Early cardio-oncology intervention in thoracic radiotherapy: prospective single-arm pilot study.

Background: While there is increasing recognition of the morbidity of cardiovascular disease in cancer survivors, including accelerated atherosclerosis following thoracic radiotherapy, patients are frequently under-optimized for cardiovascular risk.

Methods: In this prospective single-arm cohort pilot study, patients were treated with high-dose thoracic radiotherapy and had early consultation with cardio-oncology. Twenty patients were enrolled.

De novo RUNX1-driven acute myeloid leukemia requiring integrative genetics.

Copy number variants are common in myeloid malignancies and may hold diagnostic, prognostic or therapeutic significance. We present a case of acute myeloid leukemia driven by a RUNX1 deletion with no prior history of a myeloid neoplasm. Discovery of the underlying genetic lesion required multiple testing platforms highlighting the strengths and weaknesses of each test type.

Analytical validation of the LungLB test: a 4-color fluorescence in-situ hybridization assay for the evaluation of indeterminate pulmonary nodules.

Background: Evaluation of indeterminate pulmonary nodules (IPNs) often creates a diagnostic conundrum which may delay the early detection of lung cancer. Rare circulating genetically abnormal cells (CGAC) have previously demonstrated utility as a biomarker for discriminating benign from malignant small IPNs in the LungLB assay. CGAC are identified using a unique 4-color fluorescence in-situ hybridization (FISH) assay and are thought to reflect early cell-based events in lung cancer pathogenesis and the anti-tumor immune response.

Molecular characterization of a rare case of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 rearrangements.

Quadruple-hit lymphomas are extremely rare non-Hodgkin lymphomas with a reported dismal prognosis in the few reported cases. A "quadruple hit" has been defined by the presence of concurrent MYC, BCL2, BCL6, and CCND1 chromosomal rearrangements. We report a new case of a quadruple hit lymphoma in a 73-year-old Hispanic man who presented with an enlarging left-sided neck mass.

Gene Expression Profiling of Fibroepithelial Lesions of the Breast.

Fibroepithelial lesions of the breast (FELs) are a heterogeneous group of neoplasms exhibiting a histologic spectrum ranging from fibroadenomas (FAs) to malignant phyllodes tumors (PTs). Despite published histologic criteria for their classification, it is common for such lesions to exhibit overlapping features, leading to subjective interpretation and interobserver disagreements in histologic diagnosis. Therefore, there is a need for a more objective diagnostic modality to aid in the accurate classification of these lesions and to guide appropriate clinical management.

Two distinct pathogenic pathways of digital papillary adenocarcinoma - BRAF mutation or low-risk HPV infection.

Digital papillary adenocarcinoma (DPA) is a rare neoplasm that can exhibit local recurrence and distant metastasis. We present a series of eight cases of DPA showing two distinct clinical presentations, morphologies, immunophenotypes, and molecular features. Four cases were characterized by painless, slow-growing nodules located on the digits.

Molecular characterization of visible low-grade dysplastic lesions in patients with inflammatory bowel disease.

We studied pathogenic gene mutations and tumor mutation burden (TMB) in visible low-grade dysplastic lesions in patients with inflammatory bowel disease (IBD). The dysplastic lesions with histologically normal mucosa in the background (group 1) were compared with dysplastic lesions occurring either in a background of chronic active colitis (group 2) or associated with synchronous carcinomas regardless of the status of the background mucosa (group 3). The TMB in group 3 was consistently higher in comparison to the group 1 and group 2 lesions, although the difference was not statistically significant.

Molecular Testing for Diagnostics, Prognostication, and Treatment Stratification in Cancers.

Precision cancer care, for essentially all cancer types, now requires molecular diagnostics to assess mutations, chromosomal alterations, and gene expression to personalize treatments for individual patients. Advances in the diagnostics and treatment options have moved the field forward from fundamental discoveries beginning in the 1960s to the development of many targeted therapies that can be as specific as targeting a single-base-pair mutation. Herein is a brief historical perspective on cancer precision medicine with current diagnostic, prognostic, and treatment stratification guidance for early- and late-stage cancers.

MYC-Nonamplified Secondary Lymphatic-Type Angiosarcoma With Prominent Lymphocytic Infiltrate Following Radiation Therapy for Myxoid Liposarcoma.

Cutaneous angiosarcomas (AS) are uncommon and morphologically heterogeneous. Recently, a distinctive lymphatic-type AS with prominent lymphocytic infiltrate has been observed. Although conventional AS typically bear poor prognosis, lymphatic-type AS with prominent lymphocytic infiltrate and pseudolymphomatous AS show prolonged survival with rare extracutaneous spread.

miR766-3p and miR124-3p Dictate Drug Resistance and Clinical Outcome in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with poor prognosis, which is mainly due to drug resistance. The biology determining the response to chemo-radiotherapy in HNSCC is poorly understood. Using clinical samples, we found that miR124-3p and miR766-3p are overexpressed in chemo-radiotherapy-resistant (non-responder) HNSCC, as compared to responder tumors.

Comparative Upper Respiratory Tract Transcriptomic Profiling Reveals a Potential Role of Early Activation of Interferon Pathway in Severe COVID-19.

Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19) is known to cause mild to acute respiratory infection and sometimes progress towards respiratory failure and death. The mechanisms driving the progression of the disease and accumulation of high viral load in the lungs without initial symptoms remain elusive. In this study, we evaluated the upper respiratory tract host transcriptional response in COVID-19 patients with mild to severe symptoms and compared it with the control COVID-19 negative group using RNA-sequencing (RNA-Seq).

PD-L1 Over-Expression Varies in Different Subtypes of Lung Cancer: Will This Affect Future Therapies?

Programmed death-ligand (PD-L) 1 and 2 are ligands of programmed cell death 1 (PD-1) receptor. They are members of the B7/CD28 ligand-receptor family and the most investigated inhibitory immune checkpoints at present. PD-L1 is the main effector in PD-1-reliant immunosuppression, as the PD-1/PD-L pathway is a key regulator for T-cell activation.

Gastrointestinal Stromal Tumors (GIST): A Population-Based Study Using the SEER Database, including Management and Recent Advances in Targeted Therapy.

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) system. Most GISTs originate from the interstitial cells of Cajal (ICC), the pacemaker cell situated between the circular and longitudinal layers of the muscularis propria along the GI tract. In this population-based study using the SEER database, we sought to identify demographic, clinical, and pathologic factors that affect the prognosis and survival of patients with this neoplasm.

Case series - COVID-19 is unlikely to affect male fertility: Results of histopathological and reverse transcriptase polymerase chain reaction analysis.

Introduction: We aimed to analyze the testicular histopathology of men who died with active COVID-19 infection.

Methods: We performed autopsy of eight consecutive men who died of COVID-19 pneumonia. Lung and testis tissue of all men were stained for SARS-CoV-2 nucleocapsid, angiotensin-converting enzyme 2 (ACE-2) receptor immunohistochemistry (IHC).

US Severe Acute Respiratory Syndrome Coronavirus 2 Epsilon Variant: Highly Transmissible but With an Adjusted Muted Host T-Cell Response.

Background: The multiple mutations comprising the epsilon variant demonstrate the independent convergent evolution of severe acute respiratory syndrome coronavirus (SARS-CoV-2), with its spike protein mutation L452R present in the delta (L452R), kappa (L452R), and lambda (L452Q) variants.

Methods: Coronavirus disease 2019 (COVID-19) variants were detected in 1017 patients using whole-genome sequencing and were assessed for outcome and severity. The mechanistic effects of the epsilon versus non-epsilon variants were investigated using a multiomic approach including cellular response assays and paired cell and host transcriptomic and proteomic profiling.

Detecting the "undetectable" alterations: Use of NGS to uncover high-risk alterations.

Copy number variants are common in patients with myeloid malignancies and may confer diagnostic, prognostic or therapeutic relevance. However, detection of these variants may require multiple testing modalities, which may not be available or ordered on all cases. We present a case that highlights the efficacy of copy number analysis by next generation sequencing to identify clinically relevant variants that may otherwise be missed by conventional cytogenetics and typical florescent in situ hybridization panels.

Severe breakthrough COVID-19 with a heavily mutated variant in a multiple myeloma patient 10 weeks after vaccination.

Background: Patients with multiple myeloma have unpredictable responses to vaccination for COVID-19. Anti-spike antibody levels can determine which patients develop antibodies at levels similar to healthy controls, and are a known correlate of protection.

Case Report: A multiple myeloma patient developed protective anti-spike antibodies after vaccination (608 IU/mL), but nonetheless developed severe breakthrough COVID-19 just 10 weeks following his second vaccination with mRNA-1273.

Evaluation of tumor mutational burden in small early hepatocellular carcinoma and progressed hepatocellular carcinoma.

While researchers know that tumor mutational burden (TMB) is low in hepatocellular carcinoma (HCC), prior studies have not investigated TMB in cirrhosis, small early HCC and progressed HCC. HCC (n = 18) and cirrhosis (n = 6) cases were identified. TMB was determined by a 1.

Transmission risk of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to healthcare personnel following unanticipated exposure to aerosol-generating procedures: Experience from epidemiologic investigations at an academic medical center.

Healthcare personnel (HCP) with unprotected exposures to aerosol-generating procedures (AGPs) on patients with coronavirus disease 2019 (COVID-19) are at risk of infection with severe acute respiratory coronavirus virus 2 (SARS-CoV-2). A retrospective review at an academic medical center demonstrated an infection rate of <1% among HCP involved in AGPs without a respirator and/or eye protection.

Emergence of a Novel SARS-CoV-2 Variant in Southern California.

This research describes findings of sequencing and phylogenetic analyses of SARS-CoV-2 isolates from symptomatic patients cared for at Cedar-Sinai Medical Center in November-December 2020 during a regional surge in cases and hospitalizations.