Epstein-Barr Virus-associated gastric cancer: a histopathologic study with comprehensive molecular profiling.

A subset of gastric cancers (GCs) is linked to Epstein-Barr virus (EBV) infection. This study aims to characterize the histopathological and molecular features of EBV-associated GCs (EBVaGCs), focusing on predictive biomarkers and genomic and transcriptomic analysis. A total of 35 primary EBVaGCs were considered.

Pathology of the malignant colorectal polyp: Issues in morphologic criteria and recommendations from the Italian Group of Gastrointestinal Pathologists.

Malignant colorectal polyps (MCPs) are early-stage colorectal cancers (CRC) generally diagnosed following endoscopic removal of otherwise bland lesions. Due to nodal metastatic potential and risk of residual disease, diagnosis and risk stratification of MCPs are critical for determining appropriate clinical management, which can range from clinical/endoscopic/imaging follow-up to radical surgery with locoregional lymphadenectomy. Although a dedicated multidisciplinary team should discuss this decision, the MCP histopathologic assessment is crucial and raises several issues.

Lights and shadows of microsatellite status characterization in gastrointestinal cancers in the era of cancer precision therapy.

The introduction of immunotherapy has dramatically changed the paradigm of solid tumor treatment with the creation of novel therapeutic opportunities even for tumors that currently lack valid therapeutic options in the advanced or metastatic setting. Initially, the role of deficient mismatch repair status (dMMR)/microsatellite instability (MSI) as a predictive biomarker was confined to colorectal cancer. In 2017, MSI/dMMR became the first true agnostic biomarker to stratify patient response to immune checkpoint inhibitors.

Increased [F]DPA-714 Uptake in the Skeletal Muscle of SOD1 Mice: A New Potential of Translocator Protein 18 kDa Imaging in Amyotrophic Lateral Sclerosis.

Purpose: The skeletal muscle has been proposed to contribute to the progressive loss of motor neurons typical of amyotrophic lateral sclerosis (ALS). However, this mechanism has not yet been clarified due to the lack of suitable imaging tools. Here, we aimed to verify whether PET imaging of the translocator protein 18 kDa (TSPO) can detect a muscular abnormality in an experimental model of ALS.

Thyroid lesions of neuroendocrine origin? Thinking of a "polka-dotted" zebra! Case series from three Italian referral centers and review of the literature.

Background: Neuroendocrine neoplasms (NENs) may metastasize very rarely to the thyroid. The current paper aims at identifying peculiar thyroid nodule's features that could prompt their diagnosis and analyzing therapeutic approach and patient's outcome.

Materials And Methods: A case series of three patients have been collected from three Italian referral centers.

HER2, HER3, and Mismatch Repair Protein Expression in Stage IV Small Bowel Adenocarcinoma: Results From a Multicenter Series.

Small bowel adenocarcinoma (SBA) is a rare and aggressive malignancy. One-third of SBA cases are diagnosed at an advanced stage, often with limited treatment options. Recent clinical trials have underscored the importance of testing predictive biomarkers for therapy response in advanced solid tumors, particularly with respect to antibody-drug conjugates and immunotherapy.

Barriers and Facilitators in Diagnostic Pathways That Align Universal Tumor Screening and Mainstream Genetic Testing for Lynch Syndrome in Colorectal Cancer: Protocol for a Scoping Review With a Narrative Synthesis.

Background: Approximately 3% of colorectal cancers (CRCs) are due to Lynch syndrome (LS), a hereditary cancer syndrome caused by pathogenic variants (PVs) in the mismatch repair (MMR) genes. Patients with CRC and LS have elevated lifetime risks for a range of cancers and require personalized treatment and targeted surveillance. Relatives of people affected by LS who share the same PV also have elevated cancer risks and can benefit from preventive measures and/or risk-reducing surgeries.

One protocol to rule them all: a pilot study to identify the best fixation and decalcification approach for bone marrow biopsy immunohistochemistry.

Objective: Standardization of the pre-analytical phases of bone marrow trephine biopsy (BM) has yet to be achieved. In particular, several fixative and decalcifying reagents with specific benefits and drawbacks are described, but only a few direct comparisons are available. This study aims to test the most used fixation and decalcification protocols and evaluate their effect on tissue antigenicity via immunohistochemistry (IHC).

Immunohistochemical biomarker scoring in gastroesophageal cancers: Can computers help us?

The increasing complexity of cancer diagnostics and treatment selection has placed a growing burden on pathologists, particularly in the evaluation of immunohistochemical (IHC) biomarkers. In gastroesophageal cancers (GEC), both adenocarcinoma and squamous cell carcinoma subtypes, multiple prognostic and predictive biomarkers must be assessed to guide therapy. These evaluations require meticulous scoring, are time-consuming, and suffer from inter- and intra-observer variability.

Autoimmune chronic atrophic gastritis: association between chronic proton pump inhibitors use and more severe atrophy and gastric intestinal metaplasia.

Introduction And Aim: Autoimmune chronic atrophic gastritis (ACAG) is a chronic autoimmune disorder whose diagnostic complexity arises from diverse symptoms mimicking other gastrointestinal disorders, often leading to misdiagnosis. Despite diagnosis, patients are often treated with proton pump inhibitors (PPIs) before consulting a gastroenterologist, emphasizing the need for accurate identification and management of ACAG in primary care. This study aimed to explore factors influencing disease progression.

Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases.

Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness.

Heterogeneity of predictive biomarker expression in gastric and esophago-gastric junction carcinoma with peritoneal dissemination.

Background: Temporal and spatial molecular heterogeneity contributes to resistance to targeted and immune therapies in gastric and esophagogastric junction carcinoma (G/EGJ). This study evaluates differences in biomarker expression between primary G/EGJ and paired peritoneal metastases (PM).

Methods: We analyzed 74 cases of primary G/EGJ and paired PM using immunohistochemistry for HER2, PD-L1, Claudin18 (CLDN18), DNA mismatch repair (MMR) proteins, p53, E-cadherin, and in situ hybridization for EBER.

Histologic alterations are common in Monogenic Disease patients with 'healthy' endoscopy: Results from a GIPAD-GIPPI multicenter study.

Objective: Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before 6 years of age, encompassing 'pure' IBD (Crohn's Colitis/Ulcerative Colitis)/non IBD colitis, and monogenic diseases (MDs), the latter often related to primary immunodeficiency disorders. A multidisciplinary approach is imperative for correct therapeutic management, as endoscopy and histology are not always completely informative. In this setting, the study aims to describe the extent/features of histologic lesions in both endoscopically damaged mucosa and otherwise endoscopically healthy (normal/near normal) mucosa.

Adenomyoma/adenomyomatosis-associated mural intracholecystic neoplasms: analysis of clinico-pathologic, imaging, and molecular features of a consecutive case series.

Adenomyoma/adenomyomatosis (AM) of the gallbladder is generally considered an incidental and innocuous finding; however, neoplastic lesions, including intracholecystic neoplasms (ICNs), flat-type dysplasia, and carcinomas, may arise within AM. AM-associated ICNs, composed of mural cystically dilated glands containing florid papillary proliferations lined by mucinous and/or overtly dysplastic epithelium, are very rare and poorly characterized. This study aimed at investigating the clinico-radiologic, phenotypic/immunophenotypic, and molecular features of a mono-institutional case series of four AM-ICNs (0.

Oncocytic and spindle cell typical carcinoids of lung: different immunophenotype and biological behavior.

Pulmonary typical carcinoids (TCs) are uncommon, well-differentiated neuroendocrine tumors of the lung that do not exhibit necrosis and have fewer than two mitoses per 2 mm, as defined by the current World Health Organization classifications. Despite their low-grade status and favorable prognostic impact, the protein expression profile and morphological characteristics associated with tumor progression and metastatic spread remain largely unidentified. Oncocytic and spindle cell histological variants are acknowledged for their role in differential diagnosis, though their clinical significance remains a topic of debate.

MLH1 gene promoter methylation status partially overlaps with CpG methylator phenotype (CIMP) in colorectal adenocarcinoma.

Background: RAS/BRAF mutations, mismatch DNA repair complex deficiency (MMRd)/microsatellite instability (MSI), and CpG methylator phenotype (CIMP) are key molecular actors in colorectal carcinogenesis. To date, conflicting evidence about the correlations between these molecular features has been reported.

Materials And Methods: A retrospectively selected cohort of 123 CRCs was divided into 3 groups based on the molecular characteristics: MMR proficient (MMRp)/BRAF p.

Pre-Surgical Endoscopic Biopsies Are Representative of Esophageal and Esophago-Gastric Junction Adenocarcinoma Histologic Classes and Survival Risk.

The Esophageal Adenocarcinoma Study Group Europe (EACSGE) recently proposed a granular histologic classification of esophageal-esophago-gastric junctional adenocarcinomas (EA-EGJAs) based on the study of naïve surgically resected specimens that, when combined with the pTNM stage, is an efficient indicator of prognosis, molecular events, and response to treatment. In this study, we compared histologic classes of endoscopic biopsies taken before surgical resection with those of the surgical specimen, to evaluate the potential of the EACSGE classification at the initial diagnostic workup. A total of 106 EA-EGJA cases with available endoscopic biopsies and matched surgical resection specimens were retrieved from five Italian institutions.

Detecting BRAF mutations in colorectal cancer in clinical practice: An Italian experts' position paper.

BRAF p.V600E exon 15 hotspot mutation can identify a molecular subgroup of metastatic colorectal cancer (mCRC) patients exhibiting poor prognosis under the conventional chemotherapy regimen. Recently, the chemotherapy-free combination of encorafenib and cetuximab has been approved as the standard of care for previously treated BRAF p.

Comparative Targeted Genome Profiling between Solid and Liquid Biopsies in Gastroenteropancreatic Neuroendocrine Neoplasms: A Proof-of-Concept Pilot Study.

Introduction: Clinical presentation and genetic profile of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly variable, hampering their management. Sequencing of circulating tumor DNA from liquid biopsy (LB) has been proposed as a less invasive alternative to solid biopsy (SB). Our aim was to compare the mutational profile (MP) provided by LB with that deriving from SB in GEP-NETs.

Prognostic and Predictive Roles of HER2 Status in Non-Breast and Non-Gastroesophageal Carcinomas.

The oncogene , also known as or , is located on chromosome 17 (q12). It encodes a tyrosine kinase receptor, the human epidermal growth factor receptor 2 (HER2), involved in neoplastic proliferation, tumor angiogenesis, and invasiveness. Over the past years, the introduction of various anti-HER2 therapies has significantly improved outcomes for patients with HER2-positive breast and gastroesophageal carcinomas.

Be bold, start cold! cold formalin fixation of colorectal cancer specimens granted superior DNA and RNA quality for downstream molecular analysis.

The use of cold formalin fixation (CFF; i.e., fixating tissue samples with 4 °C precooled formalin) recently attracted further attention owing to its putative improved ability to preserve nucleic acid compared with standard room temperature formalin (SFF).

Medullary carcinomas of the nonampullary small intestine: association with coeliac disease, mismatch repair deficiency, PD-L1 expression, and favourable prognosis.

Aim: Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs).

Methods And Results: Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs.

Clinicopathologic Features of Primary Immunodeficiency Monogenic Disease-related Very Early Onset Inflammatory Bowel Disease: Focus on Gastrointestinal Histologic Features in IFIH1 Mutations.

Very early onset inflammatory bowel disease (VEO-IBD) is a clinical term referring to IBD-like symptomatology arising in children younger than 6 years. VEO-IBD may be due to polygenic etiology in "pure" IBD (Crohn disease-CD and ulcerative colitis-UC), or it may be caused by primary immunodeficiency underlined by monogenic disease. Primary immunodeficiency monogenic diseases have a Mendelian inheritance and affect the immune system with multiorgan morbidity and possible effects on the gastrointestinal system.