BACKGROUND Ovarian small cell carcinoma, hypercalcaemic type (SCCOHT) is a rare and lethal disease affecting young women. As histological diagnosis is challenging and urgent, there is a clear need for a robust diagnostic test. While mutations in the chromatin-remodelling gene, SMARCA4, appear to be typical, it may not be feasible routinely to be clinically relevant. METHODS Previous studies have described the value of SMARCA4 IHC to differentiate SCCOHT from ovarian neoplasms (ON), with similar histologic appearances. We aimed to evaluate its clinical utility among a cohort of 44 SCCOHT and 94 rare ON frequently misdiagnosed as SCCOHT. RESULTS Forty-three percent (16/36) of SCCOHT had been classified locally as non-SCCOHT confirming the diagnosis challenge. Sensitivity and specificity of SMARCA4 IHC were excellent at 88% and 94%, respectively. In a community setting with a much lower prevalence of the disease, estimated PPV is 40% while NPV remained high at 99%. Finally, among the 16 SCCOHT misclassified locally, SMARCA4 IHC testing would have resulted in corrected diagnosis in 88% of cases. CONCLUSIONS SMARCA4 IHC is a highly sensitive, and specific test for the diagnosis of SCCOHT and is of huge clinical utility in providing a timely and accurate diagnosis of this challenging disease.

中文翻译：

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通过免疫组织化学检测 SMARCA4 在罕见卵巢肿瘤中的临床应用。

背景技术卵巢小细胞癌，高钙血症型（SCCOHT）是一种影响年轻女性的罕见且致命的疾病。由于组织学诊断具有挑战性和紧迫性，因此显然需要可靠的诊断测试。虽然染色质重塑基因 SMARCA4 中的突变似乎是典型的，但临床相关性可能不可行。方法 先前的研究描述了 SMARCA4 IHC 区分 SCCOHT 与具有相似组织学表现的卵巢肿瘤 (ON) 的价值。我们旨在评估其在一组 44 名 SCCOHT 和 94 名经常被误诊为 SCCOHT 的罕见 ON 中的临床效用。结果 43% (16/36) 的 SCCOHT 在当地被归类为非 SCCOHT，证实了诊断挑战。SMARCA4 IHC 的灵敏度和特异性分别为 88% 和 94%。在疾病流行率低得多的社区环境中，估计 PPV 为 40%，而 NPV 仍然高达 99%。最后，在 16 个本地错误分类的 SCCOHT 中，SMARCA4 IHC 测试会导致 88% 的病例得到正确诊断。结论 SMARCA4 IHC 是一种用于诊断 SCCOHT 的高度敏感和特异的检测方法，在为这种具有挑战性的疾病提供及时准确的诊断方面具有巨大的临床效用。