Interobserver Reproducibility in the Diagnosis of Invasive Micropapillary Carcinoma of the Urinary Tract Among Urologic Pathologists

Department of Pathology, Stanford University, Stanford, CA, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 09/2010; 34(9):1367-76. DOI: 10.1097/PAS.0b013e3181ec86b3
Source: PubMed


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.

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Available from: Antonio Lopez-Beltran
    • "The clinical utility of establishing criteria for cytopathologic identification of uPC depends, to an extent, on interobserver reproducibility of those criteria. However, in their study of the histopathologic diagnosis of uPC, Sangoi et al., found that interobserver reproducibility was only moderate (κ = 0.54).[24] It is possible that one or more of the cases classified in the current study as uPC would be interpreted as CUC or, inversely, one or more of the cases classified in the current study as CUC would be interpreted as uPC at another institution. "
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    ABSTRACT: The micropapillary variant of urothelial carcinoma (uPC) is a rare variant of urothelial carcinoma that carries a poor prognosis. Definitive surgery may represent optimal management of low stage tumors. Urine cytology is indispensable in the screening and follow-up of urinary tract cancer. However, cytopathological criteria for diagnosis of uPC and its differentiation from conventional urothelial carcinoma (CUC) are not well-defined. Twenty-five cases of histologically confirmed micropapillary uPC from 21 patients were compared to 25 cases of histologically confirmed high-grade CUC. In uPC cases, cell clusters were identified in 13 of 25 specimens from 10 patients. Six of the 13 specimens containing cell clusters corresponded to surgical pathology specimens in which micropapillary carcinoma accounted for at least 50% of total carcinoma. In contrast, only 1 of the 12 urine specimens devoid of cell clusters corresponded to surgical specimens in which micropapillary carcinoma accounted for at least 50% of total carcinoma. Cytomorphologic features of urinary specimens from patients with histologically confirmed micropapillary carcinoma were generally similar to those from patients with high-grade CUC, making it difficult to distinguish these entities in exfoliative urine specimens. Further investigation of the core cytopathological characteristics of uPC is warranted to refine its diagnostic criteria by exfoliative urine cytology.
    No preview · Article · Feb 2013 · CytoJournal
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    • "Moreover, they state that due to the associated aggressive behaviour, the proportion of micropapillary differentiation should be reported in all cases, even if it represents less than 10% of the specimen, as it has prognostic relevance [22]. Additionally, inter-observer reproducibility of the diagnosis of MPC is low [23], which may lead to treatment delays or the use of inappropriate therapeutic strategies adversely affecting patients’ survival. Therefore, pathologists should be aware of the histologic subtypes on diagnosis. "
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    ABSTRACT: Background Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO) 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. Methods We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC) and 9 micropapillary (MPC) carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. Results Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis). Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters) showed a hazard ratio of 3.2 (p=0.045) for PUC in contrast to patients suffering from MPC. Conclusions Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.
    Full-text · Article · Feb 2013 · BMC Cancer
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    • "The most important differential diagnosis for urinary tract MPC is its distinction from conventional UC with prominent retraction artifacts, which issue has been elegantly addressed in a recent consensus study by Sangoi et al. [6]. In that study, the agreement among uropathologists for the diagnosis of MPC was only moderate and the authors provide a few diagnostically useful morphologic observations. "
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    ABSTRACT: Micropapillary carcinoma (MPC) of urinary tract is an uncommon variant of urothelial carcinoma with significant diagnostic and prognostic implications. Though MPC shows characteristic microscopic features, there exists interobserver variability and also it needs to be differentiated from the metastasis from other organs. The prognosis is generally poor, depending on the proportion of the micropapillary component in some reports. Early cystectomy in cases with only lamina propria invasion may be indicated according to recent studies. This review outlines the general features of this entity and briefly comments on the controversies and the recent development.
    Full-text · Article · Oct 2011 · Advances in Urology
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