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.

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Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms ‘BRAF,’ ‘mutation,’ and ‘cancer/tumor.’ These results were filtered to include manuscripts that focused on diagnostic tests for determining BRAF mutation status. Numerous BRAF testing methods were identified, including DNA-based companion diagnostic tests and DNA- and protein-based laboratory-developed tests. Herein we review the characteristics of each method and highlight the strengths and weaknesses that should be considered before use and when interpreting results for each patient. Molecular profiling has shown that mutation load increases with melanoma tumor progression and that unique patterns of genetic changes and evolutionary trajectories for different melanoma subtypes can occur. Discordance in the BRAF mutational status between primary and metastatic lesions, as well as intratumoral heterogeneity, is known to occur. Additionally, the development of acquired resistance to combination BRAF and MEK inhibitor therapy is still a formidable obstacle. Therefore, tumor heterogeneity and the development of acquired resistance have important implications for molecular testing and ultimately the treatment of patients with advanced-stage melanoma. Overall, this information may help community oncologists more accurately and effectively interpret results of diagnostic tests within the context of recent data characterizing melanoma tumor progression.

The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

Lymphoepithelioma-like carcinoma (LELCA) of the urinary bladder is a rare variant of bladder cancer characterized by a malignant epithelial component densely infiltrated by lymphoid cells. It is characterized by indistinct cytoplasmic borders and a syncytial growth pattern. These neoplasms deserve recognition and attention, chiefly because they may be responsive to chemotherapy. We report on the clinicopathologic features of 13 cases of LELCA recorded since 1981. The chief complaint in all 13 patients was hematuria. Their ages ranged from 58 years to 82 years. All tumors were muscle invasive. A significant lymphocytic reaction was present in all of these tumors. There were three pure LELCA and six predominant LELCA with a concurrent transitional cell carcinoma (TCC). The remainder four cases had a focal LELCA component admixed with TCC. Immunohistochemistry showed LELCA to be reactive against epithelial membrane antigen and several cytokeratins (CKs; AE1/AE3, AE1, AE3, CK7, and CK8). CK20 and CD44v6 stained focally. The lymphocytic component was composed of a mixture of T and B cells intermingled with some dendritic cells and histiocytes. Latent membrane protein 1 (LMP1) immunostaining and in situ hybridization for Epstein-Barr virus were negative in all 13 cases. DNA ploidy of these tumors gave DNA histograms with diploid peaks (n=7) or non-diploid peaks (aneuploid or tetraploid; n=6). All patients with pure and 66% with predominant LELCA were alive, while all patients having focal LELCA died of disease. Our data suggest that pure and predominant LELCA of the bladder appear to be morphologically and clinically different from other bladder (undifferentiated and poorly differentiated conventional TCC) carcinomas and should be recognized as separate clinicopathological variants of TCC with heavy lymphocytic reaction relevant in patient management.

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While undergrading of prostate cancer used to be prevalent, some now tend to overgrade. Minimum diagnostic criteria for GP 4 and 5 in biopsies need to be better defined. Image libraries reviewed by experts may be useful for standardization.

Inflammatory myofibroblastic tumor of the genitourinary tract should be considered a neoplasm of uncertain malignant potential, and routine surveillance and close clinical followup are recommended. Aggressive therapy (radical cystectomy, radiation or chemotherapy) is unwarranted given the indolent and often benign clinical course for the majority of cases. To understand the diagnostic and prognostic implications future emphasis should be placed on the link between genetic abnormalities, and clinical course, therapeutic response and ultimate outcome.