LIMITS OF TRANSURETHRAL RESECTION IN DETECTING RARE HISTOLOGICAL VARIANTS WITHIN LARGE UROTHELIAL BLADDER TUMORS

Introduction/Aim: Rare histotypes represent almost 10% ofbladder tumors, although more often represented as small fociwithin large and invasive transitional cell tumors of the bladder(TCCB). It might be clinically relevant that rare histologicalvariants 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 TURBTto detect rare histological variants in patients-candidates tocystectomy for bladder cancer with clinical and radiologicalfeatures of invasiveness. Materials and Methods: The clinicaland pathologic data of 340 patients submitted to TURBT and/orcystectomy for bladder cancer, between January 2010 and July2015, were reviewed. The presence of uncommon histotypeswithin urothelial bladder carcinoma has been assessed. Thediagnosis of rare variants of bladder cancer was made accordingto WHO criteria. Standard hematoxilyn-eosin stain was adoptedand 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, neurospecificenolase (NSE), CK7, c-kit and TTF1; Mesenchymal tumors, keratin, EMA, vimentin and CEA and, sometimes,hCG. Additional immunohistochemistry was adopted whenrequired to improve the pathological diagnosis. Candidatepatients to cystectomy, for reason other than large bladder tumorwith radiologic imaging suggestive of bladder wall infiltration,i.e. Tis, multiple and/or recurrent non muscle invasive andpatients submitted to TURBT at other centers, were excluded.Inferential statistical analysis was performed. Results: Out of340 patients, 35 (10.3%) showed rare histotypes of bladdercancer, i.e. in 30 cases (32%) out of 94 radical cystectomies andin 5 (2%) out of 246 TURBTs. The rare histotypes weredistributed as follows: squamous carcinoma 11 (31%),sarcomatoid 8 (23%), undifferentiated 6 (17%), neuroendocrine3 (9%), micropapillary 2 (6%), adenocarcinoma 1 (3%), mixed4 (11%). TCCB with histological rare variants showed atcystectomy considerable size (average diameter=7.7×6.7 cm;range=4.5×5-11×9 cm), while 13 (43%) were pT4 category. In13 patients (37%), the uncommon histotype was detected at thepre-operative TURBT, while, in 22 (63%), it was recognizedonly in the cystectomy specimen. Regarding the correlationbetween TURBT and re-TUR, rare histotypes were notidentified at the first TURBT in 9 patients (26%) but found atre-TURBT in 4 patients (44%) and at cystectomy in 5 patients(56%) (Figure 1). Conversely, an atypical component diagnosedat first TURBT was not confirmed by a subsequent re-TUR inonly 1 patient (3%). Discussion: Although the importantprognostic role of rare histologic variants of bladder cancer iswell-recognized, TURBT is not standardized in relation totumor size. Unrecognized rare histotypes might have importanttherapeutic implications since they are probably less responsiveto neoadjuvant chemotherapy or bladder-sparing approaches,thus benefiting early cystectomy. The inaccuracy of TUR ineveryday clinical practice in detecting uncommon variants couldbe explained by the inadequacy of sampling of large tumors.The “pre-cystectomy” TUR is often considered a limited biopsyto confirm the tumor and to demonstrate the infiltration of themuscular layer. As a matter of fact, pathologists often do notanalyze a sufficient amount of tissue to identify differenthistological compone