Pancreas

• General term for benign, low or high grade dysplastic or malignant mucin producing epithelium within the pancreas
• 4 most prevalent types
  1. Simple mucinous cyst / mucinous nonneoplastic cyst (MNC)
  2. Mucinous cystic neoplasm (MCN)
  3. Intraductal papillary mucinous neoplasm (IPMN)
  4. Mucin producing pancreatic ductal adenocarcinoma
• 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)

Comparison of essential features of the 4 types of pancreatic mucinous tumors

	Simple mucinous cyst / MNC	MCN	IPMN	Pancreatic ductal adenocarcinoma
Age, decade	Sixth - seventh	Fourth - fifth	Sixth - seventh	Sixth - eighth
Location	Head = body = tail	Body / tail > head	Head > body / tail	Head > body / tail
Sex predilection	F > M	F >>> M	Main duct: M > F Branch duct: F > M	M > F
CEA	↑	↑	↑	N / A
Amylase	↓	↓	↑	N / A
Pancreatic duct communication	Rare	No	Yes	Yes
Precursor for invasive carcinoma	No	Yes	Yes	N / A
Cytologic atypia	No	Low grade / high grade	Low grade / high grade	N / A
Epithelium type	Flat	Flat or papillary	Papillary	Flat or papillary
Ovarian stroma	No	Yes	No	N / A
Molecular mutations	KMT2C, KRAS, BRAF, RNF43, CDKN2A, TP53, SMAD4	KRAS, RNF43 (low grade); SMAD4, TP53 (high grade)	GNAS, KRAS, RNF43, TP53	KRAS, TP53, CDKN2A, SMAD4, BRCA1/2

• Simple mucinous cyst / mucinous nonneoplastic cyst
• Mucinous cystic neoplasm / mucinous cystadenoma
• Intraductal papillary mucinous neoplasm / carcinoma in situ
• Pancreatic ductal adenocarcinoma / duct cell adenocarcinoma / infiltrating duct carcinoma / tubular adenocarcinoma

• 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)
• Mucinous cystic neoplasm (MCN)
  • More than half of patients are asymptomatic
  • Causes compression of adjacent structures
  • Symptoms include a palpable mass in the epigastric region and nonspecific abdominal pain or distension (World J Gastrointest Oncol 2020;12:642)
• Intraductal papillary mucinous neoplasm (IPMN)
  • Majority are asymptomatic; often incidental
  • Symptoms present in 2 - 20% of patients and include epigastric pain, weight loss, diabetes and jaundice (Gut Liver 2015;9:571, Arch Pathol Lab Med 2022;146:298)
• Pancreatic ductal adenocarcinoma
  • Most commonly reported symptoms: loss of appetite (~45%), jaundice (~41%) and abdominal pain (40%)
  • Other symptoms include weight loss, back pain, new onset diabetes, depression, migratory thrombophlebitis and acute pancreatitis (Clin Gastroenterol Hepatol 2004;2:510)

Contributed by Katrina Krogh, M.D.

Contributed by Jen Rytych, M.D. and Katrina Krogh, M.D.

• JAMA Surg 2022;157:723, WHO Classification of Tumours Editorial Board: Digestive System Tumours, 5th Edition, 2019

A 55 year old woman presents with a pancreatic cyst incidentally detected on abdominal imaging. The cyst is located in the head of the pancreas and measures ~3 cm in size. Endoscopic ultrasound guided fine needle aspiration (EUS FNA) is performed and analysis of the cyst fluid reveals the following laboratory values: high CEA level, elevated amylase and low viscosity. A picture of the resection specimen is shown above. Which of the following statements is true about the most likely diagnosis?

1. This lesion can display multiple histologic subtypes that resemble gastric, intestinal or pancreatobiliary epithelium
2. This lesion does not commonly connect with the pancreatic duct system
3. This lesion is not a precursor for invasive ductal adenocarcinoma
4. VHL is the most commonly mutated gene in this lesion

A. This lesion can display multiple histologic subtypes that resemble gastric, intestinal or pancreatobiliary epithelium. This lesion in the head of the pancreas with elevated CEA and amylase levels in the cyst fluid is an intraductal papillary mucinous neoplasm (IPMN). The epithelium in IPMNs most commonly resembles gastric epithelium, with intestinal and pancreatobiliary types being less common. Answer B is incorrect because IPMNs connect with the pancreatic duct system, which causes an increase in amylase levels in the cyst fluid. Other pancreatic cysts such as mucinous cystic neoplasm (MCN) and simple mucinous cysts do not typically connect with the pancreatic duct system. Answer C is incorrect because invasive carcinomas are found in ~30 - 50% of main duct IPMNs and ~24% of branch duct IPMNs. Answer D is incorrect because VHL is commonly mutated in serous cystadenomas, not IPMNs.

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Reference: Mucinous pancreatic tumor overview

A 45 year old woman presents with abdominal discomfort and a large cystic lesion in the tail of the pancreas on abdominal imaging. Endoscopic ultrasound guided fine needle aspiration (EUS FNA) is performed and analysis of the cyst fluid reveals elevated levels of CEA, CA 19-9 and low amylase. A picture of the resection specimen is shown above. Which of the following statements about this pancreatic lesion is true?

1. This lesion contains ovarian type stroma and is most commonly seen in females
2. This lesion is most commonly seen in older men with a history of chronic pancreatitis
3. This lesion is typically a benign cystic tumor that contains serous fluid
4. These lesions are typically associated with elevated levels of amylase and CEA in the cyst fluid

A. This lesion contains ovarian type stroma and is most commonly seen in females. This female patient with a cystic lesion in the tail of the pancreas with elevated CEA, CA 19-9 and low amylase has a mucinous cystic neoplasm (MCN). MCNs are characterized by the presence of ovarian type stroma and are seen almost exclusively in females (> 95%). Answer B is incorrect because pancreatic ductal adenocarcinomas are more commonly associated with older men with a history of chronic pancreatitis. MCNs are seen in female patients and are not associated with chronic pancreatitis. Answer C is incorrect because serous cystadenomas are benign cystic tumors that contain serous fluid. MCNs contain mucin and are characterized as low grade or high grade lesions with ~16% associated with invasive carcinoma. Answer D is incorrect because the cyst fluid of MCNs typically has elevated CEA and CA 19-9 but has low amylase levels because they do not connect to the pancreatic duct system. The presence of elevated amylase and CEA levels in pancreatic cyst fluid is most often associated with an intraductal papillary mucinous neoplasm (IPMN).

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Reference: Mucinous pancreatic tumor overview