Recurrent lung adenocarcinoma with isolated pancreatic metastasis: Whipple resection after discordant tumor-origin testing

What happened, in summary

This 81-year-old woman had right-lung adenocarcinoma surgically removed in December 2016, followed by adjuvant chemotherapy. In July 2021, she developed recurrence in a mediastinal lymph node and received radiation plus chemotherapy, with an excellent response. Surveillance showed no further recurrence or metastasis through July 2024. In November 2024, CT found a new 16 mm nodule in the head of the pancreas with mild extrahepatic bile duct dilation, while the lungs showed no suspicious mass. PET-CT showed the pancreatic nodule was hypermetabolic and did not identify other suspicious sites. Endoscopic ultrasound-guided fine-needle aspiration showed moderately differentiated adenocarcinoma. The key question was whether this was a new pancreatic primary or isolated metastasis from her prior lung cancer. Immunohistochemistry showed CK7, CA19.9, weak patchy CDX2 positivity, CK20 negativity, nonspecific cytoplasmic TTF-1 staining, and Napsin A positivity. This pattern favored metastatic lung adenocarcinoma over primary pancreatic cancer. NGS found KRAS G13C, STK11 splice site 920+1G>T, and KEAP1 V155F, a co-mutation profile that also supported lung origin. Because the pancreatic lesion was solitary and she wished to proceed, she underwent a Whipple procedure. The resected pancreas contained a 2.1 cm moderately to poorly differentiated invasive adenocarcinoma involving the pancreatic head and 2 of 21 lymph nodes. Microarray expression profiling was indeterminate and leaned toward gastrointestinal or pancreaticobiliary origin, creating diagnostic tension, but the report concluded that the IHC and NGS findings better supported isolated pancreatic metastasis from lung adenocarcinoma. This case is clinically important because a solitary pancreatic adenocarcinoma in a lung cancer survivor can look like a new pancreatic primary. The treatment path was therefore shaped by both pathology and molecular testing, not imaging alone.