Integrating Molecular Sequencing Into the Pathological Diagnosis of Clinically Suspected Non-Small Cell Lung Carcinomas

Cancer panel sequencing has been rapidly adopted into clinical practice for the detection of actionable genetic variants in advanced non-small cell lung carcinomas. Unexpected molecular results may lead to reexamination of the clinical diagnosis; however, this scenario has not been systematically evaluated. We reviewed cancer panel next-generation sequencing results from 1007 consecutive patients performed for the clinical indication of non-small cell lung carcinoma along with the corresponding clinical history and anatomical pathology findings. The final integrative diagnosis was a cancer of extrapulmonary origin in 12 of 1007 patients (1.2%). Molecular evidence supporting the final diagnoses included the detection of an UV radiation-associated mutational signature (n = 6), gene fusions (n = 2), and mutations (n = 4). The integrative diagnoses included undifferentiated melanoma, cutaneous squamous cell, and basal cell carcinomas, thyroid carcinoma, urothelial carcinoma, hepatocellular carcinoma, pancreatic adenocarcinoma, intrahepatic chol-angiocarcinoma, and synovial sarcoma. A small but nonnegligible proportion of clinically suspected non-small cell lung carcinomas had a final diagnosis of cancer of extrapulmonary origin after clinical next-generation sequencing. The integration of clinical, microscopic, and molecular evidence can aid diagnosis and guide personalized oncology care.(c) 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.

Automated summary

The use of cancer panel sequencing in clinical practice for detecting genetic variants in lung cancer has become common. However, the possibility of unexpected molecular results leading to a reevaluation of the clinical diagnosis has not been systematically evaluated. This study reviewed the sequencing results of 1007 lung cancer patients and found that 12 of them (1.2%) had a final diagnosis of cancer originating from outside the lungs. Integrating clinical, microscopic, and molecular evidence can aid in diagnosis and personalized oncology care.