Circulating Interleukins as Biomarkers in Non-Small Cell Lung Cancer Patients: A Pilot Study Compared to Normal Individuals.

Identifying biomarkers in non-small cell lung cancer (NSCLC) can improve diagnosis and patient stratification. We evaluated plasmas and sera for interleukins (IL)-11, IL-6, IL-8, IL-17A, and IL-33 as biomarkers in primary NSCLC patients undergoing surgical treatment against normal volunteers. Exhaled-breath condensates (EBCs), a potential source without invasive procedures, were explored in normal individuals.

Metastatic Leiomyoma With Malignant Transformation Harboring RAB2A-PLAG1 Fusion-A Case Report and Review With Molecular Analysis.

Metastasizing leiomyoma is a rare condition characterized by the development of benign-appearing smooth muscle neoplasms at extrauterine sites in patients with a history of uterine leiomyoma. These lesions occur most commonly in the lung, with the abdominopelvic and mediastinal lymph nodes being other reported sites. Malignant transformation of metastasizing leiomyoma is extremely rare, with only a few cases described in the literature.

Training immunophenotyping deep learning models with the same-section ground truth cell label derivation method improves virtual staining accuracy.

Introduction: Deep learning (DL) models predicting biomarker expression in images of hematoxylin and eosin (H&E)-stained tissues can improve access to multi-marker immunophenotyping, crucial for therapeutic monitoring, biomarker discovery, and personalized treatment development. Conventionally, these models are trained on ground truth cell labels derived from IHC-stained tissue sections adjacent to H&E-stained ones, which might be less accurate than labels from the same section. Although many such DL models have been developed, the impact of ground truth cell label derivation methods on their performance has not been studied.

Oncogene-Driven Non-Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations.

Unlabelled: Non-small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these "nonsmoking-related oncogenes" (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients.

Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer.

Background: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay.

Practical challenges in lung cancer pathology: bedside care to treatment decisions.

Purpose Of Review: Lung cancer is one of the most common malignancies in the whole world, and the pulmonologist is generally the first medical professional to meet the patient and decide what method of tumour sampling is preferable in each specific case. It is imperative for pulmonary physicians to be aware of the intricacies of the diagnostic process, and understand the multiple challenges that are encountered, from the moment the tissue specimen leaves their offices and is sent to the pathology laboratory, until the diagnosis reaches the patient and treating physician.

Recent Findings: The new 2021 WHO classification of thoracic tumours recommended a minimum immunohistochemical (IHC) diagnostic panel for nonsmall cell lung cancer (NSCLC), and following publications of different institutional and country-based guidelines, advocated basic molecular testing for epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and programmed cell death ligand 1 (PD-L1) to be initiated by the diagnosing pathologist in all cases of biopsy or resection specimens.

Three shades of an unusual mediastinal tumour.

Thoracic SMARCA4-deficient undifferentiated tumour (SMARCA4-UT) is an unusual and aggressive tumour. While there are approximately 100 cases of this tumour reported in the literature, there are very few detailed descriptions of its cytomorphologic characteristics, and only rare cases in which primary diagnosis was made on cytologic material. Herein we present a case with a detailed description of the appearance on three specimen types: transbronchial needle aspiration (TBNA) cytology, transbronchial needle biopsy (TBNB) and effusion cytology.

Standardized Classification of Lung Adenocarcinoma Subtypes and Improvement of Grading Assessment Through Deep Learning.

The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training.

Imaging and treatment with Gallium and Lutetium-DOTATATE in a rare SSTR2 and ESWR1-CREM fusion positive undifferentiated round cell tumour of the lung.

The authors present a 45-year-old lady with a rare undifferentiated round cell tumour of the lung with a ESWR1-CREM fusion gene that progressed despite multiple lines of therapy. The tumour was Somatostatin Receptors Type 2 (SSTR2) positive and avid on Gallium-DOTATATE imaging. This allowed for novel treatment with Peptide Receptor Radionuclide Therapy (PRRT) using Lutetium-DOTATATE after all other standard of care options were exhausted.

PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer.

Aim: To determine the prognostic value of programmed death-ligand 1 (PD-L1) score in early-stage epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), contrasted against EGFR-wildtype NSCLC.

Methods: Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1st January 2010-31st December 2019 at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary end-points were 2-year disease-free survival (DFS) and 5-year overall survival (OS) by Kaplan-Meier method.

A Randomized Phase 2 Trial of Nivolumab Versus Nivolumab-Ipilimumab Combination in EGFR-Mutant NSCLC.

Introduction: Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC.

Methods: This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)-resistant NSCLC, with crossover permitted on disease progression.

Pathological Findings in COVID-19 and Non-COVID-19 Vaccine-Associated Lymphadenopathy: A Systematic Review.

COVID-19 vaccine-associated lymphadenopathy (C19-VAL) is increasingly encountered with the widespread use of the vaccine in controlling the outbreak. We aim to characterize the pathological findings of COVID-19 and non-COVID-19 vaccine-associated lymphadenopathy (NC19-VAL). A search for studies that reported pathological findings in vaccine-associated lymphadenopathy on PubMed and Google Scholar was performed on 11 December 2021.

Overcoming the Interobserver Variability in Lung Adenocarcinoma Subtyping: A Clustering Approach to Establish a Ground Truth for Downstream Applications.

Context.—: The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability.

Objective.

Clinical and Genomic Features of Exon 20 Insertion Mutations and Characterization of Expression by Immunohistochemistry in East Asian Non-Small-Cell Lung Cancer.

Purpose: -altered non-small-cell lung cancer (NSCLC) represents a diverse subgroup, including mutations, amplifications, and overexpression. However, exon 20 insertion mutations are emerging as a distinct molecular subtype with expanding therapeutic options. We describe the molecular epidemiology and genomic features of -altered NSCLC in an Asian tertiary cancer center.

A single tertiary institution review of the international system for serous fluid cytopathology and the impact of cell block and ancillary studies on its performance.

Introduction: We sought to assess the utility of the International System for Serous Fluid Cytopathology (TIS) in the context of our department's routine practice.

Materials And Methods: We examined 1028 archived effusion cytology (pleural, peritoneal, and pericardial) cases from 2018 to 2019, and re-classified them along the international system into the following diagnostic categories: nondiagnostic (ND), negative for malignancy (NFM), atypia cells of undetermined significance (AUS), suspicious for malignancy (SFM), and malignant (MAL).

Results: The full distribution of the cases examined was as follows: ND 2.

Obtaining spatially resolved tumor purity maps using deep multiple instance learning in a pan-cancer study.

Tumor purity is the percentage of cancer cells within a tissue section. Pathologists estimate tumor purity to select samples for genomic analysis by manually reading hematoxylin-eosin (H&E)-stained slides, which is tedious, time consuming, and prone to inter-observer variability. Besides, pathologists' estimates do not correlate well with genomic tumor purity values, which are inferred from genomic data and accepted as accurate for downstream analysis.

Association of Clinicopathologic and Molecular Tumor Features With Recurrence in Resected Early-Stage Epidermal Growth Factor Receptor-Positive Non-Small Cell Lung Cancer.

Importance: The recently published ADAURA study has posed a significant dilemma for clinicians in selecting patients for adjuvant osimertinib. Risk factors for recurrence in early-stage epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) also remain undefined.

Objective: To determine clinicopathologic characteristics and recurrence patterns of resected early-stage EGFR-positive NSCLC, using wildtype EGFR as a comparator cohort, and identify features associated with recurrence.

Revisiting neoadjuvant therapy in non-small-cell lung cancer.

Despite the rapidly evolving treatment landscape in advanced non-small-cell lung cancer (NSCLC), developments in neoadjuvant and adjuvant treatments have been nascent by comparison. Establishing overall survival benefit in the early-stage setting has been challenging because of the need for large trials and long-term survival data. Encouraged by improved treatment outcomes with a biomarker-driven approach in advanced NSCLC, and recognising the need to improve survival outcomes in early-stage NSCLC, there has been renewed interest in revisiting neoadjuvant strategies.

Autoimmune pulmonary alveolar proteinosis with a history of vaping and vitamin E-positive bronchoalveolar lavage.

Pulmonary alveolar proteinosis (PAP) can be due to primary autoimmune and secondary causes, including e-cigarette, or vaping, product use-associated lung injury. We present a 33-year-old male presenting with PAP and a history of vaping. Serum anti-granulocyte-macrophage colony-stimulating factor antibodies were present.

Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities.

Purpose: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in -mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in -negative resistance.

Experimental Design: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic -mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M) and -negative (T790M) disease.

Results: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M tumors, orthogonally validated using multiplex IHC.

Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study-An Asian Tertiary Cancer Center Experience.

Purpose: Precision oncology has transformed the management of advanced cancers through implementation of advanced molecular profiling technologies to identify increasingly defined subsets of patients and match them to appropriate therapy. We report outcomes of a prospective molecular profiling study in a high-volume Asian tertiary cancer center.

Patients And Methods: Patients with advanced cancer were enrolled onto a prospective protocol for genomic profiling, the Individualized Molecular Profiling for Allocation to Clinical Trials Singapore study, at the National Cancer Center Singapore.

Intratumoral CD39CD8 T Cells Predict Response to Programmed Cell Death Protein-1 or Programmed Death Ligand-1 Blockade in Patients With NSCLC.

Introduction: Programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade is currently widely used in the treatment of metastatic NSCLC. Despite available biomarker stratification, clinical responses vary. Thus, the search for novel biomarkers with improved response prediction is ongoing.

A sleeve gastrectomy with pseudo-infiltrative pancreatic heterotopia and fundic gland polyps.

No abstract available.

Experimental and bioinformatics considerations in cancer application of single cell genomics.

Single cell genomics offers an unprecedented resolution to interrogate genetic heterogeneity in a patient's tumour at the intercellular level. However, the DNA yield per cell is insufficient for today's sequencing library preparation protocols. This necessitates DNA amplification which is a key source of experimental noise.