Practical Applications of Molecular Testing in the Cytologic Diagnosis of Pancreatic Cysts

Mingjuan Lisa Zhang,Martha B. Pitman

doi:10.3390/jmp2010002

Mingjuan Lisa Zhang, Martha B. Pitman

Open Access

https://doi.org/10.3390/jmp2010002

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Abstract

Mucinous pancreatic cysts are precursor lesions of ductal adenocarcinoma. Discoveries of the molecular alterations detectable in pancreatic cyst fluid (PCF) that help to define a mucinous cyst and its risk for malignancy have led to more routine molecular testing in the preoperative evaluation of these cysts. The differential diagnosis of pancreatic cysts is broad and ranges from non-neoplastic to premalignant to malignant cysts. Not all pancreatic cysts—including mucinous cysts—require surgical intervention, and it is the preoperative evaluation with imaging and PCF analysis that determines patient management. PCF analysis includes biochemical and molecular analysis, both of which are ancillary studies that add significant value to the final cytological diagnosis. While testing PCF for carcinoembryonic antigen (CEA) is a very specific test for a mucinous etiology, many mucinous cysts do not have an elevated CEA. In these cases, detection of a KRAS and/or GNAS mutation is highly specific for a mucinous etiology, with GNAS mutations supporting an intraductal papillary mucinous neoplasm. Late mutations in the progression to malignancy such as those found in TP53, p16/CDKN2A, and/or SMAD4 support a high-risk lesion. This review highlights PCF triage and analysis of pancreatic cysts for optimal cytological diagnosis.

Highlights

Radiologic detection of pancreatic cysts in asymptomatic patients has increased in recent years, and distinguishing benign cystic lesions versus those with malignant potential is essential for patient management
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with pancreatic cyst fluid (PCF) analysis is the standard of care for the preoperative diagnosis of pancreatic cysts [1,2,3,4]
Cytology alone cannot distinguish between intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN); this distinction has important implications, as surgical resection is recommended for all MCNs regardless of grade, while important implications, as surgical resection is recommended for all MCNs regardless of most low-grade branch-duct IPMNs can be managed without surgery

Summary

Introduction

Radiologic detection of pancreatic cysts in asymptomatic patients has increased in recent years, and distinguishing benign cystic lesions versus those with malignant potential is essential for patient management. Cytologic evaluation provides high specificity but lower sensitivity for the detection of a mucinous cyst. Even with minimal amounts of cyst fluid, PCFPCF can be triaged for cytology, CEA/amylase. Even with minimal amounts of cyst fluid, can be triaged for cytology, CEA/amanalysis, and molecular testing PCF is very thick, a direct smear should be made, as the chemistry lab will the specimen for CEA due to high viscosity. PCF almost always shows a very high amylase level (≥250 U/L) and low CEA level SCAs are lined by nonmucinous cuboidal cells with uniform round a recent case series [19]. Cytology shows cuboidal cellsnon-mucinous with non-mucinous cytoplasm and Cytology shows cuboidal cells with cytoplasm and uniform, bland centrally located nuclei. 25% of sporadic cases [22]. tumors can harbor VH mutations or promoter hypermethylation in up to 25% of sporadic cases [22]

Lymphoepithelial Cyst

Intraductal Papillary Mucinous Neoplasm

Mucinous Cystic Neoplasm

Findings

Molecular Testing in Practice