kenneth d. chi, md...• phlegmon • pseudocyst • traumatic pancreatitis • wegner’s disease...

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

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 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 centro-acinar 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

Solid pseudopapillary

Age 50-70s 50-70s 50-70s 50-70s 20-30s

Gender F > M Exclusively F F = M F = M F > M

Clinical Incidental Incidental Pancreatitis Pancreatitis Incidental

Imaging Honeycomb Central scar

Large septations Dilated main duct

Dilated duct branch

Solid/cystic mass

Cytology Glycogen positive cuboidal cells

Mucinous, columnar cells



Branching papillae with myxoid stroma

DNA K-ras mutation, high DNA amount

K-ras mutation, high DNA amount

K-ras mutation, high DNA amount

Fluid CEA <5-20ng/ml >200 ng/ml in 75%

>200 ng/ml in 75%

>200 ng/ml in 75%

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.

http://prezi.com/hd1zf_qiw7zj/?utm_campaign=share&utm_medium=copy&rc=ex0share

March 27, 2015

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

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.

≥3cm size increased risk of malignancy 3x

Solid component increased risk 8x

EUS-FNA sensitivity of about 60% and specificity of about 90%

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.

The negative predictive value for an unremarkable EUS is very high, therefore can follow more conservative follow-up

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.

If any interval change is seen, then recommend EUS-FNA.

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.

Authors cautioned that some patients may elect to continue surveillance or if strong family hx pancreas cancer is present.

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.

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

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.

Post-op mortality rates range from a low of 2% in centers of excellence to approximately 7% in less experienced institutions.

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.

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.

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.

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

10. The AGA suggests against routine surveillance of pancreatic cysts without high-grade dysplasia or malignancy at surgical resection.

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

1. The AGA recommends that before starting any pancreatic cyst surveillance program, patients should have a clear understanding of programmatic risks and benefits.

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

kenneth d. chi, md...• phlegmon • pseudocyst • traumatic pancreatitis • wegner’s disease...

Documents