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 with 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 value.

METHODS

This single university-affiliated tertiary care center study included data from 237 vitreous biopsies performedbetween 1999 and 2017 in patients with suspected VRL. From 1999 to 2008-2009, cytologic smears were the sole test performed (84 cases). The protocol initiated in 2008-2009 added the 4 additional diagnostic tests (153 cases). The sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and diagnostic yield were calculated. Parameters were calculated for tests individually, for all 5 combined, and all possible 2-, 3-, and 4-test combinations. For cytologic smears, diagnostic parameters were calculated both before and after the addition of adjunctive tests to our protocol and for the entire cohort.

RESULTS

Of the 237 vitreous biopsies, 50 samples (21%) were from patients with confirmed central nervous system lymphoma and/or actively treated central nervous system, 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%–60%) for flow cytometry. For smears, the sensitivity pre-protocol was 73% (39%–94%), compared with 87% (69%–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, with sensitivity 92%, specificity 98%, and diagnostic yield 100%.

CONCLUSIONS

The combination of cytologic smears, IHC, and cytokine analysis seems to be a reasonable and sufficient protocol for the diagnosis of suspected VRL. IgH gene rearrangement and flow cytometry may be the most expendable tests from our protocol.

中文翻译：

---

玻璃体视网膜淋巴瘤：优化诊断率和准确性

目的

为了确定在检测玻璃体视网膜淋巴瘤 (VRL) 时，与单独的细胞学涂片相比，增加辅助检测，包括免疫组织化学 (IHC)、细胞因子分析、流式细胞术和 IgH 基因重排检测，是否能实现更好的诊断参数。确定这些测试中的哪一个或测试组合提供了最大的诊断效用。

设计

回顾性审查以评估诊断价值。

方法

这项单一的大学附属三级护理中心研究包括 1999 年至 2017 年间对疑似 VRL 患者进行的 237 次玻璃体活检的数据。从 1999 年到 2008-2009 年，细胞学涂片是唯一进行的检查（84 例）。2008-2009 年启动的协议增加了 4 项额外的诊断测试（153 例）。计算敏感性、特异性、阳性预测值、阴性预测值、诊断准确性和诊断率。为单独的测试、所有 5 个组合以及所有可能的 2、3 和 4 测试组合计算参数。对于细胞学涂片，在我们的方案和整个队列中添加辅助测试之前和之后都计算了诊断参数。

结果

在 237 份玻璃体活检中，50 份样本 (21%) 来自确诊为中枢神经系统淋巴瘤和/或积极治疗中枢神经系统、全身或眼内淋巴瘤的患者。涂片诊断率 (95% CI) 为 90% (85%–93%)，IHC 为 82% (72%–89%)，细胞因子分析为 91% (85%–96%)，76% (67%) –84%) 用于 IgH 基因重排，50% (40%–60%) 用于流式细胞术。对于涂片，方案前的敏感性为 73% (39%–94%)，而方案后的敏感性为 87% (69%–96%)。IgH 基因重排是唯一表现出低敏感性 (40%) 的测试。涂片、IHC 和细胞因子分析的组合表现出最高的诊断参数，敏感性为 92%，特异性为 98%，诊断率 100%。

结论

细胞学涂片、IHC 和细胞因子分析的组合似乎是诊断疑似 VRL 的合理且充分的方案。IgH 基因重排和流式细胞术可能是我们协议中最消耗性的测试。