Cystic Neoplasms of the Pancreas: A Surgical Perspective Great Debates & Updates in GI Malignancies Cystic Neoplasms of the Pancreas: A Surgical Perspective Michael A. Choti, MD Department of Surgery UT Southwestern Medical Center Dallas, Texas

Disclosures none

An Increasing Clinical Dilemma Pancreatic Cysts: An Increasing Clinical Dilemma Pancreatic cysts are being diagnosed with increasing frequency 2.3% of CT routine CT scans identify cysts1 2.4% - 13% found on MRI scans2 The spectrum of malignant risk is variable and the management is unclear What is the risk of malignancy? How morbid is the invasive management? Observe vs Operate? 1Laffan et al (AJR 2008) 2DeJong et al (Scan J Gastro 2012), Lee et al (AJG 2010)

Classification of Pancreatic Cysts No Malignant Potential Pseudocyst Lymphoepithelial cyst Retention cyst Congenital cyst Endometrial cyst Cystic lymphangioma Cavernous hemangioma Serous cystic adenoma* Malignant Potential Intraductal papillary mucinous neoplasm Mucinous cystic neoplasm Intraductal tubular carcinoma Malignant Cystic ductal adenocarcinoma Cystic neuroendocrine tumor Solid pseudopapillary neoplasm Cystic pancreatoblastoma Cystic acinar cystadenocarcinoma Mature cystic teratoma *Low malignant potential Law et al. www.co-gastroenterology.com (2013)

Classification of Pancreatic Cysts Cystic Pancreatic Lesions Non-neoplastic Pseudocyst Retention Cyst Foregut Duplication Cyst Neoplastic Cystic Degeneration of Solid Neoplasm Serous Mucinous Solid Pseudopapillary Neoplasm (SPEN/Franz/Hamoudi) Cystic pNET Serous Cystadenoma Mucinous Cystic Neoplasm (MCN) Intraductal Papillary Mucinous Neoplasm (IPMN)

Classification of Pancreatic Cysts Patient History and Demographics Age, gender, history of pancreatitis Imaging Characteristics CT, MRI, EUS Fluid Characteristics Cyst Aspiration – amylase, CEA (mucin), cytology

Clinical Classification Cystic Degeneration of Solid Neoplasm Solid Pseudopapillary Neoplasm (SPEN/Franz/Hamoudi) Cystic pNET

Solid Pseudopapillary Neoplasm (Franz or Hamoudi Tumor) Very uncommon ~800 total cases in all case series up to 2008 Most common in young females Imaging characteristics Solid and cystic, large Central calcification No communication with the pancreatic duct Cyst fluid features Serous fluid (low CEA) Low amylase Loosely cohesive epithelial cells with focal hemorrhage Positive staining for nuclear beta-catenin Malignant potential All should be resected Reddy et al., JACS 2008

Cystic Neuroendocrine Tumors 10-15% pNETs are cystic Behavior similar to typical pNET Imaging features Solid rim of arterial enhancement on CT No communication with duct Focal Cyst fluid features Serous (low CEA) Low Amylase Clear malignant potential Management same as typical pNET Bordeianou et al.

Clinical Classification Serous Cystadenoma Serous

Serous Cystic Neoplasms (Serous Cystadenoma) 10-15% of all cystic neoplasms Predilection for females (60s) 80% in HOP, 80% asymptomatic Imaging characteristics Microcystic/honeycomb and loculated Unifocal, Central calcification No communication with the pancreatic duct Cyst fluid features Lined with simple cuboidal or flattened epithelium Thin serous fluid Very low malignant potential Resect only when symptomatic Galanas et al., JOGS 2007

Clinical Classification Mucinous Mucinous Cystic Neoplasm (MCN) Intraductal Papillary Mucinous Neoplasm (IPMN)

Aram F. Hezel et al. Genes Dev. 2006; 20: 1218-1249

Mucinous Cystic Neoplasm (MCN) Relatively uncommon (1/5th of resected cysts) Predilection for middle-aged women 95% female, median age 45 Imaging characteristics “Macrocystic”, unifocal Well demarcated Body/Tail No communication with Pancreatic Duct Cyst fluid features Mucinous (high CEA) Low amylase Ovarian-type stroma Malignant association (6-36%) All should be resected Crippa et al., Annals of Surgery, 2007

IPMN Relatively common Occur in both males and females with equal frequency Tend to occur in the elderly Imaging characteristics Ductal dilatation often present Often multifocal, macrocystic Communicate with duct Cyst fluid features Mucin (high CEA) High Amylase Malignant potential Dependent on further sub-classification

IPMN Classified by Relationship to Pancreatic Duct Main Duct IPMN Branch Duct IPMN

Cross-Sectional Imaging Pancreas Protocol CT Non-invasive Fast Relatively inexpensive Extremely accurate in demonstrating defining characteristics Limitations Involves radiation Solid Component MRI Non-invasive Extremely accurate in demonstrating defining characteristics Sensitive in determining solid component Limitations Less readily available than CT Relatively Expensive

Endoscopic Ultrasound Extremely accurate in demonstrating defining characteristics Gold standard for identifying a solid component Able to obtain fluid and tissue (Cyst aspiration, FNA or Core biopsy) Limitations More invasive Expensive for routine screening

IPMN with Mural Nodule on EUS Marchegiani & Fernandez-del Castillo. Adv Surg 48 (2014)

Cyst Aspiration & Biopsy FNA or Core Biopsy Level of dysplasia Able to perform IHC Limitations Often indeterminate Loss of cytoarchitecture False negatives(dysplasia/cancer) Cyst Aspiration Helpful in differentiating serous from mucinous Solid component CEA level Genetic analysis “The Future” Limitations Highly operator dependent Often cannot obtain fluid GI tract contamination

Mutations Associated with Cyst Fluid Law/Hruban et al. www.co-gastroenterology.com (2013)

International Consensus Guidelines for Management of IMPN and MCN of the Pancreas Tanaka, Pancreatology, 2012

International Consensus Guidelines for the Management of MCN and IPMN (“Sendai Criteria”) Indications for Surgical Resection Main Duct IPMN Branch Duct IPMN Defined as diffuse ductal dilatation > 3 mm at the neck of the pancreas All Main Duct IPMN are resected in a patient who can tolerate an operation Symptoms Pain, jaundice weight loss, pancreatitis Rapid Growth 0.5 cm/6 months Size > 3 cm Solid Component (mural nodule) Tanaka, Pancreatology, 2006

62 year old female No history of pancreatitis CT Scan Cyst fluid Unifocal Tail lesion Non-dilated pancreatic duct Cyst fluid Mucinous (high CEA) Low amylase Diagnosis: MCN

66 year old male Non-specific abd pain CT Scan Cyst fluid Multi-focal HOP lesion Mildly dilated pancreatic duct Cyst fluid Mucinous (high CEA) high amylase Diagnosis: IPMN

45 year old female History of breast cancer CT Scan Cyst fluid Unifocal-focal TOP lesion Non-dilated pancreatic duct Cyst fluid serous (low CEA) low amylase Diagnosis: IPMN

Summary Pancreatic cysts are being identified with increasing frequency. Significant variability exists in the malignant potential and management recommendations of pancreas cysts. While advances have been made in imaging and molecular assessment, current tools for differentiating high risk patients and guiding us in management and surveillance are limited. Currently, mucinous neoplasms meeting the guideline criteria (Senai) should be resected. Presumed IPMN must be followed closely. Patients with pancreatic cysts benefit from a multidisciplinary team approach, which includes gastroenterologists, pancreatic surgeons, radiologists, cytopathologists and pathologists.

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