Evaluation of Pancreatic Cystic Lesions Peter Darwin, MD Director, Therapeutic Endoscopy University of Maryland Hospital Division of Gastroenterology

Cystic Lesions of the Pancreas Case Presentations Differential EUS evaluation Management Complications

Case 1 27 year old woman referred for evaluation of recurrent pancreatitis with a cystic lesion –Initially admitted 1/03 with acute pancreatitis and a 3 cm cyst of pancreatic body. MRCP - –EUS/FNA 11/05 of a 4 cm cystic collection. Histology showed histiocytes, inflammatory cells and debris. Mucin stain negative. CEA 390 ng/ml, amylase 91,700 U/l. –What is the most likely diagnosis?

Case 2 77 year old woman with virtual colonoscopy that demonstrated a 1.5 cm cystic lesion of the pancreatic head EUS/FNA showed a multi-septated cyst with clear/thin fluid. Mucin stain was positive and CEA in the fluid 546 ng/ml What is the appropriate next step?

Differential –Simple (Congenital) Cyst –Cystic Neoplasm Serous Mucinous Cystic degeneration IPMT –Inflammatory Pseudocyst

Simple Cyst (Retention cyst) Asymptomatic Thin walled, no septations Thin clear fluid Collapses with FNA No malignant potential

Simple Cyst

Serous Cystadenoma Usually found incidentally Microcystic with a “honeycomb” appearance; rarely has a macrocystic component; central calcification Thin, clear fluid Cuboidal epithelium that stains positive for glycogen Little to no malignant potential

Mucinous Cystadenoma Usually found incidentally but can cause abdominal pain and a palpable mass Macrocystic, occasionally septated; peripheral calcifications, solid components Fluid: Viscous or stringy, clear Cytology: Mucinous columnar cells with variable atypia; fluid stains positive for mucin Malignant potential: 30% lifetime risk

Cyst Adenocarcinoma Presents with painless jaundice, abdominal/back pain or rarely pancreatitis Primarily solid mass with cystic spaces Bloody ± debris Malignant adenocarcinoma may be seen, but varying degrees of atypia may be present in the specimen

Inflammatory Pseudocyst –History of moderate to severe pancreatitis –Anechoic, thick-walled, rare septations –Fibrous lining of cyst (no epithelium) –FNA-> Thin, muddy-brown fluid –Cytology-> Neutrophils, macrophages, histiocytes; negative staining for mucin –Malignant potential: None

Pseudocyst

Intraductal Papillary Mucinous Neoplasm (IPMN) 3 types: main duct, branch type and mixed History of pancreatitis, abdominal pain, or found incidentally Imaging: Dilated main pancreatic duct or side branches Fluid: Viscous or stringy, clear Cytology: Mucinous columnar cells with variable atypia; fluid stains positive for mucin Malignant potential 20 to 30% lifetime risk

IPMN main duct

IPMN side branch

Solid Pseudopapillary Neoplasm Usually found incidentally; rarely causes abdominal discomfort Solid and cystic components Bloody + necrotic debris Monomorphic cells with round nuclei and eosinophilic or foamy cytoplasm; immunostaining Locally invasive (similar to Desmoids)

Pseudo

7.5 / 12 MHz. 7.5 MHz. UC-30P UM-130

Can EUS alone Differentiate Between Malignant and Benign Cystic Lesions ? 48 patients with surgical/pathologic correlation EUS images reviewed 2 blinded endosonographers Assessed for wall, solid component, septae, lymphadenopathy and # of cysts EUS features cannot reliably differentiate Ahmad N, Kochman M, Lewis J, Ginsberg G. Am J Gastro 2001;96:

EUS-Guided FNA Results for FNA cytology are variable –Mucinous vs nonmucinous epithelium Tumor Markers –CEA, CA 72-4, CA 125, –CA 19-9, CA 15-3 Molecular analysis

Cyst Fluid Analysis in the Differential Diagnosis of Pancreatic Cystic Lesions: a Pooled Analysis Pub Med review of articles with cyst fluid analysis –At least 7 patients –Diagnosis of cystadenoma made by pathology –Pseudocyst diagnosed by history and follow up van der Waaij L, van Dullemen H, Porte R. Gastro Endo 2005;62:

CEA FREE DNA Pancreatic Cyst Fluid  DNA QUANTITY & QUALITY REFLECT LINING CELL PROLIFERATION  KRAS & GNAS POINT MUTATION (ONCOGENE)  LOSS OF HETEROZYGOSITY (LOH) MUTATIONS (25) (TUMOR SUPPRESSOR GENES) DETACHED LINING CELLS Second line molecular analysis targets both cellular and free DNA designed to complement cytology and other first line information. Multiple molecular parameters reflects multiple pathways of neoplasia development and progression

PFTG – Pancreatic Cysts

Performance of PFTG (n=492) in Diagnosing Malignant Outcome The National Pancreatic Cyst Registry

Complications of EUS Pancreatitis (2%-3%) Hemorrhage within the cyst (<1%) Infection (<1%) The prevailing opinion is to administer an antibiotic, e.g., a fluoroquinolone, prior to aspiration and possibly several days post.

Serous Cystadenoma Management determined by symptoms, progression, and lesion location. Symptomatic or enlarging serous cystadenomas should be resected. Small, asymptomatic, and nonenlarging serous cystadenomas can be observed

Mucinous Cystadenoma Consider for resection Potential for malignant change (30% lifetime) Distal pancreatectomy should be performed for lesions in the body or tail of the pancreas Pancreaticoduodenectomy for lesions in the pancreatic head.

Ethanol Lavage: Initial Pilot Study Background: lavage ablates liver cysts Methods: post evacuation, lavaged with ethanol (5% to 80%) Observations: 25 patients – no symptoms – resolution in 8 patients (35%) Conclusions: subset had long-term resolution. Further studies needed. Gan S, Thompson C, Bounds B, Brugge W. Gastro Endo 2005;61:

Prospective multicenter randomized double blinded study EUS lavage Baseline SA Post procedure SA Complete ablation Complications Saline N=15 Ethanol (1) N=36 Ethanol (2) N= cm cm 2 0/ cm cm 2* 2/ cm cm 2** 10/23 1 *P=.002 ** P=.0001 ETOH vs saline Brugge W, et al. Am J of Gastro 2007;106:S192

Revised International Consensus Guidelines for the Management of Patients With Mucinous Cysts Tanaka M, et al. Panceatology 12(2012)

Solid Pseudopapillary Neoplasm Solid pseudopapillary neoplasms are locally aggressive lesions, which should be resected surgically if possible. The type of resection is determined by the location of the tumor

Endoscopic Management of Pseudocysts Can be considered for mature pseudocysts, infected pseudocysts, and in selected cases of organized necrosis. Symptomatic lesions= (abdominal pain, gastric outlet obstruction, early satiety, weight loss, or jaundice) 82-84% success rate Complication rates occurring in 5% to 16% Recurrence rates ranging from 4% to 18%

Endoscopic Management Prophylactic antibiotics Special care must be taken to avoid drainage of cystic neoplasms, pseudoaneurysms, duplication cysts, and other noninflammatory fluid collections. Pseudocyst size is not an indication for drainage ERCP prior

Hookey L, et. al. Gastro Endo 2006;63:

Complications of Drainage Bleeding Infection Perforation Pancreatitis Aspiration Stent migration Death