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  • Autori: Guarneri, A.; Scalici Gesolfo, C.; Di Maida, F.; Caruana, G.; Billone, S.; Moschini, M.; Colombo, R.; Simonato, A.; Serretta, V.
  • Anno di pubblicazione: 2016
  • Tipologia: Proceedings (TIPOLOGIA NON ATTIVA)
  • OA Link:


Introduction/Aim: Rare histotypes represent almost 10% of bladder tumors, although more often represented as small foci within large and invasive transitional cell tumors of the bladder (TCCB). It might be clinically relevant that rare histological variants remain unrecognized at transurethral resection (TURBT), since they could indicate more aggressive tumors, less responsive to systemic chemotherapy and unfit for “organsparing” management. We investigated the accuracy of TURBT to detect rare histological variants in patients-candidates to cystectomy for bladder cancer with clinical and radiological features of invasiveness. Materials and Methods: The clinical and pathologic data of 340 patients submitted to TURBT and/or cystectomy for bladder cancer, between January 2010 and July 2015, were reviewed. The presence of uncommon histotypes within urothelial bladder carcinoma has been assessed. The diagnosis of rare variants of bladder cancer was made according to WHO criteria. Standard hematoxilyn-eosin stain was adopted and further immunohistochemistry was performed as follows: Micro-papillary carcinoma, MUC1, EMA, CK7, CK20; Squamous cell carcinoma, CK5/6, CK5/14; Adenocarcinoma, CK7, CK20, CEA, EMA; Small cell carcinoma, EMA, CAM5.2, synaptophysin, vimentin, chromogranin, neurospecific enolase (NSE), CK7, c-kit and TTF1; Mesenchymal tumors, keratin, EMA, vimentin and CEA and, sometimes, hCG. Additional immunohistochemistry was adopted when required to improve the pathological diagnosis. Candidate patients to cystectomy, for reason other than large bladder tumor with radiologic imaging suggestive of bladder wall infiltration, i.e. Tis, multiple and/or recurrent non muscle invasive and patients submitted to TURBT at other centers, were excluded. Inferential statistical analysis was performed. Results: Out of 340 patients, 35 (10.3%) showed rare histotypes of bladder cancer, i.e. in 30 cases (32%) out of 94 radical cystectomies and in 5 (2%) out of 246 TURBTs. The rare histotypes were distributed as follows: squamous carcinoma 11 (31%), sarcomatoid 8 (23%), undifferentiated 6 (17%), neuroendocrine 3 (9%), micropapillary 2 (6%), adenocarcinoma 1 (3%), mixed 4 (11%). TCCB with histological rare variants showed at cystectomy considerable size (average diameter=7.7×6.7 cm; range=4.5×5-11×9 cm), while 13 (43%) were pT4 category. In 13 patients (37%), the uncommon histotype was detected at the pre-operative TURBT, while, in 22 (63%), it was recognized only in the cystectomy specimen. Regarding the correlation between TURBT and re-TUR, rare histotypes were not identified at the first TURBT in 9 patients (26%) but found at re-TURBT in 4 patients (44%) and at cystectomy in 5 patients (56%) (Figure 1). Conversely, an atypical component diagnosed at first TURBT was not confirmed by a subsequent re-TUR in only 1 patient (3%). Discussion: Although the important prognostic role of rare histologic variants of bladder cancer is well-recognized, TURBT is not standardized in relation to tumor size. Unrecognized rare histotypes might have important therapeutic implications since they are probably less responsive to neoadjuvant chemotherapy or bladder-sparing approaches, thus benefiting early cystectomy. The inaccuracy of TUR in everyday clinical practice in detecting uncommon variants could be explained by the inadequacy of sampling of large tumors. The “pre-cystectomy” TUR is often considered a limited biopsy to confirm the tumor and to demonstrate the infiltration of the muscular layer. As a matter of fact, pathologists often do not analyze a sufficient amount of tissue to identify different histological components. Standardization of the TURBT strategy, including sampling of different areas of bulky tumors, could be of clinical value.