This pancreas shows a dilated duct with a gelatinous appearing pale lesion occupying the lumen.
Another case shows again a dilated duct. Most IPMNs are localized but potentially they can involve the entire pancreas.
The cut section of the above pancreas shows glistening mucinous mass.
The dilated duct is lined by papillary structures and the lumen is filled with mucin. A well-developed papillae with a vascular core is present.
The tumor is involving ampulla of Vater.
Histologically, mucinous cells line complex papillae consistent with the pancreaticobiliary subtype.
Mucinous debris and mild to moderate cytologic atypia is evident compatible with at least moderate dysplasia. This type resembles the pancreatobiliary-type of neoplasm which is less common that the intestinal variety. The nuclei in general are rounder than the intestinal-type and chromatin is more open. Most IPMNs of pancreatobiliar type show high grade dysplasia.
A filiform configuration of neoplastic cells can be appreciated.
Columnar cell contain cigar shaped nuclei resembling colonic adenomas, consistent with intestinal-type differentiation.
FNA usually yields abundant mucin which resembles thick colloid on this diff-quick stained slide. A mucinous cystic neoplasm may have a similar FNA appearance, but mucin contamination from the GI tract does not take on this viscous nature. Mucinous cystic neoplasms may contain entrapped histiocytes and debris, a feature typically lacking in IPMN. Furthermore, not all IPMNs contain tenacious mucin, so beware!
Scattered clusters of columnar cells with basally-situated nuclei and mild atypia are found. Prominent but uniform nucleoli are present. Note that sampling by FNA often does not detect focal areas of higher grade atypia. Epithelial cells are required for the FNA diagnosis but when scant and bland, the possibility of GI contamination is also raised.
The presence of papillary fragments supports the idea of IPMN but may be lacking in some FNAs.
Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic neoplasm that arises in the ductal system and is characterized by papillary proliferations, ductal dilatation, mucin production.
In terms of location, IMPNs that involve the main pancreatic duct are called main duct type and those that involve side branches of the main duct are called branch duct type.
The categorization of the different histologic subtypes of IPMNs is a bit confusing, but is worth noting because the subtypes have prognostic significance. In a 2004 paper, Adsay and colleagues clearly delineate the three major subtypes recognized thus far (Adsay, Yonezawa):
(1) Intestinal-type; also called 'villous-dark cell type' in a 1999 landmark paper by Yonezawa, this type resembles colorectal villous tumors.
(2) Pancreatobiliary-type; consists of cuboidal cells with eosinophilic cytoplasm and prominent nucleoli resembling papillary neoplasms in the biliary tract. The type exhibits complex papillary formations.
(3) Gastric or foveloar type; also called 'null' type, the neoplastic cells have basally oriented nuclei with abundant apical mucin, resembling the foveoli of gastric epithelium or pancreatic low-grade intraepithelial neoplasia (PanIN) lesions.
Adsay and colleagues examined 74 IPMNs with special attention to CDX2 (intestinal differentiation marker), MUC1 (marker of aggressive phenotype in pancreatic neoplasia) and MUC2 (marker of indolent intestinal type mucin). They found that intestinal-type IPMNs were more likely to exhibit carcinoma-in-situ (85%) or borderline atypia (15%), express CDX2 (95%) and MUC2 (92%), but not MUC1 (8%). The pancreatobiliary type were often graded as CIS (94%), express MUC1 (44%), but rarely express CDX2 or MUC2. Lastly, the pure gastric or null type were most often classied as adenomas (48%) and rarely expressed CDX2, MUC1 or MUC2 (Adsay).
What does this mean prognostically? Basically, the intestinal-type are more aggressive and more likely to have an invasive component compared to the gastric-type. The pancreatobiliary type (according to Adsay) may also be aggressive. In one review of 80 IPMNs conducted by Ban in 2006, 23% of intestinal-type IPMNs contained an invasive carcinoma in contrast to only 2% of the gastric type (Ban).
Slightly more common in men (M:F ratio of 6:4) with mean age of 64 years. Usually present with a long history of weight loss, abdominal pain, back pain, recurrent bouts of pancreatitis (Iacobuzio).
A minority (<20%) present with jaundice, a symptom which overall is more common in those with associated invasive disease. Patients with IPMNS are at increased risk for other malignancies such as those of the colorectum and stomach (Sugiyama). IPMNs have been reported in patients with Peutz-Jeghers syndrome (Su).
On endoscopy, one may see mucin extrusion from the Ampulla of Vater as IMPNs can elaborate copious amounts of mucin.
Surgical excision is usually performed. Nodal dissection is recommended for those with invasive malignancy. In some studies, asymptomatic branch-type IPMNs without mural nodules may be followed up without resection (Tanaka).
Approximately one-third of IPMNs have an associated invasive carcinoma. As mentioned above, intestinal-type IPMNs and pancreatobiliary-type IPMNs are more aggressive than gastric-type IPMNs. When comparing intestinal and pancreatobiliary types, it appears than invasive carcinomas derived from intestinal-type IPMNs tended to have a better prognosis than those whose invasive carcinomas were derived from the pancreatobiliary type (Takasu, Adsay).
Note also, that patients with IPMNS are at increased risk for other malignancies such as those of the colorectum and stomach.
In contrast to mucinous cystic neoplasms which do not involve the pancreatic ducts, arise in body/tail of the pancreas, affect women and exhibit an ovarian-type stroma, IPMN arise in the main pancreatic ducts in the head of the gland, have a predilection for men and do not have a distinctive stroma.
Similar to mucinous cystic neoplasms, IPMN are graded as adenomas, borderline, carcinoma-in-situ and invasive.
IMPNs have three main histologic subtypes (intestinal-type, pancreatobiliary-type and gastric-type), which carries prognostic implications.
Ban S, Naitoh Y, Mino-Kenudson M, et al. Intraductal papillary mucinous neoplasm (IPMN) of the pancreas: its histopathologic difference between 2 major types. Am J Surg Pathol. 2006 Dec;30(12):1561-9.
Iacobuzio-Donahue CA, Montgomery EA. Gastrointestinal and Liver Pathology: Foundations in Diagnostic Pathology. Philadelphia, PA: Elsevier; 2005: 490-3.
Su, GU et al. Germline and somatic mutations of the STK11/LKB1 Peutz-Jegher gene in pancreatic and biliary cancers. Am J Pathol 1999; 154: 1935-40.
Sugiyama M, Atoma Y. Extrapancreatic neoplasms occur with unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas. Am J Gastroenterol 1999; 94: 470-3.
Takasu N, et al. Intraductal Papillary-Mucinous Neoplasms of the Gastric and Intestinal Types May Have Less Malignant Potential Than the Pancreatobiliary Type. Pancreas. 2010 Jan 29.
Tanaka M. Intraductal papillary mucinous neoplasm of the pancreas: diagnosis and treatment. Pancreas. 2004 Apr;28(3):282-8.
Yonezawa S, Horinouchi M, Osako M, et al. Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor. Pathol Int. 1999;49:45–54.