The International Society of Urological Pathology 2012 Consensus Conference made recommendations regarding classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. Issues relating to prognostic factors were coordinated by a workgroup who identified tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading, and microvascular invasion as potential prognostic parameters. There was consensus that the main morphotypes of renal cell carcinoma (RCC) were of prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided additional prognostic information, and that clear cell tubulopapillary RCC was associated with a more favorable outcome. For tumors showing sarcomatoid or rhabdoid differentiation, there was consensus that a minimum proportion of tumor was not required for diagnostic purposes. It was also agreed upon that the underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it was further agreed upon that if the underlying carcinoma subtype was absent the tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid component. Tumor necrosis was considered to have prognostic significance, with assessment based on macroscopic and microscopic examination of the tumor. It was recommended that for clear cell RCC the amount of necrosis should be quantified. There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed upon that chromophobe RCC should not be graded. There was consensus that microvascular invasion should not be included as a staging criterion for RCC.

The classification and grading of papillary urothelial neoplasms has been a long-standing subject of controversy. Previously, numerous diverse grading schemes for bladder tumor, including the 1973 World Health Organization (WHO) classification, existed whereby one of the major limitations was poor inter-observer reproducibility among pathologists. The WHO/International Society of Urological Pathology (ISUP) consensus classification system of urothelial neoplasms of the urinary bladder was developed in 1998 and was revised most recently in 2003 (published in 2004). Importantly, the current classification system provides detailed histological criteria for papillary urothelial lesions and allows for designation of a lesion (papillary urothelial neoplasm of low malignant potential) with a negligible risk of progression. Thus, the latest system is designed to be a universally acceptable one for bladder tumors that not only could be effectively used by pathologists, urologists, and oncologists, but also stratifies the tumors into prognostically significant categories. This article outlines the 2004 WHO/ISUP classification system regarding the specific histological criteria for non-invasive papillary urothelial neoplasms and the clinical significance of each category.

A novel porin, OmpG, is produced in response to a chromosomal mutation termed cog-192. Molecular characterization ofcog-192 revealed that it is a large chromosomal deletion extending from the 3′ end of pspA through to the 5′ end of an open reading frame located immediately upstream of ompG. As a result of this 13.1-kb deletion, the expression ofompG was placed under the control of the pspApromoter. Characterization of OmpG revealed that it is quite different from other porins. Proteoliposome swelling assays showed that OmpG channels were much larger than those of the OmpF and OmpC porins, with an estimated limited diameter of about 2 nm. The channel lacked any obvious solute specificity. The folding model of OmpG suggests that it is the first 16-stranded β-barrel porin that lacks the large external loop, L3, which constricts the channels of other nonspecific and specific porins. Consistent with the folding model, circular dichroism showed that OmpG contains largely a β-sheet structure. In contrast to other Escherichia coli porins, there is no evidence that OmpG exists as stable oligomers. Although ompG DNA was present in all E. coli strains examined so far, its expression under laboratory conditions was seen only due to rare chromosomal mutations. Curiously, OmpG was constitutively expressed, albeit at low levels, in Salmonella, Shigella, and Pseudomonas species.

The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants’ responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary.

Technical advances in endoscopic equipment have led to increased ureteroscopic biopsies of the upper urinary tract, resulting in limited biopsy material. We retrospectively reviewed 76 consecutive mid-upper ureter and renal pelvis biopsies submitted for consultation from January 2004 to January 2009, where follow-up was obtainable. There were 49 (64.5%) males and 27 (35.5%) females. Thirty-nine (51.3%) of the biopsies were from the ureter with the remaining 37 (48.7%) from the renal pelvis. The mean age was 70 years for males and 71 for females (range: 24 to 89). At consultation, the most common diagnoses were benign urothelium (n=25, 32.9%); atypical (n=17, 22.4%); low-grade noninvasive papillary urothelial carcinoma (n=10, 13.2%); and high-grade noninvasive papillary urothelial carcinoma (n=8, 10.5%). In cases where a definitive diagnosis could not be reached on expert review, it was mainly because of the limited size of the biopsy, absence of papillary fronds, crush artifact, and distorted architecture. There were 7 major discrepancies between the outside and second opinion diagnosis, where all of the cases were initially diagnosed as an urothelial neoplasm, yet was non-neoplastic upon review. Strips of urothelium without well-developed fibrovascular cores, polypoid ureteritis/pyelitis, and reactive urothelium mimicked urothelial neoplasms. In 5 of these 7 cases, there was no gross lesion suspicious of a tumor present according to the urologist. Overall, 33 of the 44 (75%) cases with a mass noted by the urologist or by radiography was found to have a neoplasm at follow-up. Conversely, 24 of the 32 (75%) cases without a grossly suspected tumor had no neoplasm at follow-up. The association between the histologic presence of a neoplasm at follow-up and the presence of a clinically suspected tumor was highly significant (P<0.0001). Pathologists need to recognize that in almost 1 of the 4 renal pelvic/ureteral biopsies a definitive diagnosis cannot be made because of the inadequate tissue. Caution must be exercised in the evaluation of these limited specimens, especially in the absence of a clinically suspected tumor.