Basal cell of origin resolves neuroendocrine-tuft lineage plasticity in cancer.

Neuroendocrine and tuft cells are rare, chemosensory epithelial lineages defined by expression of ASCL1 and POU2F3 transcription factors, respectively. Neuroendocrine cancers, including small cell lung cancer (SCLC), frequently display tuft-like subsets, a feature linked to poor patient outcomes. The mechanisms driving neuroendocrine-tuft tumour heterogeneity, and the origins of tuft-like cancers are unknown.

Chemokine CCL19 and Its Receptors CCR7 and CCRL1 in Chronic Rhinosinusitis.

Background: CCL19 has been shown to predict disease severity in COVID-19 and treatment response in rheumatoid arthritis. CCL19 can exert both pro- and anti-inflammatory effects and is elevated in chronic rhinosinusitis (CRS). However, its role in CRS remains unknown.

An eosinophil peroxidase activity assay accurately predicts eosinophilic chronic rhinosinusitis.

Background: A definitive diagnosis of eosinophilic chronic rhinosinusitis (eCRS) requires invasive surgical tissue sampling and histologic enumeration of intact eosinophils. Eosinophil peroxidase (EPX) is an accurate biomarker of sinonasal tissue eosinophilia in CRS regardless of polyp status. A less invasive and rapid method that accurately identifies tissue eosinophilia would be of great benefit to patients.

Distinguishing Gastrointestinal Leiomyomas From Muscularis Propria in Biopsy Specimens by Differential Expression of S100 Immunohistochemical Stain.

Objectives: Interpreting small biopsy specimens or fine-needle aspirations of gastrointestinal tract (GI) smooth muscle lesions may be challenging when the differential diagnosis includes leiomyoma vs muscularis propria (MP). We evaluated the utility of S100 staining in distinguishing GI leiomyomas from MP.

Methods: A search was conducted in our laboratory information system for cases of leiomyomas arising within the GI tract (2004-2021).

Safety and Feasibility of Photodynamic Therapy for Ablation of Peripheral Lung Tumors.

Background: Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors.

Methods: Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10).

Using American Type Culture Collection Cell Lines to Evaluate Interlaboratory Variables for Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Immunostaining.

Context.—: Most laboratories currently use patient tissues for validating immunohistochemical stains.

Objective.

Performance of specific morphologic features in distinguishing low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions in borderline cases: a College of American Pathologists Cytopathology Committee multiobserver study.

Introduction: Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program.

Materials And Methods: Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL).

Rapid On Site Evaluation (ROSE): A Pathologists' Perspective.

Rapid on site evaluation (ROSE) has been recognized as a safeguard to help ensure adequate aspirate or biopsy sample is present for diagnostic evaluation. The method involves having a pathologist (generally a cytopathologist) on site during specimen collection to allow for feedback for the performing proceduralist. ROSE can allow for appropriate ancillary tests to be collected at the time of biopsy (eg, flow cytometry or cultures), fewer passes in the event of adequate lesional representation on initial pass(es), or adjusting the biopsy target.

Communicating Certainty in Pathology Reports.

Context.—: Pathology reports are the main modality in which results are communicated to other physicians. For various reasons, the diagnosis may be qualified on a spectrum of uncertainty.

ASCL1 represses a SOX9 neural crest stem-like state in small cell lung cancer.

ASCL1 is a neuroendocrine lineage-specific oncogenic driver of small cell lung cancer (SCLC), highly expressed in a significant fraction of tumors. However, ∼25% of human SCLC are ASCL1-low and associated with low neuroendocrine fate and high MYC expression. Using genetically engineered mouse models (GEMMs), we show that alterations in in the mouse lung induce an ASCL1 state of SCLC in multiple cells of origin.

Multiple enlarging hepatic and retroperitoneal myelolipomas in the setting of Cushing disease.

Myelolipomas are benign tumours typically occurring in the adrenal glands, made up of fat and trilineage haematopoeitic cells resembling bone marrow. Their aetiology is not well understood; however, they have a clear association with elevated serum adrenocorticotropic hormone (ACTH). Extra-adrenal myelolipomas are rare, and to our knowledge there are no previously reported cases of multiple enlarging hepatic and retroperitoneal myelolipomas in the setting of Cushing disease.

Comparison of EUS-guided conventional smear and liquid-based cytology in pancreatic lesions: A systematic review and meta-analysis.

Endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNA) has limitations of inadequate sampling and false-negative results for malignancy. It has been performed using conventional smear (CS) cytology with rapid on-site evaluation (ROSE) with reasonable diagnostic accuracy. An alternative to ROSE is liquid-based cytology (LBC).

MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate.

Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1, NEUROD1, POU2F3, or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes.

Core needle biopsy with endobronchial ultrasonography: single center experience with 100 cases.

Introduction: Adequate sampling by endobronchial ultrasound (EBUS)-transbronchial needle aspiration to meet the demands of precision medicine or histologic evaluation is challenging. There is increasing demand for core biopsy specimens with advances in therapy. Franseen enodoscopic ultrasound needles have shown promising results in gastroenterology application for obtaining core biopsies and same design has recently been extended for pulmonary use.

Prediction of survival of HPV16-negative, p16-negative oral cavity cancer patients using a 13-gene signature: A multicenter study using FFPE samples.

Objectives: To test the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer.

Materials And Methods: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay.

The Differential Diagnosis of Reparative Changes and Malignancy: Performance in the College of American Pathologists Pap Education and Proficiency Testing Programs.

Context.—: Repair is a challenging diagnosis and a significant source of false-positive (FP) interpretations in cervical cytology. No large-scale study of performance of repair in the liquid-based era has been performed.

The Lineage-Defining Transcription Factors SOX2 and NKX2-1 Determine Lung Cancer Cell Fate and Shape the Tumor Immune Microenvironment.

The major types of non-small-cell lung cancer (NSCLC)-squamous cell carcinoma and adenocarcinoma-have distinct immune microenvironments. We developed a genetic model of squamous NSCLC on the basis of overexpression of the transcription factor Sox2, which specifies lung basal cell fate, and loss of the tumor suppressor Lkb1 (SL mice). SL tumors recapitulated gene-expression and immune-infiltrate features of human squamous NSCLC; such features included enrichment of tumor-associated neutrophils (TANs) and decreased expression of NKX2-1, a transcriptional regulator that specifies alveolar cell fate.

Low-Grade Squamous Intraepithelial Lesion or High-Grade Squamous Intraepithelial Lesion? Concordance Between the Interpretation of Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion in Papanicolaou Tests: Results From the College of American Pathologists PAP Education Program.

Context.—: Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging.

Objective.

Evaluation of the SharkCore needle for EUS-guided core biopsy of pancreatic neuroendocrine tumors.

Background And Objectives: EUS guided core biopsy was once rarely performed but is now entering mainstream practice. Neuroendocrine tumors often warrant core biopsy as sufficient tissue must be obtained to allow for special staining to ensure a correct diagnosis. Traditionally these lesions were sampled with FNA needles.

Diagnostic yield and accuracy of a new cytology brush design compared to standard brush cytology for evaluation of biliary strictures.

Background: The sensitivity of brush cytology for biliary strictures has typically been low, usually 30%-60%. We compared the cellular yield and diagnostic accuracy using a new cytology brush (n = 16) versus standard biliary brushings (n = 16) in 32 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) with brushings for evaluation of a biliary stricture for malignancy.

Methods: We performed retrospective chart reviews of 16 consecutive ERCPs with brushings performed for the cytologic evaluation of a biliary stricture for malignancy using the new cytology brush between January 2016 and February 2017 at our institution.

Characterization of PD-L1 Immunohistochemical Expression in Cell Blocks With Different Specimen Fixation and Processing Methods.

Interpretative criteria for programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) have been largely based on data from formalin-fixed, paraffin-embedded tissues, despite the fact that cytologic specimens, especially cell blocks, are often the only or most readily available tissue for testing. Unlike biopsy specimens, however, cytology sample processing methods can vary markedly. The purpose of this study was to evaluate the effects of several common preanalytic variables on PD-L1 IHC.

An Update on the Risk of Lymph Node Metastasis for the Follicular Variant of Papillary Thyroid Carcinoma with the New Diagnostic Paradigm.

Previous data has shown that the risk of nodal metastases is significantly greater for classical papillary thyroid carcinoma (PTC) as compared to the follicular variant (FVPTC). Given a recent change in diagnostic paradigm and definition of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) we intended to investigate if there remains a significant difference in nodal involvement between classical PTC and FVPTC. A 6-year retrospective review of all cases with FVPTC in the diagnostic line from the University of Utah/ARUP Laboratories was conducted.

Elective Neck Dissection for Head and Neck Cutaneous Squamous Cell Carcinoma with Skull Base Invasion.

Objectives Skull base invasion from cutaneous squamous cell carcinoma (cSCC) via perineural spread affects survival and the rate of regional metastasis. Our objective is to investigate the factors associated with elective neck dissection (END) in this population and the survival difference with END compared with observation for patients with a cN0 neck. Study Design Case series with chart review.

Imaging and Outcomes for a New Entity: Low-Grade Sinonasal Sarcoma with Neural and Myogenic Features.

 Low-grade sinonasal sarcoma with neural and myogenic features (LGSSNMF) is a new, rare tumor. Our goal is to describe the imaging characteristics and surgical outcomes of this unique skull base malignancy.  Retrospective case series.