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Copyright ©The Author(s) 2018.
World J Gastrointest Oncol. Oct 15, 2018; 10(10): 317-327
Published online Oct 15, 2018. doi: 10.4251/wjgo.v10.i10.317
Table 1 Immunohistochemical markers for intraductal papillary mucinous neoplasm/intraductal tubulo-papillary neoplasm histopathological classification
Type of lesionSubtypeMUC1MUC2MUC5ACMUC6CDX2
IPMNGNegativeNegativePositive1NegativeNegative
PBPositive1NegativePositive1PositiveNegative
INTNegativePositive1Positive1NegativePositive1
ONCPositiveNegativePositivePositive1Negative
ITPNPositiveNegativeNegativePositive1Negative
Table 2 Precursor lesions and their most important histopathological and molecular features
Precursor lesionsMain histopathological featuresMolecular hallmarks
PanINNon-infiltrating lesions involving pancreatic ducts and < 0.5 cm, composed of cuboid to columnar mucinous cells, with two degrees of dysplasia: (1) Low-grade PanINs include the previously called PanIN-1 and PanIN-2; and (2) high-grade PanINs include PanIN-3KRAS somatic mutations are early molecular events (Low-grade PanINs); CDKN2A, TP53, and SMAD4 mutations are late molecular events (High-grade PanINs)
IPMNNon-infiltrating intraductal neoplasms > 1.0 cm composed of mucinous cells with papillary architecture. IPMNs have two degrees of dysplasia: (1) Low-grade IPMNs; and (2) High-grade IPMNs. IPMNs can be classified based on topography (main duct, branch duct or mixed) and also on histology (gastric, pancreaticobiliary, intestinal, or oncocytic type, see Table 1)GNAS and KRAS are altered in up to 60% and to 80% of IPMNs, respectively There are two possible carcinogenetic processes: (1) GNAS mutations cause progression to colloid carcinomas; and (2) KRAS mutations lead to conventional PDAC. Other frequently mutated genes in IPMNs are RNF43, BRAF, TP53, and SMAD4
MCNComposed of columnar cells with abundant mucin located in the upper part. There are two degrees of dysplasia: (1) Low-grade MCN; and (2) High-grade MCN. The histopathologic clues for MCN diagnosis are the lack of communication with the pancreatic ductal tree and the presence of an ovarian-like stroma under the mucinous epitheliumThere are fewer mutations and chromosomal alterations in MCNs compared with other precursors, and this could explain the lower frequency of progression of MCN to PDAC. Frequently altered genes are KRAS, CDKN2A, TP53, SMAD4, and RNF43
ITPNComposed of uniform cuboidal cells without a significant amount of mucin, arranged in densely packed tubules and back-to-back glands with a typical intraductal, tubulopapillary growthPIK3CA mutations and AKT alterations are frequently seen in ITPNs. Mutations involving KRAS, NRAS, and GNAS are very rare in ITPNs