Grading of renal cell carcinoma Delahunt, Brett; Eble, John N; Egevad, Lars ...
Histopathology,
January 2019, Letnik:
74, Številka:
1
Journal Article
Recenzirano
Grading of renal cell carcinoma (RCC) has been recognised as a prognostic factor for almost 100 years. Numerous grading systems have been proposed, initially focusing upon a constellation of ...cytological features and more recently on nuclear morphology. It has been recommended that grading of RCC should be based upon nucleolar prominence/eosinophilia for grades 1–3, while grade 4 requires nuclear anaplasia (including tumour giant cells, sarcomatoid differentiation and/or rhabdoid morphology). The grading system was adopted formally by the International Society of Urological Pathology (ISUP) and subsequently by the World Health Organisation (WHO), being designated the WHO/ISUP grading classification in the fourth edition of the WHO classification tumours of the urinary system and male genital organs (2016). This grading system has been validated for both clear cell and papillary RCC. Validation studies for chromophobe RCC failed to demonstrate a correlation between grade and outcome for both the superseded Fuhrman grading system and the WHO/ISUP grading classification, and it has been recommended that these tumours not be graded. The WHO/ISUP system has been incorporated into the structured reports of the International Cancer Collaboration on Cancer Reporting for both clear cell and papillary RCC. It is also noted that other types of RCC may be graded, but it must be emphasised in the report that this is for descriptive and diagnostic purposes, and not outcome prediction. More recent studies have shown the incorporation of the presence of tumour necrosis into RCC grading to improve outcome prediction, and this has been validated in several studies.
Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice ...require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.
The International Society of Urological Pathology (ISUP) has issued guidelines for the grading of prostate cancer based on a consensus conference held in 2014. The recommendations resulting from the ...2014 consensus conference were a further development of 2005 ISUP modified Gleason grading. In the 2014 system, morphological criteria are clarified, including updated definitions of Gleason pattern 4. In addition to the continued reporting of Gleason scores, we also recommend that Gleason scores ≤6, 3 + 4 = 7, 4 + 3 = 7, 8 and 9–10, respectively, be reported as five groups, i.e. ISUP grades 1–5. This new grading system has the dual benefit of predicting patient outcome as well as facilitating patient communication.
Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated ...regions. This methylation landscape that we referred to as Methylscape is displayed by most cancer types, thus may serve as a universal cancer biomarker. To-date most research has focused on the biological consequences of DNA Methylscape changes whereas its impact on DNA physicochemical properties remains unexplored. Herein, we examine the effect of levels and genomic distribution of methylcytosines on the physicochemical properties of DNA to detect the Methylscape biomarker. We find that DNA polymeric behaviour is strongly affected by differential patterning of methylcytosine, leading to fundamental differences in DNA solvation and DNA-gold affinity between cancerous and normal genomes. We exploit these Methylscape differences to develop simple, highly sensitive and selective electrochemical or colorimetric one-step assays for the detection of cancer. These assays are quick, i.e., analysis time ≤10 minutes, and require minimal sample preparation and small DNA input.
Intraductal carcinoma of the prostate gland (IDCP), which is now categorised as a distinct entity by WHO 2016, includes two biologically distinct diseases. IDCP associated with invasive carcinoma ...(IDCP-inv) generally represents a growth pattern of invasive prostatic adenocarcinoma while the rarely encountered pure IDCP is a precursor of prostate cancer. This review highlights issues that require further discussion and clarification. The diagnostic criterion “nuclear size at least 6 times normal” is ambiguous as “size” could refer to either nuclear area or diameter. If area, then this criterion could be re-defined as nuclear diameter at least three times normal as it is difficult to visually compare area of nuclei. It is also unclear whether IDCP could also include tumours with ductal morphology. There is no consensus whether pure IDCP in needle biopsies should be managed with re-biopsy or radical therapy. A pragmatic approach would be to recommend radical therapy only for extensive pure IDCP that is morphologically unequivocal for high-grade prostate cancer. Active surveillance is not appropriate when low-grade invasive cancer is associated with IDCP, as such patients usually have unsampled high-grade prostatic adenocarcinoma. It is generally recommended that IDCP component of IDCP-inv should be included in tumour extent but not grade. However, there are good arguments in favour of grading IDCP associated with invasive cancer. All historical as well as contemporary Gleason outcome data are based on morphology and would have included an associated IDCP component in the tumour grade. WHO 2016 recommends that IDCP should not be graded, but it is unclear whether this applies to both pure IDCP and IDCP-inv.
Aims
In 2012, the International Society of Urological Pathology (ISUP) introduced a novel grading system for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma. This system is ...incorporated into the latest World Health Organization renal tumour classification, being designated WHO/ISUP grading. This study was undertaken to compare WHO/ISUP and Fuhrman grading and to validate WHO/ISUP grading as a prognostic parameter in a series of clear cell RCC.
Methods and results
Analysis of 681 cases of ccRCC showed that 144 tumours could not be assigned a Fuhrman grade on the basis of ambiguous grading features. The application of WHO/ISUP grading resulted in a general down‐grading of cases when compared with Fuhrman grading. In a sub‐group of 374 cases, for which outcome data were available, 9.3% were WHO/ISUP grade 1, 50.3% were grade 2, 24.1% grade 3 and 16.3% grade 4, while the distribution of Fuhrman grades was 0.4% grade 1, 48.7% grade 2, 29.4% grade 3 and 21.5% grade 4. There were no recurrence/metastases amongst patients with WHO/ISUP grade 1 tumours and there was a significant difference in outcome for WHO/ISUP grades 2, 3 and 4. For Fuhrman grading the cancer‐free survival was not significantly different for grade 2 and grade 3 tumours. On multivariate analysis WHO/ISUP grade and pT staging category were found to retain prognostic significance.
Conclusions
The study demonstrates that FG cannot be applied in >20% of cases of ccRCC and the WHO/ISUP provides superior prognostic information.
Unreliable predictions can occur when an artificial intelligence (AI) system is presented with data it has not been exposed to during training. We demonstrate the use of conformal prediction to ...detect unreliable predictions, using histopathological diagnosis and grading of prostate biopsies as example. We digitized 7788 prostate biopsies from 1192 men in the STHLM3 diagnostic study, used for training, and 3059 biopsies from 676 men used for testing. With conformal prediction, 1 in 794 (0.1%) predictions is incorrect for cancer diagnosis (compared to 14 errors 2% without conformal prediction) while 175 (22%) of the predictions are flagged as unreliable when the AI-system is presented with new data from the same lab and scanner that it was trained on. Conformal prediction could with small samples (N = 49 for external scanner, N = 10 for external lab and scanner, and N = 12 for external lab, scanner and pathology assessment) detect systematic differences in external data leading to worse predictive performance. The AI-system with conformal prediction commits 3 (2%) errors for cancer detection in cases of atypical prostate tissue compared to 44 (25%) without conformal prediction, while the system flags 143 (80%) unreliable predictions. We conclude that conformal prediction can increase patient safety of AI-systems.
The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. ...Issues relating to the handling and processing of radical prostatectomy specimens were coordinated by working group 1. Most uropathologists followed similar procedures for fixation of radical prostatectomy specimens, with 51% of respondents transporting tissue in formalin. There was also consensus that the prostate weight without the seminal vesicles should be recorded. There was consensus that the surface of the prostate should be painted. It was agreed that both the prostate apex and base should be examined by the cone method with sagittal sectioning of the tissue sample. There was consensus that the gland should be fully fixed before sectioning. Both partial and complete embedding of prostates was considered to be acceptable as long as the method of partial embedding is stated. No consensus was determined regarding the necessity of weighing and measuring the length of the seminal vesicles, the preparation of whole mounts rather than standardized blocks and the methodology for sampling of fresh tissue for research purposes, and it was agreed that these should be left to the discretion of the working pathologist.
Summary Despite being discovered almost 50 years ago little is known regarding the genetic profile of ductal adenocarcinoma of the prostate (DAC). In recent years, progress has been made in the ...understanding of the genetics of acinar adenocarcinomas and at least seven genetically different subtypes have been identified. DAC is known to present at an advanced stage with a high rate of extraprostatic extension and seminal vesicle invasion, and a decreased interval to biochemical recurrence and the development of metastatic disease, when compared to acinar adenocarcinoma. Our aim was to investigate the genetic profile of DAC to determine whether there is a genomic rationale for the aggressive behaviour associated with this tumor type. Frozen tissue from 11 cases of DAC with paired benign tissue was analysed. After DNA extraction, copy-number alteration analysis was performed, as well as identification of mutations and indels. We compared the fraction of the DAC genome with copy-number alteration to previous results from 74 primary acinar adenocarcinomas of the prostate. The alteration rate in DAC was comparable to that of acinar adenocarcinoma of high Gleason score. DAC harbored somatic changes seen in advanced and/or metastatic castration-resistant acinar adenocarcinoma, which likely accounts for its aggressive biological behavior.
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