Itʼs in Her DNA: A Case Highlighting the Role of DNA Molecular Analysis in Intraductal Papillary Mucinous Neoplasm

Abstract

Intraductal papillary mucinous neoplasms (IPMN) are premalignant and require either surgical resection or long-term surveillance. We present a case highlighting the role of DNA molecular analysis in diagnosing another premalignant lesion in a woman initially thought to have only IPMN. A 76-year-old woman was referred for a pancreatic mass noted on abdominal ultrasound. Imaging was performed as a “screening” modality, given maternal history of pancreatic cancer. The patient denied weight loss. She was well appearing without jaundice. Her abdomen was soft. Liver associated enzymes and bilirubin were normal. CT scan showed several hypodense tubular structures in the head and uncinate process of the pancreas communicating with several ectatic side branches. Endoscopic ultrasonography (EUS) of the pancreas revealed anechoic cystic dilation of a side branch measuring 2.6 cm x 1.9 cm, consistent with a side branch IPMN not meeting Sendai criteria for surgical resection. Fine needle aspiration (FNA) showed a thick mucinous aspirate. Cytology revealed extracellular mucin with no evidence of high-grade dysplasia or malignancy. Carcinoembryonic antigen (CEA) was 241 ng/mL. DNA molecular analysis revealed low clonality KRAS mutation and no loss of heterozygosity, classified as likely benign. Because of the KRAS mutation, the patient was referred to surgery and underwent a Whipple procedure. Surgical pathology revealed IPMN, gastric type (intermediate grade). No high-grade dysplasia or carcinoma was noted within the cysts. However, the adjacent pancreas exhibited pancreatic intraepithelial neoplasia, intermediate grade (PanIN-2). DNA molecular analysis examines the mutation status of certain genes, notably KRAS. Studies have shown that DNA analysis increases the sensitivity of detecting mucinous cysts to 73-84% when combined with CEA and cytology, a rate higher than with EUS, cytology, and tumor markers alone. Our case demonstrates a unique instance where imaging did not meet Sendai or the revised Fukuoka criteria for surgical resection of IPMN, but DNA molecular analysis led to a decision for resection. This ultimately led to finding PanIN, thought to be the most common precursor to pancreatic ductal adenocarcinoma. Thus, DNA analysis not only helped diagnose IPMN but also proved crucial in discovering a second premalignant neoplasm. The role of DNA molecular analysis in PanIN and the association between IPMN and PanIN are areas for further research.Figure: The largest hypodense tubular structure in the uncinate process and head measures approximately 1.9 x 1.3 cm.Figure: Associated, several hypodense tubular structures in uncinate process and head which appear to communicate with ectatic side branches.Figure: EUS images showing IPMN with FNA performed.