Molecular biomarkers for the diagnosis of primary vitreoretinal lymphoma

• Published in: International journal of molecular sciences Vol. 12; no. 9; pp. 5684 - 5697
• Main Authors: Wang, Yujuan, Shen, Defen, Wang, Vinson M, Sen, H Nida, Chan, Chi-Chao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-09-2011; Molecular Diversity Preservation International (MDPI)
• Subjects: Aged; biomarker; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cells; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; gene arrangement; Gene Rearrangement; Genes, Immunoglobulin Heavy Chain - genetics; Humans; immunoglobulin heavy chain; Immunoglobulins; Immunology; Interleukin-10 - metabolism; Interleukin-6 - metabolism; Lymphocytes; Lymphoma; Lymphoma - diagnosis; Lymphoma - genetics; Lymphoma - metabolism; Male; microdissection; Middle Aged; Nervous system; Patients; Polymerase Chain Reaction; primary vireoretinal lymphoma; Receptors, Antigen, T-Cell - genetics; Reproducibility of Results; Retina; Retinal Neoplasms - diagnosis; Retinal Neoplasms - genetics; Retinal Neoplasms - metabolism; Retrospective Studies; Sensitivity and Specificity; T-cell receptor; Vitreous Body - metabolism; Vitreous Body - pathology; United States > US; T-cell receptor; primary vireoretinal lymphoma; gene arrangement; immunoglobulin heavy chain; microdissection; biomarker; polymerase chain reaction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms12095684

Primary vitreoretinal lymphoma (PVRL) or primary intraocular lymphoma, a subtype of primary central nervous system lymphoma, often masquerades as uveitis. The diagnosis of PVRL requires identification of lymphoma cells inside the eye, which is often challenging due to the frequent necrosis and admixing of PVRL cells with reactive lymphocytes. Therefore, detection of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements provide molecular diagnosis of B- and T-cell lymphoma, respectively. We retrospectively evaluated 208 cases with a clinical diagnosis of masquerade syndrome from 1998 to 2010. In 200 cases with molecular analyses using microdissection and polymerase chain reaction, we found that 110 cases had IgH gene rearrangement, 5 cases had TCR gene rearrangement, and 85 cases were negative for these two gene arrangements. The molecular data corroborated the cytopathological diagnoses of PVRL and uveitis in the majority of cases. Cytokine above the detected levels in the specimens were also measured in 80 of the 208 cases. A ratio of vitreous IL-10 to IL-6 greater than 1, suggesting PVRL, was found in 56/80 cases; 53/56 had the correct diagnosis. A ratio less than 1, suggesting uveitis, was found in 24/80 cases; 17/24 correctly confirmed the diagnosis. Moreover, the molecular data corresponded well with the clinical course of the diseases. The sensitivity and specificity of these molecular biomarkers for the diagnosis of PVRL are higher than 95%.