Mucinous cystic neoplasm

Pancreas

Exocrine tumors / carcinomas

Authors: Enoch Kuo, M.D., Raul S. Gonzalez, M.D.

Topic Completed: 1 March 2018

Minor changes: 13 July 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Mucinous cystic neoplasm[TI] pancreas

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Table of Contents

Cite this page: Kuo E, Gonzalez RS. Mucinous cystic neoplasm. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreasmcn.html. Accessed August 12th, 2020.

Definition / general

Benign or potentially low grade malignant cystic epithelial neoplasm composed of cells which contain intracytoplasmic mucin (IARC: 8470 / 0 Mucinous Cystoma [Accessed 21 March 2018])
WHO Classification:
- MCN with low grade dysplasia (adenoma)
- MCN with moderate dysplasia (borderline neoplasm)
- MCN with high grade dysplasia (carcinoma in situ)
- MCN with invasive carcinoma

Essential features

Cystic neoplastic lesion that is a precursor to pancreatic adenocarcinoma
May harbor invasive carcinoma

ICD coding

ICD-10: C25 - malignant neoplasm of pancreas (if malignant)
ICD-10: D13.6 - benign neoplasm of pancreas (if benign)

Epidemiology

Almost always women (> 95%), mean age of 45 years (Ann Surg 2008;247:571)

Sites

Distal pancreas (> 95%) (Ann Surg 2008;247:571)
Can also occur in the liver and gallbladder
Metastases usually restricted to abdominal cavity; metastases to ovary may simulate primary ovarian tumors

Pathophysiology

Ectopic ovarian stroma is thought to be seeded from primordial ovarian cells at early stages of embryonic development and cysts are later formed by hormones and growth factors released by the ovarian stroma (Am J Surg Pathol 1999;23:410)

Etiology

No known etiology

Clinical features

Usually a single lesion (Gut Liver 2015;9:571)
May present as abdominal pain or acute pancreatitis (Ann Surg 2008;247:571)
Majority are slow growing and asymptomatic (Gastroenterology Res 2014;7:44)

Diagnosis

Cytology and lab analysis of pancreatic cyst fluid from endoscopic ultrasound guided FNA
Histology of pancreatic resection

Laboratory

Elevated CEA and presence of KRAS mutation in cyst fluid supports a mucinous cyst (includes MCN and IPMN) (Ann Gastroenterol;26:122)

Radiology description

Thick walled, single, septated cyst in the body or tail of the pancreas (Gut Liver 2015;9:571)
May have nodules or calcifications

Prognostic factors

Prognosis is excellent unless there is invasive carcinoma with extracapsular or diffuse intracapsular infiltration (Am J Surg Pathol 2015;39:179, Ann Surg 2008;247:571)
Features associated with invasive carcinoma include increased cyst size (> 5 cm), intracystic papillary nodules > 1 cm in size, and elevated serum CA19-9 (Am J Surg Pathol 2015;39:179)
Less than 20% of cases have invasive carcinoma (Gut Liver 2015;9:571, Ann Surg 2008;247:571)

Case reports

38 year old woman with anaplastic carcinoma and mucinous cystic neoplasm of the pancreas during pregnancy (World J Gastroenterol 2008;14:132)
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 Japanese woman with anaplastic carcinoma combined with mucinous cystadenocarcinoma of the pancreas (Arch Pathol Lab Med 1997;121:1104)
65 year old man (JOP 2012;13:687)

Treatment

Surgical resection is indicated for all MCNs (Gut Liver 2015;9:571, Gastroenterology Res 2014;7:44)

Gross description

Large (mean 10 cm)
Typically unilocular megacysts that do not communicate with ductal system, though up to 15% communicate with main pancreatic duct (Gut Liver 2015;9:571)
Cyst wall is papillary, trabecular or thickened
Has mucoid / watery cyst contents
Must sample solid areas within the cyst

Gross images

Contributed by
Dr. Diana Agostini-Vulaj

MCN with no connection to main duct

AFIP images

Unilocular cyst

Conspicuous, irregular, solid protuberances

Multiloculated cystic lesion

Invasive tumor from tail of pancreas in 36 year old woman shows large cyst with solid tumor

Images hosted on other servers:

39 year old man with multilocular cyst with thick mucin

Microscopic (histologic) description

Large cyst lined by intestinal, pseudopyloric or gastric foveolar type epithelium that often form papillae, surrounded by characteristic dense ovarian type stroma (Gut Liver 2015;9:571)
Epithelial lining has variable atypia (none, low grade, high grade); scattered neuroendocrine cells may be present
Invasive adenocarcinoma may or may not be present (Gut Liver 2015;9:571); must sample extensively to rule out an invasive component (Am J Surg Pathol 1999;23:1320)
Calcifications are common
May have mural nodules with features of giant cell tumor, MFH or anaplastic carcinoma

Microscopic (histologic) images

Contributed by Raul S. Gonzalez, M.D.

MCN with invasion

AFIP images

Adenoma

Cyst wall containing lobular glands

Cyst wall with focal hyalinization

Low grade dysplasia

Foreign body reaction

Intermediate grade dysplasia

High grade dysplasia

Invasion: lining epithelium is desquamated

Invasion: cribriform architecture

36 year old woman

Scattered endocrine cells are serotonin+

Images hosted on other servers:

Mucinous cystic neoplasm

Low grade dysplasia

Squamous metaplasia

Cytology description

Cyst aspirates are usually acellular with thick, gelatinous mucus
Clusters of 3 dimensional atypical glandular cells with hyperchromasia predict at least moderate dysplasia (Arch Pathol Lab Med 2009;133:388)

Positive stains

Ovarian type stroma is CD10+, ER+, inhibin+, PR+, smooth muscle actin (SMA)+ and vimentin+ (Gut Liver 2015;9:571)
Epithelium stains carcinoembryonic antigen (CEA)+, CK7, CK8, CK18 and CK19 (Gut Liver 2015;9:571)
Gastric type epithelium stains MUC5AC+ (Gut Liver 2015;9:571)
DPC4 (MADH4, SMAD4), MUC5AC present in situ areas (usually lost in invasive disease) (Am J Surg Pathol 2000;24:1544, Gut Liver 2015;9:571, Arch Pathol Lab Med 2015;139:24)
Invasive component stains MUC1 positive
Cyst fluid may stain positive for alcian blue and mucicarmine
S100P in epithelium (Arch Pathol Lab Med 2015;139:24)
SF-1 in stroma (Pathol Int 2016;66:281)

Negative stains

MUC1 (except in invasive components) (Am J Surg Pathol 2002;26:466, Gut Liver 2015;9:571)
MUC2 (except for faint staining of goblet cells)
DPC4 (MADH4, SMAD4) staining is lost in invasive MCNs (Gut Liver 2015;9:571)
pVHL (Arch Pathol Lab Med 2015;139:24)

Molecular / cytogenetics description

KRAS mutations noted in in situ or invasive areas, inactivating SMAD4 and TP53 mutations in more advanced MCNs (Gut Liver 2015;9:571)
Negative for GNAS mutations

Differential diagnosis

IPMN
- Usually at the head of pancreas and communicates with the duct system (MCNs usually do not communicate with the main pancreatic duct)
- IPMNs may be positive for GNAS mutations while MCNs will be negative (Gut Liver 2015;9:571)
- Both have elevated CEA and KRAS mutation in cyst fluid
Ovarian mucinous tumors: similar clinical and histologic appearance
Pancreatic ductal adenocarcinoma, large duct variant: will have smaller cysts, clustering of ducts, and myxoid stroma (Arch Pathol Lab Med 2009;133:423)
Pancreatic ductal adenocarcinoma: cystic
Pancreatic pseudocyst: mimics MCN when MCN has denuded cyst lining
- MCN cystic fluid has high CEA content and viscosity, high expression of microRNAs, lower amylase (< 250 U/L) and elastase I than pseudocyst, although values may vary within different loculi of same neoplasm (Am J Clin Pathol 1993;100:425, Ann Gastroenterol 2013;26:122, Gastroenterology Res 2014;7:44)
Serous cystadenoma: has low levels of CEA

Board review style question #1

Which of the following findings on fine needle aspiration of a pancreatic cyst are most consistent with a mucinous cystic neoplasm?

Decreased CEA, decreased amylase, no KRAS mutation, no GNAS mutation
Elevated CEA, elevated amylase, KRAS mutation, GNAS mutated
Elevated CEA, highly elevated amylase, no KRAS mutation, no GNAS mutation
Elevated CEA, variable amylase, KRAS mutation, no GNAS mutation

Board review answer #1

D. Mucinous Cystic neoplasms have elevated CEA, variable amylase, KRAS mutation and no GNAS mutation.
If a GNAS mutation is present, then the findings will favor an IPMN (Answer B).
Decreased CEA and amylase with no KRAS or GNAS mutations favor a serous cystadenoma.
An elevated CEA and amylase without KRAS or GNAS mutations will favor a pancreatic pseudocyst (Answer C).

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