EWSR1::BEND2 Adenocarcinoma with Hyaline Pseudorosettes of the Trachea.

We describe the novel occurrence of a adenocarcinoma involving the trachea, with distinct solid and glandular components, in a 34-year-old patient. We illustrate its morphological and immunophenotypic features and describe the molecular finding of an EWSR1::BEND2 gene fusion detected by next-generation sequencing (NGS). We discuss the findings in comparison to BEND2-fusion associated neoplasms reported in the head and neck region in the literature to date.

Functional Rehabilitation in Non-Reconstructed Hemimandibulectomy Patients.

Functional rehabilitation in patients with hemimandibulectomy remains a challenge no matter what method of reconstruction is chosen by physicians. In this paper, we aim to evaluate the feasibility of an acceptable occlusal restoration in patients who have undergone hemimanidublectomy without the reestablishment of mandibular continuity. Data were collected retrospectively on 10 patients with varying degrees of mandible resection.

CRISPR-Cas9-mediated genome editing delivered by a single AAV9 vector inhibits HSV-1 reactivation in a latent rabbit keratitis model.

Herpes simples virus 1 (HSV-1) keratitis is a major cause of blindness globally. During primary infection, HSV-1 travels to the trigeminal ganglia and establishes lifelong latency. Although some treatments can reduce symptom severity and recurrence, there is no cure for HSV-1 keratitis.

Peptide Receptor Radionuclide Therapy Improves Survival in Patients Who Progress After Resection of Gastroenteropancreatic Neuroendocrine Tumors.

Background: Peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). We investigated a 2-decade experience with PRRT to determine whether PRRT confers a survival advantage to patients who progress after surgery versus other therapies.

Methods: We identified patients from our clinic who had resection/cytoreduction of GEP-NETs, then disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.

The University of Iowa Neuroendocrine Tumor Clinic.

The Iowa Neuroendocrine Tumor (NET) Clinic was founded and developed by two remarkable physicians, Thomas and Sue O'Dorisio. Tom was an Endocrinologist and close friend and colleague of Aaron Vinik. Both men were pioneers in studies of gastrointestinal hormones and the management of patients with NETs.

Suppression of HSV-1 infection and viral reactivation by CRISPR-Cas9 gene editing in 2D and 3D culture models.

Although our understanding of herpes simplex virus type 1 (HSV-1) biology has been considerably enhanced, developing therapeutic strategies to eliminate HSV-1 in latently infected individuals remains a public health concern. Current antiviral drugs used for the treatment of HSV-1 complications are not specific and do not address latent infection. We recently developed a CRISPR-Cas9-based gene editing platform to specifically target the HSV-1 genome.

SWI/SNF Complex-Deficient Undifferentiated Carcinoma of the Pancreas: Clinicopathologic and Genomic Analysis.

Inactivating alterations in the SWItch/Sucrose NonFermentable (SWI/SNF) Chromatin Remodeling Complex subunits have been described in multiple tumor types. Recent studies focused on SMARC subunits of this complex to understand their relationship with tumor characteristics and therapeutic opportunities. To date, pancreatic cancer with these alterations has not been well studied, although isolated cases of undifferentiated carcinomas have been reported.

Functional Copy-Number Alterations as Diagnostic and Prognostic Biomarkers in Neuroendocrine Tumors.

Functional copy-number alterations (fCNAs) are DNA copy-number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene-expression data from 31 pancreatic (pNETs) and 33 small-bowel neuroendocrine tumors (sbNETs).

Hepatocellular Carcinoma With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in the Absence of Cirrhosis.

This report describes a rare case of hepatocellular carcinoma (HCC) concurrent with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without traditional risk factors, such as hepatic fibrosis or chronic hepatitis. Initially presenting with hematuria, incidental imaging revealed a liver lesion, later diagnosed as moderately differentiated HCC. Notably, the patient had no history of well-established risk factors of HCC including viral hepatitis or liver cirrhosis.

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer.

Principles of Analytic Validation of Immunohistochemical Assays: Guideline Update.

Context.—: In 2014, the College of American Pathologists developed an evidence-based guideline to address analytic validation of immunohistochemical assays. Fourteen recommendations were offered.

Prioritization of Fluorescence In Situ Hybridization (FISH) Probes for Differentiating Primary Sites of Neuroendocrine Tumors with Machine Learning.

Determining neuroendocrine tumor (NET) primary sites is pivotal for patient care as pancreatic NETs (pNETs) and small bowel NETs (sbNETs) have distinct treatment approaches. The diagnostic power and prioritization of fluorescence in situ hybridization (FISH) assay biomarkers for establishing primary sites has not been thoroughly investigated using machine learning (ML) techniques. We trained ML models on FISH assay metrics from 85 sbNET and 59 pNET samples for primary site prediction.

Chemokine Receptor CXCR4 Radioligand Targeted Therapy Using 177Lutetium-pentixather for Pulmonary Neuroendocrine Cancers.

Intermediate to high-grade lung neuroendocrine tumors (NETs; i.e., atypical carcinoid tumors) and neuroendocrine carcinomas (NECs) are currently difficult to cure.

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.

Systemic Therapy for Tumor Control in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline.

Purpose: To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.

Results: Eight randomized controlled trials met the inclusion criteria for the systematic review.

Human neurotropic polyomavirus, JC virus, late coding region encodes a novel nuclear protein, ORF4, which targets the promyelocytic leukemia nuclear bodies (PML-NBs) and modulates their reorganization.

We previously reported the discovery and characterization of two novel proteins (ORF1 and ORF2) generated by the alternative splicing of the JC virus (JCV) late coding region. Here, we report the discovery and partial characterization of three additional novel ORFs from the same coding region, ORF3, ORF4 and ORF5, which potentially encode 70, 173 and 265 amino acid long proteins respectively. While ORF3 protein exhibits a uniform distribution pattern throughout the cells, we were unable to detect ORF5 expression.

p53 as Exemplar Next-Generation Immunohistochemical Marker: A Molecularly Informed, Pattern-Based Approach, Methodological Considerations, and Pan-Cancer Diagnostic Applications.

This review is based on a webinar I presented for the International Society for Immunohistochemistry and Molecular Morphology (ISIMM) in February 2022. It is intended that all ISIMM webinars will ultimately be published in AIMM as review articles. This work is also dedicated to Clive Taylor, who has deeply impacted my career.

Sequencing by avidity enables high accuracy with low reagent consumption.

We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase-polymer-nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates.