Advances in Renal Neoplasia: Recommendations From the 2012 International Society of Urological Pathology Consensus Conference.

The International Society of Urological Pathology (ISUP) 2012 Consensus Conference made recommendations regarding the classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. There was consensus that 5 entities should be recognized as novel tumors: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell papillary RCC, microphthalmia transcription factor-family translocation RCC [in particular t(6; 11) RCC], and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, 3 rare epithelial carcinomas were considered emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC, and anaplastic lymphoma kinase translocation RCC. There were also a number of suggested modifications to existing World Health Organization 2004 categories, with the new classification to be known as the ISUP Vancouver Classification. Tumor morphotype, sarcomatoid/rhabdoid differentiation, and tumor necrosis were identified as significant prognostic parameters for RCC. The ISUP Grading System was accepted with grades 1-3 of clear cell and papillary RCC being based on nucleolar prominence, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed that chromophobe RCC should not be graded. Consensus guidelines were formulated for specimen handling, and it was agreed that renal sinus invasion is present when tumor is in direct contact with fat or loose connective tissue of the sinus or if there is involvement of endothelial-lined spaces within the renal sinus, regardless of the size. The role of biomarkers in the diagnosis and assessment of prognosis of renal tumors was considered, and panels of immunohistochemical markers were identified for use in specific differential diagnostic scenarios

Vancouver-Klassifikation von Nierentumoren: Empfehlungen der Konsenskonferenz der Internationalen Gesellschaft für Uropathologie (ISUP) 2012

The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics

Grading Of Invasive Cribriform Carcinoma On Prostate Needle Biopsy: An Interobserver Study Among Experts In Genitourinary Pathology

The distinction between cribriform Gleason pattern 3 and 4 prostate cancer is controversial. Out of 3590 prostate cancers sent to one of the authors over 7 months, 30 needle biopsy cases were selected that possibly represented cribriform Gleason pattern 3 cancer. Thirty-six digital images were taken and sent to 10 experts in prostate pathology. Consensus was defined when at least 7/10 experts agreed on the grade. Sixty-seven percent (n=24) of images reached consensus (23 pattern 4; 1 pattern 3). Of the 12 nonconsensus images, 7 were favor pattern 4 (6/10 experts agreed), 1 was favor pattern 3 (6/10 experts agreed), and 4 were equivocal (<6 experts agreed). The most common criteria used to call pattern 4 in the 23 consensus pattern 4 images were in frequency: irregular contour, irregular distribution of lumens, slit-like lumens, large glands, number of glands, and small lumens. In the only consensus pattern 3 image, criteria used were regular contour, small glands, regular distribution of lumens, and uniform round lumens. Discrepancy between experts was qualified as primarily objective (different criteria present) in 38%, subjective (different interpretation of the same criteria) in 12%, and mixed (both objective and subjective) in 50%. The most frequent situation with different interpretations of the same criteria were regular versus irregular contour and small versus large glands, with the former more common. Even in this highly selected set of images thought to be the best candidates for cribriform pattern 3 from a busy consult service, most experts interpreted the cribriform patterns as pattern 4. Moreover, most of the cribriform foci investigated (73%) were associated with more definitive pattern 4 elsewhere on the needle biopsy specimen. In conclusion, most of the small cribriform cancer foci seen on needle biopsy should be interpreted as Gleason pattern 4 and not pattern 3. © 2008 Lippincott Williams & Wilkins.321015321539Amin, M.B., Schultz, D.S., Zarbo, R.J., Analysis of cribriform morphology in prostatic neoplasia using antibody to high-molecular-weight cytokeratins (1994) Arch Pathol Lab Med, 118, pp. 260-264Bailar III, J.C., Mellinger, G.T., Gleason, D.F., Survival rates of patients with prostatic cancer, tumor stage, and differentiation - preliminary report (1966) Cancer Chemother Rep, 50, pp. 129-136Bostwick, D.G., Amin, M.B., Dundore, P., Architectural patterns of high-grade prostatic intraepithelial neoplasia (1993) Hum Pathol, 24, pp. 298-310Cohen, R.J., McNeal, J.E., Baillie, T., Patterns of differentiation and proliferation in intraductal carcinoma of the prostate: Significance for cancer progression (2000) Prostate, 43, pp. 11-19Cohen, R.J., Wheeler, T.M., Bonkhoff, H., A proposal on the identification, histologic reporting, and implications of intraductal prostatic carcinoma (2007) Arch Pathol Lab Med, 131, pp. 1103-1109Egevad, L., Granfors, T., Karlberg, L., Prognostic value of the Gleason score in prostate cancer (2002) BJU Int, 89, pp. 538-542Egevad, L., Allsbrook Jr, W.C., Epstein, J.I., Current practice of Gleason grading among genitourinary pathologists (2005) Hum Pathol, 36, pp. 5-9Epstein JI, Allsbrook WC Jr, Amin MB, et al. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005;29:1228-1242Gleason, D.F., Classification of prostatic carcinomas (1966) Cancer Chemother Rep, 50, pp. 125-128Gleason, D.F., Mellinger, G.T., Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging (1974) J Urol, 111, pp. 58-64Guo, C.C., Epstein, J.I., Intraductal carcinoma of the prostate on needle biopsy: Histologic features and clinical significance (2006) Mod Pathol, 19, pp. 1528-1535Helpap, B., Egevad, L., The significance of modified Gleason grading of prostatic carcinoma in biopsy and radical prostatectomy specimens (2006) Virchows Arch, 449, pp. 622-627Lopez-Beltran, A., Mikuz, G., Luque, R.J., Current practice of Gleason grading of prostate carcinoma (2006) Virchows Arch, 448, pp. 111-118Martinez-Rodriguez, M., Ramos, D., Mayordomo, E., Analysis of cribriform Gleason grade 3 in prostatic carcinoma. 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Prognostic and predictive factors in prostate cancer: Historical perspectives and recent international consensus initiatives

An understanding of prognosis in cancer medicine is important for patient care, research and cancer control programs. In prostate cancer, prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic and biomolecular levels. Clinical stage and histologic grade have historically played major roles in defining heterogeneity in prostate cancer. More recently, serum prostate-specific antigen measurement has assumed a significant prognostic role. Over the last two decades there has been an explosion of research into biomarkers, many of which have been purported to have prognostic significance. In this paper we present an overview of the various consensus initiatives that have transpired over the last dozen years. Criteria for evaluating prognostic factors and classifications of predictive factors have emerged that have proven useful and advanced our understanding of the biology of prostate cancer. The results of these consensus initiatives form a foundation on which the current international consultation on prognosis (prediction) in prostate cancer is built. Advances in our understanding of the new and promising prognostic factors will require a more rigorous evidence-based approach to the analysis of published studies. Furthermore, appropriate mathematical models for the analysis of the multiple factors that influence a prognostic system will have to be employed

Prognostic factors and reporting of prostate carcinoma in radical prostatectomy and pelvic lymphadenectomy specimens

This paper, based on the activity of the Morphology-Based Prognostic Factors Committee of the 2004 World Health Organization-sponsored International Consultation, describes various methods of handling radical prostatectomy specimens for both routine clinical use and research purposes. The correlation between radical prostatectomy findings and postoperative failure is discussed in detail. This includes issues relating to pelvic lymph node involvement, detected both at the time of frozen section and in permanent sections. Issues of seminal vesicle invasion, including its definition, routes of invasion and relationship to prognosis, are covered in detail. The definition, terminology and incidence of extra-prostatic extension are elucidated, along with its prognostic significance relating to location and extent. Margins of resection are covered in terms of their definition, the etiology, incidence and sites of positive margins, the use of frozen sections to assess the margins and the relationship between margin positivity and prognosis. Issues relating to grade within the radical prostatectomy specimen are covered in depth, including novel ways of reporting Gleason grade and the concept of tertiary Gleason patterns. Tumor volume, tumor location, vascular invasion and perineural invasion are the final variables discussed relating to the prognosis of radical prostatectomy specimens. The use of multivariate analysis to predict progression is discussed, together with proposed modifications to the TNM system. Finally, biomarkers to predict progression following radical prostatectomy are described, including DNA ploidy, microvessel density, Ki-67, neuroendocrine differentiation, p53, p21, p27, Bcl-2, Her-2/neu, E-cadherin, CD44, retinoblastoma proteins, apoptotic index, androgen receptor status, expression of prostate-specific antigen and prostatic-specific acid phosphatase and nuclear morphometry

Prognostic and predictive factors and reporting of prostate carcinoma in prostate needle biopsy specimens

The information provided in the surgical pathology report of a prostate needle biopsy of carcinoma has become critical in the subsequent management and prognostication of the cancer. The surgical pathology report should thus be comprehensive and yet succinct in providing relevant information consistently to urologists, radiation oncologists and oncologists and, thereby, to the patient. This paper reflects the current recommendations of the 2004 World Health Organization-sponsored International Consultation, which was co-sponsored by the College of American Pathologists. It builds on the existing work of several organizations, including the College of American Pathologists, the Association of Directors of Anatomic and Surgical Pathologists, the Royal Society of Pathologists, the European Society of Urologic Pathology and the European Randomized Study of Screening for Prostate Cancer