Abstract
Purpose :
The cytologic smear has been the “gold standard” in diagnosing vitreoretinal lymphoma (VRL). Adjunctive tests include immunohistochemistry (IHC), cytokine analysis (IL-10:IL-6), IgH gene rearrangement by PCR, and flow cytometry. In 2008 our institution initiated a protocol for VRL diagnosis incorporating these tests in addition to smears. We retrospectively analyzed the diagnostic utility of this protocol compared to the smears-only approach, investigating each added assay to derive an optimized diagnostic protocol for VRL.
Methods :
We reviewed 237 vitreous biopsies performed for suspected VRL from 1999-2017. From 1999 to 2008, cytologic smears (Pap and Diff-Quik) were the sole diagnostic test performed (82 cases). The protocol initiated in 2008 added IHC, IL ratio, IgH PCR, and flow cytometry (155 cases). Patients with a biopsy-proven history of either CNS or systemic lymphoma were defined as “positive” for the disease (49/237 cases = 21%). The diagnostic yield, sensitivity (Sn), specificity (Sp), positive and negative predictive values (+PV and -PV), and diagnostic accuracy (Ac) of the 5 assays were calculated, for each test individually and in combination.
Results :
Yields were 89% for smears, 84% for IHC, 93% for IL ratio, 78% for IgH PCR, and 51% for flow cytometry. For smears, the Sn pre-protocol was 67% compared to 90% post-protocol, while the Sp, +PV, -PV, and Ac were similar (86-99%). Sn, Sp, +PV, -PV, and Ac were 92%, 98%, 96%, 96%, and 96% for IHC; 69%, 96%, 73%, 95%, and 92% for IL ratio; 67%, 100%, 100%, 98%, and 98% for flow; and 42%, 93%, 50%, 90%, and 85% for IgH PCR. For smears and IHC combined, diagnostic yield was 96% while Sn, Sp, +PV, -PV, and Ac were 93%, 94%, 90%, 96%, and 94%. For IHC and IL ratio combined, the yield was 100%, while Sn, Sp, +PV, -PV, and Ac were 92%, 95%, 85%, 97%, and 94%.
Conclusions :
The increase in Sn of the cytologic smears post-protocol (from 67 to 90%) may point to influence of IHC, as these were analyzed simultaneously. IHC also showed high diagnostic parameters, achieving 100% diagnostic yield with the addition of IL ratio. Flow and IgH PCR, while highly specific, suffered from lower diagnostic yields and sensitivities. The combination of cytologic smears, IHC, and cytokine analysis may be a reasonable and sufficient protocol for the diagnosis of suspected VRL. Flow cytometry may add utility in some cases, and IgH PCR appears to be the most dispensable test from our protocol.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.