Myoid gonadal stromal tumours are characterised by recurrent chromosome-level copy number gains: molecular assessment of a multi-institutional series.

Myoid gonadal stromal tumours (MGST) represent a rare type of testicular sex cord-stromal tumour that has recently been recognised as a distinct entity by the World Health Organization (WHO) classification of genitourinary tumours. MGSTs affect adult men and have been reported to behave in an indolent fashion. Histologically, MGSTs are pure spindle cell neoplasms that coexpress SMA and S100 protein. Given that the molecular features of these neoplasms remain largely undescribed, we evaluated a multi-institutional series of MGSTs using DNA and RNA sequencing. This study included 12 tumours from 12 patients aged 28 to 57 years. Tumour sizes ranged from 0.6 to 4.3 cm. Aggressive histologic features, such as vascular invasion, necrosis, invasive growth, and atypical mitoses were invariably absent. Mitotic activity was low, with a median of less than 1 mitosis per 10 high power fields (HPF; maximum: 3 mitoses per 10 HPF). Molecular analyses did not identify recurrent mutations or gene fusions. All cases with interpretable copy number variant data (9/10 cases sequenced successfully) demonstrated a consistent pattern of chromosome arm-level and whole-chromosome-level copy number gains indicative of ploidy shifts, with recurrent gains involving chromosomes 3, 6, 7, 8, 9, 11, 12, 14q, 15q, 17, 18q, 20, and 21q. Similar findings have also been recognised in pure spindle cell and spindle-cell predominant sex cord-stromal tumours without S100 protein expression. MGSTs are characterised by ploidy shifts and may be part of a larger spectrum of spindle cell-predominant sex cord-stromal tumours, including cases without S100 protein expression.

Incorporating Prognostic Biomarkers into Risk Assessment Models and TNM Staging for Prostate Cancer.

In current practice, prostate cancer staging alone is not sufficient to adequately assess the patient's prognosis and plan the management strategies. Multiple clinicopathological parameters and risk tools for prostate cancer have been developed over the past decades to better characterize the disease and provide an enhanced assessment of prognosis. Herein, we review novel prognostic biomarkers and their integration into risk assessment models for prostate cancer focusing on their capability to help avoid unnecessary imaging studies, biopsies and diagnosis of low risk prostate cancers, to help in the decision-making process between active surveillance and treatment intervention, and to predict recurrence after radical prostatectomy. There is an imperative need of reliable biomarkers to stratify prostate cancer patients that may benefit from different management approaches. The integration of biomarkers panel with risk assessment models appears to improve prostate cancer diagnosis and management. However, integration of novel genomic biomarkers in future prognostic models requires further validation in their clinical efficacy, standardization, and cost-effectiveness in routine application.

pT1 high-grade bladder cancer: histologic criteria, pitfalls in the assessment of invasion, and substaging.

Most patients with bladder carcinoma are diagnosed with non-muscle-invasive disease, stage Ta, and pT1. Stage remains as the single most important prognostic indicator in urothelial carcinoma. Among the pT1 bladder cancer patients, recurrence and progression of disease occur in 50% and 10%, respectively. The identification of high-risk patients within the pT1 subgroup remains an important clinical goal and an active field of research. Substaging of pT1 disease has been claimed as important histologic discriminator by the 2016 World Health Organization (WHO) classification of the genitourinary tract tumors and by the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual supporting its implementation in clinical practice. Interobserver variation in pT1 diagnosis and the associated pitfalls in pT1 assessment are the critical pathological issues. The aim of this review paper is to provide the practicing pathologist with the state of the art of morphological and immunohistochemical features useful for the diagnosis of early invasive bladder carcinomas, including practical clues on how to avoid relevant interpretative pitfalls, and to summarize the current status of pT1 substaging.

Digital versus light microscopy assessment of extraprostatic extension in radical prostatectomy samples.

Focal or non-focal/extensive extraprostatic extension of prostate carcinoma is an important pathologic prognostic parameter to be reported after radical prostatectomy. Currently, there is no agreement on how to measure and what are the best cutoff points to be used in practice. We hypothesized that digital microscopy would potentially provide more objective measurements of extraprostatic extension, thus better defining its clinical significance. To further our knowledge on digital prostate pathology, we evaluated the status of extraprostatic extension in 107 consecutive laparoscopic radical prostatectomy samples, using digital and conventional light microscopy. Mean linear and radial measurements of extraprostatic extension by digital microscopy significantly correlated to pT status (p = 0.022 and p = 0.050, respectively) but only radial measurements correlated to biochemical recurrence (p = 0.042) and grade groups (p = 0.022). None of the measurements, whether conventional or digital, were associated with lymph node status. Receiving operating characteristic analysis showed a potential cutoff point to assess linear measurements by conventional (< vs. > 24.21 mm) or digital microscopy (< vs. > 15 mm) or by radial measurement (< vs. > 1.6 mm). Finally, we observed an association between the number of paraffin blocks bearing EPE with pT (p = 0.041) status (digital microscopy), and linear measurements by conventional (p = 0.044) or digital microscopy (p = 0.045) with lymph node status. Reporting EPE measurements by digital microscopy, both linear and radial, and the number of paraffin blocks with EPE, might provide additional prognostic features after radical prostatectomy.

PD-L1 assessment in urothelial carcinoma: a practical approach.

Five programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of locally advanced or metastatic urothelial carcinoma of the bladder and the upper urinary tract. Due to restrictions by the FDA and EMA first-line treatment with Atezolizumab and Pembrolizumab in platinum-ineligible patients requires immunohistochemical PD-L1 testing. In the second-line setting all drugs are approved without PD-L1 testing. Used PD-L1 assays in clinical trials include the 28-8 pharmDx (Nivolumab), the 22C3 pharmDx (Pembrolizumab), Ventana SP142 (Atezolizumab), and the Ventana PD-L1 SP263 assays (Durvalumab). Differences in antibodies, needed platforms and testing algorithms have raised questions about interchangeability and comparability among these assays and their diagnostic use. We provide a practical review about the current recommendations, used assays and algorithms of PD-L1 testing in urothelial carcinoma to help oncologists, urologists and pathologists to understand analytical features, differences in antibody assays, differences in scoring algorithms and comparability of various PD-L1 assays. We reviewed and summarized published studies from the last four years (2016-2019) on PD-L1 testing in bladder cancer and present a condensed practical guideline including pre-analytical, analytical and test-specific issues.