Primäres intraokuläres Lymphom: Relevanz der diagnostischen Vitrektomie

Zusammenfassung

Primär intraokuläre Lymphome sind sehr seltene Tumoren, die sich noch weiter in primär vitreoretinale und die noch viel selteneren primär uvealen Lymphome unterteilen lassen. In den letzten Jahrzehnten hat die Inzidenz des primär vitreoretinalen Lymphoms (PVRL) deutlich zugenommen. Die differenzialdiagnostische Abgrenzung zur posterioren Uveitis ist mitunter schwierig und daher kommt es in einigen Fällen zur verschleppten Diagnosestellung mit einer verzögerten Therapieeinleitung. Dies ist insbesondere deshalb fatal, weil das primär vitreoretinale Lymphom häufig mit dem primären ZNS-Lymphom assoziiert ist. Goldstandard zur Diagnosesicherung vor Therapieeinleitung ist der zytologische bzw. histologische Nachweis von Lymphomzellen. Hierzu wird eine diagnostische Vitrektomie mit Glaskörperbiopsie, evtl. kombiniert mit einer transretinalen Biopsie, durchgeführt. Zytokinanalyse, Durchflusszytometrie sowie molekulare Diagnostik sind lediglich ergänzende Maßnahmen, sofern genügend Probenmaterial vorhanden ist. Sobald die Diagnose eines Lymphoms gestellt ist, muss in interdisziplinärer Zusammenarbeit zwischen Onkologen und Ophthalmologen ein Therapiekonzept erarbeitet werden.

Abstract

Primary intraocular lymphomas are rare tumours that can be further subdivided into primary vitreoretinal and the even rarer primary uveal lymphoma. The incidence of primary vitreoretinal lymphoma (PVRL) has increased during the last few decades. Differential diagnostic distinction between lymphoma and posterior uveitis is often difficult, so that adequate diagnosis and treatment is often delayed. This is fatal, because PVRL is often associated with primary central nervous lymphoma. To confirm the diagnosis, prior treatment of cytological or histological detection of lymphoma cells is the gold standard. Therefore, a diagnostic vitrectomy should be performed with vitreous biopsy and sometimes transretinal biopsy. Cytokine analysis, as well as flow cytometry and molecular tests, are only additional methods that can be employed in case enough tumour material is available. After the diagnosis has been made, an interdisciplinary treatment concept must be developed by oncologists and ophthalmologists together.

Schlüsselwörter

okuläre Tumoren - Lymphom - transretinale Biopsie - Glaskörperbiopsie - diagnostische Vitrektomie - Masquerade-Syndrom

Key words

lymphoma - transretinal biopsy - vitreous biopsy - diagnostic vitrectomy - masquerade syndrome - ocular tumours

• Literatur

• 1 Swerdlow SH, Campo E, Pileri SA. et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127: 2375-2390
• 2 Coupland SE. Molecular pathology of lymphoma. Eye (Lond) 2013; 27: 180-189
• 3 Davis JL. Diagnosis of intraocular lymphoma. Ocul Immunol Inflamm 2004; 12: 7-16
• 4 Coupland SE, Damato B. Lymphomas involving the eye and the ocular adnexa. Curr Opin Ophthalmol 2006; 17: 523-531
• 5 Cao X, Shen D, Callanan DG. et al. Diagnosis of systemic metastatic retinal lymphoma. Acta Ophthalmol 2011; 89: e149-e154
• 6 Coupland SE, Chan CC, Smith J. Pathophysiology of retinal lymphoma. Ocul Immunol Inflamm 2009; 17: 227-237
• 7 Chan CC, Rubenstein JL, Coupland SE. et al. Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium. Oncologist 2011; 16: 1589-1599
• 8 Coupland SE, Anastassiou G, Bornfeld N. et al. Primary intraocular lymphoma of T-cell type: report of a case and review of the literature. Graefes Arch Clin Exp Ophthalmol 2005; 243: 189-197
• 9 Hormigo A, DeAngelis LM. Primary ocular lymphoma: clinical features, diagnosis, and treatment. Clin Lymphoma 2003; 4: 22-29
• 10 Coupland SE, Damato B. Understanding intraocular lymphomas. Clin Exp Ophthalmol 2008; 36: 564-578
• 11 Hochberg FH, Miller DC. Primary central nervous system lymphoma. J Neurosurg 1988; 68: 835-853
• 12 DeAngelis LM, Yahalom J, Heinemann MH. et al. Primary CNS lymphoma: combined treatment with chemotherapy and radiotherapy. Neurology 1990; 40: 80-86
• 13 Hong JT, Chae JB, Lee JY. et al. Ocular involvement in patients with primary CNS lymphoma. J Neurooncol 2011; 102: 139-145
• 14 Coupland SE, Heimann H, Bechrakis NE. Primary intraocular lymphoma: a review of the clinical, histopathological and molecular biological features. Graefes Arch Clin Exp Ophthalmol 2004; 242: 901-913
• 15 Whitcup SM, Chan CC, Buggage RR. et al. Improving the diagnostic yield of vitrectomy for intraocular lymphoma. Arch Ophthalmol 2000; 118: 446
• 16 Peterson K, Gordon KB, Heinemann MH. et al. The clinical spectrum of ocular lymphoma. Cancer 1993; 72: 843-849
• 17 Chan CC, Buggage RR, Nussenblatt RB. Intraocular lymphoma. Curr Opin Ophthalmol 2002; 13: 411-418
• 18 Levasseur SD, Wittenberg LA, White VA. Vitreoretinal lymphoma: a 20-year review of incidence, clinical and cytologic features, treatment, and outcomes. JAMA Ophthalmol 2013; 131: 50-55
• 19 Hormigo A, Abrey L, Heinemann MH. et al. Ocular presentation of primary central nervous system lymphoma: diagnosis and treatment. Br J Haematol 2004; 126: 202-208
• 20 Mochizuki M, Singh AD. Epidemiology and clinical features of intraocular lymphoma. Ocul Immunol Inflamm 2009; 17: 69-72
• 21 Kimura K, Usui Y, Goto H. et al. Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma. Jpn J Ophthalmol 2012; 56: 383-389
• 22 Gill MK, Jampol LM. Variations in the presentation of primary intraocular lymphoma: case reports and a review. Surv Ophthalmol 2001; 45: 463-471
• 23 Smith JR, Rosenbaum JT. Neurological concomitants of uveitis. Br J Ophthalmol 2004; 88: 1498-1499
• 24 Whitcup SM, de Smet MD, Rubin BI. et al. Intraocular lymphoma. Clinical and histopathologic diagnosis. Ophthalmology 1993; 100: 1399-1406
• 25 Chan CC. Molecular pathology of primary intraocular lymphoma. Trans Am Ophthalmol Soc 2003; 101: 275-292
• 26 Gass JD, Sever RJ, Grizzard WS. et al. Multifocal pigment epithelial detachments by reticulum cell sarcoma. A characteristic funduscopic picture. Retina 1984; 4: 135-143
• 27 Buettner H, Bolling JP. Intravitreal large-cell lymphoma. Mayo Clin Proc 1993; 68: 1011-1015
• 28 De Smet MD, Nussenblatt RB, Davis JL. et al. Large cell lymphoma masquerading as a viral retinitis. Int Ophthalmol 1990; 14: 413-417
• 29 Sen HN, Bodaghi B, Hoang PL. et al. Primary intraocular lymphoma: diagnosis and differential diagnosis. Ocul Immunol Inflamm 2009; 17: 133-141
• 30 Shah GK, Kleiner RC, Augsburger JJ. et al. Primary intraocular lymphoma seen with transient white fundus lesions simulating the multiple evanescent white dot syndrome. Arch Ophthalmol 2001; 119: 617-620
• 31 Ishida T, Ohno-Matsui K, Kaneko Y. et al. Fundus autofluorescence patterns in eyes with primary intraocular lymphoma. Retina 2010; 30: 23-32
• 32 Egawa M, Mitamura Y, Hayashi Y. et al. Spectral-domain optical coherence tomographic and fundus autofluorescence findings in eyes with primary intraocular lymphoma. Clin Ophthalmol 2014; 8: 335-341
• 33 Velez G, Chan CC, Csaky KG. Fluorescein angiographic findings in primary intraocular lymphoma. Retina 2002; 22: 37-43
• 34 Gonzales JA, Chan CC. Biopsy techniques and yields in diagnosing primary intraocular lymphoma. Int Ophthalmol 2007; 27: 241-250
• 35 Sagoo MS, Mehta H, Swampillai AJ. et al. Primary intraocular lymphoma. Surv Ophthalmol 2014; 59: 503-516
• 36 Davis JL, Solomon D, Nussenblatt RB. et al. Immunocytochemical staining of vitreous cells. Indications, techniques, and results. Ophthalmology 1992; 99: 250-256
• 37 Rajagopal R, Harbour JW. Diagnostic testing and treatment choices in primary vitreoretinal lymphoma. Retina 2011; 31: 435-440
• 38 Mruthyunjaya P, Jumper JM, McCallum R. et al. Diagnostic yield of vitrectomy in eyes with suspected posterior segment infection or malignancy. Ophthalmology 2002; 109: 1123-1129
• 39 Kanavi MR, Soheilian M, Hosseini SB. et al. 25-gauge transconjunctival diagnostic vitrectomy in suspected cases of intraocular lymphoma: a case series and review of the literature. Int J Ophthalmol 2014; 7: 577-581
• 40 Metz CH, Schueler A, Metz K. et al. [Transretinal biopsy of intraocular lymphoma]. Klin Monatsbl Augenheilkd 2015; 232: 845-849
• 41 Mastropasqua R, Thaung C, Pavesio C. et al. The role of chorioretinal biopsy in the diagnosis of intraocular lymphoma. Am J Ophthalmol 2015; 160: 1127-1132.e1
• 42 Davis JL, Miller DM, Ruiz P. Diagnostic testing of vitrectomy specimens. Am J Ophthalmol 2005; 140: 822-829
• 43 Margolis R, Brasil OF, Lowder CY. et al. Vitrectomy for the diagnosis and management of uveitis of unknown cause. Ophthalmology 2007; 114: 1893-1897
• 44 Wang Y, Shen D, Wang VM. et al. Molecular biomarkers for the diagnosis of primary vitreoretinal lymphoma. Int J Mol Sci 2011; 12: 5684-5697
• 45 Missotten T, Tielemans D, Bromberg JE. et al. Multicolor flowcytometric immunophenotyping is a valuable tool for detection of intraocular lymphoma. Ophthalmology 2013; 120: 991-996
• 46 Davis JL, Viciana AL, Ruiz P. Diagnosis of intraocular lymphoma by flow cytometry. Am J Ophthalmol 1997; 124: 362-372
• 47 Chan CC, Sen HN. Current concepts in diagnosing and managing primary vitreoretinal (intraocular) lymphoma. Discov Med 2013; 15: 93-100
• 48 Sugita S, Takase H, Sugamoto Y. et al. Diagnosis of intraocular lymphoma by polymerase chain reaction analysis and cytokine profiling of the vitreous fluid. Jpn J Ophthalmol 2009; 53: 209-214
• 49 Akpek EK, Maca SM, Christen WG. et al. Elevated vitreous interleukin-10 level is not diagnostic of intraocular-central nervous system lymphoma. Ophthalmology 1999; 106: 2291-2295
• 50 Chan CC, Whitcup SM, Solomon D. et al. Interleukin-10 in the vitreous of patients with primary intraocular lymphoma. Am J Ophthalmol 1995; 120: 671-673
• 51 Cassoux N, Giron A, Bodaghi B. et al. IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma. Invest Ophthalmol Vis Sci 2007; 48: 3253-3259
• 52 Margolis R. Diagnostic vitrectomy for the diagnosis and management of posterior uveitis of unknown etiology. Curr Opin Ophthalmol 2008; 19: 218-224
• 53 Davis JL. Intraocular lymphoma: a clinical perspective. Eye (Lond) 2013; 27: 153-162
• 54 Wolf LA, Reed GF, Buggage RR. et al. Vitreous cytokine levels. Ophthalmology 2003; 110: 1671-1672
• 55 Tuo J, Shen D, Yang HH. et al. Distinct microRNA-155 expression in the vitreous of patients with primary vitreoretinal lymphoma and uveitis. Am J Ophthalmol 2014; 157: 728-734
• 56 Kakkassery V, Schroers R, Coupland SE. et al. Vitreous microRNA levels as diagnostic biomarkers for vitreoretinal lymphoma. Blood 2017; 129: 3130-3133
• 57 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. Blood 2015; 126: 76-79
• 58 Berenbom A, Davila RM, Lin HS. et al. Treatment outcomes for primary intraocular lymphoma: implications for external beam radiotherapy. Eye (Lond) 2007; 21: 1198-1201
• 59 Peʼer J, Hochberg FH, Foster CS. Clinical review: treatment of vitreoretinal lymphoma. Ocul Immunol Inflamm 2009; 17: 299-306
• 60 Soussain C, Choquet S, Fourme E. et al. Intensive chemotherapy with thiotepa, busulfan and cyclophosphamide and hematopoietic stem cell rescue in relapsed or refractory primary central nervous system lymphoma and intraocular lymphoma: a retrospective study of 79 cases. Haematologica 2012; 97: 1751-1756
• 61 Grimm SA, McCannel CA, Omuro AM. et al. Primary CNS lymphoma with intraocular involvement: International PCNSL Collaborative Group Report. Neurology 2008; 71: 1355-1360
• 62 Nussenblatt RB, Chan CC, Wilson WH. et al. International Central Nervous System and Ocular Lymphoma Workshop: recommendations for the future. Ocul Immunol Inflamm 2006; 14: 139-144