The 2022 International Society of Urological Pathology consensus conference on current issues in bladder cancer made recommendations regarding adoption of a three-tier grading system, grading of cancers with grade heterogeneity, grading and reporting of bladder cancers with subtype/divergent differentiation, and mandatory subcategorisation of T1 bladder cancers.

Prostate adenocarcinoma (PRAD) is a common cancer diagnosis among men globally, yet large gaps in our knowledge persist with respect to the molecular bases of its progression and aggression. It is mostly indolent and slow-growing, but aggressive prostate cancers need to be recognized early for optimising treatment, with a view to reducing mortality.
Based on TCGA transcriptomic data pertaining to PRAD and the associated clinical metadata, we determined the sample Gleason grade, and used it to execute: (i) Gleason-grade wise linear modeling, followed by five contrasts against controls and ten contrasts between grades; and (ii) Gleason-grade wise network modeling via weighted gene correlation network analysis (WGCNA). Candidate biomarkers were obtained from the above analysis and the consensus found. The consensus biomarkers were used as the feature space to train ML models for classifying a sample as benign, indolent or aggressive.
The statistical modeling yielded 77 Gleason grade-salient genes while the WGCNA algorithm yielded 1003 trait-specific key genes in grade-wise significant modules. Consensus analysis of the two approaches identified two genes in Grade-1 (SLC43A1 and PHGR1), 26 genes in Grade-4 (including LOC100128675, PPP1R3C, NECAB1, UBXN10, SERPINA5, CLU, RASL12, DGKG, FHL1, NCAM1, and CEND1), and seven genes in Grade-5 (CBX2, DPYS, FAM72B, SHCBP1, TMEM132A, TPX2, UBE2C). A RandomForest model trained and optimized on these 35 biomarkers for the ternary classification problem yielded a balanced accuracy ∼ 86% on external validation.
The consensus of multiple parallel computational strategies has unmasked candidate Gleason grade-specific biomarkers. PRADclass, a validated AI model featurizing these biomarkers achieved good performance, and could be trialed to predict the differentiation of prostate cancers. PRADclass is available for academic use at: https://apalania.shinyapps.io/pradclass (online) and https://github.com/apalania/pradclass (command-line interface).

暂无摘要。

Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of this study was to validate the new guidelines for canine meningiomas. To evaluate the inter-observer agreement, 5 veterinary surgical pathologists graded 158 canine meningiomas following the human grading system alone or with the new guidelines. The inter-observer agreement for histologic grade and each of the grading criteria (mitotic grade, invasion, spontaneous necrosis, macronucleoli, small cells, hypercellularity, pattern loss and anaplasia) was evaluated using the Fleiss kappa index. The diagnostic accuracy (sensitivity and specificity) was assessed by comparing the diagnoses obtained with the 2 grading systems with a consensus grade (considered the reference classification). The consensus histologic grade was obtained by agreement between 4 experienced veterinary neuropathologists following the guidelines. Compared with the human grading alone, the canine-specific guidelines increased the inter-observer agreement for: histologic grade (κ = 0.52); invasion (κ = 0.67); necrosis (κ = 0.62); small cells (κ = 0.36); pattern loss (κ = 0.49) and anaplasia (κ = 0.55). Mitotic grade agreement remained substantial (κ = 0.63). The guidelines improved the sensitivity in identifying grade 1 (95.6%) and the specificity in identifying grade 2 (96.2%) meningiomas. In conclusion, the new grading guidelines for canine meningiomas are associated with an overall improvement in the inter-observer agreement and higher diagnostic accuracy in diagnosing grade 1 and grade 2 meningiomas.

The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based proposals on the applications of grading in noninvasive urothelial carcinoma with mixed grades, invasive urothelial carcinoma including subtypes (variants) and divergent differentiations, and in pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. By 2004 WHO grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high-grade, and the rare invasive low-grade tumors show only limited superficial invasion. While by 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached if T1 tumors should be graded either by the 2004 WHO system or by the 1973 WHO system. Because of the concern for underdiagnosis and underreporting with potential undertreatment, participants unanimously recommended that the presence of urothelial carcinoma subtypes and divergent differentiations should be reported. There was consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiation should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high-grade according to the 2004 WHO grading system. However, participants strongly acknowledged that subtypes and divergent differentiations should not be considered as a homogenous group in terms of behavior. Thus, future studies should focus on individual subtypes and divergent differentiations rather than lumping these different entities into a single clinicopathological group. Likewise, clinical recommendations should pay attention to the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. There was consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the International Society of Urological Pathology Working Group 2 proceedings addresses some of the issues on grading beyond its traditional application, including for papillary urothelial carcinomas with mixed grades and with invasive components. Reporting of subtypes and divergent differentiation is also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors.

暂无摘要。

Grade is a key prognostic factor in determining progression in nonmuscle invasive papillary urothelial carcinomas. The 2 most common grading methods in use worldwide are the World Health Organization (WHO) 2004 and 1973 schemes. The International Society of Urological Pathology (ISUP) organized the 2022 consensus conference in Basel, Switzerland on current issues in bladder cancer and tasked working group 1 to make recommendations for future iterations of bladder cancer grading. For this purpose, the ISUP developed in collaboration with the European Association of Urology a 10-question survey for their memberships to understand the current use of grading schemes by pathologists and urologists and to ascertain the areas of potential improvements. An additional survey was circulated to the ISUP membership for their opinion on interobserver variability in grading, reporting of urine cytology, and challenges encountered in grade assignment. Comprehensive literature reviews were performed on bladder cancer grading prognosis and interobserver variability along with The Paris System for urine cytology. There are notable differences in practice patterns between North American and European pathologists in terms of used grading scheme and diagnosis of papillary urothelial neoplasm of low malignant potential. Areas of common ground include difficulty in grade assignment, a desire to improve grading criteria, and a move towards subclassifying high-grade urothelial carcinomas. The surveys and in-person voting demonstrated a strong preference to refine current grading into a 3-tier scheme with the division of WHO 2004 high grade into clinically relevant categories. More variable opinions were voiced regarding the use of papillary urothelial carcinoma with low malignant potential.

High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.

Gastrointestinal pancreas (GEP) is the most common site of neuroendocrine neoplasms (NENs). In 2019, the World Health Organization (WHO) classification for GEP NET was updated to include a new category of well-differentiated high-grade (Ki 67>20%) GEP-NET G3, distinct from high-grade poorly differentiated neuroendocrine carcinoma (NEC). As a new category, NET G3 are considered a molecularly, radiologically, and prognostically distinct entity compared to NEC and NET G1/G2. The management of NET G3 remains a challenge awaiting future trials taking into consideration the unique characteristics of this new category. The latest NCCN clinical guidelines of neuroendocrine and adrenal tumors firstly gave the recommendation of diagnosis and treatment of G3 NET separately from NEC and G1/G2 NET. Hereon,we aim to summarize the management of G3 NET in combination with the new NCCN guidelines and the current evidences.
胃肠胰是神经内分泌肿瘤最好发的部位。2019年WHO重新发布了胃肠胰神经内分泌肿瘤的分级标准，将细胞分化好、Ki67增殖指数>20%的肿瘤从原来的G3级神经内分泌癌（G3 NEC）分离出来，定义为G3级神经内分泌瘤（G3 NET）。G3 NET做为一个新的分级，在分子学、影像学以及预后方面均与NEC和G1/G2 NET表现不同，并且在诊治上仍有待探索。2021年神经内分泌肿瘤美国国立综合癌症网络（NCCN）指南也首次单独对G3 NET的诊治进行了推荐。在此，我们结合新版NCCN指南对G3 NET的诊治进行了总结。.

OBJECTIVE: To evaluate the role of alkaline phosphatase (ALP) as marker of bone metastases in patients of genitourinary cancers compared to bone scan, and to correlate with NCCN guidelines.
METHODS: This retro-prospective, observational study included all newly diagnosed patients of renal, bladder (muscle invasive) and prostate cancers who presented from July 2014 to March 2017. For diagnosis of bone metastases, ALP groups (raised/normal) were compared with bone scan (positive/negative). Sub-group analysis was done on patients with normal ALP levels and positive bone scan.
RESULTS: 150 patients were included and stratified depending on bone scan findings. Hemoglobin values were significantly different between two groups in renal and prostate cancers (p=0.015 and 0.002 respectively). AL values were significantly different between two groups in prostate cancers (p=0.0008), but not for others. Three out of seven patients with bone metastases for renal cancers (42.9%) and all three for bladder cancers had normal ALP values, no bone symptoms, and would have been missed. For prostate cancers, out of 23 who had bone metastases, ALP was normal in ten. All these ten had Gleason score of > 8 and all except one had S. PSA > 20ng/ml. All cases would have been detected irrespective of ALP values.
CONCLUSIONS: ALP has limited sensitivity but reasonable negative predictive value for bone metastases in genitourinary cancers. Current guidelines may miss significant number of cases with bone metastases for renal and bladder cancers. Current guidelines have good accuracy for prostate cancers, since PSA and Gleason score are independent predictors of bone metastases.