目的：探讨浆膜腔积液样本联合 ICC 对常见类型卵巢癌的诊断效能，比较其与原 发灶组织病理学的一致性，并建立基于浆膜腔积液细胞学的诊断标准。 方法：回顾性纳入 2017 年 6 月 14 日至 2019 年 11 月 30 日临床拟诊“卵巢/盆腔肿 物”的 610 例患者浆膜腔积液样本，其中 519 例有原发灶组织病理学结果。对照原 发灶组织学结果，以“可疑癌”为细胞学恶性阈值，评估浆膜腔积液阳性病例的 良恶性诊断的符合率。进一步筛选出 150 例晚期（Ⅲ~Ⅳ期）卵巢癌患者（HGSOC 138 例、OCCC 8 例、LGSOC 1 例、EEC 3 例）。由于部分亚型病例数量较少，补充 纳入 2019 年 12 月 1 日至 2025 年 4 月 16 日期间的 18 例晚期卵巢癌病例，包括 LGSOC 6 例、OCCC 8 例和 EEC 4 例。最终共计纳入 168 例晚期（Ⅲ~Ⅳ期）卵巢 癌患者，具体亚型分布为 HGSOC 138 例、OCCC 16 例、LGSOC 7 例和 EEC 7 例。 复阅总结以上 4种类型卵巢癌的细胞形态学鉴别要点，并检测上述样本中的 ICC标 志物（PAX8、WT-1、p53、p16、HNF1β、Napsin A、Vimentin 及 Ki67），通过加 权 Kappa 检验评估 ICC 与原发灶免疫组化的一致性，并分析各标志物以及联合使 用时的诊断效能。 结果：浆膜腔积液细胞病理学与原发灶良恶性诊断符合率达 99.49%（389/391）。 HGSOC、LGSOC、OCCC 在细胞学形态上有一定的区分，而 EEC 与 HGSOC 在细 胞形态上则难于区分，并且 ICC 表达也与 HGSOC 很相近。PAX8 在浆膜腔积液样 本 与 原 发 灶 中 一 致 性 极 高 （Kappa=0.846， 一 致 率 97.30%）， 其 次 为 WT-1 （Kappa=0.738）和 HNF1β（Kappa=0.655），呈良好的一致性；p53、p16、Napsin A 及 Vimentin 具有微弱的一致性。PAX8+/WT≥2+/p53 过表达（60%过表达阈值） /HNF1β<2+ 诊断 HGSOC 的灵敏度为 45.31%，特异度为 96.67%，是识别 HGSOC 最特异且兼顾较高灵敏度的表达模式。PAX8+/WT-1-/HNF1β≥2+ or Napsin A+ 是 诊断 OCCC的最佳的免疫细胞化学表达模式，灵敏度为 87.50%，特异度为 100%。 结论：1、基于浆膜腔积液样本的形态学诊断在判断卵巢肿瘤良恶性方面具有极高 的准确性。2、扇贝形的肿瘤细胞簇轮廓、肿瘤细胞大小的高度一致性、不存在核 大于中性粒细胞 4 倍的肿瘤细胞以及低核质比是 LGSOC 与 HGSOC 鉴别的高特异 度的形态学特征。OCCC 在浆膜腔积液样本中表现出“树莓”状排列及胞浆内透明 小球的独特形态学特点。3、浆膜腔积液样本的免疫表型与原发灶组织样本相比基 本一致。为减少混杂因素的影响，建议在浆膜腔积液样本中对浆液性癌和透明细 胞癌的判定阈值进行适度调整，即将 WT-1 和 HNF1β上调至 2+以上，同时将 p53 过表达的阈值适度下调至 60%。

Objective: To evaluate the diagnostic efficacy of serous cavity effusion samples combined with ICC for common types ovarian cancer, to assess its consistency with primary lesion histopathology, and to establish a diagnostic standard based on cytopathology of serous cavity effusion. Methods: A retrospective analysis was conducted on 610 patients with serous cavity effusion samples clinically diagnosed as "ovarian/pelvic masses" from June 14, 2017 to November 30, 2019. Among these, 519 cases had histopathological results from the primary lesions. Compared to the histological findings of the primary lesion, using "suspected cancer" as the cytological malignancy threshold, the concordance rate of benign and malignant diagnoses in positive cases of serous cavity effusion was assessed. Additionally, 150 patients with advanced (stage Ⅲ-Ⅳ) ovarian cancer (138 HGSOC, 8 OCCC, 1 LGSOC, and 3 EEC) were selected. Due to the relatively limited number of cases in certain subtypes, an additional 18 cases of advanced ovarian cancer were included from December 1, 2019 to April 16, 2025, including 6 cases of LGSOC, 8 cases of OCCC and 4 cases of EEC. Ultimately, a total of 168 patients with advanced-stage (Stage III-IV) ovarian cancer were enrolled. The subtype distribution was as follows: 138 cases of HGSOC, 16 cases of OCCC, 7 cases of LGSOC, and 7 cases of EEC. Subsequently, the cytopathological sections of serous cavity effusion samples from the enrolled cases were systematically reviewed to summarize the key points of cytopathological differentiation for the aforementioned four types of ovarian cancer. Furthermore ICC markers, including PAX8, WT-1, p53, p16, HNF1β, Napsin A, Vimentin, and Ki67, were further detected in these samples. The concordance between ICC findings and the primary lesion was evaluated using the weighted Kappa test, and the diagnostic efficacy of each marker, as well as their combined use, was systematically analyzed. Results: The concordance rate between the cytopathology of serous cavity effusion and the diagnosis of benign and malignant primary lesions was 99.49% (389/391). HGSOC, LGSOC, and OCCC exhibit distinct cytological morphologies. However, EEC and HGSOC are challenging to differentiate based on cell morphology alone, as their immunohistochemical expressions of ICC are also highly similar. PAX8 demonstrated an extremely high level of consistency between serous cavity effusion samples and the primary lesion (Kappa = 0.846, consistency rate 97.30%), followed by WT-1 (Kappa = 0.738) and HNF1β (Kappa = 0.655), which exhibited good consistency. In contrast, p53, p16, Napsin A, and Vimentin showed weak consistency. The sensitivity of PAX8+, WT-1北京协和医学院中国医学科学院硕士学位论文 Abstract 7 ≥2+, p53 overexpression (with a threshold of 60% overexpression), and HNF1β<2+ in diagnosing HGSOC was 45.31%, with a specificity of 96.67%. This represents the most specific expression pattern for identifying HGSOC and demonstrates relatively high sensitivity. Additionally, PAX8+, WT-1-,HNF1β ≥2+ or Napsin A+ constitute the immunocytochemical expression pattern for diagnosing OCCC, achieving a sensitivity of 87.50% and a specificity of 100%. Conclusion: 1. Morphological diagnosis utilizing serous cavity effusion samples demonstrates exceptionally high accuracy in distinguishing between the benign and malignant nature of ovarian tumors. 2. Key morphological features with high specificity for differentiating LGSOC from HGSOC include the scallop-shaped contour of tumor cell clusters, the high uniformity of tumor cell size, the absence of tumor cells with nuclei exceeding four times the size of neutrophil nuclei, and a relatively low nucleoplasmic ratio. Additionally, OCCC exhibits distinct morphological characteristics in serous cavity effusion samples, such as a "raspberry"-like arrangement and transparent small spheres within the cytoplasm. 3. The immunophenotype of serous cavity effusion samples is largely consistent with that of primary lesion tissue samples. To minimize the impact of confounding factors, it is advisable to moderately adjust the determination thresholds for serous carcinoma and clear cell carcinoma in serous cavity effusion samples. Specifically, this involves increasing WT-1 and HNF1β expression levels to above 2+ and simultaneously lowering the threshold for p53 overexpression to 60%.