Pancreatic Mixed Acinar-neuroendocrine Carcinoma in a Patient With a Germline PTEN Variant: A Case Report and Genomic Literature Review.

Background/aim: Cowden syndrome (CS)/PTEN hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline PTEN variants. While patients with CS/PHTS have increased risk of various cancers, pancreatic cancer is not typically associated with this syndrome. We report a rare case of pancreatic mixed acinar-neuroendocrine carcinoma in a patient with a germline PTEN variant, aiming to understand its molecular characteristics and clinical implications.

Case report: A male in his late 40s presented with pancreatic cancer and hepatic metastases. His medical history included thyroid cancer and familial gastrointestinal malignancies. Liver biopsy revealed mixed acinar-endocrine carcinoma. Cancer genome profiling identified pathogenic variants in GNAS and TP53, along with a germline PTEN variant (V201fs*1), leading to a diagnosis of CS. Notably, KRAS mutations, commonly found in pancreatic cancer, were absent. The patient showed extreme resistance to multiple chemotherapy regimens, including FOLFIRINOX, gemcitabine plus nab-paclitaxel, and cisplatin plus etoposide, resulting in rapid clinical decline.

Conclusion: This case highlights a rare presentation of pancreatic cancer in CS/PHTS with distinct molecular and histological features. The absence of KRAS mutation and presence of germline PTEN variant may have contributed to the aggressive clinical course and treatment resistance. These findings underscore the need for further research into the molecular mechanisms of PTEN-associated pancreatic cancers and the development of targeted therapeutic strategies.