Well-differentiated SMARCB1-deficient Pancreatic Malignancy With Indolent Liver Metastases

SMARCB1-deficient pancreatic neoplasms are rare and typically present as aggressive, undifferentiated carcinomas. To date, only a single well-differentiated SMARCB1-deficient pancreatic malignancy that cannot be assigned to an established histological category has been reported. We describe the second such case and provide the first longitudinal observation of its untreated metastatic course.

A 66-year-old woman underwent distal pancreatectomy for a pancreatic tail malignancy and developed liver metastases six years later. Two small hypervascular liver nodules were initially interpreted as hemangiomas. During two years of observation, they enlarged gradually and additional hypovascular nodules appeared, whereas tumor markers remained negative and fluorodeoxyglucose positron emission tomography showed no abnormal hepatic uptake. Partial hepatectomy of five lesions was performed for diagnostic and therapeutic purposes. Both the primary pancreatic tumor and the liver lesions comprised bland glandular/tubular proliferations of cells with clear-to-eosinophilic cytoplasm, complete loss of SMARCB1/INI1 expression, CK7 negativity, CK19 positivity, and a Ki-67 labeling index of 1-2%. The immunophenotype of the metastases was identical to that of the primary tumor, establishing a diagnosis of hepatic metastases from a well-differentiated SMARCB1-deficient pancreatic malignancy.

This well-differentiated SMARCB1-deficient pancreatic malignancy is biologically distinct from conventional pancreatic ductal adenocarcinoma and SMARCB1-deficient undifferentiated carcinoma. As in the only previous case, it produced metachronous liver metastases yet followed an unexpectedly indolent course. Clinicians managing pancreatic malignancies should recognize this emerging tumor, because its metastases may mimic benign lesions, remain occult on metabolic imaging and be amenable to local treatment after a prolonged disease-free interval.