The pathology of urinary bladder lesions with an inverted growth pattern

Inverted lesions in the urinary bladder have been the source of some difficulty in urological pathology. The two common ones are von Brunn＇s nests and cystitis cystic/cystitis glandularis, which are considered normal variants of urothelium. Apart from them, a number of other rare urothelial lesions with inverted growth pattern occur in the urinary bladder. Some of them are only reactive conditions, just as pseudocarcinomatous hyperplasia. Some are benign tumors, namely inverted papilloma. Whereas others are malignant neoplasms, including inverted papillary urothelial neoplasm of low malignant potential （PUNLMP）, non-invasive inverted papillary urothelial carcinoma （low-grade and high-grade）, and invasive urothelial carcinoma （inverted, nested and big nested variants）. Because of the overlapping morphological features of all the inverted lesions mentioned above, even between high-grade invasive carcinoma and psendoearcinomatous hyperplasia which are only a kind of reactive conditions, it is very important for the surgical pathologist to recognize and be familiar with these inverted lesions in urinary bladder. In this article, we review these spectrums of inverted lesions of the urinary bladder. Emphasis is placed on histogenesis, morphology, differential diagnosis of these lesions, and the pathologic grading of the non-invasive inverted neoplasms, such as inverted papilloma, inverted PUNLMP, non-invasive inverted papillary urothelial carcinoma with low-grade, and non-invasive inverted papillary urothelial carcinoma with high-grade.

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer(RATICAL):a nationwide multicenter retrospective study

Background:Anaplastic lymphoma kinase(ALK)test in advanced non-small cell lung cancer(NSCLC)can help physicians provide target therapies for patients harboring ALK gene rearrangement.This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.Methods:In this real-world study(ChiCTR2000030266),patientswith advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1,2018 and December 31,2019 were retrospectively analyzed.Interpretation training was conducted before the study was initiated.Quality controls were performed at participating centers using immunohistochemistry(IHC)-VENTANA-D5F3.The positive ALK gene rearrangement rate and consistency rate were calculated.The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.Results:The overall ALK gene rearrangement rate was 6.7%in 23,689 patients with advanced NSCLC and 8.2%in 17,436 patients with advanced lung adenocarcinoma.The quality control analysis of IHC-VENTANA-D5F3 revealed an intrahospital consistency rate of 98.2%(879/895)and an inter-hospital consistency rate of 99.2%(646/651).IHC-VENTANA-D5F3 was used in 53.6%,real-time polymerase chain reaction(RT-PCR)in 25.4%,next-generation sequencing(NGS)in 18.3%,and fluorescence in-situ hybridization(FISH)in 15.9%in the adenocarcinoma subgroup.For specimens tested with multiple methods,the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0%(822/839)for FISH,98.7%(1,222/1,238)forNGS,and 91.3%(146/160)for RT-PCR.The overall ALK gene rearrangement rateswere higher in females,patients of≤35 years old,never smokers,tumor cellularity of>50,and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup(all P<0.05).Conclusions:This study highlights the real-world variability and challenges of ALK test in advanced NSCLC,demonstrating a predominant use of IHCVENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients.These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

DPHL:A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery

To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.