LAUSR

PURPOSE To determine whether the addition of adjunctive tests, including immunohistochemistry [IHC], cytokine analysis, flow cytometry, and IgH gene rearrangement testing, achieves improved diagnostic parameters compared to cytologic smears alone in the detection of vitreoretinal lymphoma (VRL). To determine which of these tests or combination of tests provide the greatest diagnostic utility. DESIGN Retrospective review to assess diagnostic utility. METHODS Setting: Single university-affiliated tertiary care center. PARTICIPANTS Data was analyzed from 237 vitreous biopsies at a single center between 1999-2017 in patients with suspected VRL. From 1999 to 2008-2009, cytologic smears (Pap and Diff-Quik) were the sole test performed (84 cases). The protocol initiated in 2008-2009 added the four additional diagnostic tests (153 cases). Main Outcomes and Measurements: Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and diagnostic yield were calculated for each test. Parameters were calculated for tests individually, for all five combined, and all possible two-, three-, and four-test combinations. For cytologic smears, diagnostic parameters were calculated both before ("pre-protocol") and after ("post-protocol") the addition of adjunctive tests to our institution's protocol, as well as for the entire cohort. RESULTS Of the 237 vitreous biopsies in this study, 50 samples (21%) were from patients with confirmed CNS lymphoma and/or actively treated CNS, systemic, or intraocular lymphoma. Diagnostic yields (95% CI) were 90% (85-93%) for smears, 82% (72-89%) for IHC, 91% (85-96%) for cytokine analysis, 76% (67-84%) for IgH gene rearrangement, and 50% (40 to 60%) for flow cytometry. For smears, the sensitivity pre-protocol was 73% (39-94%), compared to 87% (69 to 96%) post-protocol. IgH gene rearrangement was the only test exhibiting low sensitivity (40%). The combination of smears, IHC, and cytokine analysis exhibited the highest diagnostic parameters, including a sensitivity of 92%, specificity 98%, and a 100% diagnostic yield. CONCLUSIONS The combination of cytologic smears, immunohistochemistry, and cytokine analysis appears to be a reasonable and sufficient protocol for the diagnosis of suspected vitreoretinal lymphoma. IgH gene rearrangement and flow cytometry may be the most expendable tests from our protocol.