Updates on Urothelial Carcinoma of the Upper Urinary Tract with a Focus on Molecular Findings.

Urothelial carcinoma (UC) of the upper urinary tract (UUT) is rare, constituting 5% to 10% of UCs, with a higher prevalence in males and older adults. It encompasses various subtypes and, unlike UC of the bladder, often presents as invasive disease. Molecular studies reveal frequent FGFR3 and TP53 mutations, guiding therapeutic strategies.

Information mismatch in PHH3-assisted mitosis annotation leads to interpretation shifts in H&E slide analysis.

The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation.

Full-length target sequences of GeoMx digital spatial profiling probes reveal that gene-promiscuity predicts probe sensitivity to EDTA tissue decalcification.

GeoMx Digital Spatial Profiling (Nanostring) is a commercial spatial transcriptomics method to selectively analyze regions of interest within intact tissue sections. We show that decalcification with ethylene-diamine-tetra-acetic (EDTA) variably attenuates probe counts, while probes that are more resistant to this effect consequently appear overexpressed after quantile normalization. By determining the undisclosed full-length target sequences of probes used in the human whole transcriptome panel, hereby updating target transcripts and genes, we find that the gene-promiscuity of probes is an important factor that determines sensitivity to EDTA incubation.

A single-center retrospective comparison of pT1 substaging methods in bladder cancer.

Substaging of T1 urothelial cancer is associated with tumor progression and its reporting is recommended by international guidelines. However, it has not been integrated in risk stratification tools and there is no agreement on the best method to use for its reporting. We aimed to investigate the applicability, interobserver variability, and prognostic value of histological landmark based and micrometric (aggregate linear length of invasive carcinoma (ALLICA), microscopic vs.

Cribriform versus Intraductal: How to Determine the Difference.

Over the years, our understanding of cribriform and intraductal prostate cancer (PCa) has evolved significantly, leading to substantial changes in their classification and clinical management. This review discusses the histopathological disparities between intraductal and cribriform PCa from a diagnostic perspective, aiming to aid pathologists in achieving accurate diagnoses. Furthermore, it discusses the ongoing debate surrounding the different recommendations between ISUP and GUPS, which pose challenges for practicing pathologists and complicates consensus among them.

Clofarabine Has a Superior Therapeutic Window as compared to Gemcitabine in Preclinical Bladder Cancer Models.

Current standard-of-care systemic therapy options for locally advanced and metastatic bladder cancer (BC), which are predominantly based on cisplatin-gemcitabine combinations, are limited by significant treatment failure rates and frailty-based patient ineligibility. We previously addressed the urgent clinical need for better-tolerated BC therapeutic strategies using a drug screening approach, which identified outstanding antineoplastic activity of clofarabine in preclinical models of BC. To further assess clofarabine as a potential BC therapy component, we conducted head-to-head comparisons of responses to clofarabine versus gemcitabine in preclinical in vitro and in vivo models of BC, complemented by in silico analyses.

Clinical Management of Intraductal Carcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) has emerged as a distinct entity with significant clinical implications in prostate cancer (PCa) management. Despite historically being considered an extension of invasive PCa, IDC-P shows unique biological characteristics that challenge traditional diagnostic and therapeutic settings. This review explores the clinical management of IDC-P.

Clinical parameters for the prediction of occult lymph node metastasis in patients with negative PSMA-PET.

Background: Depending on the risk of LN metastasis ePLND at RP is recommended. As ePLND has potential side effects, and diagnostics have improved substantially, our objective was to evaluate the performance of the Briganti 2019 nomogram in a contemporary cohort with preoperative negative PSMA-PET.

Methods: Patients with intermediate- and high-risk prostate cancer (CaP), undergoing RP and ePND at our center with preoperative negative [Ga]Ga-PSMA-11 PET were included.

Metastatic Translocated Renal Cell Carcinoma in a Kidney Transplant Patient - a Case Report and Review of the Literature.

-altered renal cell carcinomas are rare tumours. Here, we report the exceptional case of such a tumour in the setting of solid organ transplantation and with already metastatic disease at the time of diagnosis. The primary tumour occurred in the native kidney and only focally showed biphasic morphology whereas the metastasis, among others to the transplant kidney, showed nonspecific, albeit different morphology, but both had consistent translocation.

Update on classification of oncocytic neoplasms of the kidney.

Purpose Of Review: This review provides a summary of recent developments in classification of renal oncocytic neoplasms that were incorporated in the fifth edition WHO classification of renal tumors, released in 2022.

Recent Findings: Besides the distinct entities of renal oncocytoma and chromophobe renal cell carcinoma, the WHO now acknowledges a heterogeneous group of oncocytic tumors of the kidney that can be reported as 'oncocytic renal neoplasms of low malignant potential'. Case series by multiple institutions have revealed recurrent patterns of morphological features, protein marker expression, and genetic alterations within these neoplasms that may permit further subclassification in the future.

Mitosis domain generalization in histopathology images - The MIDOG challenge.

The density of mitotic figures (MF) within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of MF by pathologists is subject to a strong inter-rater bias, limiting its prognostic value. State-of-the-art deep learning methods can support experts but have been observed to strongly deteriorate when applied in a different clinical environment.

Update on Flat and Papillary Urothelial Lesions: Genitourinary Pathology Society Consensus Recommendations.

The reporting recommendations on "flat and papillary urothelial neoplasia," published in 2 position articles by the Genitourinary Pathology Society in July 2021, was a collective contribution of 38 multidisciplinary experts aiming to clarify nomenclature, classification of flat and papillary urothelial neoplasia and controversial issues. In this review, we discuss some of these recommendations including nomenclature, practical approaches, and their importance for clinical practice.

A novel molecular signature identifies mixed subtypes in renal cell carcinoma with poor prognosis and independent response to immunotherapy.

Background: Renal cell carcinoma (RCC) is a heterogeneous disease comprising histologically defined subtypes. For therapy selection, precise subtype identification and individualized prognosis are mandatory, but currently limited. Our aim was to refine subtyping and outcome prediction across main subtypes, assuming that a tumor is composed of molecular features present in distinct pathological subtypes.

Histological patterns, subtypes and aspects of prostate cancer: different aspects, different outcomes.

Purpose Of Review: The most common prostatic cancers (PCa) are acinary adenocarcinomas. Histological subtypes have been variably defined. The purpose of this review is to discuss unusual histological patterns and subtypes of acinar adenocarcinoma, as well as other types of PCa and their prognostic and therapeutic relevance.

Molecular uropathology and cancer genetics for the urologist: key findings for classification and diagnosis.

Purpose Of Review: To highlight the latest changes in prostate cancer (PCa), urothelial carcinoma, upper tract urothelial carcinoma (UTUC) and renal cell carcinoma (RCC) diagnosis and the impact of genetics in this field.

Recent Findings: Breast cancer1/2 mutations start to play a major role in PCa treatment with regard to personalized medicine. In urothelial carcinoma an overlap between histological pathological and molecular findings exists, fibroblast growth factor receptor alteration are starting to play a major role, programmed death-ligand 1 although problematic is still important in the treatment setting.

Brief update of the new WHO classification for urothelial carcinoma.

Purpose Of Review: Six years after the release of the 4th edition of the WHO classification on male and genitourinary tumors in 2016, the upcoming 5th edition will be released in 2022. This review will discuss significant changes in the new WHO classification for urothelial carcinoma.

Recent Findings: Substantial progress has been made during the last 6 years, especially in the molecular definition of bladder cancer, but also in treatment approaches.

Basal cell carcinoma of the prostate: a case report responding to the FGFR inhibitor pemigatinib and literature review.

Purpose Of Review: Due to the limited number of cases, there are no guidelines for basal cell carcinoma (BCC) of the prostate. This review combines an unpublished case report of a 55-year-old patient with BCC with an assessment of the latest literature.

Recent Findings: BCC of the prostate has previously been described in only approximately 140 cases.

Nonmuscle-invasive bladder cancer, old problems, new insights.

Purpose Of Review: Nonmuscle-invasive bladder cancer (NMIBC) is the most frequent bladder cancer and represents around 75% of bladder cancers. This review will discuss known challenges and recent advances in staging, grading and treatment stratification based on pathology.

Recent Findings: Pathological staging and grading in NMIBC remains challenging and different techniques exist.

Molecular and Pharmacological Bladder Cancer Therapy Screening: Discovery of Clofarabine as a Highly Active Compound.

Background: The heterogeneity of bladder cancers (BCs) is a major challenge for the development of novel therapies. However, given the high rates of recurrence and/or treatment failure, the identification of effective therapeutic strategies is an urgent clinical need.

Objective: We aimed to establish a model system for drug identification/repurposing in order to identify novel therapies for the treatment of BC.

Updated pathology reporting standards for bladder cancer: biopsies, transurethral resections and radical cystectomies.

Aim: Optimal management of bladder cancer requires an accurate, standardised and timely pathological diagnosis, and close communication between surgeons and pathologists. Here, we provide an update on pathology reporting standards of transurethral resections of the bladder and cystectomies.

Methods: We reviewed recent literature, focusing on developments between 2013 and 2021.