腹腔积液诊断卵巢浆液性癌的细胞病理学特征分析

Cytopathological characterization of ascites for the diagnosis of serous ovarian carcinoma

目的分析总结卵巢浆液性癌(SOC)腹腔积液中肿瘤细胞的病理形态学及免疫细胞化学特点。方法采集2015年1月至2021年7月南京医科大学附属无锡人民医院收治的61例肿瘤患者的浆膜腔积液标本,包括32例SOC、10例胃肠道腺癌、5例胰腺导管腺癌、6例肺腺癌、4例良性间皮增生和1例恶性间皮瘤患者的腹腔积液,2例恶性间皮瘤患者的胸腔积液,1例恶性间皮瘤患者的心包积液,离心后制成常规涂片,将剩余积液离心后制成细胞蜡块并行常规HE染色和免疫细胞化学染色,分析其细胞形态学和免疫细胞化学特点。抽取患者空腹肘静脉血5 ml,检测血清肿瘤标志物糖类抗原125(CA125)、癌胚抗原(CEA)和糖类抗原19-9(CA19-9)的水平。结果32例SOC患者中,5例为低级别浆液性癌(LGSOC),27例为高级别浆液性癌(HGSOC)。29例(90.6%)SOC患者血清CA125增高,但与纳入研究的非卵巢原发病变患者间差异均无统计学意义(均P>0.05);9例胃肠道腺癌和5例肺腺癌患者血清CEA阳性,阳性率高于SOC患者(均P<0.001);5例胃肠道腺癌和5例胰腺导管腺癌患者血清CA19-9阳性,阳性率高于SOC患者(均P<0.05)。4例良性间皮增生患者的血清CA125、CEA和CA19-9均在正常范围内。LGSOC肿瘤细胞异型性小,聚集成小簇状或微乳头状,部分患者可见砂砾体;背景细胞较少,以淋巴细胞为主;制成细胞蜡块后,乳头结构更为明显。HGSOC肿瘤细胞异型性大,细胞核增大明显,且大小不等,可相差3倍以上,有时可见到核仁及核分裂象;肿瘤细胞多聚集成巢团状、乳头状及梅花状;背景细胞较多,以组织细胞为主。免疫细胞化学染色显示,AE1/AE3、细胞角蛋白7(CK7)、配对盒基因8(PAX-8)、CA125、肾母细胞瘤基因(WT1)在32例SOC中均为弥漫阳性表达。抑癌基因p53在5例LGSOC中均呈局灶阳性,在23例HGSOC中呈弥漫阳性表达,在另外4例HGSOC中呈阴性表达。胃肠道腺癌和肺腺癌多有手术史,胰腺导管腺癌的肿瘤细胞往往形成较小的细胞巢。间皮源性病变多有特征性"开窗"现象,免疫细胞化学可协助鉴别诊断。结论结合患者的临床表现、腹腔积液涂片及细胞块中的细胞形态学特点,可为SOC的诊断提供重要的线索,辅以免疫细胞化学检测可进一步提高诊断的准确性。

Objective To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma(SOC).Methods Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People′s Hospital of Nanjing Medical University from January 2015 to July 2021,including ascites from 32 SOC,10 gastrointestinal adenocarcinomas,5 pancreatic ductal adenocarcinomas,6 lung adenocarcinomas,4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients,pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma.Serous cavity effusion samples of all patients were collected,conventional smears were made through centrifugation,and cell paraffin blocks were made through centrifugation of remaining effusion samples.Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics.The levels of serum tumor markers carbohydrate antigen 125(CA125),carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)were detected.Results Of the 32 SOC patients,5 had low-grade serous ovarian carcinoma(LGSOC)and 27 had high-grade serous ovarian carcinoma(HGSOC).29(90.6%)SOC patients had elevated serum CA125,but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study(P>0.05);The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma,and the positive rate was higher than that in SOC patients(P<0.001);The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma,and the positive rate was higher than that in SOC patients(P<0.05).The serum CA125,CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia.LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern,and psammoma bodies could be observed in some LGSOC cases.The background cells were fewer and lymphocytes were predominant;the papillary structure was more obvious after making cell wax blocks.HGSOC tumor cells were highly heterogeneous,with significantly enlarged nuclei and varying sizes,which could be more than 3-fold different,and nucleoli and nuclear schizophrenia could be observed in some cases;tumor cells were mostly clustered into nested clusters,papillae and prune shapes;there were more background cells,mainly histiocytes.Immunocytochemical staining showed that AE1/AE3,CK7,PAX-8,CA125,and WT1 were diffusely positively expressed in 32 SOC cases.P53 was focally positive in all 5 LGSOCs,diffusely positive in 23 HGSOCs,and negative in the other 4 HGSOCs.Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery,and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests.Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic"open window"phenomenon.Conclusion Combining the clinical manifestations of the patient,the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC,and the immunocytochemical tests can further improve the accuracy of the diagnosis.