When to operate pancreatic intraductal papillary mucinous neoplasm: Literature review

Table 1 Histologic features of intraductal papillary mucinous neoplasms according to cell types

Histological subtype	Histological features	Associated carcinoma	Prognosis
Gastric	Foveolar-like cells, may be associated with intestinal metaplasia, low-grade dysplasia. Mainly branch duct	Ductal/tubular adenocarcinoma	Slightly better prognosis than PDC not associated with IPMNs
Intestinal	Tall columnar epithelium (villous adenoma like), low to high-grade dysplasia. Often main duct affected	Mucinous/colloid carcinoma	Better than PDC
Pancreatobiliary	Cuboidal cells, thin branching or complex papillae (cholangio-papillary like tumors). High-grade dysplasia often main duct affected	Ductal/tubular adenocarcinoma	Slightly better prognosis than PDC not associated with IPMNs
Oncocytic	Arborizing papillae	Rare	-

IPMNs: Intraductal papillary mucinous neoplasms; PDC: Pancreatic ductal carcinoma.

Table 2 It summarizes the differential diagnosis of intraductal papillary mucinous neoplasms

Intraductal oncocytic papillary neoplasm	Intraductal tubulopapillary neoplasm	Mucinous cystic neoplasm	Pancreatic intraepithelial neoplasia	Simple mucinous cyst	Retention cyst
Variable sizes. Arborizing lined by oncocytic cells. It has a different molecular genetic alteration in one of the following genes, ARHGAP26, ASXL1, EPHA8 and ERBB4. DNAJB1-PRKACA fusions. MUC1 and MUC6 positivity	Variable sizes subtype originating from peribiliary cysts. Tributary epithelial cells forming papillary and tubular patterns. High-grade dysplasia solid growth with necrotic foci, little or invisible mucin with intracytoplasmic mucin is present. No mutations in KRAS2 positivity for MUC1+, MUC6+ and negativity for MUC2-	Variable sizes. This cyst is lined by epithelial mucinous layer and stroma of ovarian type. No anatomical communication with pancreatic duct or its branches radiologically	Occult mass. Detected microscopically. Epithelial differentiation towards gastric foveolar epithelium	> 1 cm. Flat epithelium (differentiated towards gastric mucinous type). No papillae. Little atypia	> 1 cm. Simple flat epithelial lining. No papillae. Little atypia

Table 3 It summarizes the indications of surgery and surveillance/follow-up for intraductal papillary mucinous neoplasms

Items	IAP (2006)	American Gastroenterological Association (2015)	IAP (2017)
Indications for surgery	Size of the cyst is ≥ 3 cm. Mural nodule. Dilatation of MPD ≥ 5 mm. Positive fine needle aspiration cytology	High risk features: The size of cyst is ≥ 3 cm; solid part; dilated MPD. High-grade dysplasia or cancer on cytology	HRS include: Sign (jaundice); nodules enhancement ≥ 5 mm; MPD ≥ 10 mm. High-grade dysplasia or cancer on cytology WF: Cyst size is ≥ 3 cm; acute pancreatitis as a complication of IPMN. Thickened and enhancing cyst wall. Dilated MPD caliber 5-9 mm is associated with abrupt change of with distal pancreatic atrophy. Presence of lymphadenopathy. Elevated serum carbohydrate antigen 19-9. Cyst growth rate > 5 mm/2 years
Surveillance and follow-up	BD-IPMNs ≤ 30 mm without symptoms, or mural nodules, or positive cytology. MRI/MRCP or CT. Size ≤ 20 mm: Follow-up every 6-12 months. Size 20-30 mm: Follow-up every 3-6 months. The intermission can be prolonged if there are no changes after 2 years	BD-IPMNs ≤ 30 mm without solid component, or dilated MPD, or high-grade dysplasia/cancer. MRI. Years 1, 2, 5 from initial diagnosis; it can be considered to discontinue, if there are no changes after year	No HRS/WF: MRI/MRCP, CT size < 10 mm: The follow-up at 6 months from diagnosis every 2 years (if no change). No HRS/WF: MRI/MRCP, CT size 10-20 mm: The follow-up at 6 months from diagnosis yearly per 2 years. No HRS/WF: MRI/MRCP, EUS, size 20-30 mm, do EUS in 3-6 months, yearly EUS or MRI. No HRS, WF present: Size < 30 mm, MRI/MRCP EUS, every 3-6 months: EUS or MRI

BD-IPMNs: Branch-duct intraductal papillary mucinous neoplasms; CT: Computerized tomography; EUS: Endoscopic ultrasound; HRS: High-risk stigmata; IAP: International Association of Pancreatology; IPMNs: Intraductal papillary mucinous neoplasms; MPD: Main pancreatic duct; MRCP: Magnetic resonance cholangiopancreatography; MRI: Magnetic resonance imaging; WF: Worrisome feature.