Synchronous Pulmonary Adenocarcinomas: Correlation Among Morphology, Next-Generation Sequencing/Single-Gene Analysis Molecular Testing, and Clinical Outcomes With Eighth Edition AJCC Criteria

• Published in: American journal of clinical pathology 2020-07, Vol.154 (1), p.57-69
• Main Authors: Pagan, Carlos A, Shu, Catherine A, Crapanzano, John P, Lagos, Galina G, Stoopler, Mark B, Rizvi, Naiyer A, Heymann, Jonas J, Sonett, Joshua R, Fernandes, Helen, Saqi, Anjali
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Carcinoma; Comparative analysis; Diagnosis; Discordance; DNA sequencing; Genetic aspects; Histology; Lung cancer; Molecular diagnostic techniques; Mutation; Next-generation sequencing; Nucleotide sequencing; Tumors
• ISSN: 0002-9173; 1943-7722
• DOI: 10.1093/AJCP/AQAA023

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 classified as concordant, discordant, or indeterminate. For discordant cases, comprehensive histologic assessment (CHA) was performed. Results: Forty-seven cases with 108 synchronous tumors were identified 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 sufficient for objectively assessing a relationship if the driver mutations are distinct. Relatedness of mutations require CMR with a larger NGS panel (eg, 50 genes). Key Words: Lung adenocarcinoma; Synchronous; Molecular; Next-generation sequencing; Multiple