LUNG CANCER

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Specimen Handling & Ancillary Testing

General Handling Considerations

+Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology
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This is the official CAP, IASLC and AMP guidelines for ancillary testing of lung cancer.


Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

Lindeman NI, Cagle PT, Aisner DL, et al.

This is the official CAP, IASLC and AMP guidelines for ancillary testing of lung cancer. It reviews and updates the 2013 guidelines and provides recommendations including cytology sample testing and recommendations for and against IHC testing.
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+Measurement Bias of Gross Pathologic Compared With Radiologic Tumor Size of Resected Lung Adenocarcinomas: Implications for the T-Stage Revisions in the Eighth Edition of the American Joint Committee on Cancer Staging Manual
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This article emphasized the importance of accurate gross tumor size measurement by the pathologists.


Measurement Bias of Gross Pathologic Compared With Radiologic Tumor Size of Resected Lung Adenocarcinomas: Implications for the T-Stage Revisions in the Eighth Edition of the American Joint Committee on Cancer Staging Manual

Anderson, Heidinger, Chen, et al.

This article emphasized the importance of accurate gross tumor size measurement by the pathologists.
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+Tumor Spread Through Air Spaces Is an Independent Predictor of Recurrence-free Survival in Patients With Resected Lung Squamous Cell Carcinoma
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Tumor spread through air spaces (STAS) is a recognized pattern of invasion in lung adenocarcinoma. The authors investigate this pattern in squamous cell carcinomas and show that STAS is associated with aggressive tumor behavior.


Tumor Spread Through Air Spaces Is an Independent Predictor of Recurrence-free Survival in Patients With Resected Lung Squamous Cell Carcinoma

Kadota, Kyuichi; Kushida, Yoshio; Katsuki, Naomi, et al.  

Tumor spread through air spaces (STAS) is a recognized pattern of invasion in lung adenocarcinoma. The authors investigate this pattern in squamous cell carcinomas and show that STAS is associated with aggressive tumor behavior. 
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+Do More With Less: Tips and Techniques for Maximizing Small Biopsy and Cytology Specimens for Molecular and Ancillary Testing
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The authors describe their techniques and experience in handling small biopsy specimens to increase yields for ancillary testing.


Do More With Less: Tips and Techniques for Maximizing Small Biopsy and Cytology Specimens for Molecular and Ancillary Testing

Aisner DL, Rumery MD, Merrick DT, et al.

The authors describe their techniques and experience in handling small biopsy specimens to increase yields for ancillary testing. This is a very helpful reference for laboratories looking to decrease QNS rates.
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+Pathologists' Staging of Multiple Foci of Lung Cancer
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The article highlights the difficulties with staging multiple synchronous lung tumors.


Pathologists' Staging of Multiple Foci of Lung Cancer

Robert J. Homer, MD, PhD

The article highlights the difficulties with staging multiple synchronous lung tumors. This paper should be added also: Frank Schneider, Veronica Derrick, Jon M Davison, Diane Strollo, Pimpin Incharoen and Sanja Dacic. Morphological and molecular approach to synchronous non-small cell lung carcinomas: impact on staging. Modern Pathology (2016) 29, 735–742; doi:10.1038.
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Immunohistochemistry (IHC) and special stains

NEW+PD-L1 Expression Heterogeneity in Non-Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsies and Whole Sections
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PD-L1 expression determination defines eligibility for treatment with pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC). This study was designed to better define which value across core biopsies from the same case more closely reflects the PD-L1 expression status on whole sections and how many biopsies are needed for confident classification of tumors in terms of PD-L1 expression.


PD-L1 Expression Heterogeneity in Non-Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsies and Whole Sections

E. Munari, G. Zamboni, G. Lunardi, et al.

PD-L1 expression determination defines eligibility for treatment with pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC). This study was designed to better define which value across core biopsies from the same case more closely reflects the PD-L1 expression status on whole sections and how many biopsies are needed for confident classification of tumors in terms of PD-L1 expression.
https://www.jto.org/article/S1556-0864(18)30543-4/pdf

NEW+BRAF Mutant Lung Cancer: PD-L1 Expression, Tumor Mutational Burden, Microsatellite Instability Status and Response to Immune Check-point Inhibitors
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The status of immune check-point inhibitors in BRAF mutant NSCLC is studied and analyzed.


BRAF Mutant Lung Cancer: PD-L1 Expression, Tumor Mutational Burden, Microsatellite Instability Status and Response to Immune Check-point Inhibitors

Dudnik E, Peled N, Nechushtan H, et al.

To view the full text of this article, the user will need a subscription.

The status of immune check-point inhibitors in BRAF mutant NSCLC is studied and analyzed.
https://www.jto.org/article/S1556-0864(18)30552-5/pdf

+Practical Approach of Sub-classification of NSCLC in FNA Samples Using Current WHO Criteria: Evidence Based Practice and Role of IHC Markers - Case 2
Article-iconThis course will discuss diagnostic evaluation in the role of IHC markers.

Practical Approach of Sub-classification of NSCLC in FNA Samples Using Current WHO Criteria: Evidence Based Practice and Role of IHC Markers - Case 2

Momin T. Siddiqui M.D.

This course will discuss diagnostic evaluation in the role of IHC markers.

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+Mini Course 4 - Practical Approach of Sub-classification of NSCLC in FNA samples Using Current WHO Criteria: Evidence-based Practice and the Role of IHC Markers. Moving from Targeted Therapy to Immunotherapy
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This course will discuss what we should know in the area of immunotherapy and the clinical challenge of sub-classification of lung caners using cytological specimens and the importance of collaboration with clinical teams (oncologists, radiologists, surgeons, etc.)


Mini Course 4 - Practical Approach of Sub-classification of NSCLC in FNA samples Using Current WHO Criteria: Evidence-based Practice and the Role of IHC Markers. Moving from Targeted Therapy to Immunotherapy

Qing Kay Li, MD, PhD, FCAP

This course will discuss what we should know in the area of immunotherapy and the clinical challenge of sub-classification of lung caners using cytological specimens and the importance of collaboration with clinical teams (oncologists, radiologists, surgeons, etc.)
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+Mini Course 3 - Practical Approach of Sub-classification of NSCLC in FNA samples Using Current WHO Criteria: Evidence-based Practice and the Role of IHC Markers. Moving from Targeted Therapy to Immunotherapy
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This course will discuss 3 different case studies regarding the critical role of cytopathology in the sub-classification of lung cancer and the utility/limitation of IHC markers.


Mini Course 3 - Practical Approach of Sub-classification of NSCLC in FNA samples Using Current WHO Criteria: Evidence-based Practice and the Role of IHC Markers. Moving from Targeted Therapy to Immunotherapy

Qing Kay Li, MD, PhD, FCAP

This course will discuss 3 different case studies regarding the critical role of cytopathology in the sub-classification of lung cancer and the utility/limitation of IHC markers.
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+Mini Course 2 - Practical Approach of Sub-classification of NSCLC in FNA samples Using Current WHO Criteria: Evidence-based Practice and the Role of IHC Markers. Moving from Targeted Therapy to Immunotherapy
Article-icon

This course will discuss the critical role of cytopathology in the sub-classification of lung cancer and the utility/limitation of IHC markers.


Mini Course 2 - Practical Approach of Sub-classification of NSCLC in FNA samples Using Current WHO Criteria: Evidence-based Practice and the Role of IHC Markers. Moving from Targeted Therapy to Immunotherapy

Qing Kay Li, MD, PhD, FCAP

This course will discuss the critical role of cytopathology in the sub-classification of lung cancer and the utility/limitation of IHC markers.
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+Relationship of Lymph Node Micrometastasis and Micropapillary Component and Their Joint Influence on Prognosis of Patients With Stage I Lung Adenocarcinoma
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This study looked at 235 stage I lung cancer specimens, searched for lymph node micrometastases and evaluated outcomes in cases with micropapillary architecture.


Relationship of Lymph Node Micrometastasis and Micropapillary Component and Their Joint Influence on Prognosis of Patients With Stage I Lung Adenocarcinoma

Dai C, Xie H, Kadeer X, et al.

This study looked at 235 stage I lung cancer specimens, searched for lymph node micrometastases and evaluated outcomes in cases with micropapillary architecture. The study found worse outcomes for patients with micrometastases and micropapillary architecture but did not seperate out data for isolated tumor cells (<0.2mm).
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+ALK Testing in Non-Small Cell Lung Carcinoma: What Now?
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This editorial provides an excellent, terse review of the current status of PD-L1 testing in NSCLC.


ALK Testing in Non-Small Cell Lung Carcinoma: What Now?

Kerr K.

This editorial provides an excellent, terse review of the current status of PD-L1 testing in NSCLC.
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+Expression of TdT in Merkel Cell Carcinoma and Small Cell Lung Carcinoma
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A study investigating several IHC markers to aid in the distinction between small cell carcinoma and Merkel cell carcinoma


Expression of TdT in Merkel Cell Carcinoma and Small Cell Lung Carcinoma

Michael Sidiropoulos, MD, MSc; Wedad Hanna, MD; Simon J. Raphael, MD; Zeina Ghorab, MD

A study investigating several IHC markers to aid in the distinction between small cell carcinoma and Merkel cell carcinoma
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+Tissue-Sparing Application of the Newly Proposed IASLC/ATS/ERS Classification of Adenocarcinoma of the Lung Shows Practical Diagnostic and Prognostic Impact
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A study investigating use of a limited IHC panel to confirm the subtype of NSCLC to preserve tissue for other molecular testing


Tissue-Sparing Application of the Newly Proposed IASLC/ATS/ERS Classification of Adenocarcinoma of the Lung Shows Practical Diagnostic and Prognostic Impact

William Sterlacci, MD; Spasenija Savic, MD; Thomas Schmid, MD, et al

A study investigating use of a limited IHC panel to confirm the subtype of NSCLC to preserve tissue for other molecular testing
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+Warranting Investigation of Primary Lung Adenocarcinoma in Patients with an Extrapulmonary Malignancy and Lung Nodules Due to High Frequency
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A study investigating the utility of TTF-1 and napsin A to distinguish pulmonary adenocarcinoma from metastatic adenocarcinomas


Warranting Investigation of Primary Lung Adenocarcinoma in Patients with an Extrapulmonary Malignancy and Lung Nodules Due to High Frequency

Bing Zhu, MD, PhD; Shavari Dalal, MD; David W.Kamp, MD; Ziaoqi Lin, MD, PhD

A study investigating the utility of TTF-1 and napsin A to distinguish pulmonary adenocarcinoma from metastatic adenocarcinomas
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+Comparative Immunohistochemical Analysis of IMP3, GLUT1, EMA, CD146, and Desmin for Distinguishing Malignant Mesothelioma from Reactive Mesothelial Cells
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A study evaluating the utility of 5 immunomarkers for distinguishing mesothelioma from reactive mesothelial cells


Comparative Immunohistochemical Analysis of IMP3, GLUT1, EMA, CD146, and Desmin for Distinguishing Malignant Mesothelioma from Reactive Mesothelial Cells

Hiroshi Minato, MD, Nozomu Kurose, MD, Mana Fukushima, MD, et al.

A study evaluating the utility of 5 immunomarkers for distinguishing mesothelioma from reactive mesothelial cells
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+Immunohistochemistry for the Novel Markers Glypican 3, PAX8, and p40 (ΔNp63) in Squamous Cell and Urothelial Carcinoma
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A study evaluating the utility of glypican 3, PAX8, and p40 for distinguishing urothelial carcinoma from squamous cell carcinoma arising in various anatomic sites


Immunohistochemistry for the Novel Markers Glypican 3, PAX8, and p40 (ΔNp63) in Squamous Cell and Urothelial Carcinoma

Michael P. Gailey, DO, Andrew M. Bellizzi, MD

A study evaluating the utility of glypican 3, PAX8, and p40 for distinguishing urothelial carcinoma from squamous cell carcinoma arising in various anatomic sites
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+Immunohistochemistry in the Differential Diagnostics of Primary Lung Cancer: AN Investigation Within the Southern Swedish Lung Cancer Study
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A study evaluating differential expression of CK5, p63, TTF-1, and napsin A in pulmonary non-small cell carcinoma subtypes


Immunohistochemistry in the Differential Diagnostics of Primary Lung Cancer: AN Investigation Within the Southern Swedish Lung Cancer Study

Hans Brunnstrom, MD, PhD, Leif Johansson, MD, PhD, Karin Jirstrom, MD, PhD, Mats Jonsson, PhD, Per Jonsson, MD, PhD, Maria Planck, MD, PhD

A study evaluating differential expression of CK5, p63, TTF-1, and napsin A in pulmonary non-small cell carcinoma subtypes
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+Value of Claudin-4 Immunostaining in the Diagnosis of Mesothelioma
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A study investigating the utility of claudin-4 as a marker to distinguish mesothelioma from metastatic carcinoma involving the pleura


Value of Claudin-4 Immunostaining in the Diagnosis of Mesothelioma

Nelson G. Ordonez, MD

A study investigating the utility of claudin-4 as a marker to distinguish mesothelioma from metastatic carcinoma involving the pleura
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+Napsin A Expression in Primary Mucin-Producing Adenocarcinomas of the Lung
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A study highlighting the limitations of using napsin A immunohistochemistry for establishing that a mucinous adenocarcinoma arose in the lung


Napsin A Expression in Primary Mucin-Producing Adenocarcinomas of the Lung

Jeffrey Wu, peiguo G. Chu, MD, PhD, Zhong Jiang, MD, and Sean K. Lau, MD

A study highlighting the limitations of using napsin A immunohistochemistry for establishing that a mucinous adenocarcinoma arose in the lung
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+Genetic and Immune Profiles of Solid Predominant Lung Adenocarcinoma Reveal Potential Immunotherapeutic Strategies 
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The authors show that solid predominant lung adenocarcinomas are associated with adaptive immune resistance, higher cytotoxic activity, and enhanced immunogenicity. Their findings suggest that patients with solid predominant lung adenocarcinoma may represent a potential selective group that will benefit from adjuvant PD-1 blockade immunotherapy.


Genetic and Immune Profiles of Solid Predominant Lung Adenocarcinoma Reveal Potential Immunotherapeutic Strategies

Dong D, Zhang C, Li Y, et al.

The authors show that solid predominant lung adenocarcinomas are associated with adaptive immune resistance, higher cytotoxic activity, and enhanced immunogenicity. Their findings suggest that patients with solid predominant lung adenocarcinoma may represent a potential selective group that will benefit from adjuvant PD-1 blockade immunotherapy.
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+Recent Advances in Targeting ROS1 in Lung Cancer 
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This review discusses the biology and diagnosis of ROS1-rearranged NSCLC, and current and emerging treatment options for this disease.


Recent Advances in Targeting ROS1 in Lung Cancer

Lin J. and Shaw A.

This review discusses the biology and diagnosis of ROS1-rearranged NSCLC, and current and emerging treatment options for this disease.
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+Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms 
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The article provides a practical approach in the interpretation and immunohistochemical selection of lung/pleura–based neoplasms obtained from small biopsy samples.


Application of Immunohistochemistry in the Diagnosis of Pulmonary and Pleural Neoplasms

Woo J, Reddy O, Koo M, et al.

The article provides a practical approach in the interpretation and immunohistochemical selection of lung/pleura–based neoplasms obtained from small biopsy samples.
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+Programmed Death Ligand-1 (PD-L1) Expression in Either Tumor Cells or Tumor-Infiltrating Immune Cells Correlates With Solid and High-Grade Lung Adenocarcinomas 
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Lung adenocarcinoma subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells correlate with high histologic grade, solid subtype, and high smoking pack-years.


Programmed Death Ligand-1 (PD-L1) Expression in Either Tumor Cells or Tumor-Infiltrating Immune Cells Correlates With Solid and High-Grade Lung Adenocarcinomas

Driver B, Miller R, Miller T, et al.

Lung adenocarcinoma subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells correlate with high histologic grade, solid subtype, and high smoking pack-years.
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+A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible For Treatment with Crizotinib
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Authors present data on the recently approved Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ), the only immunohistochemistry (IHC)-based assay linked to treatment outcome.


A Sensitive ALK Immunohistochemistry Companion Diagnostic Test Identifies Patients Eligible For Treatment with Crizotinib

Thorne-Nuzzo, Williams, Catallini, et al.

Authors present data on the recently approved Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ), the only immunohistochemistry (IHC)-based assay linked to treatment outcome. The results show that ALK (D5F3) IHC is an effective option to accurately and rapidly identify patients with ALK-positive NSCLC.
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+The differential diagnosis between pleural sarcomatoid mesothelioma and spindlecell/pleomorphic (sarcomatoid) carcinomas of the lung: Evidence-Based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center
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The authors suggest guidelines to distinguish sarcomatoid malignant mesotheliomas from spindle cell and pleomorphic carcinomas of the lung.


The differential diagnosis between pleural sarcomatoid mesothelioma and spindlecell/pleomorphic (sarcomatoid) carcinomas of the lung: Evidence-Based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center

Marchevsky, LeStang, Hiroshim, et al.

The authors suggest guidelines to distinguish sarcomatoid malignant mesotheliomas from spindle cell and pleomorphic carcinomas of the lung.
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+MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma
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A study evaluating the utility of MUC4 as an IHC marker of mesothelial differentiation for evaluation of malignant sarcomatoid pleural proliferations.


MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

Amatya VJ, et al.

A study evaluating the utility of MUC4 as an IHC marker of mesothelial differentiation for evaluation of malignant sarcomatoid pleural proliferations
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+Reevaluation and Reclassification of Resected Lung Carcinomas Originally Diagnosed as Squamous Cell Carcinoma Using Immunohistochemical Analysis
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This article discusses the importance of using immunohistochemistry in accurate classification of lung carcinomas, even on resection specimens.


Reevaluation and Reclassification of Resected Lung Carcinomas Originally Diagnosed as Squamous Cell Carcinoma Using Immunohistochemical Analysis

Kadota, Kyuichi MD, PhD; Nitadori, Jun-ichi MD, PhD; Rekhtman, Natasha MD, et al.

This article discusses the importance of using immunohistochemistry in accurate classification of lung carcinomas, even on resection specimens.
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+Biomarker Testing in Lung Carcinoma Cytology Specimens: A Perspective From Members of the Pulmonary Pathology Society
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This article focuses on the opportunities and challenges of using cytologic specimens for molecular diagnosis of lung cancer and the role of cytopathology in the molecular era.


Biomarker Testing in Lung Carcinoma Cytology Specimens: A Perspective From Members of the Pulmonary Pathology Society

Roy-Chowdhuri S, Aisner DL, Allen TC, Beasley MB, et al.

This article focuses on the opportunities and challenges of using cytologic specimens for molecular diagnosis of lung cancer and the role of cytopathology in the molecular era.
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+Immunohistochemistry of Pulmonary Biomarkers: A Perspective From Members of the Pulmonary Pathology Society
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This article discusses the application and utility of immunohistochemistry stains including predictive biomarkers in non-small cell lung cancer


Immunohistochemistry of Pulmonary Biomarkers: A Perspective From Members of the Pulmonary Pathology Society

Erik Thunnissen, Timothy Craig Allen, Julien Adam, et al.

This article discusses the application and utility of immunohistochemistry stains including predictive biomarkers in non-small cell lung cancer
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+Programmed Death Ligand-1 Immunohistochemistry--A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society
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A nice review of the current state of PD-L1 testing and challenges associated with implementation of this testing in laboratories


Programmed Death Ligand-1 Immunohistochemistry--A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society

Sholl LM, et al.

A nice review of the current state of PD-L1 testing and challenges associated with implementation of this testing in laboratories
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+The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases
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A study of diagnostic reproducibility of small cell carcinoma, evaluating the use of IHC to more accurately diagnose small cell carcinoma.


The Use of Immunohistochemistry Improves the Diagnosis of Small Cell Lung Cancer and Its Differential Diagnosis. An International Reproducibility Study in a Demanding Set of Cases

Thunnissen E, et al.

A study of diagnostic reproducibility of small cell carcinoma, evaluating the use of IHC to more accurately diagnose small cell carcinoma.
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+Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma
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A study evaluating the best panel of IHC markers for distinguishing solid adenocarcinoma from solid epithelioid mesothelioma


Utility and pitfalls of immunohistochemistry in the differential diagnosis between epithelioid mesothelioma and poorly differentiated lung squamous cell carcinoma

Kushitani K, et al.

A study evaluating the best panel of IHC markers for distinguishing solid adenocarcinoma from solid epithelioid mesothelioma
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FISH and molecular testing

NEW+Practical Approach of Sub-classification of NSCLC in FNA Samples Using Current WHO Criteria: Evidence Based Practice and Role of IHC Markers - Case 3
Article-iconThis course will discuss Molecular Signaling Cascades and Recommendations for Molecular Testing.

Practical Approach of Sub-classification of NSCLC in FNA Samples Using Current WHO Criteria: Evidence Based Practice and Role of IHC Markers - Case 3

Momin T. Siddiqui M.D.

This course will discuss Molecular Signaling Cascades and Recommendations for Molecular Testing.
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NEW+Mini Course 1 - Practical Approach of Sub-classification of NSCLC in FNA samples Using Current WHO Criteria: Evidence-based Practice and the Role of IHC Markers. Moving from Targeted Therapy to Immunotherapy
Article-icon

This course will review the progression in the lung cancer field, and the current recommendation of the WHO and IASLC (International Association for the Study of Lung Cancer)


Mini Course 1 - Practical Approach of Sub-classification of NSCLC in FNA samples Using Current WHO Criteria: Evidence-based Practice and the Role of IHC Markers. Moving from Targeted Therapy to Immunotherapy

Qing Kay Li, MD, PhD, FCAP

This course will review the progression in the lung cancer field, and the current recommendation of the WHO and IASLC (International Association for the Study of Lung Cancer)
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NEW+Cytology Smears in the Era of Molecular Biomarkers in Non-Small Cell Lung Cancer
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This article reviews the pathologic, immunophenoptypic and cytogenetic features of 4 cases of lymphohistiocytoid mesothelioma.


Cytology Smears in the Era of Molecular Biomarkers in Non-Small Cell Lung Cancer

Lozano M, Echeveste J, Abengozar M, et al.

Review the use of cytology smears for NGS and FISH to detect mutations and translocations and showing their predictive value. Work is in progress to evaluate PD-L1 on cell blocks and DNA methylation of promoter genes.
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NEW+Histopathologic and Cytogenetic Features of Pulmonary Adenoid Cystic Carcinoma
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This study looked at frquency of MYB rearrangement in 40 archived cases of pulmonary adenoid cystic carcinoma and found 41% sensitivity and 100% specificity for this finding.


Histopathologic and Cytogenetic Features of Pulmonary Adenoid Cystic Carcinoma

Roden AC, Greipp PT, Knutson DL, et al.

This study looked at frquency of MYB rearrangement in 40 archived cases of pulmonary adenoid cystic carcinoma and found 41% sensitivity and 100% specificity for this finding.
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+Correlation of Cytomorphology and Molecular Findings in EGFR+, KRAS+, and ALK+ Lung Carcinomas
Article-icon

A study investigating cytologic features of tumors with confirmed mutations in EGFR or KRAS or rearrangements in ALK


Correlation of Cytomorphology and Molecular Findings in EGFR+, KRAS+, and ALK+ Lung Carcinomas

Zaibo Li, MD, PhD; Sanja Dacic, MD, PhD; Liron Pantanowitz, MD, et al.

A study investigating cytologic features of tumors with confirmed mutations in EGFR or KRAS or rearrangements in ALK
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+A Quick Look at the Current Landscape of Molecular Testing in Lung Cancer – Case 2
Article-icon

This mini course discusses testing options for ALK and ROS1 rearrangements in lung adenocarcinoma.


A Quick Look at the Current Landscape of Molecular Testing in Lung Cancer – Case 2

Anna P. Matynia, M.D.

Course Description: This mini course discusses testing options for ALK and ROS1 rearrangements in lung adenocarcinoma.
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+A Quick Look at the Current Landscape of Molecular Testing in Lung Cancer – Case 1
Article-icon

This mini course discusses selecting appropriate tissue acceptable for molecular testing, different types of EGFR mutations in lung adenocarcinoma, and testing options for EGFR testing.


A Quick Look at the Current Landscape of Molecular Testing in Lung Cancer – Case 1

Anna P. Matynia, M.D.

Course Description: This mini course discusses selecting appropriate tissue acceptable for molecular testing, different types of EGFR mutations in lung adenocarcinoma, and testing options for EGFR testing.
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+ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers 
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NSCLC with ROS1 rearrangement have distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.


ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers

Bergethon K, Shaw A, Katayama R, et al.

NSCLC with ROS1 rearrangement have distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.
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+Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer 
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In this study, it was shown that crizotinib had marked antitumor activity in patients with advanced ROS1-rearranged non-small cell lung cancer.


Crizotinib in ROS1-Rearranged Non-Small Cell Lung Cancer

Shaw A, Solomon B, Arnaoutakis K, et al.

In this study, it was shown that crizotinib had marked antitumor activity in patients with advanced ROS1-rearranged non-small cell lung cancer.
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+Molecular Diagnostics of Lung Cancer in the Clinic 
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This review will explore the indications for and pitfalls of routine NGS and plasma genotyping in the clinic, including the intersection of these technologies.


Molecular Diagnostics of Lung Cancer in the Clinic

Sholl L.

This review will explore the indications for and pitfalls of routine NGS and plasma genotyping in the clinic, including the intersection of these technologies.
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+Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic Configuration at Resistance 
Article-icon

This is a case report of the first clinical evidence of efficacy generated by combination therapy consisting of first- and third-generation EGFR tyrosine kinase inhibitors targeting concomitant EGFR T790M and C797S in trans.


Lung Adenocarcinoma Harboring EGFR T790M and In Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs and Shifts Allelic Configuration at Resistance

Wang Z, Yang J, Huang J, et al.

This is a case report of the first clinical evidence of efficacy generated by combination therapy consisting of first- and third-generation EGFR tyrosine kinase inhibitors targeting concomitant EGFR T790M and C797S in trans.
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+Whole Cancer Genome Sequencing by Next-Generation Methods
Article-icon

Review of older NGS platforms. It is from 2011 but worth including for historical background.


Whole Cancer Genome Sequencing by Next-Generation Methods

Jeffrey S. Ross, MD and Maureen Cronin, PhD

Review of older NGS platforms. It is from 2011 but worth including for historical background.
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+Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non–Small Cell Lung Cancer
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The feasibility of plasma testing for detecting EGFR mutations in advanced NSCLC is discussed.


Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non–Small Cell Lung Cancer

Jenkins, Yang, Ramalingam, et al.

The feasibility of plasma testing for detecting EGFR mutations in advanced NSCLC is discussed.
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+Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non–Small Cell Lung Cancer
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Different types and their respective optional therapies for EGFR-mutated NSCLCs are discussed.


Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non–Small Cell Lung Cancer

Castellanos, Feld, Horn, et al.

Different types and their respective optional therapies for EGFR-mutated NSCLCs are discussed.
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+Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling
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Mutation analysis for potential targeted therapy is recommended in these highly aggressive lung tumors


Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling

Schrock, Framptom, et al.

Mutation analysis for potential targeted therapy is recommended in these highly aggressive lung tumors
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+Improving Selection Criteria for ALK Inhibitor Therapy in Non–Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry
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This study evaluates the diagnostic role of ALK immunohistochemistry (IHC) in identification of ALK rearrangement compared to FISH.


Improving Selection Criteria for ALK Inhibitor Therapy in Non–Small Cell Lung Cancer: A Pooled-Data Analysis on Diagnostic Operating Characteristics of Immunohistochemistry

Jiang, Long MD, PhD; Yang, Haihong MD, PhD; He, Ping MD, PhD, et al.

This study evaluates the diagnostic role of ALK immunohistochemistry (IHC) in identification of ALK rearrangement compared to FISH. Authors conclude that IHC scores of 0 and 3+ were nearly 100% concordant with FISH-negative and FISH-positive status, respectively. However, IHC scores 1+ and 2+ might require further confirmatory testing by FISH assay. IHC assay using D5F3 and 5A4 antibodies reliably detected NSCLC with ALK rearrangement and may be useful as a screening method to identify these tumors.
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+Molecular Testing Turnaround Time for Non-Small Cell Lung Cancer in Routine Clinical Practice Confirms Feasibility of CAP/IASLC/AMP Guideline Recommendations: A Single-center Analysis
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Study analyzes one center's TAT for molecular testing, finding an average of 9 working days from the time the material is received in the laboratory.


Molecular Testing Turnaround Time for Non-Small Cell Lung Cancer in Routine Clinical Practice Confirms Feasibility of CAP/IASLC/AMP Guideline Recommendations: A Single-center Analysis

DiStasio M, Chen Y, Rangachari D, Costa DB, Heher YK, VanderLaan PA.

Study analyzes one center's TAT for molecular testing, finding an average of 9 working days from the time the material is received in the laboratory.
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+Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology
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Reviews guidelines for testing EGFR and ALK alterations.


Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology

Lindeman NI, Cagle PT, Beasley MB, et al.

Reviews guidelines for testing EGFR and ALK alterations.
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+Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs
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This article reviews the findings from the Lung Cancer Mutation Consortium project.


Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs

Kris MG, Johnson BE, Berry LD, et al.

This article reviews the findings from the Lung Cancer Mutation Consortium project. The project looked at frequency of 10 driver mutations in tumors from 1007 patients.
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+Associations Between Mutations and Histologic Patterns of Mucin in Lung Adenocarcinoma: Invasive Mucinous Pattern and Extracellular Mucin Are Associated With KRAS Mutation
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This study investigates the association between mucinous histologic features of lung adenocarcinoma and driver mutations.


Associations Between Mutations and Histologic Patterns of Mucin in Lung Adenocarcinoma: Invasive Mucinous Pattern and Extracellular Mucin Are Associated With KRAS Mutation

Kadota, Kyuichi MD, PhD; Yeh, Yi-Chen MD D'Angelo, Sandra P. MD, et al.

This study investigates the association between mucinous histologic features of lung adenocarcinoma and driver mutations. They find mucinous lung adenocarcinomas are associated with KRAS mutation.
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+KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma
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The prognostic significance of KRAS and EGFR driver mutations is investigated in a large cohort of early-stage lung adenocarcinomas.


KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma

Kadota, Kyuichi MD, PhD; Sima, Camelia S. MD, MS; Arcila, Maria E. MD, et al.

The prognostic significance of KRAS and EGFR driver mutations is investigated in a large cohort of early-stage lung adenocarcinomas.
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+Biomarkers in Lung Adenocarcinoma: A Decade of Progress
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This is an overview of the molecular biomarkers that are used prognostically and therapeutically in advanced lung adenocarcinoma.


Biomarkers in Lung Adenocarcinoma: A Decade of Progress

Lynette M. Sholl, MD

This is an overview of the molecular biomarkers that are used prognostically and therapeutically in advanced lung adenocarcinomas
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+Testing for ROS1 in non-small cell lung cancer: a review with recommendations
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A nice review of ROS1 testing methods and handling issues.


Testing for ROS1 in non-small cell lung cancer: a review with recommendations

Bubendorf L, et al.

A nice review of ROS1 testing methods and handling issues.
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+Comparison of Next-Generation Sequencing and Mutation-Specific Platforms in Clinical Practice
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Single gene assay is compared to next generation sequencing for EGFR and KRAS, and authors found comparable results for these two genes.

Comparison of Next-Generation Sequencing and Mutation-Specific Platforms in Clinical Practice

John W. J. Hinrichs, PhD; W.T. Marja van Blokland; Michiel J. Moons, et al.

Single gene assay is compared to next generation sequencing for EGFR and KRAS, and authors found comparable results for these two genes.
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+Non-p.V600E BRAF Mutations Are Common Using a More Sensitive and Broad Detection Tool
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The authors showed that there are different variants of BRAF mutations in various tumors, including lung adenocarcinomas.


Non-p.V600E BRAF Mutations Are Common Using a More Sensitive and Broad Detection Tool

Jamal Carter, MD; Li-Hui Tseng, MD, PhD, Gang Zheng, MD, PhD, et al.

The authors showed that there are different variants of BRAF mutations in various tumors, including lung adenocarcinomas; lung adenocarcinomas also showed more unique BRAF mutations and a higher prevalence of exon 11 mutations and non–codon 600.
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+Molecular Testing for Targeted Therapy in Advanced Non-Small Cell Lung Cancer
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The utility of EGFR/KRAS/ALK testing was studied in EBUS samples and showed that EBUS can be effectively used not just for diagnosis but also for complete mutational testing


Molecular Testing for Targeted Therapy in Advanced Non-Small Cell Lung Cancer

Chiara Casadio, MD; Juliana Guarize, MD; Stefano Donghi, MD, et al.

The utility of EGFR/KRAS/ALK testing was studied in EBUS samples and showed that EBUS can be effectively used not just for diagnosis but also for complete mutational testing
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+BRAF Alternations as Therapeutic Targets in Non-Small-Cell Lung Cancer
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BRAF mutation as a targetable driver mutation is discussed in this article.


BRAF Alternations as Therapeutic Targets in Non-Small-Cell Lung Cancer

Tu Nguyen-Ngoc, MD, PhD; Hasna Bouchaab, MD; Alex A Adjei, MD, PhD, et al.

BRAF mutation as a targetable driver mutation is discussed in this article.
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+Identification of Factors Affecting the Success of Next-Generation Sequencing Testing in Solid Tumors
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In this study they identified the most common factors that affect NGS efficacy.


Identification of Factors Affecting the Success of Next-Generation Sequencing Testing in Solid Tumors

Rashmi S. Goswami, MD, PhD, Rajyalakshmi Luthra, PhD, Rajesh R. Singh, PhD, et al.

In this study they identified the most common factors that affect NGS efficacy.
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