Abstract
Differentiating between primary pancreatic adenocarcinoma with pulmonary metastasis and primary lung adenocarcinoma with pancreatic metastasis presents a significant diagnostic challenge due to histological similarities. This distinction is crucial as it directly impacts treatment strategies and patient outcomes. We present a case of a 74-year-old female with concurrent pancreatic and pulmonary masses discovered during a routine health screening. Initial evaluations suggested primary pancreatic cancer with pulmonary metastasis based on imaging characteristics. However, molecular analysis revealed the absence of KRAS mutation in the pancreatic lesion, which is highly unusual for primary pancreatic adenocarcinoma. Further immunohistochemical studies showed thyroid transcription factor-1 (TTF-1) positivity, and genetic testing identified an EGFR exon 19 deletion (E746_A750del), confirming the diagnosis of metastatic lung adenocarcinoma to the pancreas. This case highlights the critical importance of molecular profiling in distinguishing between primary and metastatic lesions when conventional diagnostic methods are inconclusive. The absence of KRAS mutation in a pancreatic adenocarcinoma should prompt consideration of metastatic disease, particularly from the lung. This case illustrates that comprehensive molecular and immunohistochemical analyses can prevent misdiagnosis and ensure appropriate targeted therapy selection in cases with diagnostic uncertainty.