Challenges in lung and thoracic pathology

Abstract

Thoracic pathology is a highly subspecialized and challenging area of diagnostic surgical pathology with significant recent updates in the classification of neoplastic and non-neoplastic diseases. Advances in our understanding of the genomics of thoracic tumors are reshaping histologic classifications to make themmore clinically relevant. Although molecular biology has greatly helped to better understand known diseases and define new entities, international collaborations and exchange of expertise and sample collections have becomemore important than ever. If anything, the current COVID19 pandemic with its urgent necessity to learn as much as possible and as soon as possible about a severe lung disease that most of us had never encountered before has dramatically shown the need for (and the power of) coordinated efforts of the global research community. Metovic and colleagues start by describing the histologic and molecular classification of neuroendocrine tumors of the lung. They provide a detailed approach to the histologic and immunohistochemical diagnosis of carcinoids, small cell and large cell neuroendocrine carcinomas. The authors discuss the genomic heterogeneity of pulmonary neuroendocrine tumors and the differences between low and high-grade neoplasms. Molecular signatures that do not necessarily follow the morphologic features could redefine the histological classification and provide better guidance for clinical management and tailored treatments for patients with pulmonary neuroendocrine tumors. Poorly differentiated and undifferentiated malignant neoplasms represent a diagnostically challenging group of tumors for thoracic pathologists. NUT carcinoma and thoracic SMARCA4 deficient undifferentiated tumors are examples of neoplasms that can only be diagnosed in the appropriate clinical settings and with the help of molecular techniques or specific immunohistochemical surrogate markers. The review of Chatzopoulos and Boland provides a detailed update on the historical relevance, clinico-pathologic features, genetics and differential diagnosis of these two unique thoracic tumors. Immune-checkpoint inhibitor therapies have led to remarkable response rates and survival in a subset of patients with NSCLC. However, not all of the patients will show response to these therapies, and predictive biomarkers are still being investigated. Uruga and Mino-Kenudson review the pre-analytical, analytical, and post-analytical challenges associated with PD-L1 implementation in pathology laboratories. TMB has been extensively studied as an alternative or complementary biomarker of response to immune checkpoint inhibitors. The main issue with the assessment of TMB is the lack of a standardized approach. In addition, microsatellite instability (MSI) as a predictive biomarker in lung cancer is of limited value. Other potential biomarkers predicting the response to immune checkpoint inhibitors include immune cell profiling of the tumor microenvironment such as CD8+ T-cell density, IHN-g related mRNA profile, and the expression of MHC class I molecules, among others. The treatment options for patients diagnosed with lung carcinomas have significantly changed in the past two decades. The development of new treatments is a rapidly evolving field and the identification of predictive biomarkers of response provides a personalized approach to the treatment of lung cancer patients. Canberk and Engels summarize testing approaches to the standard of care biomarkers such as EGFR, ALK, ROS that are outlined in many national and international guidelines for molecular testing in lung cancer patients. Despite liquid biopsies paving their way into clinical practice, an adequate tissue sample remains the gold standard. Molecular laboratories are becoming more technically * Sanja Dacic [email protected]