A quantitative method for assessing treatment-related changes within the airway mucosa in patients with chronic bronchitis.

Background: No standardized method has yet been established for evaluating airway mucosal aberrancies associated with chronic obstructive pulmonary disease (COPD) or chronic bronchitis (CB). While goblet cell hyperplasia (GCH) is an established pathognomonic hallmark of the CB disease process, no standardized method exists for acquiring mucosal biopsies and assessing morphologic airway mucosa alterations. Additionally, the impacts from interventions targeting the airway mucosa are not well defined.

Tools, techniques, and challenges in preparing cytology specimens for ancillary studies: results of the ASC Optimizing Cytology and Small Biopsy Specimen Processing for Ancillary Studies task force survey.

Introduction: Ancillary testing on cytopathology and other small biopsy specimens is crucial for diagnosis and provides critical information to clinicians. Testing is dependent on preanalytic factors and would benefit from standardization of specimen collection protocols across laboratories. To assess institutional practices and areas of need for evidence-based standards, we surveyed current practices across cytopathology laboratories.

Rapid examination of lung tissues by nonlinear microscopy.

Objectives: Traditional histopathology is a time-intensive and labor-intensive process involving tissue formalin fixation, paraffin embedding, and microtoming into thin sections for H&E staining. Frozen section analysis is a modality used during surgery to quickly evaluate tissue, but it has limitations, such as the size and number of the specimens that can be analyzed as well as difficulties with fatty and bony tissues. Our objective was to investigate the performance of nonlinear microscopy, a fluorescence microscopy technique, for the rapid examination of resected lung tumors.

The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors.

Introduction: Mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors have not been extensively studied in either robust preclinical models or patient-derived rebiopsy specimens. We sought to characterize on-target resistance mutations identified in exon 20 insertion-mutated lung cancers treated with mobocertinib or poziotinib and evaluate whether these mutations would or would not have cross-resistance to next-generation inhibitors zipalertinib, furmonertinib, and sunvozertinib.

Methods: We identified mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors and then used preclinical models of EGFR exon 20 insertion mutations (A767_V769dupASV, D770_N771insSVD, V773_C774insH) plus common EGFR mutants to probe inhibitors in the absence/presence of EGFR-T790M or EGFR-C797S.

Binary subclassification scheme (AUS-Nuclear versus AUS-Other) adequately risk-stratifies thyroid fine needle aspiration specimens classified as Atypia of Undetermined Significance.

Introduction: The Bethesda System for Reporting Thyroid Cytopathology previously described 4 subclasses of atypia within the Atypia of Undetermined Significance (AUS) category: nuclear (AUS-Nuc), architectural (AUS-A), oncocytic (AUS-Onc), and atypia not otherwise specified (AUS-NOS). Accumulating evidence supports a binary AUS subclassification scheme based primarily on the presence of nuclear atypia only. The purpose of this study is to compare the risk stratification of binary versus 4-tier AUS subclassification systems among AUS nodules with molecular and/or histologic follow-up.

exon 20 insertion mutations and mutations in lung cancer: a narrative review on approved targeted therapies from oral kinase inhibitors to antibody-drug conjugates.

Background And Objective: This review will provide an overview of and mutations in non-small-cell lung cancer (NSCLC) with a focus on recent clinical approvals.

Methods: We obtained data from the literature in accordance with narrative review reporting guidelines.

Key Content And Findings: mutations are present in up to 15-20% of all NSCLCs; amongst these, 10% correspond to kinase domain insertions in exon 20.

EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors.

Background: The epidermal growth factor receptor (EGFR)-K745_E746insIPVAIK and others with XPVAIK amino-acid insertions are exon 19 insertion mutations, which, at the structural modeling level, resemble EGFR tyrosine kinase inhibitor (TKI)-sensitizing mutants. An important unmet need is the characterization of therapeutic windows plus clinical outcomes of exon 19 XPVAIK amino-acid insertion mutations to available EGFR TKIs.

Methods: We used preclinical models of EGFR-K745_E746insIPVAIK and more typical EGFR mutations (exon 19 deletion, L858R, L861Q, G719S, A763_Y764insFQEA, other exon 20 insertion mutations) to probe representative 1st (erlotinib), 2nd (afatinib), 3rd generation (osimertinib), and EGFR exon 20 insertion active (mobocertinib) TKIs.

Deletion Exons 2 to 19: Case Report of a Rare ALK Inhibitor-Responsive Lung Cancer Driver Oncogene.

internal deletions of nonkinase domain exons occur in 0.01% of lung cancers with genomic aberrations. We report a lung adenocarcinoma with a previously undescribed somatic deletion of exons 2 to 19 with dramatic and sustained (>23 mo) response to alectinib.

Multi-institutional 10-year retrospective review of amoeba diagnosed on cytologic evaluation of anal pap tests: what is the significance?

Introduction: Intestinal amoebae are usually transmitted via ingestion of amoebic cysts in fecally contaminated water or food. However, other modes of transmission include sexual contact through anal-oral sex. While the primary role of anal cytology is the detection of anal cancer and precursor lesions, organisms can also be identified.

Massive Thymic Hyperplasia Masquerading as Cancer: A Case Report and Review of the Literature.

A 34-year-old woman presenting with abdominal pain, chest pressure, weight loss, and tachycardia was found to have an 11.4-cm anterior mediastinal mass associated with intrathoracic lymphadenopathy on chest computed tomography (Fig. 1).

Risk stratification of cytologically indeterminate thyroid nodules with nondiagnostic or benign cytology on repeat FNA: Implications for molecular testing and surveillance.

Background: Evidence guiding the management of cytologically indeterminate thyroid nodules with nondiagnostic (ND) or benign cytology on repeat fine-needle aspiration (FNA) is limited. This study evaluates the utility of molecular testing and estimates the risk of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and cancer among such nodules.

Methods: This was a retrospective single-institution review of thyroid nodules from adults that were classified as atypia of undetermined significance (AUS) or follicular neoplasm (FN) on initial FNA and underwent repeat FNA for cytology and Afirma testing (June 2013-July 2021).

Leveraging thoughtful quality metric selection for individual and system improvements: the atypical category and use of dashboards.

Quality management is integral to the practice of cytopathology, especially given the heavily manual workflows and expanding ancillary testing requirements inherent to the cytopathology laboratory. Monitoring quality data like turnaround time, specimen unsatisfactory rates, and diagnostic category utilization rates allows for better understanding of performance with opportunities for targeted improvement if there are variations from that which is expected. However, there are costs to quality monitoring including the time and resources needed, and, in already taxed systems, quality management risks being viewed as just another box to check.

Molecular testing of cytology specimens: overview of assay selection with focus on lung, salivary gland, and thyroid testing.

Ancillary and molecular testing of cytopathology specimens has emerged as a reliable and useful tool to provide diagnostic information and treatment-related biomarker status for the management of cancer patients. The cytology specimens obtained through minimally invasive means have proven suitable testing substrates for a variety of ancillary tests, including immunohistochemistry, fluorescence in situ hybridization, as well as polymerase chain reaction and next generation sequencing molecular techniques. By focusing specifically on the cytology specimen, this review provides an overview of basic testing considerations and assay selection in addition to updates on the ancillary testing of cytologic tumor specimens from the lung, salivary gland, and thyroid.

Review of the Pathologic Characteristics in Myhre Syndrome: Gain-of-Function Pathogenic Variants in cause a Multisystem Fibroproliferative Response.

Myhre syndrome, caused by pathogenic variants in , is characterized by compact body habitus with short stature, distinctive craniofacial appearance, stiff skin, cardiovascular abnormalities (valve stenosis, coarctation, hypoplasia, or stenosis of aorta), effusions of potential spaces (pericardium, pleura, peritoneum), restricted movement of the joints (including thorax), and hearing loss. Lung and airway disease has been reported, but not always well-defined, to include interstitial lung disease, large airway obstruction, and pulmonary arterial hypertension. Excessive fibroproliferation of tissues especially following trauma or surgical instrumentation has been recognized, although these may also present spontaneously.

Complete pathologic response to short-course neoadjuvant alectinib in mediastinal node positive (N2) ALK rearranged lung cancer.

Objectives: Neoadjuvant therapy prior to surgical resection for locally advanced lung cancer has evolved to incorporate systemic cytotoxic chemotherapy +/- immunotherapy +/- radiotherapy. The role of neoadjuvant precision therapies remains understudied.

Materials And Methods: We report cases with major and complete pathologic responses to off-label neoadjuvant alectinib.