanda A (1998) Cutaneous T-cell lymphoma with intracerebral and bilateral intraocular spread. Neurol Res 20:307–312PubMedGoogle Scholar
  72. 72.
    Yahalom C, Cohen Y, Averbukh E et al (2002) Bilateral iridociliary T-cell lymphoma. Arch Ophthalmol 120:204–207PubMedGoogle Scholar
  73. 73.
    Young TL, Himelstein BP, Rebsamen SL et al (1996) Intraocular Ki-1 lymphoma in a 2-year-old boy. J Pediatr Ophthalmol Strabismus 33:268–270PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Sarah E. Coupland
    • 1
    • 2
  • Gerasimos Anastassiou
    • 3
  • Norbert Bornfeld
    • 3
  • Michael Hummel
    • 1
  • Harald Stein
    • 1
  1. 1.Department of Pathology, Charité-Medical Faculty BerlinCampus Benjamin FranklinBerlinGermany
  2. 2.Department of PathologyUniversitätsklinikum Benjamin FranklinBerlinGermany
  3. 3.Department of OphthalmologyUniversity Hospital EssenEssenGermany

Personalised recommendations