Primary Intraocular Lymphoma: The Masquerade Syndrome

This chapter aims to provide a complete knowledge over the primary intraocular lymphoma (PIOL) and a correct clinical approach towards this rare condition, to avoid delays in diagnosis, which is considered the most important prognostic factor. A PIOL arises with no specific symptoms and could mimic both inflammatory and non-inflammatory ocular conditions. Also known as reticulum cell sarcoma in the past, PIOL is an ocular malignant condition, with a strong bond with primary central system lymphoma (PCNSL). This linkage is underlined by the fact that approximately 30% of the patients with PIOL have also PCNSL at presentation, while 45–90% will develop PCSNL in the following months. A correct diagnosis is currently achieved by the means of many different techniques: cytology, flow cytometry, immunohistochemistry, molecular analysis, and cytokines assay. Treatment of this condition has been completely revolutionized with the introduction of monoclonal antibodies directed against specific proteins present on the surface of lymphomatous cells.

The Diagnostic Value of Genetic Mutation Analysis and Mutation Profiling of cfDNA in Intraocular Fluid for VRL

Vitreoretinal lymphoma (VRL) is a rare but aggressive masquerade syndrome, which would be easily confused with uveitis. The diagnostic gold standard remains the pathologic examination of ocular specimen with invasiveness and low sensitivity. To improve the safety and accuracy of VRL diagnosis, alternative techniques using intraocular fluid (IOF) samples are emerging. In this study, we aimed to test the diagnostic value of genetic mutation analysis of circulating cell-free DNA (cfDNA) in IOF for VRL and exhibit the mutation profile for revealing the molecular characteristics of VRL. Twenty-three suspected VRL patients were selected as the training group, who had genetic mutation analysis using a panel containing 446 tumor-related genes. Another external cohort including 5 VRL patients and 5 uveitis patients was selected for further validation. In training group, all of VRL patients had obtained 23 (IQR 13.5, 36.0) cfDNA mutations in IOF (sensitivity 100%), and 2 out of 6 uveitis patients had one and four mutations respectively (specificity 67%). The latter were identified as clonal hematopoiesis mutations. In validation group, all of VRL patients were positive and all of uveitis patients were negative for mutation analysis (sensitivity and specificity 100%). VRL patients from the two groups were characterized by the high mutation frequencies of PIM1 (21/22, 90.91%), MYD88 (17/22, 77.27%), CD79B (11/22, 50.00%), ETV6 (11/22, 50.00%) and IRF4 (11/22, 50.00%), and 77.27% were MCD subtype with PI3K-Akt signaling pathway alternation. In conclusion, it demonstrated a new mini-invasive and feasible method for VRL diagnosis using a panel of 466 tumor-related genes.

Acute Elevation of Intraocular Pressure in Patient with Hyperlipidemic Myeloma

Purpose: To introduce a rare case of patient with hyperlipidemic myeloma and ocular manifestation in the form of masquerade syndrome with acute elevation of intraocular pressure (IOP) and hyperviscous retinopathy. Results: 55-year-old man with newly diagnosed hyperlipidemic myeloma and hyperviscous syndrome was acutely referred to our glaucoma outpatient clinic due to problems with his left eye: sudden pain, blurred vision, redness of the eye and IOP of 44 mm Hg. We excluded attack of angle closure glaucoma and found the presence of whitish material in the anterior chamber and blood obstructing the iridocorneal angle. Glaucoma therapy was initiated and lavage of the anterior chamber of the left eye with sampling of the aqueous humour for biochemical and cytological examination was performed. Identification of trace amount of cryoprotein in the samples of humour proved diagnosis of masquerade syndrome. Finding of the hyperviscous retinopathy and nonperfusion of wide peripheral areas of retina in both eyes was indicated to laser coagulation of these areas. The patient underwent in the meantime three times plasmapheresis, four cycles of biological therapy and autologous stem cell transplantation reaching complete remission of the myeloma. Local and systemic therapy led to significant clinical finding improvement on the anterior segment and fundus of both eyes. Conclusions: Masquerade syndrome can be complicated by acute elevation of IOP. Diagnostic lavage of the anterior chamber, local therapy, systemic therapy and close interdisciplinary cooperation contributed to right diagnosis, IOP normalisation, ocular and general condition improvement.

Masquerade Syndromes and Uveitis; Clinics, Diagnosis, and Treatment

The term “masquerade syndrome” is used to describe all conditions where the presence of cells either in the anterior chamber, vitreous, or both but unrelated to any immune-mediated uveitis entities. Although masquerade syndromes can be caused by benign conditions such as intraocular foreign body, retinitis pigmentosa, ocular ischemic syndrome, etc., malignant masquerade syndromes are the important ones in this group of disorders. Hematologic malignancies such as lymphoma and leukemia, ocular metastasis of systemic tumors, paraneoplastic retinopathies, and retinoblastoma are neoplastic masquerade syndromes mimicking ocular inflammatory diseases. A delay in the diagnosis and treatment of these diseases can result in serious morbidity and mortality. Careful clinical examination and detailed ancillary investigation of all patients older than 50 years of age with chronic uveitis are crucial to prevent systemic dissemination, worsening of the causal disease, and mortality