Elsevier

Human Pathology

Volume 41, Issue 8, August 2010, Pages 1159-1164
Human Pathology

Original contribution
Invasive micropapillary urothelial carcinoma of the bladder,☆☆

https://doi.org/10.1016/j.humpath.2009.11.018Get rights and content

Summary

In this report, we present the clinicopathologic features of 13 cases of the invasive micropapillary variant of urothelial carcinoma. This is a rare and aggressive variant of bladder cancer recognized by the current World Health Organization classification of urologic tumors. The micropapillary component varied from 50% to 100% of the tumor specimen; in 10 cases, the micropapillary component composed greater than 70% of the tumor, with 5 cases showing pure micropapillary carcinoma. The architectural pattern of the tumor varied from solid expansile nests with slender papillae within tissue retraction spaces to pseudoglandular growth with prominent ring-like structures (2 cases, 15%) and invasive micropapillary carcinoma with squamous differentiation (2 cases, 15%); a streaking solid architectural pattern of micropapillary carcinoma was additionally present in 2 cases (15%). At histology, the individual tumor cells had abundant eosinophilic cytoplasm and nuclei with prominent nucleoli and irregular distribution of chromatin, and frequent mitotic figures. Most neoplastic cells had nuclei of low to intermediate nuclear grade with occasional nuclear pleomorphism. Eight mixed cases had concurrent conventional high-grade urothelial carcinoma with squamous or glandular differentiation in 3 and 1 case(s), respectively. All patients had advanced-stage cancer (>pT2), and 8 (62%) had lymph node metastasis. Immunohistochemical staining demonstrated that both micropapillary and associated conventional urothelial carcinomas were positive for MUC1 and 2, cytokeratin 7, PTEN, p53, and Ki-67. Her2Neu, uroplakin, cytokeratin 20, 34βE12, CA125, and p16 were positive in 4, 10, 8, 7, 3, and 3 cases, respectively. MUC5A, MUC6, and CDX2 were negative in all micropapillary cases. Follow-up information was available in all cases (range, 2-21 months; mean, 10 months). Eleven of patients died of disease from 2 to 14 months, and 2 patients were alive with disease at 14 and 21 months. Univariate statistical analysis showed survival differences between invasive micropapillary and conventional urothelial carcinomas (P < .0001). In summary, invasive micropapillary variant of urothelial carcinoma is an aggressive variant associated with poor prognosis that presents at an advanced clinical stage. The immunophenotype of invasive micropapillary carcinoma supports urothelial origin; the immunoreactivity to Her2Neu and PTEN might be relevant in terms of future targeting therapy. The morphologic diversity of micropapillary carcinoma may represent a diagnostic pitfall in limited samples, where its distinction from conventional urothelial carcinoma is critical for its clinical management.

Introduction

Invasive micropapillary urothelial carcinoma, a rare variant of urothelial carcinoma with histologic appearance similar to micropapillary carcinomas arising in the ovary, lung, breast, or other anatomical locations [1], [2], [3], [4], [5], [6], [7], [8], [9], has been recognized in the current World Health Organization (WHO) classification of urothelial neoplasms and may pose a significant differential diagnostic problem, particularly if it is the predominant or exclusive pattern in a limited biopsy sample [10]. There are limited data available about the pathologic and immunohistochemical characteristics as well as the clinical behavior of this pathologic entity [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]. A reverse cellular polarization, as seen by the MUC1 cellular distribution, seems to be relevant in the pathogenesis of invasive micropapillary carcinomas [15].

Since the initial description by Amin et al [3], more than 100 cases have been reported, mostly as single case report or small sample series [1], [2], [3], [8], [10], [11], [12], [13], [14], [16], [17], [18], [20]. Two recent series of 24 and 12 cases [11], [19], respectively, have addressed the issue of differential diagnosis from secondary invasive micropapillary carcinoma or poorly differentiated conventional urothelial carcinoma with retraction artifact. Samaratunga et al [8], Johansson et al [17], and Kamat et al [13] reported on the clinical significance of micropapillary carcinomas, both superficial and invasive type. These studies concluded that patients have a variable clinical course, with some patients dying rapidly and others experiencing prolonged survival. This probably reflects that the reported series are nonhomogeneous and that the entity is not fully well characterized. [1], [2], [7] Hence, more reports on larger series are needed to elucidate the clinical significance and differential diagnostic implications of this interesting morphologic variant of bladder cancer.

Herein, we present a large sequential series of 13 invasive micropapillary urothelial carcinomas of the bladder supplemented with an extensive immunohistochemical study.

Section snippets

Materials and methods

This study included resection and surgical specimens from 13 patients collected in a series of 2197 (0.6%) bladder tumor specimens studied from 1998 to 2008 at the uropathology practice of one of the authors (A. L. B.). The cases spanned a period of 11 years, with the earliest case diagnosed in 1998 and the last one in 2007. Clinical information was obtained from patients' records, and an average of 16 hematoxylin and eosin slides (range, 7-26 slides) from each case was evaluated. The following

Results

Clinicopathologic features of the 13 patients are summarized in Table 1. In all 13 patients, there was hematuria with dysuria (3 patients) or frequency (4 patients). Their ages ranged from 61 to 83 years (mean, 68 years; median, 63 years). The diagnosis of invasive micropapillary carcinoma of the bladder was made on transurethral resection of bladder (TURB) in 3 cases (53 gr, 55 gr, and 63 gr resection chips, respectively) and TURB followed by cystoprostatectomy or cystectomy with hysterectomy

Discussion

More than 90% of bladder carcinomas are urothelial carcinomas [1], [2]. A small group of tumors is recognized as pathologic variants of invasive bladder cancer due to their unique histologic appearance [1], [2], [7], [10]. These uncommon variant entities are distinct enough to be recognized separately in the current WHO classification system [10]. These variants are significant from the diagnostic, prognostic, and/or therapeutic perspective [1], [2], [3], [4], [5], [6], [7], [8], [9], [11], [12]

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  • Cited by (0)

    No potential conflicts of interest.

    ☆☆

    Supported in part by the grant SAF2007-64942, Ministry of Education and Research, Madrid, Spain.

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