Kenneth D. Chi, MD Medical Director GI Lab Advocate Lutheran General Hospital

Kenneth D. Chi, MD Medical Director GI Lab Advocate Lutheran General Hospital Advances in Digestive Health for the Primary Care Physician Symposium May 2, 2015

None

Case Presentation Types of Pancreatic mass lesions Solid lesions Cystic lesions Diagnostic algorithm Cyst management guidelines (Update April 2015) Summary

68 y.o. woman in otherwise good health, presents from her PCP office holding a MRI report (outside hospital) taken during workup of abdominal pain. She has circled the words 2.2cm mass-like abnormality in the tail of the pancreas in the report.

No weight loss, no appetite changes. No pain. No prior pancreatitis hx, no fam hx panc dz No prior abdominal wall trauma No loose stools or steatorrhea

What do you tell her and how do you proceed?

Cystadenomas (serous, mucinous) IPMN Cystic teratoma Choledochocele cyst Congenital cyst Intrapancreatic accessory spleen Eosinophillic pancreatitis Focal pancreatitis Inflammatory myofibroblastic tumor Lymphoid hyperplasia Phlegmon Pseudocyst Traumatic pancreatitis Wegner s disease Xanthogranulomatous pancreatitis Benign pancreatic cysts Hydatid cyst Dysontogenic cysts Lymphoepithelial cysts Pancreatic dermoid cysts Parasitic cysts (echinococcus) Retention pancreatic cysts Mucinous tumor with dysplasia IPMN with dysplasia Solid pseudopapillary tumor Ascaris lubricoides Candida albicans CMV Coxsackievirus Mumps Mycobacterium avium complex Mycobacterium tuberculosis Kaposi s sarcoma Lipoma Lymphangioma Pancreatic Castelman s Disease Pancreatic Hamartoma Pancreatic sarcoma Plexiform neurofibroma Schwannoma Teratoma Adenosquamous carcinoma Anaplastic tumors Clear cell sugar tumor Colloid carcinoma Granulocytic sarcoma Leukemia Lymphoma Primitive neuroectodermal tumor Ductal adenocarcinoma Osteoclast-like Giant Cell tumor Serous cystadenocarcinoma Mucinous cystadenocarcinoma Acinar cell carcinoma Pancreatoblastoma Solid-pseudopapillary carcinoma Ampullary adenocarcinoma Kaposi s sarcoma Lipoma Lymphangioma Pancreatic Castelman s Disease Pancreatic Hamartoma Pancreatic sarcoma Plexiform neurofibroma Schwannoma Teratoma Breast Colon Lung Lymphoma Melanoma Renal cell carcinoma Eosinophillic pancreatitis Focal pancreatitis Inflammatory myofibroblastic tumor Lymphoid hyperplasia Phlegmon Pseudocyst Traumatic pancreatitis Wegner s disease Xanthogranulomatous pancreatitis ACTH secreting tumor Carcinoid tumor Gastrinoma GRF-secreting tumor Insulinoma PP secreting tumor Somatostatinoma VIPoma Breast Colon Lung Lymphoma Melanoma Renal cell carcinoma Adenosquamous carcinoma Anaplastic tumors Clear cell sugar tumor Colloid carcinoma Granulocytic sarcoma Leukemia Lymphoma Primitive neuroectodermal tumor

Type Examples Benign (exocrine) Cystadenomas (serous, mucinous) IPMN Cystic teratoma Borderline Mucinous tumor with dysplasia IPMN with dysplasia Solid pseudopapillary tumor Malignant Ductal adenocarcinoma Osteoclast-like Giant Cell tumor Serous cystadenocarcinoma Mucinous cystadenocarcinoma Acinar cell carcinoma Pancreatoblastoma Solid-pseudopapillary carcinoma Ampullary adenocarcinoma

Type Examples Endocrine ACTH secreting tumor Carcinoid tumor Gastrinoma GRF-secreting tumor Insulinoma PP secreting tumor Somatostatinoma VIPoma Cystic Lesions Benign pancreatic cysts Hydatid cyst Dysontogenic cysts Lymphoepithelial cysts Pancreatic dermoid cysts Parasitic cysts (echinococcus) Retention pancreatic cysts

Type Examples Congenital Choledochocele cyst Congenital cyst Intrapancreatic accessory spleen Infectious Masses Ascaris lubricoides Candida albicans CMV Coxsackievirus Mumps Mycobacterium avium complex Mycobacterium tuberculosis Mesenchymal Tumors Kaposi s sarcoma Lipoma Lymphangioma Pancreatic Castelman s Disease Pancreatic Hamartoma Pancreatic sarcoma Plexiform neurofibroma Schwannoma Teratoma

Type Examples Metastatic Lesions Breast Colon Lung Lymphoma Melanoma Renal cell carcinoma Non-islet cell tumors Adenosquamous carcinoma Anaplastic tumors Clear cell sugar tumor Colloid carcinoma Granulocytic sarcoma Leukemia Lymphoma Primitive neuroectodermal tumor

Type Examples Pancreatic inflammatory mass Eosinophillic pancreatitis Focal pancreatitis Inflammatory myofibroblastic tumor Lymphoid hyperplasia Phlegmon Pseudocyst Traumatic pancreatitis Wegner s disease Xanthogranulomatous pancreatitis

Pancreatic Incidentaloma First described by Ho and Kostiuk 1996 Significant imaging advances in CT, MRI, U/S have led to better diagnosis/staging But also increased the incidental discovery of asymptomatic pancreatic lesions About 15% patients undergoing MRI for other indications harbor unsuspected cysts These findings can trigger significant anxiety for patients and their physicians

Aim is to determine the benign or malignant nature of the lesion Obsessive search for small incidental tumors has, on the other hand, risk that these patients may undergo extensive diagnostic evaluation and tx without positive impact on their health, + potential complications

The rate of malignancy in Pancreatic Incidentalomas has been reported to be as high as 32%, which is higher than other organ incidentalomas (kidney, adrenal, liver) Winter JM, et al. Ann Surg. 2006; 243:673-80.

History Each patient with a PI should be asked Prior hx pancreatitis? Any prior abdominal wall trauma? Family hx pancreatic cancer? Presence of any warning signs/symptoms? Any prior imaging studies to compare? This information could change workup from an aggressive approach to a more conservative

Age and comorbidities Lesion found in healthy 44 y.o. might be approached more aggressively than same lesion found in an 84 y.o. with multiple medical issues Location of lesion in the pancreas

Pancreatic lesions require careful evaluation and should be evaluated in a multidisciplinary fashion

- Physician - Assistants - Nurse Practitioners - Nurses - Psychologists - Social Workers - Nutritionists - Endocrinologists - Palliative Care

Pancreatic Protocol CT scan / MRI Endoscopic Ultrasound (EUS) and FNA has revolutionized the diagnosis and treatment of pancreatic lesions

Able to diagnose and confirm: Solid vs. Cystic Most solid lesions end up being resected Cystic lesions pose more of a diagnostic dilemma Accurate size and location of lesion Relationship with vessels Fine needle aspiration (FNA) and biopsy Cytology Core biopsy Drainage (pseudocysts)

EUS

EUS Cyst FNA

Cyst fluid analysis CEA level = 76 ng/ml Level < 192 favors benign serous cyst Level > 192 favors pre-cancerous mucinous type Cytology returned benign What is the differential diagnosis of this cystic lesion?

Benign Lined by glycogen-rich cells that originate from pancreatic centroacinar cells Usually microcystic (cluster of small cystic spaces honeycomb ) Mostly in woman >60 yrs old Malignant degeneration is exceedingly rare central scar on gross specimen

Exclusively found in woman (80-90%) Age usually >40 yrs Secrete mucin similar to IPMNs Unlike IPMNs, are lined with ovarian-like stroma Classically appear as septated, but can be unilocular Usually in body and tail Usually do not communicate with main duct Have malignant potential (11%-38%)* * Reddy, RP et al. Clin Gastroenterol Hepatol 2004; 2:1026.

First described by Ohhashi in Japan in 1982 Incidence 2/100,000 Prevalence 26/100,000 Age >60, prevalence increases to 99/100,000* 3 types: Main duct IPMN Main duct is dilated >1cm Cancer prevalence 57-92% Side branch IPMN Disease confined to a side duct Cancer prevalence 6-46% Mixed Ohhashi K., Murakami Y., Maruyama M. Prog Dig Endosc (1982) 20: pp348-351. * Reid-Lombardo et al. Incidence, prevalence, and management of IPMN in Olmsted County, Minnesota, 1984-2005. Pancreas 2008; 37: 139-44.

Aka Franz tumor Young woman (avg. 24) ; 10:1 Usually located in tail of panc, well demarcated Both solid and cystic components Cytology shows characteristic branching papillae with myxoid stroma Rare tumor; makes up <1% of all panc neoplasms Behavior less aggressive; 95% survival @ 5 yrs (post resection) Mets 15% cases, usually liver.

Larger size (>3cm, 9.3% risk * ) <3cm, malignant <5% 3-5cm, malignant 15% >5cm, malignant >30% ** Thickened irregular cyst wall Internal solid component, or mass Possibly calcification of the cyst wall Main pancreatic duct dilitation Cyst fluid CEA level >192 ng/dl (sens 73%, spec 83%) *** DNA molecular analysis * Wu, BU et al. Am J Gastroenterol. 2014 Jan; 109(1): 121-9. ** Grobmyer SR, et al. J Surg Oncol. 2009; 100(5):372 *** Brugge, WR et al. Gastroenterology 2004; 126:1330.

Serous cystadenoma Mucinous cystadenoma Main duct IPMN Branch duct IPMN Age 50-70s 50-70s 50-70s 50-70s 20-30s Gender F > M Exclusively F F = M F = M F > M Solid pseudopapillary Clinical Incidental Incidental Pancreatitis Pancreatitis Incidental Imaging Cytology DNA Honeycomb Central scar Glycogen positive cuboidal cells Large septations Mucinous, columnar cells K-ras mutation, high DNA amount Fluid CEA <5-20ng/ml >200 ng/ml in 75% Dilated main duct Mucinous, columnar cells K-ras mutation, high DNA amount >200 ng/ml in 75% Dilated duct branch Mucinous, columnar cells K-ras mutation, high DNA amount >200 ng/ml in 75% Solid/cystic mass Branching papillae with myxoid stroma Malignant Rare Moderate High Low-mod Mod-high Treatment Only if sx Resection Resection & post rx surveillence Close monitor or resect with surveillence Resection Adapted from Khalid, A, Brugge, WR. Am J Gastroenterol 2007; 102:2339.

March 27, 2015

2. The AGA suggests that patients with pancreatic cysts <3cm without a solid component or a dilated pancreatic duct undergo MRI for surveillance in 1 year and then every 2 years for a total of 5 years if there is no change in cyst size or characteristics. Estimated that an incidental cyst on MRI has 10 in 100,000 chance of mucinous invasive malignancy and 17 in 100,000 chance of being a ductal cancer

3. The AGA suggests that pancreatic cysts with at least 2 high-risk features, such as size 3cm, a dilated main pancreatic duct, or presence of an associated solid component, should be examined by EUS-FNA. 3cm size increased risk of malignancy 3x Solid component increased risk 8x EUS-FNA sensitivity of about 60% and specificity of about 90%

4. The AGA suggests that patients without concerning EUS-FNA results should undergo MRI surveillence after 1 year and then every 2 years to ensure no change in risk of malignancy. The negative predictive value for an unremarkable EUS is very high, therefore can follow more conservative follow-up

5. The AGA suggests that significant changes in the characteristics of the cyst, including the development of a solid component, increasing size of the pancreatic duct, and/or diameter 3cm, are indications for EUS-FNA. If any interval change is seen, then recommend EUS- FNA.

6. The AGA suggests against continued surveillance of pancreatic cysts if there has been no significant change in the characteristics of the cyst after 5 years of surveillance or if the patient is no longer a surgical candidate. Authors cautioned that some patients may elect to continue surveillance or if strong family hx pancreas cancer is present.

7. The AGA suggests that patients with both a solid component and a dilated pancreatic duct and/or concerning features on EUS and FNA should undergo surgery to reduce the risk of mortality from carcinoma. Normally this would be considered a strong recommendation, but to do so assumes that everyone undergoing surgery will benefit Most beneficial in high-grade dysplasia group Post-op mortality from surgery 2% and high morbidity rate, the true benefit is unclear

8. The AGA recommends that if surgery is considered for a pancreatic cyst, patients are referred to a center with demonstrated expertise in pancreatic surgery. Post-op mortality rates range from a low of 2% in centers of excellence to approximately 7% in less experienced institutions.

9. The AGA suggests that patients with invasive cancer or dysplasia in a cyst that has been surgically resected should undergo MRI surveillance of any remaining pancreas every 2 years. The authors point out that clinicians may elect to offer more frequent surveillance for cancer resections, or if concern that lesion was not fully resected.

10. The AGA suggests against routine surveillance of pancreatic cysts without highgrade dysplasia or malignancy at surgical resection. Continued surveillance in this group is unlikely to be cost-effective Bottom line is the vast majority of asymptomatic cysts are low risk and will prove to be non-lethal

1. The AGA recommends that before starting any pancreatic cyst surveillance program, patients should have a clear understanding of programmatic risks and benefits. The AGA s initial motherhood statement is the most important to convey to patients Patients should understand their probability of their cyst becoming malignant, and may elect not to undergo surveillance

Cyst fluid analysis CEA level 76 ng/ml Level < 192 favors benign serous cyst Level > 192 favors pre-cancerous mucinous type Cytology returned benign Diagnosis likely Serous cystadenoma based on history and CEA level Patient opted for conservative management with surveillance imaging.

Most pancreatic incidentalomas end up being benign and only require conservative mgmt Recent pancreatic cyst guidelines favor a less aggressive approach The more complicated cases should be reviewed through a multi-disciplinary approach to outline treatment standards and provide a customized treatment plan for each patient