Clinicopathologic Characteristics of Brain Metastasis of Pancreatic Ductal Adenocarcinoma

Brain metastasis (BRM) of pancreatic ductal adenocarcinoma (PDAC) is rare. The clinicopathological characteristics of BRM have not been defined. We reviewed the clinicopathologic and molecular features of 18 PDAC patients who underwent resection of primary tumor (RPT) and developed BRM, along with 2 patients who had BRM resection without RPT and compared with 679 patients without BRM who received neoadjuvant therapy (NAT) and pancreatectomy. There were 11 males and 9 females (median age: 60.7 y). The median intervals to BRM were 47.0, 44.4, and 31.6 months from dates of diagnosis, surgery, and first metastasis to other sites, respectively. Five patients underwent resection for BRM and showed unique cystic papillary growth patterns with detached cell clusters. All BRMs had mutant p53 staining, 4 had retained SMAD4, and 3 were focally positive for CK17. Among 18 patients who underwent RPT, 12 received NAT. Patients with BRMs have lower tumor stage ( P <0.001) and better tumor response ( P =0.01) at RPT. The median overall survival (OS) for 18 patients with BRM after RPT was 62.3 months compared with 42.4 months for those without BRM (n=679, P =0.59). The median survival was 3.3 months from BRM diagnosis for all patients and 6.9 months for 5 patients who underwent brain surgery. In summary, BRM represents a late event in PDAC patients, occurs after patients developed metastasis to other organs, and has distinct cystic papillary growth pattern. The prognosis for patients who underwent RPT and developed BRM is similar to those who underwent RPT without BRM.