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Pancreatic Cysts Poke Me, Chop Me, Leave Me Alone!!!
Arthi Sanjeevi, MDUniversity of South Florida, Tampa, Fl
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Clinical Presentation• Incidental finding
• Acute and Chronic Pancreatitis
• Vague abdominal pain
• Jaundice
• Weight loss
• New onset Diabetes
• Family History
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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.
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Key Questions?
Real or Pseudo?
Benign or Neoplastic?
Malignancy potential?
Surgical Risk?
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Types of Cysts
• Pseudocysts
• True Cyst
• Cystic Neoplasms of Pancreas
• Cystic degeneration on solid tumors
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Non Neoplastic Cysts
• Epithelial Cyst
• Retention Cysts
• Mucinous non-neoplastic cyst
• Lymphoepithelial cyst
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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
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Mucinous Non NeoplasticCyst
od Pathol 2002;15(2):154–158
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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 / [
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Lymphoepithelial Cyst
• 9k
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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.
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Pancreatic Pseudocyst
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Drainage of Pancreatic Fluid Collection
• Acute pancreatic fluid collection
• Pancreatic pseudocyst
• Walled off pancreatic necrosis
• Abscess drainage
• Necrosectomy
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Abcess Drainage
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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
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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
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Serous Cystadenoma
5029 Barrowe Dr
Tampa, FL
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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.
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Serous Cystadenoma
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EUS Image
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Cytology LPF
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Indications for Resection
• Symptomatic
• Size >4cm
• Uncertainty on true nature of lesion
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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
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Mucinous Cystadenoma
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MCN: Resected specimen
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MCN
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Spectrum of primary MCNs
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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
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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
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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
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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
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Posterior Wall Enhancement
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Egg Shells and Nodules
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MCN Cyst
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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.
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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
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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
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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
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Fish Mouth on IPMN
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Main Duct IPMN
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ERCP - Main Duct IPMN
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EUS - Main Duct IPMN
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Mural Nodule -Br Duct IPMN
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ERCP- Side Branch IPMN
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Branch Duct IPMN
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Mixed IPMN
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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
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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
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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%
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Solid Pseudopapillary Tumor
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Cystic PNET
•
MP, McGrath KM. Cystic neoplasms of the pancreas. Gastroenterol Clin N Am 2007;36:365e76.
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PNET
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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
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Cyst Fluid Analysis
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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
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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.
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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