Mutations Are Rare and Diverse in Myelodysplastic Syndromes: Case Series and Review of the Literature.

Objectives: To investigate and characterize mutations in myelodysplastic syndrome (MDS), we present three cases with diverse mutations and review the literature.

Methods: The institutional SoftPath software was used to find MDS cases between January 2020 and April 2022. The cases with a diagnosis of a myelodysplastic/myeloproliferative overlap syndrome including MDS/MPN with ring sideroblasts and thrombocytosis were excluded.

Respondents of health survey powered by the innovative NURO app exhibit correlations between exercise frequencies and diet habits, and between stress levels and sleep wellness.

Nurosene's NURO app (nurosene.com) is an innovative smartphone application that gathers and analyzes active self-report metrics from users, empowering them with data-driven health machine intelligence. We present the data collected and analyzed from the initial round of participants who responded to a 12-question survey on their life-style and health status.

Upregulation of polycistronic microRNA-143 and microRNA-145 in colonocytes suppresses colitis and inflammation-associated colon cancer.

Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted to regulate ADAM17.

Deep-learning approaches to identify critically Ill patients at emergency department triage using limited information.

Study Objective: Triage quickly identifies critically ill patients, facilitating timely interventions. Many emergency departments (EDs) use emergency severity index (ESI) or abnormal vital sign triggers to guide triage. However, both use fixed thresholds, and false activations are costly.

Reference Laboratory Testing for Neurologic Disorders.

Laboratory testing plays a critical role in the diagnosis and monitoring of patients with neurologic disorders. Although common tests are often performed in a central hospital laboratory, an increasing number of essential but esoteric tests are performed at reference laboratories or other outside health care facilities. In this article, we analyze recent trends in neurologic disease testing within the overall context of reference laboratory testing and discuss strategies to facilitate the provision of high-quality, cost-effective laboratory services.

Molecular Pathology Economics 101: An Overview of Molecular Diagnostics Coding, Coverage, and Reimbursement: A Report of the Association for Molecular Pathology.

Widespread indications for use of molecular diagnostics in various aspects of clinical medicine have driven proliferation of testing. The rapid adoption and continuous technological evolution of molecular diagnostics have often strained the development and maintenance of a functional underlying framework of coding, coverage, and reimbursement policies, thereby presenting challenges to various stakeholders, including molecular professionals, payers, and patients. A multidisciplinary working group convened by the Association for Molecular Pathology Economic Affairs Committee was tasked to describe the complex landscape of molecular pathology economics and highlight opportunities for member engagement.

Losartan and Vitamin D Inhibit Colonic Tumor Development in a Conditional Apc-Deleted Mouse Model of Sporadic Colon Cancer.

Colorectal cancer is a leading cause of cancer deaths. The renin-angiotensin system (RAS) is upregulated in colorectal cancer, and epidemiologic studies suggest RAS inhibitors reduce cancer risk. Because vitamin D (VD) receptor negatively regulates renin, we examined anticancer efficacy of VD and losartan (L), an angiotensin receptor blocker.

Oral MEK 1/2 Inhibitor Trametinib in Combination With AKT Inhibitor GSK2141795 in Patients With Acute Myeloid Leukemia With RAS Mutations: A Phase II Study.

Background: With proven single-agent activity and favorable toxicity profile of MEK-1/2 inhibition in advanced leukemia, investigation into combination strategies to overcome proposed resistance pathways is warranted. Resistance to MEK inhibition is secondary to upstream hyperactivation of RAS/RAF or activation of the PI3K/PTEN/AKT/mTOR pathway. This phase II multi-institution Cancer Therapy Evaluation Program-sponsored study was conducted to determine efficacy and safety of the combination of the ATP-competitive pan-AKT inhibitor GSK2141795, targeting the PI3K/AKT pathway, and the MEK inhibitor trametinib in RAS-mutated relapsed/refractory acute myeloid leukemia (AML).

The Undergraduate Training in Genomics (UTRIG) Initiative: early & active training for physicians in the genomic medicine era.

Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4.

Telomere Diagnostics for Pancreatic Neoplasms and Cysts.

This commentary highlights the article by Hata et al that examines markers for assessing pancreatic neoplastic progression.

Mutations in TP53, PIK3CA, PTEN and other genes in EGFR mutated lung cancers: Correlation with clinical outcomes.

Introduction: The degree and duration of response to epidermal growth factor receptor (EGFR) inhibitors in EGFR mutated lung cancer are heterogeneous. We hypothesized that the concurrent genomic landscape of these tumors, which is currently unknown in view of the prevailing single gene assay diagnostic paradigm in clinical practice, could play a role in clinical outcomes and/or mechanisms of resistance.

Methods: We retrospectively probed our institutional lung cancer database for tumors with EGFR kinase domain mutations that were also evaluated by more comprehensive molecular profiling, and evaluated tumor response to EGFR tyrosine kinase inhibitors (TKIs).

The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer: A Report of the Association for Molecular Pathology.

Clinical utility describes the benefits of each laboratory test for that patient. Many stakeholders have adopted narrow definitions for the clinical utility of molecular testing as applied to targeted pharmacotherapy in oncology, regardless of the population tested or the purpose of the testing. This definition does not address all of the important applications of molecular diagnostic testing.

ADAM17 is a Tumor Promoter and Therapeutic Target in Western Diet-associated Colon Cancer.

Purpose: Epidermal growth factor receptors (EGFR) are required for tumor promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by releasing pro-EGFR ligands. ADAM17 is regulated by G-protein-coupled receptors, including CXCR4.

The clinical utility of molecular genetic cancer profiling.

Introduction: Next-Generation-Sequencing (NGS) has enabled gene mutation profiling - cataloguing sequence variants and modifications in clinical assays encompassing tens to thousands of genes in tumors and in germlines. The clinical benefit of applying multi-gene NGS to diverse applications in various malignancies remains to be demonstrated.

Areas Covered: Applications of gene mutation profiling in oncology include screening cancer-prone families, classification of malignancies, treatment selection, and monitoring the response to treatment of solid tumors (the 'liquid biopsy').

A Suggested Molecular Pathology Curriculum for Residents: A Report of the Association for Molecular Pathology.

Molecular pathology is an essential element of pathology training. As more molecular tests have become available, there is an increasing need for pathology trainees to receive a strong foundation in molecular pathology. Appointed by the Training and Education Committee of the Association for Molecular Pathology, the Molecular Curriculum Task Force has developed a suggested curriculum in molecular pathology for residents.

Experience with targeted next generation sequencing for the care of lung cancer: insights into promises and limitations of genomic oncology in day-to-day practice.

Introduction: Tumor genotyping using single gene assays (SGAs) is standard practice in advanced non-small-cell lung cancer (NSCLC). We evaluated how the introduction of next generation sequencing (NGS) into day-to-day clinical practice altered therapeutic decision-making.

Methods: Clinicopathologic data, tumor genotype, and clinical decisions were retrospectively compiled over 6 months following introduction of NGS assay use at our institution in 82 patient-tumor samples (7 by primary NGS, 22 by sequential SGAs followed by NGS, and 53 by SGAs).

Reporting incidental findings in genomic scale clinical sequencing--a clinical laboratory perspective: a report of the Association for Molecular Pathology.

Advances in sequencing technologies have facilitated concurrent testing for many disorders, and the results generated may provide information about a patient's health that is unrelated to the clinical indication, commonly referred to as incidental findings. This is a paradigm shift from traditional genetic testing in which testing and reporting are tailored to a patient's specific clinical condition. Clinical laboratories and physicians are wrestling with this increased complexity in genomic testing and reporting of the incidental findings to patients.

Genetic profiling of advanced radioactive iodine-resistant differentiated thyroid cancer and correlation with axitinib efficacy.

Biomarkers predicting which patients with advanced radioiodine-resistant differentiated thyroid cancer (DTC) may benefit from multi-kinase inhibitors are unavailable. We aimed to describe molecular markers in DTC that correlate with clinical outcome to axitinib. Pretreatment thyroid cancer blocks from 18 patients treated with axitinib were collected and genomic DNA was isolated.

Tumor suppressors miR-143 and miR-145 and predicted target proteins API5, ERK5, K-RAS, and IRS-1 are differentially expressed in proximal and distal colon.

The colon differs regionally in local luminal environment, excretory function, and gene expression. Polycistronic microRNA (miR)-143 and miR-145 are downregulated early in colon cancer. We asked if these microRNAs (miRNAs) might be differentially expressed in the proximal vs.

The renin-angiotensin system mediates EGF receptor-vitamin d receptor cross-talk in colitis-associated colon cancer.

Purpose: We previously showed that EGF receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D suppresses tumorigenesis. EGFR-vitamin D receptor (VDR) interactions, however, are incompletely understood. Vitamin D inhibits the renin-angiotensin system (RAS), whereas RAS can activate EGFR.

Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: The Papanicolaou Society of Cytopathology Guidelines.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound guided fine needle aspiration, terminology and nomenclature of pancreatobiliary disease, ancillary testing and post-biopsy management. All documents are based on the expertise of the authors, a review of the literature, discussion of the draft document at several national and international meetings and synthesis of selected online comments of the draft document. This document presents the results of these discussions regarding the use of ancillary testing in the cytologic diagnosis of biliary and pancreatic lesions.

Genomic aberrations in myeloid sarcoma without blood or bone marrow involvement: characterization of formalin-fixed paraffin-embedded samples by chromosomal microarrays.

Myeloid sarcoma (MS) is a presentation of acute myeloid leukemia (AML) as a tumor mass outside of the bone marrow. Viable cells from MS are frequently unavailable for cytogenetic studies. We therefore investigated whether chromosomal microarray analysis (CMA) using formalin-fixed paraffin-embedded (FFPE) tissues can detect clinically important genetic abnormalities in MS.

Utilization of ancillary studies in the cytologic diagnosis of biliary and pancreatic lesions: the Papanicolaou Society of Cytopathology guidelines for pancreatobiliary cytology.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pancreatobiliary cytology including indications for endoscopic ultrasound-guided fine-needle aspiration, terminology and nomenclature of pancreatobiliary disease, ancillary testing, and post-biopsy management. All documents are based on the expertise of the authors, a review of the literature, discussions of the draft document at several national and international meetings, and synthesis of selected online comments of the draft document. This document presents the results of these discussions regarding the use of ancillary testing in the cytologic diagnosis of biliary and pancreatic lesions.

Pancreatic ductal adenocarcinoma with autoimmune pancreatitis-like histologic and immunohistochemical features.

Autoimmune pancreatitis (AIP) often manifests as a mass lesion causing obstructive jaundice, clinically mimicking pancreatic carcinoma. A diagnosis of AIP may obviate the need for surgical resection, as most patients respond to steroid treatment. However, it is not clear whether these 2 conditions can coexist.

Detection and quantification of BCR-ABL1 fusion transcripts by droplet digital PCR.

Monitoring BCR-ABL1 fusion transcripts by real-time quantitative RT-PCR has become an important clinical test for the management of patients with chronic myeloid leukemia. However, it has some inherent limitations with regard to its lower limit of detection and limit of quantification. Improvement in the lower limit of detection could aid clinicians in selecting candidates for discontinuation of tyrosine kinase inhibitors without relapse.