Hui Yiang, Lombardo Kara A, Quddus M Ruhul, Matoso Andres
Department of Pathology and Laboratory Medicine, Rhode Island Hospital.
Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University.
Appl Immunohistochem Mol Morphol. 2018 Jan;26(1):e1-e6. doi: 10.1097/PAI.0000000000000566.
Focal micropapillary features in invasive urothelial carcinoma is sometimes difficult to distinguish from retraction artifact morphologically. Cell polarity reversal has been demonstrated in micropapillary tumors by epithelial membrane antigen (EMA) immunostaining. We have previously described the use of E-cadherin as a cell polarity marker in ovarian micropapillary serous borderline tumors. The aim of this study was to evaluate the utility of immunohistochemistry for EMA and E-cadherin in differentiating micropapillary urothelial carcinoma from retraction artifact. We identified 29 invasive urothelial carcinomas with micropapillary features and 30 invasive urothelial carcinomas without reported micropapillary features but with areas of retraction artifact. Cell polarity reversal was considered present if E-cadherin showed membranous apical cup-like staining or if EMA demonstrated a well-defined basal staining towards the stroma. Twenty-seven of 29 cases (93%) of urothelial carcinoma with micropapillary features demonstrated EMA or E-cadherin staining patterns consistent with cell polarity reversal. Staining consistent with micropapillary architecture was identified with both markers in 20 of these 27 cases (74%). Six cases showed reversal of polarity by E-cadherin alone, whereas 1 case showed polarity reversal by EMA alone. Retraction artifacts showed circumferential staining by E-cadherin and lacked well-defined basal staining by EMA. Three cases originally classified as with retraction artifact showed reversal of cell polarity by both EMA and E-cadherin and were reclassified as micropapillary. Our data show that pathologists can reliably make this distinction in most cases. However, in some cases with ambiguous features, EMA and E-cadherin immunostaining may aid in resolving this diagnostic dilemma.
浸润性尿路上皮癌中的局灶性微乳头特征有时在形态学上难以与收缩伪像区分开来。通过上皮膜抗原（EMA）免疫染色已在微乳头肿瘤中证实了细胞极性反转。我们之前曾描述过在卵巢微乳头浆液性交界性肿瘤中使用E-钙黏蛋白作为细胞极性标志物。本研究的目的是评估EMA和E-钙黏蛋白免疫组化在区分微乳头尿路上皮癌与收缩伪像方面的效用。我们识别出29例具有微乳头特征的浸润性尿路上皮癌以及30例未报告有微乳头特征但有收缩伪像区域的浸润性尿路上皮癌。如果E-钙黏蛋白显示膜性顶端杯状染色，或者EMA显示朝向基质的明确基底染色，则认为存在细胞极性反转。29例具有微乳头特征的尿路上皮癌病例中有27例（93%）显示EMA或E-钙黏蛋白染色模式与细胞极性反转一致。在这27例病例中的20例（74%）中，两种标志物均识别出与微乳头结构一致的染色。6例仅通过E-钙黏蛋白显示极性反转，而1例仅通过EMA显示极性反转。收缩伪像显示E-钙黏蛋白呈周缘染色，且缺乏EMA的明确基底染色。3例最初归类为有收缩伪像的病例通过EMA和E-钙黏蛋白均显示细胞极性反转，并被重新归类为微乳头型。我们的数据表明，病理学家在大多数情况下能够可靠地做出这种区分。然而，在一些特征不明确的病例中，EMA和E-钙黏蛋白免疫染色可能有助于解决这一诊断难题。
