Rodolfo Montironi

Best practices recommendations in the application of immunohistochemistry in urologic pathology: Report from the International Society of Urological Pathology Consensus Conference

Members of the International Society of Urological Pathology (ISUP) participated in a half-day consensus conference to discuss guidelines and recommendations regarding best practice approaches to use of immunohistochemistry (IHC) in differential diagnostic situations in urologic pathology, including bladder, prostate, testis and, kidney lesions. Four working groups, selected by the ISUP leadership, identified several high-interest topics based on common or relevant challenging diagnostic situations and proposed best practice recommendations, which were discussed by the membership. The overall summary of the discussions and the consensus opinion forms the basis of a series of articles, one for each organ site. This Special Article summarizes the overall recommendations made by the four working groups. It is anticipated that this ISUP effort will be valuable to the entire practicing community in the appropriate use of IHC in diagnostic urologic pathology.

[Vancouver classification of renal tumors: Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)].

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.

Vancouver-Klassifikation von Nierentumoren

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.

Immunotherapy in genitourinary cancers: where are we going?

ABSTRACT Introduction: Tumour-associated inflammation is involved with the development of genitourinary cancers. A growing understanding of the interactions between immune cells and cancer provides the basis for immunomodulating approaches. Area covered: Immunotherapies targeting immune checkpoints and tumour-associated antigens are providing a new approach in patients with prostate and bladder cancer and renal cell carcinoma. The possibility to integrate such therapeutic agents in the current scenario, both in sequential or combined approaches, relies on a comprehension of the pro-tumourigenic activity of the immune system and the mechanisms of cancer-related immunosuppression. Expert commentary: Treatment of genitourinary cancers is being revolutionized by the recent development of new immunotherapeutic approaches. The next step will be the identification of the sequences or combinations between novel and effective immunotherapies and currently approved targeted agents and chemotherapies.

The role of precision medicine for the treatment of metastatic renal cell carcinoma

ABSTRACT Introduction: The progressive understanding of the molecular and biochemical alterations of renal cell carcinoma (RCC) has drastically changed the course of this tumor through the development of new molecular targeted drugs. Furthermore, an increasing knowledge of disease molecular pathways and genetic mutations are turning RCC in different kind of tumors each one with different clinical behaviours, outcomes and treatment chances. Areas covered: After angiogenetic inhibitors which are the current first treatment choice other target drugs are emerging as agents able to improve survival of patients with RCC. However, since that RCC involves different kind of tumors resulting by specific gene alterations the choice of the most favourable treatment could be difficult. Expert commentary: Which factors must be considered before planning treatment strategy? May a better genetic disease knowledge be a support able to help clinicians during decision making and tailored drugs development? These questions are an open challenge whose responses could revolutionise the course of this disease.

Vancouver-Klassifikation von Nierentumoren@@@Vancouver classification of renal tumors: Empfehlungen der Konsenskonferenz der Internationalen Gesellschaft für Uropathologie (ISUP) 2012@@@Recommendations of the 2012 consensus conference of the International Society of Urological Pathology (ISUP)

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.

Tumors and Tumor-Like Conditions of Urinary Bladder, Renal Pelvis, Ureter and Urethra

Chapter 2 presents main clinical and pathologic characteristics of tumors and tumor-like conditions arising in the urinary bladder, upper urinary tract and the urethra. Emphasis is placed on rare and recently described entities. Diagnostic pathologic and immunohistochemical features useful in differential diagnosis are key characteristics described in text and tables. Representative images illustrate both common and rare tumors and tumor-like conditions of the urinary bladder, upper urinary tract and the urethra.

Renal Tumors and Tumor-Like Conditions

Chapter 1 presents main clinical and pathologic characteristics of tumors and tumor-like conditions arising in the kidney. Emphasis is placed on rare and recently described entities. Diagnostic pathologic and immunohistochemical features useful in differential diagnosis are key characteristics described in text and tables. Representative images illustrate both common and rare tumors and tumor-like conditions of the kidney