A comparison of the histopathologic features of thyroid carcinomas with NTRK fusions to those with other malignant fusions.

Background: Chromosomal rearrangements involving one of the NTRK genes result in oncogenic driver mutations in thyroid carcinoma (TC) and serve as a target for therapy. We compared the clinicopathologic features of thyroid carcinomas with NTRK fusions vs. thyroid neoplasms with other malignancy associated gene fusions within our institution.

Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment.

An "induced PARP inhibitor (PARPi) sensitivity by epigenetic modulation" strategy is being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARPi treatments. To expand its clinical applications and identify more efficient combinations, we performed a drug screen by combining PARPi with 74 well-characterized epigenetic modulators that target five major classes of epigenetic enzymes. Both type I PRMT inhibitor and PRMT5 inhibitor exhibit high combination and clinical priority scores in our screen.

Reactive oxygen species in endothelial signaling in COVID-19: Protective role of the novel peptide PIP-2.

Introduction: Recent research suggests that endothelial activation plays a role in coronavirus disease 2019 (COVID-19) pathogenesis by promoting a pro-inflammatory state. However, the mechanism by which the endothelium is activated in COVID-19 remains unclear.

Objective: To investigate the mechanism by which COVID-19 activates the pulmonary endothelium and drives pro-inflammatory phenotypes.

Differentiated high grade thyroid carcinomas: Diagnostic consideration and clinical features.

Background: Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of Endocrine and Neuroendocrine Tumors. This new entity has been minimally described in the literature, and additional cases classified as such are missing.

Materials And Methods: Cases of DHGTCs diagnosed at our institution from 2012 to 2022 were identified, and the following were reviewed: cytologic and histologic diagnoses, ancillary testing, immunohistochemical staining, treatments, and patient outcomes.

Utilizing Histopathology to Predict Success with Macrolide Therapy in CRS Patients.

There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy.

Serotonin reduction in post-acute sequelae of viral infection.

Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction.

An investigation into noninvasive follicular thyroid neoplasms with papillary-like nuclear features: does the initial proposal on noninvasive follicular thyroid neoplasms with papillary-like nuclear features behavior hold true?

Current management of patients with noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) is lobectomy with close clinical follow-up. Because this entity is still young, we present our 5-year institutional experience with NIFTP since that time. Cases of NIFTP diagnosed from 2017 to 2022 were identified.

The next phase in patient safety education: Towards a standardized, tools-based pathology patient safety curriculum: ' .

Patient safety education is a mandated Common Program Requirement of the Accreditation Council for Graduate Medical Education and for the Royal College of Physicians and Surgeons of Canada in all medical residency and fellowship programs. Although many hospitals and healthcare environments have general patient safety education tools for trainees, few to none focus on the unique training milieu of pathologists, including a mix of highly automated and manual error-prone processes, frequent multiplicity of events, and lack of direct patient relationships for error disclosure. We established a national Association of Pathology Chairs-Program Directors Section Workgroup focused on patient safety education for pathology trainees entitled Training Residents in Patient Safety (TRIPS).

Inflammatory and Infectious Disorders in Endocrine Pathology.

A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes.

Does the presence of capsule influence prognosis in poorly differentiated thyroid carcinoma?

We collected all cases of poorly differentiated thyroid carcinoma at our institution diagnosed between 2007 and 2022 to investigate the role of tumor capsule in these neoplasms along with other histologic factors that may lead to adverse patient outcomes. After the exclusion of those meeting criteria for differentiated high-grade thyroid carcinoma or anaplastic carcinoma, we were left with 65 cases with a poorly differentiated component. Four of those cases (6.

Update on Sinonasal Tract Malignancies: Advances in Diagnostic Modalities.

Context.—: Sinonasal tract malignancies are rare cancers with frequent morphologic overlap. Given the similar histologic profiles seen in many of these entities, they often present a diagnostic challenge to the practicing pathologist.

Sinonasal Amoebiasis: An Unexpected Cause of Sinonasal Necroinflammatory Disease.

While amoebic infection is widely known as a cause of gastroenteritis, keratitis, and meningoencephalitis, amoebae are challenging to recognize at unexpected sites. Despite multiple case reports of sinonasal amoebiasis, amoebic infection is not regularly considered in the differential diagnosis of sinonasal necroinflammatory disease. Here, we aim to characterize the pathologic features of sinonasal amoebiasis to facilitate better recognition.

Decrease in Angiotensin-Converting Enzyme activity but not concentration in plasma/lungs in COVID-19 patients offers clues for diagnosis/treatment.

Although several therapeutics are used to treat coronavirus disease 2019 (COVID-19) patients, there is still no definitive metabolic marker to evaluate disease severity and recovery or a quantitative test to end quarantine. Because severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects human cells via the angiotensin-converting-enzyme 2 (ACE2) receptor and COVID-19 is associated with renin-angiotensin system dysregulation, we evaluated soluble ACE2 (sACE2) activity in the plasma/saliva of 80 hospitalized COVID-19 patients and 27 non-COVID-19 volunteers, and levels of ACE2/Ang (1-7) in plasma or membrane (mACE2) in lung autopsy samples. sACE2 activity was markedly reduced (p < 0.

Isolated Otologic Involvement of IgG4 Related Disease: A Case Report and Review of Literature.

Immunoglobulin G4 related disease (IgG4-RD) is a systemic autoimmune disease process that classically presents with multi-organ involvement; however isolated involvement of various structures within the body has also been described. Histopathologic examination is considered the gold standard for diagnosis. Glucocorticoids are well established as first-line treatment, but relapses are common, and consultation with rheumatology, immunology, and/or oncology teams is almost always warranted for proper medical management and disease maintenance.

A benchmark for oncologic outcomes and model for lethal recurrence risk after transoral robotic resection of HPV-related oropharyngeal cancers.

Objectives: Increasing use of transoral robotic surgery (TORS) is likely to impact outcomes for HPV+ oropharyngeal squamous cell carcinomas (OPSCCs). We aimed to describe oncologic outcomes for a large HPV+ OPSCC cohort after TORS and develop a risk prediction model for recurrence under this treatment paradigm.

Materials And Methods: 634 HPV+ OPSCC patients receiving TORS-based therapy at a single institution were reviewed retrospectively to describe survival across the entire cohort and for patients suffering recurrence.

YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia.

Persistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly 5% of cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative cancers at the same anatomical site, prompting the hypothesis that an HPV-encoded protein inactivates the Hippo pathway and activates the Hippo effector yes-associated protein (YAP1). The HPV E7 oncoprotein is required for HPV infection and for HPV-mediated oncogenic transformation.

Pulmonary vascular inflammation with fatal coronavirus disease 2019 (COVID-19): possible role for the NLRP3 inflammasome.

Background: Pulmonary hyperinflammation is a key event with SARS-CoV-2 infection. Acute respiratory distress syndrome (ARDS) that often accompanies COVID-19 appears to have worse outcomes than ARDS from other causes. To date, numerous lung histological studies in cases of COVID-19 have shown extensive inflammation and injury, but the extent to which these are a COVID-19 specific, or are an ARDS and/or mechanical ventilation (MV) related phenomenon is not clear.

Subcellular Detection of SARS-CoV-2 RNA in Human Tissue Reveals Distinct Localization in Alveolar Type 2 Pneumocytes and Alveolar Macrophages.

The widespread coronavirus disease 2019 (COVID-19) is caused by infection with the novel coronavirus SARS-CoV-2. Currently, we have limited understanding of which cells become infected with SARS-CoV-2 in human tissues and where viral RNA localizes on the subcellular level. Here, we present a platform for preparing autopsy tissue for visualizing SARS-CoV-2 RNA using RNA fluorescence in situ hybridization (FISH) with amplification by hybridization chain reaction.

The Cancer Surfaceome Atlas integrates genomic, functional and drug response data to identify actionable targets.

Cell-surface proteins (SPs) are a rich source of immune and targeted therapies. By systematically integrating single-cell and bulk genomics, functional studies and target actionability, in the present study we comprehensively identify and annotate genes encoding SPs (GESPs) pan-cancer. We characterize GESP expression patterns, recurrent genomic alterations, essentiality, receptor-ligand interactions and therapeutic potential.