The utility of KRAS mutation analysis in differentiating a lung primary mucinous carcinoma from a metastatic colorectal mucinous carcinoma

A 58-year old male has a past medical history of a rectal low-grade mucinous adenocarcinoma with a KRAS codon 12/13 mutation (GGT>GAT), for which he received neoadjuvant chemotherapy and radiation.  Five months after diagnosis, the patient underwent a low anterior resection showing persistent tumor with the pathological staging being (ypT3, ypN0, ypMx).  Six months after surgery, follow-up PET scan showed two right upper lung nodules measuring 1.0 and 1.8 cm.  Subsequent video-assisted thoracic surgery with a lung wedge resection revealed two tumors: a mucinous adenocarcinoma and an acinar-predominant adenocarcinoma.  The mucinous adenocarcinoma showed similar cytologic features as the rectal tumor; however, it showed more of a lepidic pattern.  The immunohictochemical profile of the lung mucinous adenocarcinoma was positive CK7 (cytoplasmic), negative CK20, TTF1, napsin-A, and CDX2.  KRAS codon 12/13 analysis also showed a mutation in the lung, however it was different compared to the previous rectal tumor and showed a GGT>AGT mutation.  The acinar adenocarcinoma had a wild-type KRAS.  In this case, we favored a primary lung mucinous carcinoma over a metastasis from the rectum based on the lepidic morphology, CK20 negativity and differing KRAS codon 12 mutations.  A year after the resection of the lung adenocarcinomas, the patient presented with dyspnea and abnormal liver functions.  Abdominal US and MRI revealed multiple liver lesions (up to 1.9 cm).  Core liver biopsies showed a poorly-differentiated mucinous adenocarcinoma with positive CK7 (cytoplasmic) and negative CK20, TTF-1, napsin-A, CDX2 and HSA.  KRAS codon 12/13 analysis also showed a mutation GGT>AGT, similar to that of the lung mucinous adenocarcinoma.  The immunohistochemical profile and the KRAS mutation sequence of the hepatic tumor suggests a metastasis from the lung primary and corroborates the earlier premise that the lung tumor is distinct from the rectal one.  In conclusion, in the unusual circumstance of a lung mucinous adenocarcinoma in a patient with established gastrointestinal mucinous primary, KRAS mutation analysis sequencing could help distinguish whether the lung mucinous is a primary tumor or metastasis from colorectal origin.