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 capecitabine and temozolomide (CAPTEM) regimen is active in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs), with response rates ranging from 30 to 70%. Small retrospective studies suggest that O 6 -methylguanine DNA methyltransferase (MGMT) deficiency predicts response to temozolomide. High tumor proliferative activity is also commonly perceived as a significant predictor of response to cytotoxic chemotherapy. It is unclear whether chromosomal instability (CIN), which correlates with alternative lengthening of telomeres (ALT), is a predictive factor. In this study, we evaluated 143 patients with advanced pNET who underwent treatment with CAPTEM for radiographic and biochemical response. MGMT expression (n = 52), grade (n = 128) and ALT activation (n = 46) were investigated as potential predictive biomarkers. Treatment with CAPTEM was associated with an overall response rate (ORR) of 54% by RECIST 1.1. Response to CAPTEM was not influenced by MGMT expression, proliferative activity or ALT pathway activation. Based on these results, no biomarker-driven selection criteria for use of the CAPTEM regimen can be recommended at this time.

The AJCC and ENETS TNM classifications for pancreatic NETs are prognostic for recurrence-free survival and can be adopted in clinical practice.

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.

Non-conventional dysplasias of the tubular gut: a review and illustration of their histomorphological spectrumThe increasing use of gastrointestinal endoscopic procedures has led to the recognition by histopathologists of non-conventional (or special-type) dysplasias of the gastrointestinal tract. These lesions can be recognised in association with prevalent underlying gastrointestinal conditions, such as Barrett oesophagus, chronic atrophic gastritis, and inflammatory bowel disease. The diagnosis of these special types can be challenging, and their biological behaviours are not fully characterised. The aim of this review is to provide a global view of non-conventional dysplastic lesions observed in the various segments of the tubular gastrointestinal tract and describe their salient features. Furthermore, as the clinical implications of these various subtypes have not been broadly tested in practice and are not represented in most management guidelines, we offer guidance on the best management practices for these lesions.

The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and the results of this were used to inform the focus of conference discussion. On formal voting a ≥65% majority was considered a consensus agreement. For specimen handling it was agreed that with radical nephrectomy specimens the initial cut should be made along the long axis and that both radical and partial nephrectomy specimens should be inked. It was recommended that sampling of renal tumors should follow a general guideline of sampling 1 block/cm with a minimum of 3 blocks (subject to modification as needed in individual cases). When measuring a renal tumor, the length of a renal vein/caval thrombus should not be part of the measurement of the main tumor mass. In cases with multiple tumors, sampling should include at a minimum the 5 largest tumors. There was a consensus that perinephric fat invasion should be determined by examining multiple perpendicular sections of the tumor/perinephric fat interface and by sampling areas suspicious for invasion. Perinephric fat invasion was defined as either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia. It was agreed upon that renal sinus invasion is present when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma, or if there is involvement of any endothelium-lined spaces within the renal sinus, regardless of the size. When invasion of the renal sinus is uncertain, it was recommended that at least 3 blocks of the tumor-renal sinus interface should be submitted. If invasion is grossly evident, or obviously not present (small peripheral tumor), it was agreed that only 1 block was needed to confirm the gross impression. Other recommendations were that the renal vein margin be considered positive only when there is adherent tumor visible microscopically at the actual margin. When a specimen is submitted separately as "caval thrombus," the recommended sampling strategy is to take 2 or more sections to look for the adherent caval wall tissue. It was also recommended that uninvolved renal parenchyma be sampled by including normal parenchyma with tumor and normal parenchyma distant from the tumor. There was consensus that radical nephrectomy specimens should be examined for the purpose of identifying lymph nodes by dissection/palpation of the fat in the hilar area only; however, it was acknowledged that lymph nodes are found in <10% of radical nephrectomy specimens.

No abstract

No abstract