Deep learning-based quantification of eosinophils and lymphocytes shows complementary prognostic effects in colorectal cancer patients.

The immune microenvironment of colorectal cancer is a major component of the disease and influences not only tumor progression and patient outcome but also therapy response. Expanding on existing studies which have explored the prognostic value of the adaptive immune response with lymphocytes, our study integrates innate immune cells, specifically eosinophils, in a combined analysis. To evaluate the prognostic significance of eosinophils within the context of lymphocyte infiltration, we analyzed a large collective of 1625 colorectal cancer cases from four different centers.

Impact of multikinase inhibitors in reshaping the treatment of advanced gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine tumors (NETs) pose a considerable challenge due to their increasing incidence and frequently late-stage diagnosis. The arrival of multikinase inhibitors (MKIs) into clinical practice has brought notable progress in the management of advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This review aims at exploring the impact of MKIs in reshaping the treatment landscape for advanced GEP-NETs.

Characteristics and treatment outcome in a prospective cohort of 639 advanced high-grade digestive neuroendocrine neoplasms (NET G3 and NEC). The NORDIC NEC 2 study.

Background: Digestive high-grade neuroendocrine neoplasms (HG-NEN) are rare and classified as neuroendocrine carcinomas (NEC) or neuroendocrine tumours G3 (NET G3), and differ in clinical and molecular characteristics, response to treatment and prognosis.

Methods: Prospective multicenter study registering clinical data on patients with digestive HG-NEN. Treatment outcome in patients with advanced disease was compared after centralized pathological re-evaluation.

Pancreatic neuroendocrine neoplasms (pNENs): Genetic and environmental biomarkers for risk of occurrence and prognosis.

Pancreatic neuroendocrine neoplasms (pNENs) are rare and heterogeneous tumors arising from neuroendocrine cells, representing approximately 10 % of all Gastro-Entero-Pancreatic neuroendocrine neoplasms. While most pNENs are sporadic, a subset is associated with genetic syndromes such as multiple endocrine neoplasia type 1 (MEN1) or von Hippel-Lindau disease (VHL). pNENs are further classified into functioning and non-functioning tumors, with distinct clinical behaviors, prognoses, and treatment approaches.

Basic science and translational implications of current knowledge on neuroendocrine tumors.

Neuroendocrine tumors (NETs) are a diverse group of malignancies that can occur in various organs, with a notable prevalence in the lungs and gastrointestinal tract, which are the focus of this Review. Although NETs are rare in individual organs, their incidence has increased over recent decades, highlighting the urgent need for current classification systems to evolve by incorporating recent advances in the understanding of NET biology. Several omics studies have revealed molecular subtypes, which, when integrated into existing classification frameworks, may provide more clinically relevant insights for patients with NETs.

[Neuroendocrine tumors].

Neuroendocrine tumors (NETs) are a diverse group of neoplasms that originate from neuroendocrine cells throughout the body. Diagnosing NETs presents unique challenges due to their varied presentation, morphology, and biological behavior. This article provides an overview of the key diagnostic principles relevant to general pathologists, emphasizing the importance of a multidisciplinary approach that integrates clinical, radiological, histopathological, and immunohistochemical data.

Screening and surveillance practices for Multiple Endocrine Neoplasia type 1-related Neuroendocrine Tumours in European Neuroendocrine Tumor Society Centers of Excellence (ENETS CoE)-An ENETS MEN1 task force questionnaire study.

Multiple Endocrine Neoplasia type 1 (MEN1) Clinical Practice Guidelines (2012) are predominantly based on expert opinion due to limited available evidence at the time, leaving room for interpretation and variation in practices. Evidence on the natural course of MEN1-related neuroendocrine tumours (NET) and the value of screening programs has increased and new imaging techniques have emerged. The aim of this study is to provide insight in the current practices of screening and surveillance for MEN1-related NETs in ENETS Centers of Excellence (CoEs).

ARX, PDX1, ISL1, and CDX2 Expression Distinguishes 5 Subgroups of Pancreatic Neuroendocrine Tumors With Correlations to Histology, Hormone Expression, and Outcome.

Many pancreatic neuroendocrine tumors (PanNETs) fall into 2 major prognostic subtypes based on DAXX/ATRX-induced alternative lengthening of telomerase phenotype and alpha- and beta-cell-like epigenomic profiles. However, these PanNETs are still flanked by other PanNETs that do not fit into either subtype. Furthermore, despite advanced genotyping, PanNETs are generally not well-characterized in terms of their histologic and hormonal phenotypes.

Treatment outcome according to genetic tumour alterations and clinical characteristics in digestive high-grade neuroendocrine neoplasms.

Background: Chemotherapy has limited efficacy in advanced digestive high-grade neuroendocrine neoplasms (HG-NEN) and prognosis is dismal. Predictive markers for palliative chemotherapy are lacking, and prognostic markers are limited.

Methods: Digestive HG-NEN patients (n = 229) were prospectively included 2013-2017.

3D Virtual Histopathology by Phase-Contrast X-Ray Micro-CT for Follicular Thyroid Neoplasms.

Histological analysis is the core of follicular thyroid carcinoma (FTC) classification. The histopathological criteria of capsular and vascular invasion define malignancy and aggressiveness of FTC. Analysis of multiple sections is cumbersome and as only a minute tissue fraction is analyzed during histopathology, under-sampling remains a problem.

Patient derived tumoroids of high grade neuroendocrine neoplasms for more personalized therapies.

There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced high-grade GEP-NEN patients and applied this model for targeted rapid ex vivo pharmacotyping, next-generation sequencing, and perturbational profiling. We used tissue-matched PD tumoroids to profile individual patients, compared ex vivo drug response to patients' clinical response to chemotherapy, and investigated treatment-induced adaptive stress responses.

External validation of a deep learning-based algorithm for detection of tall cells in papillary thyroid carcinoma: A multicenter study.

The tall cell subtype (TC-PTC) is an aggressive subtype of papillary thyroid carcinoma (PTC). The TC-PTC is defined as a PTC comprising at least 30% epithelial cells that are three times as tall as they are wide. In practice, this definition is difficult to adhere to, resulting in high inter-observer variability.

Pancreatic Neuroendocrine Microtumors (WHO 2022) Are Not Always Low-Grade Neoplasms: A Case with a Highly Increased Proliferation Rate.

Traditionally considered non-functional low proliferative benign neuroendocrine proliferations measuring less than 5 mm, pancreatic (neuro)endocrine microadenomas are now classified as pancreatic neuroendocrine microtumors in the 2022 WHO classification of endocrine and neuroendocrine tumors. This case report discussed the features of an incidentally identified 4.7-mm glucagon-expressing pancreatic neuroendocrine microtumor with MEN1 mutation only, chromosomally stable and an epigenetic alpha-like phenotype.

Syndromic MEN1 parathyroid adenomas consist of both subclonal nodules and clonally independent tumors.

Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary hyperplasia". Whether these tumors represent a multi-glandular clonal disease or hyperplasia has not been robustly proven so far. Loss of Menin protein expression is associated with inactivation of both alleles and a good surrogate for a MEN1 gene mutation.

[Practical application of immunohistochemistry in pancreatic neuroendocrine neoplasms : Tips and pitfalls].

Pancreatic neuroendocrine neoplasms (PanNEN) are rather rare entities. Morphology, combined with immunohistochemistry, allows typing and grading, thereby leading therapeutic decisions. Depending on tumor stage and differential diagnosis, a broad diagnostic panel may be required.

European Neuroendocrine Tumour Society (ENETS) 2023 guidance paper for nonfunctioning pancreatic neuroendocrine tumours.

This ENETS guidance paper for well-differentiated nonfunctioning pancreatic neuroendocrine tumours (NF-Pan-NET) has been developed by a multidisciplinary working group, and provides up-to-date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF-Pan-NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN.

Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms.

Background: The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients.

Methods: Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m for 7 days every 2 weeks.

Müller matrix polarimetry for pancreatic tissue characterization.

Polarimetry is an optical characterization technique capable of analyzing the polarization state of light reflected by materials and biological samples. In this study, we investigate the potential of Müller matrix polarimetry (MMP) to analyze fresh pancreatic tissue samples. Due to its highly heterogeneous appearance, pancreatic tissue type differentiation is a complex task.

Pathologist Computer-Aided Diagnostic Scoring of Tumor Cell Fraction: A Swiss National Study.

Tumor cell fraction (TCF) estimation is a common clinical task with well-established large interobserver variability. It thus provides an ideal test bed to evaluate potential impacts of employing a tumor cell fraction computer-aided diagnostic (TCFCAD) tool to support pathologists' evaluation. During a National Slide Seminar event, pathologists (n = 69) were asked to visually estimate TCF in 10 regions of interest (ROIs) from hematoxylin and eosin colorectal cancer images intentionally curated for diverse tissue compositions, cellularity, and stain intensities.

Germline pathogenic variants in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms.

High-grade gastroenteropancreatic (HG-GEP) neuroendocrine neoplasms (NENs) are highly aggressive cancers. The molecular etiology of these tumors remains unclear, and the prevalence of pathogenic germline variants in patients with HG-GEP NENs is unknown. We assessed sequencing data of 360 cancer genes in normal tissue from 240 patients with HG-GEP NENs; 198 patients with neuroendocrine carcinomas (NECs) and 42 with grade 3 neuroendocrine tumors (NET G3).