Editors Choice
Lung Cancer in Japan
Japan is located in East Asia and consists of five large islands and numerous smaller islands, with a total of 6852 islands (Fig. 1). Mountainous areas cover 75% of the country, and the population is concentrated in the plains along the coast. Because it is an island nation and because of the policy of seclusion that lasted for more than 300 years during the Edo period, it is almost ethnically homogeneous. The total population is 125.36 million, ranking 11th in the world. The average life expectancy of men is 81 years, and that of women is 87 years, making Japan a country with one of the highest life expectancies in the world.An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping
Because molecular-targeted drugs against MET exon 14 (METex14) skipping have been approved, molecular testing of the alteration has added to clinical guidelines. There are several such assays, but methodological issues have been reported.The International Association for the Study of Lung Cancer Global Survey on Programmed Death-Ligand 1 Testing for NSCLC
Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is required to determine the eligibility for pembrolizumab monotherapy in advanced NSCLC worldwide and for several other indications depending on the country. Four assays have been approved/ Communauté Européene–In vitro Diagnostic (CV-IVD)–marked, but PD-L1 IHC seems diversely implemented across regions and laboratories with the application of laboratory-developed tests (LDTs).The Promises and Challenges of Tumor Mutation Burden as an Immunotherapy Biomarker: A Perspective from the International Association for the Study of Lung Cancer Pathology Committee
Immune checkpoint inhibitor (ICI) therapies have revolutionized the management of patients with NSCLC and have led to unprecedented improvements in response rates and survival in a subset of patients with this fatal disease. However, the available therapies work only for a minority of patients, are associated with substantial societal cost, and may lead to considerable immune-related adverse events. Therefore, patient selection must be optimized through the use of relevant biomarkers. Programmed death-ligand 1 protein expression by immunohistochemistry is widely used today for the selection of programmed cell death protein 1 inhibitor therapy in patients with NSCLC; however, this approach lacks robust sensitivity and specificity for predicting response.The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for Residual Tumor Descriptors for Non–Small Cell Lung Cancer
Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un).Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer
Since the 2015 WHO classification was introduced into clinical practice, immunohistochemistry (IHC) has figured prominently in lung cancer diagnosis. In addition to distinction of small cell versus non–small cell carcinoma, patients’ treatment of choice is directly linked to histologic subtypes of non–small cell carcinoma, which pertains to IHC results, particularly for poorly differentiated tumors. The use of IHC has improved diagnostic accuracy in the classification of lung carcinoma, but the interpretation of IHC results remains challenging in some instances.PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project
The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples.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
In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing.Interobserver Variation among Pathologists and Refinement of Criteria in Distinguishing Separate Primary Tumors from Intrapulmonary Metastases in Lung
Multiple tumor nodules are seen with increasing frequency in clinical practice. On the basis of the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment to distinguish second primary lung cancers (SPLCs) from intrapulmonary metastases (IPMs), looking for the most distinctive histologic features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients and recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM, or a combination thereof.The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer
This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS).The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification
The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes in this edition involve (1) use of immunohistochemistry throughout the classification, (2) a new emphasis on genetic studies, in particular, integration of molecular testing to help personalize treatment strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology similar to that proposed in the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (4) a completely different approach to lung adenocarcinoma as proposed by the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (5) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (6) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (7) grouping of neuroendocrine tumors together in one category, (8) adding NUT carcinoma, (9) changing the term sclerosing hemangioma to sclerosing pneumocytoma, (10) changing the name hamartoma to “pulmonary hamartoma,” (11) creating a group of PEComatous tumors that include (a) lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant) and (c) PEComa, malignant, (12) introducing the entity pulmonary myxoid sarcoma with an EWSR1–CREB1 translocation, (13) adding the entities myoepithelioma and myoepithelial carcinomas, which can show EWSR1 gene rearrangements, (14) recognition of usefulness of WWTR1–CAMTA1 fusions in diagnosis of epithelioid hemangioendotheliomas, (15) adding Erdheim–Chester disease to the lymphoproliferative tumor, and (16) a group of tumors of ectopic origin to include germ cell tumors, intrapulmonary thymoma, melanoma and meningioma.Canadian Anaplastic Lymphoma Kinase Study: A Model for Multicenter Standardization and Optimization of ALK Testing in Lung Cancer
Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals.Reproducibility of Histopathological Diagnosis in Poorly Differentiated NSCLC: An International Multiobserver Study
The 2004 World Health Organization classification of lung cancer contained three major forms of non–small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non–small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis.
