Progression of Low-Grade Neuroendocrine Tumors (NET) to High-Grade Neoplasms Harboring the NEC-Like Co-alteration of RB1 and TP53.

High-grade or grade 3 epithelial neuroendocrine neoplasms (G3 NEN) are now divided into grade 3 well-differentiated neuroendocrine tumor (G3 NET) and neuroendocrine carcinoma (NEC), both defined by Ki-67 > 20% and/or > 20 mitoses per 2 mm. NET and NEC are thought to be distinct tumors with different genetic profiles: NEC classically harbors co-alteration of TP53 and RB1, whereas NET genetics are site-dependent with frequent alterations in MEN1, ATRX, DAXX, and TSC1/2 in pancreatic NETs. Progression from NET to NEC is considered rare and is not well described.

Expanding the Spectrum of GLI1-rearranged Neoplasms of the Gastrointestinal Tract to Include Monophasic Keratin-positive Epithelial Neoplasms.

GLI1-altered tumors form a diverse group occurring in various anatomic locations. In the alimentary tract, the most established are gastroblastoma, a biphasic epithelial-mesenchymal neoplasm of the stomach, and plexiform fibromyxoma, a pure spindle cell neoplasm. The spectrum of GLI1-rearranged gastrointestinal tumors has recently expanded with reports of cases in other parts of the GI tract, some exhibiting gastroblastoma-like features and others being pure mesenchymal neoplasms.

Glutamine synthetase staining patterns in cirrhosis.

Advanced liver fibrosis can regress following the elimination of causative injuries. Glutamine synthetase (GS) immunohistochemical expression is normally in centrizonal perivenular hepatocytes but can be present in periportal hepatocytes in cases of regressed cirrhosis. This study identified periportal staining and investigated the spectrum of GS staining patterns seen in a range of cirrhotic livers with varying disease processes.

Evaluating Liver Biopsies with Well-Differentiated Hepatocellular Lesions.

Needle core biopsies of liver lesions can be challenging, particularly in cases with limited material. The differential diagnosis for well-differentiated hepatocellular lesions includes focal nodular hyperplasia, hepatocellular adenoma, and well-differentiated hepatocellular carcinoma (HCC) in noncirrhotic liver, while dysplastic nodules and well-differentiated HCC are the primary considerations in cirrhotic liver. The first part of this review focuses on histochemical and immunohistochemical stains as well as molecular assays that are useful in the differential diagnosis.

Use of orcein as an adjunct stain in the evaluation of advanced liver fibrosis.

Aims: Advanced liver fibrosis can regress following the elimination of causative injuries. Trichrome (TC) stain has traditionally been used to evaluate the degree of fibrosis in liver, although it is rarely helpful in assessing quality of fibrosis (i.e.

Integrated Genomic and Clinicopathologic Approach Distinguishes Pancreatic Grade 3 Neuroendocrine Tumor From Neuroendocrine Carcinoma and Identifies a Subset With Molecular Overlap.

Distinguishing grade 3 pancreatic neuroendocrine tumor (G3 PanNET) from neuroendocrine carcinoma (PanNEC) is a known diagnostic challenge, and accurate classification is critical because clinical behavior and therapies differ. Although current recommendations suggest that immunohistochemistry for p53, Rb, ATRX, and DAXX can distinguish most cases, some cases remain difficult to classify using this approach. In this study, we reviewed 47 high-grade neoplasms originally diagnosed as pancreatic neuroendocrine neoplasms.

Uterine Inflammatory Myofibroblastic Tumors: Proposed Risk Stratification Model Using Integrated Clinicopathologic and Molecular Analysis.

Inflammatory myofibroblastic tumor (IMT) of the uterus is a rare mesenchymal tumor with largely benign behavior; however, a small subset demonstrate aggressive behavior. While clinicopathologic features have been previously associated with aggressive behavior, these reports are based on small series, and these features are imperfect predictors of clinical behavior. IMTs are most commonly driven by ALK fusions, with additional pathogenic molecular alterations being reported only in rare examples of extrauterine IMTs.

Staging of appendiceal mucinous neoplasms: challenges and recent updates.

Low-grade appendiceal mucinous neoplasms are unique tumors of the appendix, characterized by low-grade mucinous epithelium with villiform, undulating, or flat architecture. These tumors lack infiltrative growth or destructive invasion, but can extend into the appendiceal wall by a "pushing" pattern of invasion, with a broad front that can mimic a diverticulum. These neoplasms have a propensity for peritoneal dissemination, resulting in the clinical presentation of pseudomyxoma peritonei.

An exploration in pitfalls in interpreting SDHB immunohistochemistry.

Aims: Mutations and epimutations in genes encoding the succinate dehydrogenase complex (SDHx) are associated with multiple tumour types in which identification of SDH-deficiency has significant management implications. Immunohistochemistry (IHC) for the succinate dehydrogenase B (SDHB) subunit can help to detect SDH-deficiency, which manifests as complete loss of staining in tumour cells. However, a subset of SDH-deficient tumours can show aberrant cytoplasmic SDHB-IHC staining patterns and be misinterpreted as 'retained', a diagnostic pitfall complicating interpretation.

Hepatocellular neoplasms with loss of liver fatty acid binding protein: Clinicopathologic features and molecular profiling.

HNF1A-inactivated hepatocellular adenomas (H-HCA) show steatosis, no atypia and loss of liver fatty acid binding protein (LFABP). LFABP loss also occurs in hepatocellular carcinoma (HCC). This study examines 68 LFABP-negative tumors: 33 typical H-HCA, 10 atypical hepatocellular neoplasms (AHN), 7 well-differentiated (WD) HCC, 18 moderately or poorly differentiated (MD/PD) HCC.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

Aims: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey.

Methods And Results: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification.

Corded and Hyalinized Endometrioid Adenocarcinoma (CHEC) of the Uterine Corpus are Characterized by CTNNB1 Mutations and Can Show Adverse Clinical Outcomes.

Corded and hyalinized endometrioid adenocarcinoma (CHEC) is a morphologic variant of endometrioid adenocarcinoma that is typically low-grade [International Federation of Gynecology and Obstetrics (FIGO) grade 1-2]. CHEC exhibits a biphasic appearance with gland forming adenocarcinoma merging with a diffuse component with corded growth often in a hyalinized matrix; squamous differentiation is frequent and osteoid production can be seen. This morphologic appearance can invoke a large differential diagnosis including carcinosarcoma.

Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix.

Desmoplasia describes the deposition of extensive extracellular matrix and defines primary pancreatic ductal adenocarcinoma (PDA). The acellular component of this stroma has been implicated in PDA pathogenesis and is being targeted therapeutically in clinical trials. By analyzing the stromal content of PDA samples from numerous annotated PDA data sets and correlating stromal content with both anatomic site and clinical outcome, we found PDA metastases in the liver, the primary cause of mortality to have less stroma, have higher tumor cellularity than primary tumors.

Anastomosing hemangioma of liver.

Anastomosing hemangiomas are a rare subtype of benign vascular hemangioma which most commonly arise in the genitourinary tract and retroperitoneum. In only a small number of reports has this entity been shown originating within the liver parenchyma. Despite their benign behavior, on contrast-enhanced computer tomography and magnetic resonance imaging studies anastomosing hemangiomas can demonstrate enhancement characteristics similar to primary and metastatic liver lesions.

Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study.

Aims: This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis.

Methods: A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors.

A case report of vanishing bile duct syndrome after exposure to pexidartinib (PLX3397) and paclitaxel.

Pexidartinib (PLX3397) is a small molecule tyrosine kinase and colony-stimulating factor-1 inhibitor with FDA breakthrough therapy designation for tenosynovial giant-cell tumor, and currently under study in several other tumor types, including breast cancer, non-Hodgkin's lymphoma, and glioblastoma. Here, we report a case of severe drug-induced liver injury requiring liver transplantation due to vanishing bile duct syndrome (VBDS) after exposure to pexidartinib in the I-SPY 2 Trial, a phase 2 multicenter randomized neoadjuvant chemotherapy trial in patients with Stage II-III breast cancer. We also review the current literature on this rare, idiosyncratic, and potentially life-threatening entity.

Genomic profiling of well-differentiated hepatocellular neoplasms with diffuse glutamine synthetase staining reveals similar genetics across the adenoma to carcinoma spectrum.

Well-differentiated hepatocellular neoplasms are currently classified in the World Health Organization scheme as hepatocellular adenoma or hepatocellular carcinoma. There is no recognized diagnostic category for atypical cases with borderline features, and we have designated these as atypical hepatocellular neoplasms. Diffuse glutamine synthetase staining is used as a surrogate marker to detect β-catenin activation, a well-recognized high risk feature in hepatocellular tumors.

DNA flow cytometric and interobserver study of crypt cell atypia in inflammatory bowel disease.

Aims: The pathological features and diagnostic reliability of crypt cell atypia (CCA) arising in inflammatory bowel disease (IBD) and its clinical significance are unknown.

Methods And Results: DNA flow cytometry (FCM) was performed on 14 colon biopsies of CCA from seven IBD patients (male-to-female ratio, 5:2; mean age, 53 years; mean IBD duration, 15 years) using paraffin-embedded tissue. Seven gastrointestinal pathologists were asked to diagnose each biopsy as negative for dysplasia (NEG), indefinite for dysplasia (IND), low-grade dysplasia (LGD) or high-grade dysplasia (HGD) by morphology alone, then again with knowledge of FCM results.

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance.

Blockade of RGMb inhibits allergen-induced airways disease.

Background: Allergic asthma causes morbidity in many subjects, and novel precision-directed treatments would be valuable.

Objective: We sought to examine the role of a novel innate molecule, repulsive guidance molecule b (RGMb), in murine models of allergic asthma.

Methods: In models of allergic asthma using ovalbumin or cockroach allergen, mice were treated with anti-RGMb or control mAb and examined for airway inflammation and airway hyperreactivity (AHR), a cardinal feature of asthma.