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High-grade papillary urothelial carcinoma with subepithelial connective tissue invasion (T1HG) is an aggressive disease at high risk of progression after transurethral resection/Bacillus Calmette-Guerin standardized therapy. The European Organization for Research and Treatment of Cancer has identified T1HG bladder carcinoma that is single and ≤3 cm in the largest dimension at first diagnosis as a category in which the prognosis cannot be further stratified based on conventional criteria. This category may benefit from biomarker analysis as a valuable tool to determine the patient's outcome. To further the issue of biomarkers in predicting aggressiveness in single T1HG bladder carcinoma ≤3 cm in greatest dimension at first diagnosis, we have conducted a validation study of the biomarker risk score set previously reported by our group. The study set included immunohistochemical detection of galectin-3, CD44, E-cadherin (E-CAD), CD138, p16, survivin, HYAL-1, and topoisomerase-IIα in 92 randomly selected specimens at participating institutions. Topoisomerase-IIα expression was identified as a predictor of disease-free survival. p16, survivin, and E-CAD expression predicted progression-free survival, but p16 and E-CAD also predicted overall survival. The current study validates a panel of immunohistochemical markers with the potential of being implemented in practice and supports the use of biomarkers in predicting aggressiveness in patients with first diagnosis of single T1HG bladder carcinoma ≤3 cm in greatest dimension and therefore in identifying patients who need closer surveillance or earlier aggressive treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To collect information on current practices of European pathologists for the handling and reporting of nephrectomy specimens with renal tumours., Methods and Results: A questionnaire was circulated to the members of the European Network of Uropathology, which consists of 343 pathologists in 15 European countries. Replies were received from 48% of members. These replies indicated that nephrectomy specimens are most often received in formalin. Lymph nodes are found in less than 5% of nephrectomy specimens. All respondents give an objective measure of tumour size, most commonly in three diameters. The most common method to search for capsule penetration is to slice tissue outside the tumour perpendicularly into the tumour. The most common sampling algorithm from tumours greater than 2 cm is one section for every centimetre of maximum tumour diameter. Most respondents use the 2004 WHO renal tumour classification although only slightly over half consider small papillary tumours malignant if the diameter is greater than 5 mm. The Fuhrman grading system is widely used. Almost all use immunohistochemistry for histological typing in some cases, while only 7% always use it. The most utilised special stains are CK7 (95%), CD10 (93%), vimentin (86%), HMB45 (68%), c-kit (61%) and Hale's colloidal iron (52%). Only 18% use other ancillary techniques for diagnosis in difficult cases., Conclusions: While most pathologists appear to follow published guidelines for reporting renal carcinoma, there is still a need for the development of consensus and further standardisation of practice for contentious areas of specimen handling and reporting.

Purpose: The purpose of this study is to assess the association of concomitant carcinoma in situ (CIS) with disease recurrence and cancer-related death in a multi-institutional series of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods: We collected retrospectively the data of 772 patients treated with RNU and ipsilateral bladder cuff excision at 9 international institutions in Asia, Europe, and Northern America from 1987 to 2008. Surgical specimens were processed according to standard pathologic procedures at each institution. Univariable and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality., Results: Concomitant CIS was present in 88 patients (11.4%); it was associated with more advanced pathologic stage, higher tumor grade, and presence of lymphovascular invasion (all P-values < 0.05). The five-year recurrence-free (RFS) and cancer-specific survival (CSS) estimates were 74.4 and 76.3%, respectively, in the absence of CIS compared with 56.4 and 59.9%, respectively, in the presence of CIS (P-values < 0.0001 for RFS and 0.002 for CSS, respectively). On multivariable Cox regression analyses, concomitant CIS was an independent predictor of both RFS (hazard ratio (HR): 1.9; P = 0.007) and CSS (HR: 1.7, P = 0.048). Similar findings were reconfirmed in subgroups analyses limited to T2, organ confined, and N0/Nx UTUC, or patients who did not receive adjuvant chemotherapy., Conclusions: Presence of concomitant CIS is an independent predictor of both RFS and CSS in patients treated with RNU for UTUC. This information may be useful in risk stratification of UTUC patients for follow-up and additional therapy.

Objectives: To identify the variables predictive of contralateral metachronous upper urinary tract transitional cell carcinoma (UUT-TCC) after nephroureterectomy (NFU) for non-metastatic UUT-TCC., Methods: Clinical and pathological data of 234 patients who had undergone NFU for UUT-TCC from 1989 to 2005 in three European urological centers were retrospectively collected and analyzed., Results: The median follow-up duration for the whole cohort was 34 months. Contralateral metachronous UUT-TCC was detected in 14 patients (6%). Three patients were treated by NFU, while seven patients underwent ureterectomy and reimplantation and four patients were treated by endoscopic resection plus bacillus Calmette-Guérin instillations within the UUT through a nephrostomic tube. On univariate analysis, a prior history of bladder TCC before NFU was the only factor predictive of the occurrence of contralateral UUT-TCC. Specifically, the 5-year probabilities of being free from contralateral UUT-TCC were 96.6% for the patients with de novo UUT-TCC, and 91.1% and 55.3% for those having non-muscle-invasive and muscle invasive bladder TCC before the UUT cancer, respectively. All survival differences were statistically significant (no history of bladder TCC vs history of non-muscle-invasive bladder TCC, log rank P value 0.015; history of non-muscle-invasive bladder TCC vs history of muscle-invasive bladder TCC, log rank P value 0.035)., Conclusions: In our multicenter dataset of patients who had undergone NFU for UUT-TCC, contralateral metachronous UUT-TCC occurred in 6% of the patients. A prior history of bladder TCC before NFU was the only variable predictive of UUT recurrence at univariate analysis.

Purpose: We validated the Mayo Clinic SSIGN score in an independent European sample of patients who were surgically treated for conventional RCC., Materials and Methods: In our kidney cancer database we identified 388 patients who were treated with radical or partial nephrectomy for conventional RCC between 1986 and 2000. Associations of the pathological features studied with death from RCC were evaluated using the log rank test and Cox proportional hazards regression model. The predictive ability of competing models was evaluated using the c index., Results: Median followup in the 290 patients who were alive at last followup was 5 years (range 5 months to 17 years). The estimated cancer specific survival rate 5 years following surgery was 81.3%. All features that comprise the SSIGN score except tumor size were significantly associated with death from RCC in a multivariate setting, resulting in a c index of 0.90. The median SSIGN score in the 388 patients studied was 3 (range 0 to 15). The c index in a model containing the clear cell SSIGN score was 0.88. Five-year cancer specific survival rates in patients with a score of 0 to 2, 3 to 4, 5 to 6, 7 to 9 and 10 or more were 100.0%, 90.5%, 63.6%, 46.8% and 0%, respectively., Conclusions: We provide the first external validation of the Mayo Clinic SSIGN score for conventional RCC. This simple algorithm resulted in a high degree of prognostic accuracy.