Objective: To explore the feasibility and application value of intraoperative direct immunohistochemical (IHC) staining in improving the diagnosis accuracy in difficult cases of bronchiolar adenoma (BA). Methods: Nineteen cases with single or multiple pulmonary ground-glass nodules or solid nodules indicated by imaging in Cancer Hospital of Chinese Academy of Medical Sciences from January to July 2021 and with difficulty in differential diagnosis at frozen HE sections were selected. In the experimental group, direct IHC staining of cytokeratin 5/6 (CK5/6) and p63 was performed on frozen sections to assist the differentiation of BA from in situ/micro-invasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the control group, two pathologists performed routine frozen HE section diagnosis on these 19 cases. The diagnostic results of paraffin sections were used as the gold standard. The sensitivity and specificity of BA diagnosis, consistency with paraffin diagnosis and time used for frozen diagnosis were compared between the experimental group and the control group. Results: The basal cells of BA were highlighted by CK5/6 and p63 staining. There were no basal cells in the in situ/microinvasive adenocarcinoma/adenocarcinoma/invasive mucinous adenocarcinoma. In the experimental group, the sensitivity and specificity with aid of direct IHC staining for BA were 100% and 86.7%, respectively, and the Kappa value of frozen and paraffin diagnosis was 0.732, and these were significantly higher than those in the control group (P<0.05). The average time consumption in the experimental group (32.4 min) was only 7 min longer than that in the control group (25.4 min). Conclusions: Direct IHC staining can improve the accuracy of BA diagnosis intraoperatively and reduce the risk of misdiagnosis, but require significantly longer time. Thus frozen direct IHC staining should be restricted to cases with difficulty in differentiating benign from malignant diseases, especially when the surgical modalities differ based on the frozen diagnosis.
目的： 探讨直接免疫组织化学染色技术提高术中肺肿瘤疑难病例细支气管腺瘤（bronchiolar adenoma，BA）诊断准确性的可行性及应用价值。 方法： 选取2021年1月至7月中国医学科学院肿瘤医院CT提示单发或多发肺磨玻璃结节或实性结节，术中单纯依靠冷冻HE切片肺肿瘤鉴别诊断困难病例共19例，实验组采用直接免疫组织化学染色细胞角蛋白5/6（CK5/6）和p63在冷冻切片中基底细胞的表达情况，辅助术中肺肿瘤疑难病例BA与原位/微小浸润腺癌/腺癌/浸润性黏液腺癌鉴别；对照组为两名诊断医师对这19例病例进行常规冷冻HE切片诊断。两组均以石蜡切片诊断结果为金标准，评价实验组与对照组BA诊断的灵敏度、特异度、与石蜡切片诊断的一致性及冷冻切片诊断耗时。 结果： CK5/6、p63染色显示BA存在基底细胞；在原位/微小浸润腺癌/腺癌/浸润性黏液腺癌中不存在基底细胞。实验组中直接免疫组织化学染色对术中疑难病例BA的灵敏度为100%、特异度为86.7%，冷冻与石蜡切片诊断的一致性Kappa值为0.732，均显著高于对照组（P<0.05）。实验组术中冷冻切片诊断平均耗时（32.4 min）比对照组（25.4 min）延长7 min。 结论： 采用直接免疫组织化学染色方法可以提高术中BA诊断的准确率，降低错误诊断风险，两组在术中诊断用时上差异有统计学意义，需要控制好术中冷冻免疫组织化学的临床适应证，在出现疑难的良恶性鉴别诊断、手术方式存在较大差异时具有较高的应用价值。.