ABSTRACT
PD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens2, and little is known about transcriptional programs of MANA-specific TIL. Here, we identify MANA-specific T cell clones using the MANA functional expansion of specific T cells assay3 in neoadjuvant anti-PD-1-treated non-small cell lung cancers (NSCLC). We use their T cell receptors as a 'barcode' to track and analyse their transcriptional programs in the tumour microenvironment using coupled single-cell RNA sequencing and T cell receptor sequencing. We find both MANA- and virus-specific clones in TIL, regardless of response, and MANA-, influenza- and Epstein-Barr virus-specific TIL each have unique transcriptional programs. Despite exposure to cognate antigen, MANA-specific TIL express an incompletely activated cytolytic program. MANA-specific CD8 T cells have hallmark transcriptional programs of tissue-resident memory (TRM) cells, but low levels of interleukin-7 receptor (IL-7R) and are functionally less responsive to interleukin-7 (IL-7) compared with influenza-specific TRM cells. Compared with those from responding tumours, MANA-specific clones from non-responding tumours express T cell receptors with markedly lower ligand-dependent signalling, are largely confined to HOBIThigh TRM subsets, and coordinately upregulate checkpoints, killer inhibitory receptors and inhibitors of T cell activation. These findings provide important insights for overcoming resistance to PD-1 blockade.
Subject(s)
Antigens, Neoplasm/immunology , Carcinoma, Non-Small-Cell Lung/drug therapy , Gene Expression Regulation , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Antigens, Neoplasm/genetics , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/immunology , Cells, Cultured , Humans , Immunologic Memory , Lung Neoplasms/genetics , Programmed Cell Death 1 Receptor/antagonists & inhibitors , RNA-Seq , Receptors, Interleukin-7/immunology , Single-Cell Analysis , Transcriptome/genetics , Tumor MicroenvironmentABSTRACT
SGK1 is an AGC kinase that regulates the expression of membrane sodium channels in renal tubular cells in a manner dependent on the metabolic checkpoint kinase complex mTORC2. We hypothesized that SGK1 might represent an additional mTORC2-dependent regulator of the differentiation and function of T cells. Here we found that after activation by mTORC2, SGK1 promoted T helper type 2 (TH2) differentiation by negatively regulating degradation of the transcription factor JunB mediated by the E3 ligase Nedd4-2. Simultaneously, SGK1 repressed the production of interferon-γ (IFN-γ) by controlling expression of the long isoform of the transcription factor TCF-1. Consistent with those findings, mice with selective deletion of SGK1 in T cells were resistant to experimentally induced asthma, generated substantial IFN-γ in response to viral infection and more readily rejected tumors.
Subject(s)
Asthma/immunology , Immediate-Early Proteins/metabolism , Melanoma, Experimental/immunology , Multiprotein Complexes/immunology , Poxviridae Infections/immunology , Protein Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Vaccinia virus/immunology , Adaptive Immunity/genetics , Animals , Cell Differentiation/genetics , Cells, Cultured , Endosomal Sorting Complexes Required for Transport/metabolism , Gene Expression Regulation/genetics , Hepatocyte Nuclear Factor 1-alpha , Immediate-Early Proteins/genetics , Interferon-gamma/genetics , Interferon-gamma/metabolism , Mechanistic Target of Rapamycin Complex 2 , Mice , Mice, Inbred C57BL , Mice, Knockout , Nedd4 Ubiquitin Protein Ligases , Protein Serine-Threonine Kinases/genetics , T Cell Transcription Factor 1/genetics , T Cell Transcription Factor 1/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Tumor Burden/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.
Subject(s)
Lung Neoplasms , Physicians , Humans , Lung Neoplasms/diagnosis , Consensus , Bronchoscopy/methods , Delphi Technique , Lung/pathology , Patient-Centered CareABSTRACT
BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm arising in the stomach. However, a number of other rare mesenchymal neoplasms do occur at this anatomic site, which often presents a diagnostic challenge for cytopathologists on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Our study aims to selectively present the clinico-radiological and cytopathological characteristics of these rare "non-GIST" neoplasms, as well as their differential diagnoses. MATERIAL AND METHODS: We performed a 20 year retrospective search in the cytopathology database of our two large medical institutions for non-GIST mesenchymal neoplasms arising in the stomach and diagnosed on EUS-FNA. Data regarding the patients' demographics and radiological findings were analysed. All available cytopathology specimens were reviewed. The cytomorphological characteristics and the accompanying immunohistochemical stains, when available, were subsequently analysed. RESULTS: Twenty-five cases of gastric mesenchymal tumours were selectively included in the study after excluding all cases of GIST (n = 113) diagnosed on FNA. These cases included 10 leiomyomas (40%), eight schwannomas (32%), five glomus tumours (20%), one perivascular epithelioid cell neoplasm, and one desmoid tumour. The specimen cellularity was variable and ranged from hypocellular to highly cellular. Most smears were composed of spindle cells with a few showing epithelioid morphology. Cell blocks were available in 20 cases and a range of immunohistochemical ancillary studies were performed. DOG-1, c-KIT, smooth muscle actin (SMA), and S100-protein were the most common immunomarkers done. CONCLUSION: Our study highlights important cytomorphological characteristics of rare mesenchymal neoplasms arising in the stomach. In the appropriate clinical setting and with the help of immunohistochemistry, an accurate diagnosis of these neoplasms can be achieved.
Subject(s)
Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Stomach Neoplasms , Humans , Retrospective Studies , Cytology , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/pathology , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Gastrointestinal Neoplasms/pathologyABSTRACT
We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.
Subject(s)
Acute Lung Injury , Lung Transplantation , Pneumonia , Adult , Humans , Prospective Studies , Prognosis , Retrospective Studies , Lung Transplantation/adverse effects , Acute Lung Injury/etiology , Acute Lung Injury/pathology , Lung , Pneumonia/epidemiology , Pneumonia/etiology , Pneumonia/pathology , Risk Factors , Cohort StudiesABSTRACT
BACKGROUND: Bronchoscopic lung biopsy is typically performed using transbronchial forceps. However, this method is limited by small sample size and presence of crush artifact. Cryobiopsy offers the potential to overcome these limitations with larger artifact-free samples but has not been widely adopted due to concerns over increased rates of bleeding and pneumothorax. A new, smaller 1.1-mm cryoprobe has been developed that operates in a similar fashion to forceps, though the safety profile of this cryoprobe has not yet been prospectively studied. OBJECTIVE: The aim of this study was to investigate the safety of transbronchial biopsy using a novel 1.1-mm cryoprobe. METHODS: This prospective, single-arm study enrolled patients referred for transbronchial biopsy. All procedures were performed using the 1.1-mm cryoprobe with oversheath. The primary outcome was the composite of significant complications related to the cryobiopsy procedure (bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure). Bleeding and pneumothorax were graded according to previously published scales. RESULTS: Fifty participants from two academic medical centers underwent transbronchial cryobiopsy. Indications for biopsy included evaluation of lung transplant allograft (50%), diffuse lung disease (44%), and pulmonary parenchymal lesion (6%). There were two pneumothoraces (4%), neither of which required aspiration or chest tube placement. There were no Grade 3 or 4 bleeding events. Mild bleeding (Grade ≤2) was observed in 25 cases (50%). No complications occurred that met the a priori primary outcome of bleeding Grade ≥3, pneumothorax Grade ≥2, and respiratory failure. CONCLUSIONS: Transbronchial cryobiopsy using a 1.1-mm cryoprobe is feasible with an acceptable safety profile.
Subject(s)
Frostbite , Pneumothorax , Respiratory Insufficiency , Humans , Bronchoscopy/adverse effects , Bronchoscopy/methods , Prospective Studies , Feasibility Studies , Pneumothorax/epidemiology , Pneumothorax/etiology , Biopsy/adverse effects , Biopsy/methods , Lung/pathology , Hemorrhage/epidemiology , Hemorrhage/etiology , Frostbite/complications , Frostbite/pathologyABSTRACT
BACKGROUND: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies in patients with dermatomyositis are associated with rapidly progressive interstitial lung disease (RP-ILD). Computed tomography (CT) plays a central role in the diagnosis of RP-ILD and may help characterize the temporal changes. METHODS: We report five anti-MDA5-positive dermatomyositis patients with serial CT scans spanning their acute RP-ILD disease course. RESULTS: Our case series highlights the variable imaging pattern that can manifest in this setting, including diffuse alveolar damage and nonspecific interstitial pneumonia patterns. Three patients in our series died within 4 months of their disease onset, whereas the other two patients survived. CONCLUSION: The serial CT changes in anti-MDA5 disease are dynamic and variable; therefore, it is imperative to maintain a broad differential when faced with these HRCT patterns to improve the diagnosis and management of this underrecognized entity.
Subject(s)
Dermatomyositis , Lung Diseases, Interstitial , Humans , Interferon-Induced Helicase, IFIH1 , Dermatomyositis/diagnostic imaging , Dermatomyositis/complications , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/complications , Autoantibodies , Disease ProgressionABSTRACT
Pulmonary hypertension (PH) is a debilitating disease characterized by remodeling of the lung vasculature. In rodents, resistin-like molecule-α (RELMα, also known as HIMF or FIZZ1) can induce PH, but the signaling mechanisms are still unclear. In this study, we used human lung samples and a hypoxia-induced mouse model of PH. We found that the human homolog of RELMα, human (h) resistin, is upregulated in macrophage-like inflammatory cells from lung tissues of patients with idiopathic PH. Additionally, at PH onset in the mouse model, we observed RELMα-dependent lung accumulation of macrophages that expressed high levels of the key damage-associated molecular pattern (DAMP) molecule high-mobility group box 1 (HMGB1) and its receptor for advanced glycation end products (RAGE). In vitro, RELMα/hresistin-induced macrophage-specific HMGB1/RAGE expression and facilitated HMGB1 nucleus-to-cytoplasm translocation and extracellular secretion. Mechanistically, hresistin promoted HMGB1 posttranslational lysine acetylation by preserving the NAD+-dependent deacetylase sirtuin (Sirt) 1 in human macrophages. Notably, the hresistin-stimulated macrophages promoted apoptosis-resistant proliferation of human pulmonary artery smooth muscle cells in an HMGB1/RAGE-dependent manner. In the mouse model, RELMα also suppressed the Sirt1 signal in pulmonary macrophages in the early posthypoxic period. Notably, recruited macrophages in the lungs of these mice carried the RELMα binding partner Bruton tyrosine kinase (BTK). hResistin also mediated the migration of human macrophages by activating BTK in vitro. Collectively, these data reveal a vascular-immune cellular interaction in the early PH stage and suggest that targeting RELMα/DAMP-driven macrophages may offer a promising strategy to treat PH and other related vascular inflammatory diseases.
Subject(s)
Hypertension, Pulmonary/immunology , Intercellular Signaling Peptides and Proteins/immunology , Macrophages, Alveolar/immunology , Pulmonary Artery/immunology , Vascular Remodeling/immunology , Adolescent , Animals , Cells, Cultured , Humans , Hypertension, Pulmonary/pathology , Intercellular Signaling Peptides and Proteins/deficiency , Macrophages, Alveolar/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Pulmonary Artery/pathologyABSTRACT
Thymic epithelial neoplasms are rare as these tumors represent less than 1% of all human tumors. In addition, thymic hyperplasia and thymic cysts can also present as anterior or less often superior mediastinal masses. Fine needle aspirates and core biopsies of thymic epithelial neoplasms are rarely encountered in routine pathology practices. Histologic classification of these lesions requires microscopic examination of the entire lesion as a significant number of tumors can have more than one histologic type and the status of invasion into adjacent soft tissues or organs is needed for accurate staging. Therefore, it is important to understand the limitations of the information these biopsy methods can provide. The accuracy of the diagnosis can be improved by using ancillary techniques like immunohistochemistry and flow cytometry. In this review, we are summarizing the clinical, histologic and cytologic characteristics of thymic cysts, thymic hyperplasia and thymic epithelial neoplasms including different types of thymoma and thymic carcinoma.
Subject(s)
Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/pathology , Thymus Gland/pathology , Thymus Neoplasms/diagnosis , Thymus Neoplasms/pathology , Biopsy, Fine-Needle , HumansABSTRACT
The sources of gene expression variability in human tissues are thought to be a complex interplay of technical, compositional, and disease-related factors. To better understand these contributions, we investigated expression variability in a relatively homogeneous tissue expression dataset from the Genotype-Tissue Expression (GTEx) resource. In addition to identifying technical sources, such as sequencing date and post-mortem interval, we also identified several biological sources of variation. An in-depth analysis of the 175 genes with the greatest variation among 133 lung tissue samples identified five distinct clusters of highly correlated genes. One large cluster included surfactant genes (SFTPA1, SFTPA2, and SFTPC), which are expressed exclusively in type II pneumocytes, cells that proliferate in ventilator associated lung injury. High surfactant expression was strongly associated with death on a ventilator and type II pneumocyte hyperplasia. A second large cluster included dynein (DNAH9 and DNAH12) and mucin (MUC5B and MUC16) genes, which are exclusive to the respiratory epithelium and goblet cells of bronchial structures. This indicates heterogeneous bronchiole sampling due to the harvesting location in the lung. A small cluster included acute-phase reactant genes (SAA1, SAA2, and SAA2-SAA4). The final two small clusters were technical and gender related. To summarize, in a collection of normal lung samples, we found that tissue heterogeneity caused by harvesting location (medial or lateral lung) and late therapeutic intervention (mechanical ventilation) were major contributors to expression variation. These unexpected sources of variation were the result of altered cell ratios in the tissue samples, an underappreciated source of expression variation.
Subject(s)
Lung/metabolism , Transcriptome , Acute-Phase Proteins/genetics , Alveolar Epithelial Cells/metabolism , Axonemal Dyneins/genetics , Bronchi/metabolism , Datasets as Topic , Dyneins/genetics , Epithelium/metabolism , Genotype , Humans , Mucins/genetics , Organ Specificity , Pulmonary Surfactant-Associated Protein A/genetics , Pulmonary Surfactant-Associated Protein C/genetics , Ventilator-Induced Lung Injury/genetics , Ventilator-Induced Lung Injury/pathologyABSTRACT
Tumor DNA sequencing can identify rare driver genomic alterations that suggest targets for cancer therapy, even when these drivers cannot be suspected on clinical grounds. In some cases, genomic alterations identified in the tumor can lead to a change in diagnosis with implications for prognosis and therapy. This report describes a case in which evaluation of tumor sequencing results by a molecular tumor board (MTB) led to rediagnosis of a non-small cell lung cancer as highly aggressive NUT midline carcinoma, with implications for targeted therapy using an investigational bromodomain and extraterminal (BET) inhibitor. We discuss the molecular biology and diagnosis of this rare tumor, and suggest how improved annotation of tumor sequencing reports and multidisciplinary expertise of MTBs can facilitate timely diagnosis of rare tumors and application of potential targeted therapies.
Subject(s)
Genomics/methods , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Adult , Genetic Profile , Humans , Lung Neoplasms/pathology , MaleABSTRACT
We sought to develop and characterize a novel paucibacillary model in mice, which develops necrotic lung granulomas after infection with Mycobacterium tuberculosis. Six weeks after aerosol immunization with recombinant Mycobacterium bovis bacillus Calmette-Guerin overexpressing the 30-kDa antigen, C3HeB/FeJ mice were aerosol infected with M. tuberculosis H37Rv. Six weeks later, mice were treated with one of three standard regimens for latent tuberculosis infection or tumor necrosis factor (TNF)-neutralizing antibody. Mouse lungs were analyzed by histological features, positron emission tomography/computed tomography, whole-genome microarrays, and RT-PCR. Lungs and sera were studied by multiplex enzyme-linked immunosorbent assays. Paucibacillary infection was established, recapitulating the sterilizing activities of human latent tuberculosis infection regimens. TNF neutralization led to increased lung bacillary load, disrupted granuloma architecture with expanded necrotic foci and reduced tissue hypoxia, and accelerated animal mortality. TNF-neutralized mouse lungs and sera showed significant up-regulation of interferon γ, IL-1ß, IL-6, IL-10, chemokine ligands 2 and 3, and matrix metalloproteinase genes. Clinical and microbiological reactivation of paucibacillary infection by TNF neutralization was associated with reduced hypoxia in lung granulomas and induction of matrix metalloproteinases and proinflammatory cytokines. This model may be useful for screening the sterilizing activity of novel anti-tuberculosis drugs, and identifying mycobacterial regulatory and metabolic pathways required for bacillary growth restriction and reactivation.
Subject(s)
Disease Models, Animal , Granuloma/pathology , Latent Tuberculosis/pathology , Animals , Antibodies, Neutralizing/pharmacology , Cytokines/blood , Cytokines/metabolism , Female , Granuloma/microbiology , Lung/metabolism , Lung/microbiology , Lung/physiopathology , Mice, Inbred C3H , Necrosis/microbiology , Necrosis/pathology , Transcriptome , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
BACKGROUND: Selective BRAF inhibitors, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have been approved for treatment of metastatic melanomas with a BRAF p.V600E mutation. The clinical significance of non-codon 600 mutations remains unclear, in part, due to variation of kinase activity for different mutants. METHODS: In this study, we categorized BRAF mutations according to the reported mutant kinase activity. A total of 1027 lung cancer, colorectal cancer or melanoma specimens were submitted for clinical mutation detection by next generation sequencing. RESULTS: Non-codon 600 mutations were observed in 37% of BRAF-mutated tumors. Of all BRAF mutants, 75% were kinase-activated, 15% kinase-impaired and 10% kinase-unknown. The most common kinase-impaired mutant involves codon 594, specifically, p.D594G (c.1781A > G) and p.D594N (c.1780G > A). Lung cancers showed significantly higher incidences of kinase-impaired or kinase-unknown mutants. Kinase-impaired BRAF mutants showed a significant association with concomitant activating KRAS or NRAS mutations, but not PIK3CA mutations, supporting the reported interaction of these mutations. CONCLUSIONS: BRAF mutants with impaired or unknown kinase activity as well as concomitant kinase-impaired BRAF mutations and RAS mutations were detected in lung cancers, colorectal cancers and melanomas. Different therapeutic strategies based on the BRAF mutant kinase activity and the concomitant mutations may be worthwhile.
Subject(s)
Colorectal Neoplasms/genetics , Lung Neoplasms/genetics , Melanoma/genetics , Mutation , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins B-raf/genetics , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/enzymology , Female , High-Throughput Nucleotide Sequencing , Humans , Lung Neoplasms/enzymology , Male , Melanoma/enzymology , Middle Aged , Phosphotransferases/metabolism , Polymorphism, Single Nucleotide/geneticsABSTRACT
Metastatic lung neuroendocrine carcinomas provide diagnostic challenges in identifying the cell of origin. High level calcitonin expression is not pathognomonic for medullary thyroid cancer. Tumor mutation analysis may provide essential clues regarding tissue origin and treatment targets. Oncogenic RET gene fusions have been identified in non-small cell lung cancer and non-medullary thyroid cancers, whereas RET point mutations are the key genetic finding in both inherited and sporadic MTC. Patients who receive radiation for the treatment of other cancers have an increased risk of developing a second malignancy, including a neuroendocrine carcinoma. Herein, we present a case of calcitonin-rich neuroendocrine carcinoma emerging on a background of prior radiation and chemotherapy for the treatment of Hodgkin's disease. Identification of a RET gene rearrangement (KIF5B-RET) led to initial successful treatment with selpercatinib, with eventual resistance associated with an activating mutation involving the MEK1 protein (MAP2K1 p. E102-I103 del) that led to relapse and progression of the disease.
ABSTRACT
Small biopsies of lung are routinely obtained by many methods, including several that result in cytologic specimens. Because lung cancer is often diagnosed at a stage for which primary resection is not an option, it is critical that all diagnostic, predictive, and prognostic information be derived from such small biopsy specimens. As the number of available diagnostic and predictive markers expands, cytopathologists must familiarize themselves with current requirements for specimen acquisition, handling, results reporting, and molecular and other ancillary testing, all of which are reviewed here.
Subject(s)
Lung Neoplasms , Humans , Biomarkers, Tumor , Biopsy/methods , Biopsy/trends , Lung/pathology , Lung Neoplasms/pathology , Lung Neoplasms/diagnosis , Patient Care , Specimen Handling/methodsABSTRACT
With the advancement of tissue procurement techniques, in-depth knowledge of morphology is crucial for cytopathologists to diagnose neoplastic and nonneoplastic lung diseases optimally. Cytopathologists must also be well versed in immunohistochemistry/immunocytochemistry markers and their interpretation for an accurate diagnosis.
Subject(s)
Cytodiagnosis , Immunohistochemistry , Lung Diseases , Lung Neoplasms , Humans , Cytodiagnosis/methods , Immunohistochemistry/methods , Lung/pathology , Lung Diseases/pathology , Lung Diseases/diagnosis , Lung Neoplasms/pathology , Lung Neoplasms/diagnosis , Microscopy/methodsABSTRACT
The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.