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.

CT-guided Coaxial Lung Biopsy: Number of Cores and Association with Complications.

Background Percutaneous CT-guided lung core-needle biopsy is a frequently performed and generally safe procedure. However, with advances in the management of lung cancer, there is a need for a greater amount of tissue for tumor genomic profiling and characterization. Purpose To determine whether the number of core samples obtained with percutaneous CT-guided lung biopsy is associated with postprocedural complications.

Insulinoma-associated protein-1 (INSM-1) is a useful diagnostic marker for the evaluation of primary thymic neuroendocrine neoplasms: an immunohistochemical study of 27 cases.

Insulinoma-associated protein 1 (INSM1) immunohistochemistry has been established as a sensitive and reliable immunohistochemical marker for detecting neuroendocrine differentiation in tumors across various organ systems. However, this marker has not been adequately investigated in primary thymic neuroendocrine tumors. We have studied a series of 27 cases of primary neuroendocrine carcinomas of the thymus, including 3 typical carcinoids, 18 atypical carcinoids, 4 large cell neuroendocrine carcinomas, and 2 small cell carcinomas.

Comparative genomic and immunopathologic analysis of lung adenocarcinomas with and without cytology-proven malignant pleural effusions.

Background: Lung cancer complicated by malignant pleural effusions (MPEs) is associated with significantly increased morbidity and mortality, yet the mechanisms of MPE development remain poorly understood. This study sought to elucidate whether there were specific genomic alterations and/or immunologic biomarkers associated with the presence of MPEs.

Methods: Analysis of comprehensive genomic and immunologic profiling for 275 locally advanced (stage III) or advanced (stage IV) lung adenocarcinomas was subcategorized into cytology-confirmed MPE-positive (MPE+; n = 139 stage IV) and MPE-negative (MPE-; n = 30 stage III + n = 106 stage IV) groups.

Imaging of Small Airways Disease.

Bronchiolitis refers to a small airways disease and may be classified by etiology and histologic features. In cellular bronchiolitis inflammatory cells involve the small airway wall and peribronchiolar alveoli and manifest on CT as centrilobular nodules of solid or ground glass attenuation. Constrictive bronchiolitis refers to luminal narrowing by concentric fibrosis.

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.

A brief review of the WHO reporting system for lung cytopathology.

The International Academy of Cytology has joined with the International Agency for Research on Cancer to bring together a group of experts in lung cytopathology to develop a WHO Reporting System for Lung Cytopathology (WHO System). This System aims to improve and standardize the reporting of cytopathology, facilitate communication between cytopathologists and clinicians, and improve patient care. The WHO System describes 5 categories for reporting lung cytopathology: 'Insufficient/Inadequate/Nondiagnostic', 'Benign', 'Atypical', 'Suspicious for malignancy', and 'Malignant', each one with a clear descriptive term, a definition, a risk of malignancy, and a suggested management algorithm.

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).

The World Health Organization Reporting System for Lung Cytopathology.

The International Academy of Cytology has joined with the International Agency for Research on Cancer (IARC) to bring together a group of experts in lung cytopathology to develop a WHO Reporting System for Lung Cytopathology (WHO System). This WHO System defines five categories for reporting lung cytopathology, that is, "Insufficient"/"Inadequate"/"Non-diagnostic," "Benign," "Atypical," "Suspicious for malignancy," and "Malignant," each with a clear descriptive term for the category, a definition, a risk of malignancy and a suggested management algorithm. The key diagnostic cytopathology features of each of the lesions within each category have been established by consensus and will be presented more fully in a subsequent IARC e-book and published hard cover book.