摘要目的 探讨乳腺浸润性上皮病的组织病理学、免疫组织化学染色特征,讨论其诊断与鉴别诊断.方法 收集2015年1月至2016年12月复旦大学附属肿瘤医院乳腺手术和会诊病例中9例乳腺浸润性上皮病,采用BenchMark自动免疫组织化学仪检测广谱细胞角蛋白、细胞角蛋白(CK)7、CK19、CK5/6、CK14、p63、SMMHC、Calponin、雌激素受体(ER)、孕激素受体(PR)、HER2、Ki-67、S-100蛋白等.结果 9例浸润性上皮病患者均为女性,年龄34~51岁,其中6例均因偶然发现肿块就诊,2例伴局部疼痛,2例有乳头溢液.浸润性上皮病的病理形态特征包括:(1)导管上皮增生形成形状不规则的实性细胞巢及乳头状、腺管状或条索状结构,细胞核大小、形状不一,缺乏异型性;(2)间质硬化,部分病例伴有间质细胞增生;(3)增生的上皮细胞巢可伸入周围腺管或小叶之间,形成假浸润形态.免疫组织化学染色特征:增生的上皮细胞ER、PR呈斑驳不一的阳性,高相对分子质量CK5/6和CK14阳性,同一病例中肌上皮标志物p63、SMMHC和Calponin在上皮细胞巢周围出现完整、不连续或完全缺失的染色特征,尤其病灶周边部更易出现肌上皮染色的缺失.浸润性上皮病最重要的鉴别诊断包括浸润性导管癌、导管原位癌、低级别腺鳞癌等.结论 浸润性上皮病是一种重要的假浸润性病变,缺乏真正的细胞异型性、激素受体表达斑驳不一、表达高相对分子质量CK,肌上皮标志物从完整到部分甚至完全缺失等特征是其与浸润性癌及导管原位癌鉴别的关键.

abstractsObjective To evaluate the morphological and immunohistochemical features of infiltrating epitheliosis and its differential diagnosis. Methods Nine consultation and routine cases of infiltrating epitheliosis diagnosed from January 2015 to December 2016 in Fudan University Shanghai Cancer Center were collected. All tissues were formalin-fixed paraffin-embedded and routinely HE stained. The HE slides were reviewed. Immunohistochemical staining of CKpan,CK7,CK19,CK5/6,CK14,p63,SMMHC, Calponin,ER,PR,HER2,Ki-67 and S-100 protein was performed using Ventana BenchMark automated immunostainer. Results The morphological features of infiltrating epitheliosis included:(1)Florid proliferation of epithelial cells forming solid nests or papillary, glandular and cord-like pattern. The proliferative cells possessed nuclei of varying size and shape without atypia.(2)The stroma was altered, showing varying degrees of fibrosis or sclerosis.(3)The proliferative epithelial nests might flow into the spaces within small ducts and lobules at the periphery of the lesion, resulting in pseudo-infiltration. Immunohistochemically,infiltrating epitheliosis was non-uniformly positive for ER/PR,and was positive for high molecular weight CK5/6 and CK14. Myoepithelial markers p63, SMMHC and Calponin demonstrated intact,partial or entire loss of myoepithelial cells around the epithelial nests. The loss of myoepithelial markers staining was more frequent at the periphery of the lesion. The most important differential diagnoses included invasive ductal carcinoma, ductal carcinoma in situ(DCIS), and low grade adenosquamous carcinoma,etc. Conclusions Infiltrating epitheliosis is an important pseudo-infiltrating lesion. The lack of atypia,non-uniform ER/PR expression, positivity for high molecular weight cytokeratins,and the intact to partial to entire loss of myoepithelial markers around the proliferating cell nests are the key points to differentiate it from invasive carcinomas and DCIS.