Pancreas
Exocrine tumors / carcinomas
Mucinous pancreatic tumors
Editorial Board Member: Raul S. Gonzalez, M.D.
Deputy Editor-in-Chief: Debra Zynger, M.D.
Topic Completed: 1 June 2018
Minor changes: 9 March 2020
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PubMed Search: Mucinous tumors[title] pancreas
Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Board review style question #1 | Board review answer #1 | Board review style question #2 | Board review answer #2Cite this page: Krogh K, Yang GY. Mucinous pancreatic tumors. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreasmucin.html. Accessed August 6th, 2020.
Definition / general
- Neoplasms within the pancreas characterized by predominant mucin production by the tumor cells
- Mucus: a substance that is 95 - 98% water and 2 - 5% solids, with > 60% of the solid component consisting of mucin (World J Gastroenterol 2011;17:4757)
- Mucin: a glycoprotein consisting of a polypeptide backbone with attached oligosaccharide conjugates
Essential features
- General term for benign, low or high grade dysplastic or malignant mucin producing epithelium within the pancreas
- Four most prevalent types:
- MCN and IPMN may harbor or develop into pancreatic ductal adenocarcinoma (small percentage); MCN may undergo transformation to cystadenocarcinoma as well (Pancreas 2017;46:745)
| Pancreatic ductal adenocarcinoma | MCN | IPMN | Simple Mucinous Cyst / MNC | Age, decade | 7th - 8th | 4th - 5th | 6th - 7th | 6th - 7th |
| Location | Head > body / tail | Body / tail > head | Head > body / tail | Head = body = tail |
| Sex predilection | M > F | F >>> M | M > F | F > M |
| CEA | N / A | ↑ | ↑ | ↑ |
| Amylase | N / A | Low | ↑ | Low |
| Pancreatic duct communication | Yes | No | Yes | Rare |
| Associated with invasive carcinoma | N / A | Generally no | Yes | Yes |
| Cytologic atypia | N / A | Low grade - high grade | Low grade - high grade | No |
| Epithelium type | Flat or papillary | Flat or papillary | Papillary | Flat |
| Ovarian stroma | N / A | Yes | No | No |
| Molecular mutations | KRAS, TP53, CDKN2A, SMAD4 | KRAS, SMAD4, TP53 (in situ) | GNAS, KRAS, RNF43, TP53 | KRAS |
ICD coding
Epidemiology
- Pancreatic ductal adenocarcinoma
- Most common exocrine pancreatic tumor (85 - 90%)
- 80% occur in patients 60 - 80 years old
- Slightly more common in men (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Colloid carcinoma / mucinous carcinoma is an uncommon variant with > 50% extracellular mucus production, accounting for 1 - 3%
- Mucinous cystic neoplasm (MCN)
- Rare; 2 - 5% exocrine pancreatic tumors (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Almost exclusively in women (Ann Surg 2008;247:571)
- Most common in fourth through fifth decade (Arch Pathol Lab Med 2017;141:1330)
- Intraductal papillary mucinous tumor (IPMN)
- Rare; estimated to be slightly more prevalent than MCN (Arch Pathol Lab Med 2009;133:454)
- Slightly more common in men
- Most common in sixth through seventh decade (Arch Pathol Lab Med 2017;141:1330)
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Approximately 10% of mucinous cysts of the pancreas (Pancreas 2012;41:441)
- More common in women, mean age 64 years old (Arch Pathol Lab Med 2017;141:1330)
Sites
- Pancreatic ductal adenocarcinoma
- 60 - 70% occur in pancreatic head (mainly upper half; rare in uncinate)
- Mucinous cystic neoplasm (MCN)
- Generally arising in the parenchyma with no connection to the main duct or branch ducts
- Usually involves body / tail (Ann Surg 2008;247:571)
- Intraductal papillary mucinous neoplasm (IPMN)
- Commonly in pancreatic head (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Occur equally in head / neck / uncinate and body / tail (Arch Pathol Lab Med 2017;141:1330)
Pathophysiology
- Pancreatic ductal adenocarcinoma
- Arises from pancreatic duct epithelia
- Mucinous cystic neoplasm (MCN)
- Stromal component possibly derived from ovarian primordium / Müllerian type stroma (Am J Surg Pathol 1999;23:410)
- Intraductal papillary mucinous neoplasm (IPMN)
- Histologically arising in the pancreatic main duct, branch duct or combined (Clin Gastroenterol Hepatol 2010;8:213)
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Unknown pathogenesis but may develop from acinar ductal mucinous metaplasia (Hum Pathol 2010;41:513)
Etiology
- Pancreatic ductal adenocarcinoma
- Strongly associated with cigarette smoking
- Markedly increased risk associated with hereditary pancreatitis
- Other factors: chronic pancreatitis, previous gastric surgery, radiation exposure, diabetes (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Mucinous cystic neoplasm (MCN)
- No known etiology
- Intraductal papillary mucinous neoplasm (IPMN)
- In one study, most patients with IPMN were cigarette smokers (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Unclear etiology
Clinical features
- Pancreatic ductal adenocarcinoma
- Weight loss, painless jaundice, diabetes, malaise, coexisting pancreatitis
- Mucinous cystic neoplasm (MCN)
- Clinical presentation depends on the size of tumor; > 3 cm can cause compression of adjacent structures
- Associated with diabetes mellitus
- Intraductal papillary mucinous neoplasm (IPMN)
- Majority are asymptomatic; often incidental
- Can give rise to invasive adenocarcinoma
- Some patients present with epigastric pain, weight loss, diabetes and jaundice
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Half of patients are asymptomatic; others report abdominal pain or jaundice (Arch Pathol Lab Med 2017;141:1330)
Diagnosis
- Pancreatic ductal adenocarcinoma
- Endoscopic ultrasound guided fine needle aspiration (EUS-FNA), histologic analysis upon surgical resection
- Mucinous cystic neoplasm (MCN)
- Cytology, fine needle aspiration (FNA), cyst fluid analysis
- Intraductal papillary mucinous neoplasm (IPMN)
- FNA, histologic analysis
- Must be sampled well, with special attention to papillary areas, where the highest degree of dysplasia occurs and sclerotic areas, which can indicate invasion (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- FNA, cyst fluid analysis, histologic analysis
Laboratory
- Pancreatic ductal adenocarcinoma
- Serum tumor markers include CA 19-9, CEA
- Cyst fluid has high levels of CA 19-9, DUPAN-2, CEA, SPan-1
- Mucinous cystic neoplasm (MCN)
- Serum tumor markers include CEA, CA 19-9, TAG-72, CA 15-3 or MCA and low levels of amylase
- Intraductal papillary mucinous neoplasm (IPMN)
- Serum amylase and lipase are elevated
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Cyst fluid often shows elevated CEA (Arch Pathol Lab Med 2017;141:1330)
Radiology description
Prognostic factors
- Pancreatic ductal adenocarcinoma
- Most ductal adenocarcinomas are fatal (Cancer Res 2014;74:2913)
- Survival time is longer in patients with tumors confined to the pancreas or < 3 cm in diameter
- Tumors in the body or tail tend to present at a more advanced stage
- Mucinous cystic neoplasm (MCN)
- Classified as benign or low grade (IARC: 8470/0 mucinous cystoma)
- Head lesions are uncommon but have a predilection to be a mucinous cystadenocarcinoma
- Intraductal papillary mucinous neoplasm (IPMN)
- Classified as benign, borderline and malignant
- Absence of invasive carcinoma is the most important prognostic factor (Hum Pathol 2012;43:1)
- Main duct type shows highest incidence of invasive adenocarcinoma
- Branch type without mural nodules more commonly found with low grade dysplasia (Dig Liver Dis 2012;44:257, Am J Surg Pathol 2000;24:1372)
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Not associated with progression or invasive carcinoma (Arch Pathol Lab Med 2017;141:1330)
Case reports
- 46 year old man with pancreatic mucinous cystic neoplasm with sarcomatous stroma metastasizing to liver (World J Surg Oncol 2013;11:100)
- 52 year old man with hemosuccus pancreaticus secondary to simple mucinous cyst of the pancreas (Korean J Gastroenterol 2017;70:301)
- 60 year old man with multifocal, synchronous primary ductal adenocarcinomas arising in the pancreas (Pancreatology 2015;15:S111)
- 72 year old woman with pancreatic ductal carcinoma arising in pancreas remnant 13 years after resected IPMN (Mol Clin Oncol 2018;8:417)
- 78 year old woman with IPMN with unusually low mucin mimicking intraductal tubulopapillary neoplasm (Intern Med 2017;56:3183)
Treatment
- Pancreatic ductal adenocarcinoma
- Radical resection or chemotherapy
- Mucinous cystic neoplasm (MCN)
- Surgical resection
- Intraductal papillary mucinous neoplasm (IPMN)
- Surgical resection
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Conservative treatment
Gross description
- Pancreatic ductal adenocarcinoma
- Firm, poorly defined mass, with yellow to white cut surface
- Can be difficult to differentiate from background pancreatitis
- Mucinous cystic neoplasm (MCN)
- 2 - 35 cm in greatest dimension
- Unilocular or multilocular, thick walls
- Round mass with smooth surface and fibrous pseudocapsule
- Calcifications are frequent
- Intraductal papillary mucinous neoplasm (IPMN)
- 1 - 8 cm in greatest dimension
- Cystic, multiloculated
- Grape-like clusters in branch type
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Macroscopic cyst > 1 cm, usually 3 - 12 cm
- Unilocular or multilocular (Arch Pathol Lab Med 2017;141:1330)
Gross images
Contributed by Katrina Krogh, M.D.
PDA: ill defined white lesion
MCN: unilocular cyst with thick wall
IPMN: small cysts with smooth linings
MNC: unilocular
simple cyst with
smooth thin lining
Microscopic (histologic) description
- Pancreatic ductal adenocarcinoma
- Classically shows well developed neoplastic glands that imitate normal pancreatic ducts in the background of desmoplastic stroma
- Mucin containing glands may be ruptured or poorly formed
- Most are well to moderately differentiated
- In colloid carcinoma / mucinous noncystic carcinoma, mucin accounts for > 50% of tumor and masses are large (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Mucinous cystic neoplasm (MCN)
- Two components
- Inner epithelial layer
- Outer densely cellular Müllerian / ovarian type stroma
- No connection to ducts
- Can undergo luteinization, can have hilar-like cells and immunophenotypic sex cord stromal differentiation (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Two components
- Intraductal papillary mucinous neoplasm (IPMN)
- Neoplastic columnar / mucinous epithelium with small papillary formations
- Epithelium can be intestinal, gastric, biliary or oncocytic (IOPN)
- Goblet cells, Paneth cell metaplasia or neuroendocrine cells can be seen (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Cyst lined by monolayer of cuboidal to columnar mucinous epithelium; hypocellular stroma (Hum Pathol 2010;41:513)
- Usually has gastric phenotype (Arch Pathol Lab Med 2017;141:1330)
- Few may communicate with pancreatic ducts (Arch Pathol Lab Med 2017;141:1330)
- Little to no cytologic atypia in epithelial lining; no malignant potential (Radiographics 2009;29:1749)
Microscopic (histologic) images
Contributed by Katrina Krogh, M.D.
Pancreatic adenocarcinoma, grade 2
Pancreatic mucinous adenocarcinoma
MCN: ovarian type stroma
IPMN, gastric type
IPMN, intestinal type
Simple mucinous
cyst / mucinous
nonneoplastic
cyst (MNC)
Cytology description
Positive stains
- Pancreatic ductal adenocarcinoma
- Mucinous cystic neoplasm (MCN)
- Intraductal papillary mucinous neoplasm (IPMN)
- EMA, cytokeratins, MUC2 (in oncocytic and intestinal type), HER2/c-erbB2
- MUC1 (18%), MUC6, MUC5AC (100%) (Arch Pathol Lab Med 2017;141:1330)
- Increased Ki67 and p53 are markers of progression
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
Negative stains
- Pancreatic ductal adenocarcinoma
- CK20, vimentin, synaptophysin, chromogranin, MUC2
- pVHL (positive in reactive ducts) (Arch Pathol Lab Med 2012;136:601, Hum Pathol 2013;44:503)
- DPC4 loss seen in 55%; specific for malignancy (Am J Clin Pathol 2001;116:831)
- Mucinous cystic neoplasm (MCN)
- Intraductal papillary mucinous neoplasm (IPMN)
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Trypsin, CEA, synaptophysin, chromogranin A, calretinin, alpha inhibin, MUC1 (65%), MUC2, PR
Molecular / cytogenetics description
- Pancreatic ductal adenocarcinoma
- Key drivers (Cancer Cell 2017;32:185):
- TP53 is inactivated in 75% (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- KRAS > 95%, early event (Cancer 2007;109:1561)
- CDKN2A (p16): 95%
- SMAD4: 55%
- Most frequent gains include chromosome 12 and 7; most frequent losses include 18, 13, 12, 17 and 6 (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
- Key drivers (Cancer Cell 2017;32:185):
- Mucinous cystic neoplasm (MCN)
- Unknown in benign MCN
- KRAS mutations noted in in situ or invasive MCN (Gut Liver 2015;9:571)
- Inactivating SMAD4 and TP53 mutations in more advanced MCN (Gut Liver 2015;9:571)
- Intraductal papillary mucinous neoplasm (IPMN)
- Commonly mutated: GNAS, KRAS, RNF43, TP53
- Lower frequency: CDKN2A, CTNNB1, IDH1, STK11, PTEN
- Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
- Mutations in KRAS (40%), PTEN and RNF43 have been identified in some cases (Arch Pathol Lab Med 2017;141:1330, Hum Pathol 2016;55:159)
Differential diagnosis
Board review style question #1
Which of the following statements about this pancreatic lesion is true?
- Serum amylase and lipase are typically depressed
- This lesion is more common than pancreatic ductal adenocarcinoma
- This lesion is more commonly found in males
- This lesion typically contains ovarian stroma
Board review answer #1
C. This lesion is more commonly found in males (true for pancreatic intraductal papillary
mucinous tumor (IPMN) which is shown here)
Comment Here
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Board review style question #2
Which of the following statements about this pancreatic lesion is true?
- This lesion can undergo immunophenotypic sex cord stromal differentiation
- This lesion does not undergo malignant transformation
- This lesion is more common than pancreatic ductal adenocarcinoma
- This lesion is seen equally in males and females
Board review answer #2
A. This lesion can undergo immunophenotypic sex cord stromal differentiation (true for pancreatic
mucinous cystic neoplasm which is shown here)
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