Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications.

Objectives: Our aim was to review our pathological archive to find out the actual incidence of micropapillary pattern (MPP) in our urothelial carcinoma patient population and determ

Micropapillary Pattern in Urothelial Carcinoma: A Clinicopathological Analysis

Invasive micropapillary carcinoma of the urinary bladder was described as a specific variant of primary bladder cancer by Amin et al in 1994 and was included in the most recent WHO classification of genitourinary neoplasms. This rare subtype of bladder neoplasia comprises 0.6% to 6% of urothelial carcinomas and shows a strong male predominance. The micropapillary pattern is morphologically similar to ovarian serous carcinoma, a histologic appearance that has been described in carcinomas arising in a variety of different parenchymal organs. In the urinary bladder, the micropapillary component may be found in the noninvasive, the invasive, and the metastatic foci, but it is frequently admixed with more typical patterns of invasive urothelial carcinoma or urothelial carcinoma in situ. The noninvasive component typically consists of slender, fine papillary processes rarely with a small fibrovascular core (ie, similar to the micropapillary pattern of ovarian serous neoplasia). The invasive components, and the metastases, are characterized by small nests of cells and filiform papillae with a surrounding retraction space closely mimicking angiolymphatic invasion. Most cases do not show an associated stromal reaction despite extensive invasion. Since the initial description of micropapillary carcinoma of the urinary bladder, multiple additional studies have supported it as a distinct entity, confirmed the frequent invasion of the muscularis propria at presentation, and documented its aggressive clinical course. A recent retrospective study from the M.D. Anderson Cancer Center by Kamat et al studied the efficacy of bladder sparing therapy for superficial (nonmuscle invasive; rcT1) micropapillary carcinoma of the urinary bladder in 44 patients [cT1: 35 (80%); cTa: 5 (11%); and cTis: 4 (9%)]. Micropapillary carcinoma was defined as a bladder tumor containing any component with a micropapillary pattern, regardless of extent or invasion. Twenty-seven (62%) patients had intravesical Bacillus Calmette-Guerin (BCG) therapy, 12 (27%) underwent immediate cystectomy, 4 (9%) were placed on a surveillance only protocol, and 1 (2%) had chemoradiation. Of the 27 patients who had intravesical BCG therapy, 18 (67%) progressed in stage (ZcT2), including 7/18 (39%) with nodal metastases. Overall, 30 patients (68%) were treated by cystectomy at some point in their course (18 after progression and 12 as initial treatment). Of the 18 patients undergoing cystectomy after stage progression, the median cancer-specific survival was 61.7 months and no patients were alive at 10 years. Of the 12 patients treated by immediate cystectomy, the median survival was not reached and the 10-year survival was 72%. Compared to patients treated with primary cystectomy, the patients in this study who were treated conservatively (ie, with intravesical BCG) and underwent cystectomy after stage progression had an increased incidence of nonorgan confined disease (pT3 and higher) and nodal metastases. Studies of patients undergoing conservative management with intravesical therapy for ‘‘superficial’’ conventional urothelial carcinoma (ie, nonmicropapillary) have not reported a similarly poor outcome. Kamat et al conclude that intravesical BCG therapy is ineffective in patients with micropapillary carcinoma of the urinary bladder, and, furthermore, advocate immediate cystectomy as a primary treatment modality for this aggressive variant of bladder cancer. If immediate cystectomy becomes standard practice for micropapillary carcinoma of the urinary bladder, then the pathologic diagnosis of this subtype will obviously become managerially critical. This shift in patient management would raise several important issues regarding diagnostic criteria, staging protocols, and subsequent treatment. First of all, multiple authors have suggested that micropapillary carcinoma should be aggressively restaged if muscularis propria invasion is not identified, even if uninvolved muscularis propria is present in the biopsy. One could argue that many ‘‘cT1’’ micropapillary carcinomas simply represent understaged tumors secondary to sampling bias, and not true T1 disease. In fact, the current study reported that 42% of the patients who underwent cystectomy for cT1 disease were pathologically up staged based on the resection specimen. The inclusion of an initial standardized restaging protocol in future prospective studies of cT1 micropapillary carcinoma would help to further address this issue. Second, should the volume/percentage of the micropapillary component be considered in the diagnosis of micropapillary carcinoma and subsequently in the decision for primary cystectomy? The current study included patients with any micropapillary component, regardless of the volume or percentage of the tumor. The micropapillary pattern can be quite focal, but studies of micropapillary carcinoma in other parenchymal organs (eg, breast) suggest that the volume of the micropapillary component is not critical. An analysis of the volume/percentage of the micropapillary component in future studies would be necessary to assess the clinical significance of very focal micropapillary patterns in an otherwise typical urothelial carcinoma. Third, the current study also included cases of noninvasive micropapillary carcinoma and micropapillary carcinoma in situ. Features of in situ lesions associated with micropapillary carcinoma have been described, but the pathologic definition and the associated clinical outcome of noninvasive micropapillary carcinoma of the urinary bladder needs to be further addressed given the small number of cases studied thus far. Finally,

The Clinical Management of ???Superficial??? (???pT1/cT1) Micropapillary Carcinoma of the Urinary Bladder: Are Times Changing?

Summary Micropapillary carcinoma is an uncommon variant of urothelial carcinoma with apparent high metastatic potential. The reported cases in the literature were associated with high grade and stage of disease at presentation and a poor prognosis. Micropapillary carcinoma is considered a tumor with an aggressive behavior, even though the morphology may be deceptive. The presence of a micropapillary carcinoma component in bladder biopsies should alert the urologists to the potential of higher stage disease and deep biopsies should be obtained. Two cases of micropapillary carcinoma of the urinary bladder were presented. A 71-yearold woman and a 68-year-old man presented with urinary symptoms. Cystoscopy revealed a papillary tumor on the bladder wall in both cases. Pathologic examination of transurethral resection specimen showed an invasive micropapillary carcinoma; small solid nests lying in small clear spaces that were not stained with antibody CD34. Thus, the lacunar histological pattern did not appear to represent invasion of vascular spaces. Only one case showed an association with urothelial carcinoma. No case showed muscle invasion. No recurrence or metastasis were observed after the initial diagnosis in the two cases.

Micropapillary transitional cell carcinoma of the urinary bladder: report of two cases Carcinoma micropapillare a cellule transizionali della vescica urinaria: report di due casi

Micropapillary carcinoma is an uncommon variant of urothelial carcinoma with apparent high metastatic potential. The reported cases in the literature were associated with high grade and stage of disease at presentation and a poor prognosis. Micropapillary carcinoma is considered a tumor with an aggressive behavior, even though the morphology may be deceptive. The presence of a micropapillary carcinoma component in bladder biopsies should alert the urologists to the potential of higher stage disease and deep biopsies should be obtained. Two cases of micropapillary carcinoma of the urinary bladder were presented. A 71-year-old woman and a 68-year-old man presented with urinary symptoms. Cystoscopy revealed a papillary tumor on the bladder wall in both cases. Pathologic examination of transurethral resection specimen showed an invasive micropapillary carcinoma; small solid nests lying in small clear spaces that were not stained with antibody CD34. Thus, the lacunar histological pattern did not appear to represent invasion of vascular spaces. Only one case showed an association with urothelial carcinoma. No case showed muscle invasion. No recurrence or metastasis were observed after the initial diagnosis in the two cases.

Micropapillary transitional cell carcinoma of the urinary bladder: report of two cases.

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Micropapillary transitional cell carcinoma of the urinary bladder: report of two cases Carcinoma micropapillare a cellule transizionali della vescica urinaria: report di due casi

Micropapillary transitional cell carcinoma of the urinary bladder: report of two cases.