Department of Pathology, Stanford University, Stanford, CA, USA.
Am J Surg Pathol. 2010 Sep;34(9):1367-76. doi: 10.1097/PAS.0b013e3181ec86b3.
Invasive micropapillary carcinoma (IMPC) of the urinary tract is a well-described variant of the urothelial carcinoma with aggressive clinical behavior. Recent studies have proposed that patients with IMPC on transurethral resection should be treated with radical cystectomy regardless of the pathologic stage. Despite the potentially important therapeutic implications of this diagnosis, interobserver variation in the diagnosis of IMPC has not been studied. Sixty digital images, each from hematoxylin and eosin-stained slides, representing 30 invasive urothelial carcinomas (2 images per case), were distributed to 14 genitourinary subspecialists and each pathologist was requested to classify cases as IMPC or not. These cases included "classic" IMPC (n=10) and urothelial carcinoma with retraction and variably sized nests that might potentially be regarded as IMPC (n=20). The following 13 morphologic features were recorded as positive/negative for all cases independent of the reviewers' diagnoses: columnar cells, elongate nests or processes, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial ring forms, intracytoplasmic vacuolization, multiple nests within the same lacunar space, back-to-back lacunar spaces, epithelial nest anastomosis/confluence, marked nuclear pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, and tumor nest size. In addition, a mean tumor nest size was calculated for each image based on the number of nuclei spanning the width of the nests. Interobserver reproducibility was assessed and the morphologic features were correlated with the classic IMPC and nonclassic/potential IMPC groups. In addition, the relationships between morphologic features, pathologists' interpretations, and case type (classic IMPC vs. nonclassic/potential IMPC) were evaluated using unsupervised hierarchical clustering analysis. Interobserver reproducibility for a diagnosis of IMPC in the 30 study cases was moderate (kappa: 0.54). Although classification as IMPC among the 10 "classic" IMPC cases was relatively uniform (93% agreement), the classification in the subset of 20 invasive urothelial carcinomas with extensive retraction and varying sized tumor nests was more variable. Multiple nests within the same lacunar space had the highest association with a diagnosis of classic IMPC. These findings suggest that more study of IMPC is needed to identify the individual pathologic features that might potentially correlate with an aggressive outcome and response to intravesical therapy.
尿路浸润性微乳头状癌（IMPC）是一种具有侵袭性临床行为的尿路上皮癌的典型变体。最近的研究表明，接受经尿道切除术的 IMPC 患者应无论病理分期如何，都应接受根治性膀胱切除术。尽管这一诊断具有潜在的重要治疗意义，但 IMPC 的诊断在观察者之间存在差异尚未得到研究。将 60 个数字图像（每个图像均来自苏木精和伊红染色的幻灯片，每个病例代表 2 个图像）分发给 14 名泌尿生殖专科医生，并要求每位病理学家将病例分类为 IMPC 或非 IMPC。这些病例包括“经典”IMPC（n=10）和伴有退缩和大小不等巢的尿路上皮癌，这些巢可能被视为 IMPC（n=20）。记录了以下 13 种形态特征，无论审阅者的诊断如何，对所有病例均为阳性/阴性：柱状细胞、拉长的巢或过程、广泛的基质退缩、具有内部上皮簇状的管腔形成、上皮环形成、细胞内空泡化、同一腔隙空间内的多个巢、背靠背腔隙空间、上皮巢吻合/融合、明显的核多形性、周边定向核、随机分布核和肿瘤巢大小。此外，基于跨越巢宽度的核数计算了每个图像的平均肿瘤巢大小。评估了观察者间的可重复性，并将形态特征与经典 IMPC 和非经典/潜在 IMPC 组进行了相关性分析。此外，使用无监督层次聚类分析评估了形态特征、病理学家的解释与病例类型（经典 IMPC 与非经典/潜在 IMPC）之间的关系。在 30 例研究病例中，IMPC 的诊断观察者间的可重复性为中等（kappa：0.54）。尽管 10 例“经典”IMPC 病例的分类相对一致（93%的一致性），但在广泛退缩和大小不等的肿瘤巢的 20 例浸润性尿路上皮癌亚组中的分类则更为多变。同一腔隙空间内的多个巢与经典 IMPC 的诊断具有最高的相关性。这些发现表明，需要进一步研究 IMPC，以确定可能与侵袭性结局和对膀胱内治疗的反应相关的个别病理特征。
