Pancreatic Cysts Poke Me, Chop Me, Leave Me Alone!!!

Arthi Sanjeevi, MDUniversity of South Florida, Tampa, Fl

Clinical Presentation• Incidental finding

• Acute and Chronic Pancreatitis

• Vague abdominal pain

• Jaundice

• Weight loss

• New onset Diabetes

• Family History

Incidence

• 24,039 imaging over 7 years.

• 1.2% patients had PC, 0.7% had history of pancreatitis (1)

• 79: increased in size in 19%, no change in 59% and decreased in 22% of patients.

• 49 patients underwent surgery for 14 benign, 25 premalignant, 10 malignant

• Autopsy and MRI studies incidence may by 20-27%. [2,3]

1. Cystic pancreatic neoplasms: observe or operate. Spinelli KS, Fromwiller TE, Daniel RA, Kiely JM, Nakeeb A, Komorowski RA, Wilson SD, Pitt HA Ann Surg. 2004;239(5):651.

Key Questions?

Real or Pseudo?

Benign or Neoplastic?

Malignancy potential?

Surgical Risk?

Types of Cysts

• Pseudocysts

• True Cyst

• Cystic Neoplasms of Pancreas

• Cystic degeneration on solid tumors

Non Neoplastic Cysts

• Epithelial Cyst

• Retention Cysts

• Mucinous non-neoplastic cyst

• Lymphoepithelial cyst

True Cysts• Sporadic

• 10% in APKD

• 70% in VHL syndrome• Hemangioblastomas of the brain (cerebellum) and spine

• Retinal angiomas

• Clear cell renal cell carcinomas

• Pheochromocytomas

• Endolymphatic sac tumors of the middle ear

• Serous cystadenomas & neuroendocrine tumors

• Papillary cystadenomas of the epididymis and broad ligament

Mucinous Non NeoplasticCyst

od Pathol 2002;15(2):154–158

Lymphoepithelial Cyst• M:F- 4:1; 5- 7th decade of life

• Embryology:

• Enlarged epithelial inclusions in a peripancreatic lymph node which had undergone squamous metaplasia

• Branchial cleft cysts fused with the pancreatic remnant

• Histology: Lined by a layer of mature, stratified squamous cell epithelium, usually with keratinization and surrounded by a distinct layer of subepithelial lymphoid tissue composed of mature T-lymphocytes and including a capsule, a subcapsule sinus, and germinal centers. Cyst is filled with a dense material composed mainly of debris, keratin, and cholesterol crystals; cystic content may appear as serous, ‘curdlike’ or cheesy.

• h / [

Lymphoepithelial Cyst

• 9k

Peripancreatic Fluid Collections

• Acute peripancreatic fluid collection <4weeks oacute pancreatitis

• Pseudocyst: Maturing collection of pancreatic collection encased by reactive granulation tissue.

• Pancreatic Abscess: circumscribed collection opus.

• Organized pancreatic necrosis.

Pancreatic Pseudocyst

Drainage of Pancreatic Fluid Collection

• Acute pancreatic fluid collection

• Pancreatic pseudocyst

• Walled off pancreatic necrosis

• Abscess drainage

• Necrosectomy

Abcess Drainage

Cystic NeoplasmsSerous cystic neoplasms

Mucinous cystic neoplasms (cystadenoma/cystadenocarcinoma

Intraductal papillary mucinous neoplasms

Acinar cell cystadenocarcinoma

Cystic neuroendocrine neoplasms (functional and nonfunctional)

Solid pseudopapillary neoplasm

Cystic teratoma

Cystic choriocarcinoma

Serous Cystadenoma• Microcystic adenomas typically found in the head

• Sponge-like or honey combed appearance

• 30% of all cystic pancreatic neoplasia (1)

• Mean age: 62 years. 75% are females (Mean age of males >7 years females, and males had larger tumors) (2)

• 2-25cm at presentation; may grow in size 0.6 -2cm per year (3)

• Sporadic reports of malignancy are present (4,5,6)

1.Compagno J, Oertel JE. Microcystic adenomas of the pancreas (glycogen-richcystradenomas): a clinicopathologic study of 34 cases. Am J Clin Pathol 1978;69:289e98.2.Sakorafas GH, Sarr MG. Cystic neoplasms of the pancreas; what a clinicianshould know. Cancer Treat Rev 2005;31:507e35.3.Tseng JF, Warshaw AL, Sahani DV, Lauwers GY, Rattner DW, Fernandez-del Castillo C. Serous cystadenoma of the pancreas: tumor growth rates andrecommendations for treatment. Ann Surg 2005;242:4134. Abe H, Kubota K, Mori M, Miki K, Minagawa M, Noie T, et al. Serous cystadenoma of the pancreas with invasive growth: benign or malignant? Am J

Serous Cystadenoma

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Tampa, FL

Morphology

• Lined by a single, uniform layer of cuboidal, glycogen-rich “serous” cells, with round nuclei and abundant clear cytoplasm without atypia.

• The stroma separating these microcystic areas is a vascular fibrous connective tissue that is often is calcified-characteristic central sunburstradial, or stellate scar.

• Macrocystic and solid variant.

Serous Cystadenoma

EUS Image

Cytology LPF

Indications for Resection

• Symptomatic

• Size >4cm

• Uncertainty on true nature of lesion

MCN

• 50% of cystic tumors or pancreas

• >95% in women

• Ovarian stroma is pathognomonic

• Median age 53

• More common in body and tail.

• Macrocystic, well encapsulated (1-6), with solid component.

• Malignant potential: hyperplasia with or without atypia, borderline changes, noninvasive or carcinomas in-situ, and invasive

Mucinous Cystadenoma

MCN: Resected specimen

MCN

Spectrum of primary MCNs

Stages of MCN

• Mucinous cystadenomas: uniform, single layer of benign, columnar mucinous cells 72% of the MCNs

• Non-invasive, proliferative MCNs : atypia, dysplasipapillary endothelial infolding, and even frank changes of carcinoma in-situ in the epithelial lining,but without tissue invasion (16%)

• Mucinous cystadenocarcinomas contain areas of overt, stromal invasion beyond the epithelium (12%

ppa S, Salvia R,Warshaw AL, Domínguez I, Bassi C, Falconi M, et al. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163ected patients Ann Surg 2008;247:571e9

Genetic Mutations

• Mutation of the K-ras oncogene located on chromosome 12 p increased in frequency in progressive malignant degeneration (20% of MCNs)and 90% of the mucinous cystadenomas.

• Nuclear p53 immunoreactivity indicates a malignanttransition of the epithelium similar to ductal cancer of the pancreas

G Ong SL Rajesh A Neal CP Pollard CA Berry DP et al Cystic lesions of the pancreas Pancreatology 2008;8:236e51

Clinical Risk Factors

• Large tumor size. No malignancy with cysts <3cm, risk greater when >6cm

• Associated mass, mural nodules, asymmetrically thickened wall, x16 more likely. 64 vs 4%

• Age >55 years

Salvia R,Warshaw AL, Domínguez I, Bassi C, Falconi M, et al. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163 resected patie1e9.

Tan YM, Chung YF, Chow PK, Cheow PC, Wong WK, et al. A review of mucinous cystic neoplasms of the pancreas defined by ovarian-type stroma: clinicopathologicWorld J Surg 2006;30:2236e45

Imaging Risk Factors• Egg shell or peripheral calcification

• Eccentrically located mass within a cystic area or multiple papillary invaginations.

• Wall or septal/papillary enhancement on US

• Recognizable pericystic mass/reaction

• Local invasion of adjacent vascular structures

• Biliary or pancreatic ductal obstruction

• Evidence on PHT: splenic vein occlusion, ascites

• Mets to LiverJ M i I R dh d D H d P G d OJ M i i l f h i i f d di i diffi l i Cli R di l 2000 55 187 9

Posterior Wall Enhancement

Egg Shells and Nodules

MCN Cyst

Prognosis in MCN

• Long Term survival 50-70% [1-4]

• In true invasive carcinoma, 5-year survival rates15-35% [5]

• [(15e35%)

ppa S, Salvia R,Warshaw AL, Domínguez I, Bassi C, Falconi M, et al. Mucinous cystic neoplasm of the pancreas is not an aggressive entity: lessons from 163ed patients. Ann Surg 2008;247:571e9.r MG, Murr M, Smyrk TC, Yeo CJ, Fernandez-del-Castillo C, Hawes RH, et al. Primary cystic neoplasms of the pancreas: neoplastic disorders of emergingtance-current state of the art and unanswered questions. J Gastrointest Surg 2003;7:417e28.

Mucinous Neoplasia

• 25% of all cystic neoplasms

• Described by Ohashi et al. in Japan in 1982, as mucinous secreting cancer of the pancreas

• 1996 formally defined by WHO: Intraductal mucin-producingneoplasm with tall columnar, mucin-containing epithelium with or without papillary projections, involving the main pancreatic duct and/or major side branches and lacking ovarian stroma increase.

• More common in men usually in the 6-7th decade

• Typically in head may be multifocal, or whole organ

IPMN

• Intraductal mucin-producing neoplasm with tall columnar, mucin-containing epithelium with or without papillary projections, lacking ovarian strom

• Morphological types: Main Duct, Side Branch or mixed

• Histological Type: Intestinal, Gastric, Pancreatobiliary, Oncocytic and Null

• Histological Severity: benign, borderline (adenoma with mild to moderate dysplasia), and (c) carcinoma

Risk of Malignancy

• 40% of main duct IPMN already habour cancer

• Main Duct IPMN: 40-60%, high as 90% with duct >1cm and mural nodule

• Branch Duct IPMN: 6-46%, more with >3cm or mixed type, <10% with <2cm cyst

• Age >70yrs

• Presence of symptoms

I d l i i i h

Fish Mouth on IPMN

Main Duct IPMN

ERCP - Main Duct IPMN

EUS - Main Duct IPMN

Mural Nodule -Br Duct IPMN

ERCP- Side Branch IPMN

Branch Duct IPMN

Mixed IPMN

Tx for IPMN

• Single branch-duct IPMN, a local anatomic resection is essentially curative.

• Non-invasive, main-duct IPMNs, occurrence in the remnant gland has been found with variable rates (0-10%) [1,2]

• In invasive disease reccurrence occurs in peripancreatic and extrapancreatic sites, 50-90% of patients

• Recurrent disease after partial pancreatectomy 67% vs 62% with total pancreatectomy [3]

M, Smyrk TC, Yeo CJ, Fernandez-del-Castillo C, Hawes RH, et al. Primary cystic neoplasms of the pancreas: neoplastic disorders of emerging importance-current stquestions. J Gastrointest Surg 2003;7:417e28.ri S Adsay V Fernandez del Castillo C Falconi M Shimizu M et al International consensus guidelines for management of intraductal papillary mucinous neoplasm

Survival In IPMN

• The 5-year survival after curative resection of IPMNwithout invasive cancer is >70.[1,2]

• After resection of invasive IPMN, even with negativmargins,5-year survival ranges from 30 to 50%[2,3,4]

• Resectable ductal adenocarcinoma 6-25%, 1 year survival

Rare Cystic Tumors of Pancreas-Solid Pseudopapillary Tumor

• Origin from primordial, pluripotent stem cells of the pancreas oincorporation of primitive ovarian cells

• F:M-20:1, 3rd decade of life

• Encapsulated lesions with solid and cystic areas. The solid component composed of pseudopapillae with a fibrovascular stalk forms pseudorosettes

• Positive for vimentin, neuron-specific enolase, CD10, CD56, alpha-1 antitrypsin (AAT), galectin-3, and progesterone receptors

• Malignant potential is 5%

Solid Pseudopapillary Tumor

Cystic PNET

•

MP, McGrath KM. Cystic neoplasms of the pancreas. Gastroenterol Clin N Am 2007;36:365e76.

PNET

TEST ACCURACY

• CT correctly characterizes 60% of cystic lesions [1,2]

• Learning Curve! Inaccuracy in dx improved from 37% to 9%. [3,4]

• MRI: No radiation risk, 80% accuracy espy in IPMN [5]

• EUS alone 73% with FNA and cytology 97% [6]

a R, Molinari E, Biasutti C, Falconi M, Pederzoli P. Management of 100 consecutive cases of pancreatic serous cystadenoma: wait for symptomversa? World J Surg 2003;27:319-23.

Graziani R, Bicego E, Bergamo-Andreis IA, Guarise A, Valdo M, et al. Serous cystadenoma of the pancreas: report of 30 cases with emphasis put Assist Tomogr 1997;21:373-82.Compton CC Lewandrowski K Cardenosa G Mueller PR Cystic tumors of the pancreas: new clinical radiologic and pathologic observations in 67 pa

Cyst Fluid Analysis

Pancreatic Cyst Fluid Analysis

• COOP study [1]:

• The optimal cyst fluid CEA cutoff of 192 ng/ml

• 79% sensitive for differentiating mucinous from nonmucinous.

• The accuracy of cytology was poor(59%).

• No combination of tests, including EUS appearance, was more accuratthan CEA alone.

• PANDA Study [2]:

wandrowski K, Lee-Lewandrowski E, et al. Diagnosis of pancreatic cystic neoplasms: a report of the Cooperative Pancreatic Cyst Study. Gastroenterology

PANDA study

• Pancreatic cyst fluid DNA analysis

• Cyst fluid k-ras mutation was helpful in the diagnosis of mucinous cysts (odds ratio 20.9, specificity 96%)

• The criteria of a high amplitude k-ras mutation followed by allelic loss showed maximum specificity (96%) for malignancy.

• All malignant cysts with negative cytologic evaluation (10/40) could be diagnosed as malignant by using DNA analysis.

Take Home Message• Chop me:

• Increasing under observation

• Symptomatic

• Radiological and cytological +ve features in fit older pt

• Poke Me: • Pre-op characterization will change management

• Leave Me Alone!• Other co morbidities with Cyst <3cm or Cyst <2cm