KRAS Mutation Analysis Helps to Differentiate Between Pulmonary Metastasis from Colon Adenocarcinoma In Situ and Primary Lung Adenocarcinoma

Abstract

A 69-year-old woman never-smoker was noted to have a solitary 4-cm lesion in the left upper lobe on routine preoperative chest x-ray before elective hip replacement. Chest computed tomography redemonstrated the spiculated 4 3.3-cm lesion. Positron emission tomography-computed tomography confirmed that the lesion was fluorodeoxyglucose-avid with no other sites of fluorodeoxyglucose avidity (Figure 1). The patient underwent a core needle biopsy of the lung lesion showing a cytokeratin (CK) 20 and caudal type homeobox transcription factor 2–positive adenocarcinoma, which was negative for CK7 and thyroid transcription factor-1. The expected immunohistochemical markers for a primary lung adenocarcinoma are CK7 and thyroid transcription factor-1, whereas the usual markers for a primary colorectal adenocarcinoma are CK20 and caudal type homeobox transcription factor 2. The patient underwent a video-assisted thoracoscopic lobectomy and mediastinal lymphadenectomy revealing a 3.8-cm adenocarcinoma with the same histologic (Figure 2A) and immunophenotype (Figure 3) as the previous biopsy. One inferior mediastinal lymph node (level 9L) was also involved with tumor, and levels 5, 10L, 11L, and 12L nodes were negative for disease. A colonoscopy, upper endoscopy, and capsule video enteroscopy did not show any evidence of a primary tumor. Seven years before the discovery of the lung mass, she had a 2-cm sigmoid adenoma with areas of high-grade dysplasia (Figure 2B) and carcinoma in situ resected endoscopically in a piecemeal fashion. Her resected lung tumor was sent for genetic testing and found to harbor a Kirsten ras sarcoma viral oncogene homolog (KRAS) gene codon 12 GGT to GTT (glycine to valine) missense mutation (KRAS G12V). The tumor was wild-type for the epidermal growth factor receptor gene. Given there was no evidence of primary colorectal tumor on endoscopy, the archived, paraffin-embedded sigmoid adenoma was also genotyped and found to carry the same KRAS codon 12 GTT transversion. This suggested that the lung tumor was a late recurrence from the original KRAS mutant sigmoid carcinoma in situ. She was subsequently found to have multiple new pulmonary lesions.