Diagnostic Value of Next-Generation Sequencing (NGS) and Microarray in Characterizing Tumor Origin: A Challenging and Educational Case

Patient: Female, 81-year-old Final Diagnosis: Solitary pancreatic head mass, favor metastatic adenocarcinoma from lung primary Symptoms: 16 mm mass in the head of pancreas with mild extrahepatic bile duct dilation to 10 mm in caliber Clinical Procedure: — Specialty: Molecular Pathology • Cytology • Gastroenterology and Hepatology • Pathology Objective: Unusual clinical course Background This report describes the case of an 81-year-old woman with a history of resected right-lung adenocarcinoma and presenting with a solitary nodule in the head of the pancreas, which demonstrated diagnostic challenges differentiating between metastasis of lung cancer versus primary pancreatic adenocarcinoma during the pathology workup. Differentiating between primary and metastasis in an isolated pancreatic lesion in a patient with a history of lung carcinoma is critical for patient treatment and management. Histology comparison, immunohistochemical characterization, and molecular studies, including next-generation sequencing (NGS) and microarray, are often utilized to differentiate between these two. Case Report An 81-year-old woman with history of surgically resected right-lung adenocarcinoma in 2016 followed by adjuvant chemotherapy, presented in December 2024 with a solitary hypermetabolic pancreatic head nodule on positron emission tomography-computed tomography (PET CT). Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the pancreas lesion was consistent with moderately differentiated adenocarcinoma, showing overlapping histologic morphology and immunohistochemical profile with her prior lung adenocarcinoma. NGS identified genetic alterations favoring a lung origin. However, microarray analysis utilizing real-time RT-PCR done on the subsequently resected pancreas mass classified the lesion as more likely to be of gastrointestinal/pancreatobiliary, rather than lung origin. Conclusions Differentiating between primary versus metastasis from the lungs in a patient with an isolated pancreatic adenocarcinoma with a history of lung adenocarcinoma can be challenging, and occasionally a definite conclusion is still difficult to reach after comprehensive workups. Driver gene mutations, if present, which can be detected by NGS, may be more reliable in predicting tumor origin/type.