Turmeric supplement-associated hepatitis: a clinicopathological series of 11 cases highlighting pan-lobular and zone 3 injury.

Aims: Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over-the-counter turmeric supplements can cause drug-induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements.

Methods And Results: We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37-66 years).

MASLD in people with HIV exhibits higher fibrosis stage despite lower disease activity than in matched controls.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis stage in PWH remains unknown.

Methods: Overall, 107 liver biopsies from PWH with MASLD (MASLD-PWH) were matched to 107 biopsies from individuals with MASLD and without HIV (MASLD controls) on age at biopsy, race/ethnicity, sex, type 2 diabetes, body mass index (BMI) and alanine aminotransferase (ALT) level.

Per-patient Negative Predictive Value of the CT and MRI Liver Imaging Reporting and Data System Version 2018 Treatment Response Algorithm for Hepatocellular Carcinoma.

Background The Liver Imaging Reporting and Data System version 2018 (LI-RADS) treatment response algorithm (TRA) is a high-specificity, lower-sensitivity grading system to diagnose hepatocellular carcinoma (HCC) and recurrence after local-regional therapy. However, the emphasis on specificity can result in disease understaging, potentially leading to poorer posttransplant outcomes. Purpose To determine the negative predictive value (NPV) of pretransplant CT and MRI assessment for viable HCC on a per-patient basis using the LI-RADS TRA, considering explant pathology as the reference standard.

Assessment of large droplet fat in frozen sections of donor liver biopsies: utility and interobserver variability of the newly described Banff method compared to a simplified Average of Fields method.

Aims: There is great variability in the assessment and reporting of fat in frozen sections of donor liver biopsies. The Banff Working Group has proposed a novel method and definition for scoring large droplet fat (LDF) in donor liver biopsies. This study compares the Banff method with a simpler Average of Fields (AF) method and evaluates the impact of different LDF definitions.

Erythrophagocytosis is not a reproducible finding in liver biopsies, and is not associated with clinical diagnosis of hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with high mortality. Liver involvement is common (based on elevated liver function tests) with most patients demonstrating acute hepatitis. Liver biopsies are frequently obtained in the setting of suspected HLH for the purpose of identification of erythrophagocytosis, and if present, this finding is thought to suggest or support the diagnosis of HLH.

Shorter leukocyte telomere length protects against NAFLD progression in children.

Leukocyte telomere length (LTL) gets shorter with each cell division and is also sensitive to reactive oxygen species damage and inflammatory processes. Studies in adults with non-alcoholic fatty liver disease (NAFLD) have found that increased fibrosis but not ALT levels are associated with shorter LTL. Few pediatric studies have been conducted; as such, we sought to evaluate potential associations between LTL and liver disease and liver disease progression in pediatric patients.

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.

The nonalcoholic steatohepatitis extended hepatocyte ballooning score: histologic classification and clinical significance.

Background And Aims: The NAFLD activity score was developed to measure histologic changes in NAFLD during therapeutic trials. Hepatocyte ballooning (HB) is the most specific feature in steatohepatitis diagnosis, yet the impact of variations in HB has not been incorporated.

Approach And Results: Liver biopsies from patients enrolled in the NASH Clinical Research Network with an initial diagnosis of NASH or NAFL (n=1688) were evaluated to distinguish classic hepatocyte ballooning (cHB) from smaller, nonclassic hepatocyte ballooning (nHB), and also to designate severe ballooning and assign an extended hepatocyte ballooning (eB) score [0 points, no ballooning (NB); 1 point, few or many nHB; 2 points, few cHB; 3 points, many cHB; 4 points, severe cHB] to the biopsy assessment.

Diagnosis and Management of Drug-Induced Liver Injury After the Use of .

, a species of flowering plant in the buckwheat family, is widely used in alternative medicine. However, a growing body of literature has implicated as a cause of drug-induced liver injury. We report a case of successful treatment of a drug-induced liver injury after consumption of an herbal tea containing .

Clinicopathologic features of de novo non-alcoholic steatohepatitis in the post-transplant setting.

Background: Non-alcoholic steatohepatitis (NASH) has become an increasingly recognized problem in patients after orthotopic liver transplant. The aims of this study were to compare the clinicopathologic features of recurrent and de novo NASH.

Methods: From 1995 to 2016, we performed a retrospective review of patients with a histological diagnosis of non-alcoholic steatohepatitis made more than 6 months after liver transplant at University of California, San Francisco.

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.

Rappaport, Glisson, Hering, and Mall-Champions of Liver Microanatomy: Microscopic and Ultramicroscopic Anatomy of the Liver Into the Modern Age.

Content available: Author Interview and Audio Recording.

Diagnostic challenges of focal nodular hyperplasia: interobserver variability, accuracy, and the utility of glutamine synthetase immunohistochemistry.

Aims: The diagnosis of focal nodular hyperplasia (FNH) and the interpretation of glutamine synthetase (GS) staining can be challenging on biopsies. We aimed to evaluate the reproducibility of needle biopsy diagnosis of FNH, the effect of GS immunohistochemistry on FNH diagnosis, and which histological features are most useful for the diagnosis of FNH.

Methods And Results: The study included virtual needle biopsies generated from 75 resection specimens (30 FNHs, 15 hepatocellular adenomas, 15 hepatocellular carcinomas, and 15 non-lesional liver specimens).

The major cap-binding protein eIF4E regulates lipid homeostasis and diet-induced obesity.

Obesity is a global epidemic leading to increased mortality and susceptibility to comorbidities, with few viable therapeutic interventions. A hallmark of disease progression is the ectopic deposition of lipids in the form of lipid droplets in vital organs such as the liver. However, the mechanisms underlying the dynamic storage and processing of lipids in peripheral organs remain an outstanding question.

Glycogenosis is common in nonalcoholic fatty liver disease and is independently associated with ballooning, but lower steatosis and lower fibrosis.

Background/aims: Glycogen synthesis and storage are normal hepatocyte functions. However, glycogenosis, defined as excess hepatocyte glycogen visible by routine H&E light microscopy, has not been well characterized in nonalcoholic fatty liver disease (NAFLD).

Methods: Glycogenosis in NAFLD liver biopsies was graded as "none", "focal" (in <50% of hepatocytes), or "diffuse" (in ≥50% of hepatocytes).

Complexities in the diagnosis of large B-cell lymphomas, classic Hodgkin lymphomas and overlapping peripheral T-cell lymphomas simplified: An evidence-based guide.

The diagnosis of a large B-cell lymphoma and classic Hodgkin lymphoma (CHL) is often straightforward. However, in select circumstances, these simple diagnoses can be quite complex. In part, diagnostic difficulty may be due to uncertainty in the evaluation of morphologic and immunophenotypic features along a biologic continuum, or alternatively arise from uncertainty in predicting the behavior and outcomes of patients.

Clinicopathological features and outcomes of parenchymal rejection in liver transplant biopsies.

Aims: The aim of this study was to perform a comprehensive retrospective analysis of liver transplant biopsies with parenchymal rejection (PR) at our institution, including histological features, laboratory values and follow-up biopsies, and to compare PR with portal-based acute cellular rejection (ACR).

Methods And Results: Biopsies from 173 patients were evaluated (retrospective database search 1990-2017), including 49 isolated PR, 35 PR with portal ACR (PR/ACR), 34 mild ACR and 52 moderate ACR cases. The rise and fall of serum liver enzymes was calculated as a measure of acute liver injury and response to immunotherapy, respectively.

Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis.

Background: Polycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD).

Methods: Retrospective study of women ages 18-45 years with biopsy-confirmed NAFLD between 2008 and 2019.

A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS.

Small nucleolar RNAs (snoRNAs) are a diverse group of non-coding RNAs that direct chemical modifications at specific residues on other RNA molecules, primarily on ribosomal RNA (rRNA). SnoRNAs are altered in several cancers; however, their role in cell homeostasis as well as in cellular transformation remains poorly explored. Here, we show that specific subsets of snoRNAs are differentially regulated during the earliest cellular response to oncogenic RAS expression.

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.

Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis.

Frequent GNAQ and GNA14 Mutations in Hepatic Small Vessel Neoplasm.

Hepatic small vessel neoplasm (HSVN) is a recently described infiltrative vascular neoplasm of the liver, composed of small vessels. Although the infiltrative nature can mimic angiosarcoma, HSVN are thought to be benign or low-grade neoplasms because they lack cytologic atypia and increased proliferation. To characterize the molecular pathogenesis of HSVN, we performed both targeted panel sequencing and exome sequencing on 18 benign or low-grade vascular neoplasms in the liver including 8 HSVN, 6 classic cavernous hemangioma (CH), and 4 variant lesions (VL) with overlapping features between HSVN and CH.

Surveillance Screening in Li-Fraumeni Syndrome: Raising Awareness of False Positives.

Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome inherited in an autosomal dominant fashion that involves a germline mutation of tumor protein 53 (TP53). With the advent of more accessible and accurate genetic testing methods, along with more widespread knowledge of LFS, asymptomatic carriers can now be more easily identified. No general surveillance protocols were previously recommended other than routine physical exams and breast and colon cancer screening at younger ages, primarily due to questions involving efficacy, cost, and clinical benefits.