Primary Intraocular Lymphoma (PIOL)
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1 Primary Intraocular Lymphoma (PIOL) Ref: Ryan SJ et al. Retina 5 th ed., original and review articles 眼科医局勉強会 岩崎優子 2016/7/4
2 PIOL and primary central nervous system lymphoma (PCNSL) Non-Hodgkin s Lymphoma (NHL) B cell lymphoma PCNSL Five year survival PVRL: 30 % PCNSL: 30 % PVRL and PCNS could transit to whole body and cause systemic lymphoma % 25 % Intraocular lymphoma PIOL Secondary Primary Vitreoretinal Lymphoma (PVRL): high-grade B-cell Hodgkin lymphoma Lymphoma Primary Choroidal Lymphoma: Low-grade B-cell lymphoma Primary iridal lymphoma: B-cell and T-cell lymphoma T cell lymphoma
3 Etiology and pathogenesis of PCNSL PCNSL is believed to originate from late-germinal center or post-germinal center lymphoid cells K Basso et al., Nat Rev Immunol
4 Etiology and pathogenesis of PCNSL Neurotropic mechanism is uncertain Hypothesis for trafficking between eye and brain: Invasion of optic nerve Seeding through shared venous drainage Common integrin expression Risk factors for the development of PCNSL Immunosuppression Epstein-Barr virus infection in AIDS patients No known risk factors in immunocompetent patients
5 Epidemiology and clinical findings of PVRL y.o. Masquerade syndrome : A group of various ocular diseases that may mimic chronic intraocular inflammation. Intraocular lymphoma Metastatic intraocular tumor Old Vitreous hemorrhage Painless, decreased visual acuity or floaters in 50 % cases Clinical findings are bilateral in 80 % cases, but are frequently asymmetric
6 Pathognomonic findings 1: Fine vitreous cells or clumps of cells Chan CC et al, Cancer Control Chan CC et al., Oncologist
7 Pathognomonic findings 2: Sub-RPE deposits Ishida T et al., Retina Chan CC et al., Oncologist
8 Nonspecific findings Keratic precipitates Iris nodules Aqueous cells Focal, multifocal, or diffuse choroidal, retinal, or chorioretinal infiltrates N Hashida et al., Transl Vis Sci Technol
9 Less commonly reported findings Perivasculitis Retinal artery occlusion Exudative retinal detachment Multifocal punched-out regions at the level of the RPE Optic atrophy Kim JL et al., Surv Ophthalmol
10 Ocular findings of intraocular lymphoma in the retrospective study of Japanese hospitals Kimura K et al., Jpn J Ophthalmol
11 Imaging FA: granularity, blockage and late staining IA: blockage Velez G et al., Retina FA, late IA, late Ishida T et al., Retina
12 Imaging FAF: hyperautofluorescence granular lesions OCT: nodular hyperreflective lesions at the RPE level Casady M et al, Retina Ishida T et al., Retina
13 Diagnosis Blood test: LDH, sil-2r Cytological evaluation Histopathological evaluation Vitreous biopsy, retinal biopsy, and subretinal biopsy The subtype was large B-cell in 73% (PCNSL with IOL), T-cell in 2%, and not specified in 25% 2-4 times larger than normal lymphocytes Pleomorphic Scant cytoplasm Kim JL et al., Surv Ophthalmol
14 Diagnosis-supplementary techniques Immunohistochemistry and flow cytometry for identifying blood cell markers Monoclonality of the immunoglobulin gene segments evaluated by PCR IL-10, IL-6 / IL-10 ratio evaluated by ELISA Elevated IL-10 (>100 pg/ml) and the IL-10/IL-6 ratio (>1.0) were positive in 18 of the 22 IOL patients Sugita S et al., Jpn J Ophthalmol Systemic evaluation e.g. gadolinium-enhanced MRI
15 Treatment Radiation: Gy Chemotherapy: Intravitreal and systemic chemotherapy using methotrexate and/or rituximab Intravitreal methotrexate therapy by Dr. Takase 400 μg/0.1ml Once/week x 4 times Once/month x 3 times
16 Prognostic factors-1 PIOL bcl-2 translocations Wallac DJ et al., Invest Ophthalmol Vis Sci Large copy number loss in 6q Wang L et al., Cancer Sci PCNSL Age > 60 y.o. Performance status > 1 Elevated LDH level High CSF protein concentration Involvement of deep regions of the brain (periventricular regions, basal ganglia, brainstem, and/or cerebellum) Presence of ocular disease Ferreri AJM et al., J Clin Oncol Presence of retinal disease Blay JY et al., J Clin Oncol
17 Prognostic factors-2 CNSL 6q abberations, 6q deletions Nakamura M et al., Cancer Res Rickert CH et al., Am Pathol Hypermethylation of the reduced folate carrier gene Ferreri AJ et al., Br J Haematol High cell density and high expression of activated STAT6 Rubenstein JL et al., Blood A B C Cellular density P-STAT6 staining Low Absent Low Positive High Strong
18 Prognostic factors-3 CNSL Increased levels of antithrombin Ⅲ in CSF Elevated CSF level of IL-10 Elevated CXCL13 and IL10 in CSF Metastatic CNSL (DLBCL) Increased levels of scd19 in CSF Systemic DLBCL High mir-21 expression in serum Roy S et al., J Clin Oncol Sasayama T et al., Neuro Oncol Rubenstein JL et al., Blood Muniz C et al., Blood Lawrie CH et al., Br J Haematol Ratio of CD4*CD8 to (CD163:CD68[M2])*PD-L1 (abstract のみ ) Keane C et al., Lancet Haematol
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