57 AJCP / Original article Am J Clin Pathol 2020;154:57-69 DOI: 10.1093/ajcp/aqaa023 © American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Synchronous Pulmonary Adenocarcinomas Correlation Among Morphology, Next-Generation Sequencing/Single-Gene Analysis MolecularTesting, and Clinical Outcomes With Eighth Edition AJCC Criteria Carlos A. Pagan, MD, 1, * Catherine A. Shu, MD, 2, * John P. Crapanzano, MD, 1 Galina G. Lagos, MD, 2 Mark B. Stoopler, MD, 2 Naiyer A. Rizvi, MD, 2 Jonas J. Heymann, MD, 1 Joshua R. Sonett, MD, 3 Helen Fernandes, PhD, 1,# and Anjali Saqi, MD, MBA 1,#, From the Departments of 1 Pathology and Cell Biology, 2 Medical Oncology, and 3 Thoracic Surgery, Columbia University Irving Medical Center/ NewYork-Presbyterian Hospital, New York, NY. Key Words: Lung adenocarcinoma; Synchronous; Molecular; Next-generation sequencing; Multiple Am J Clin Pathol July 2020;154:57-69 DOI: 10.1093/AJCP/AQAA023 ABSTRACT Objectives: To determine concordance/discordance between morphology and molecular testing (MT) among synchronous pulmonary carcinomas using targeted next generation sequencing (NGS), with and without comprehensive molecular review (CMR), vs analyses of multiple singe genes (non-NGS). Methods: Results of morphologic and MT assessment were classifed as concordant, discordant, or indeterminate. For discordant cases, comprehensive histologic assessment (CHA) was performed. Results: Forty-seven cases with 108 synchronous tumors were identifed and underwent MT (NGS, n = 23 and non-NGS, n = 24). Histology and MT were concordant, discordant, and indeterminate in 53% (25/47), 21% (10/47), and 26% (12/47) of cases, respectively. CHA of the 10 discordant cases revised results of three cases. Conclusions: There is discordance between histology and MT in a subset of cases and MT provides an objective surrogate for staging synchronous tumors. A limited gene panel is suffcient for objectively assessing a relationship if the driver mutations are distinct. Relatedness of mutations require CMR with a larger NGS panel (eg, 50 genes). Lung cancer is the leading cause of cancer-related mortality in the United States 1 and worldwide, accounting for more than 1.5 million deaths. 2 Following the National Lung Cancer Screening Trial, 3 screening for lung cancer has been adopted by several organizations (eg, American College of Chest Physicians, American Society of Clinical Oncology [ASCO], and American Thoracic Society) for high-risk individuals using low-dose computed tomog- raphy (CT) in an effort to detect cancer at an earlier stage with the intent of reducing mortality. Such screening, as well as increased use and enhanced CT technology, has resulted in identification of greater numbers of lung nodules. In fact, identification of cases with multiple nodules almost tripled between 2007 and 2010 compared to years prior. 4,5 If multiple lung tumors are encountered in a surgical resection, the relationship among them is essential for staging, prognosis, and management. When occurring at Key Points • There is discordance between histologic and molecular testing of syn- chronous lung adenocarcinomas. • Targeted next-generation sequencing provides an objective means to assess relationships among adenocarcinomas. • Consistent with overall frequencies in a western population, syn- chronous tumors most commonly harbor KRAS and/or EGFR hotspot mutations. Downloaded from https://academic.oup.com/ajcp/article/154/1/57/5799189 by guest on 12 June 2022