Intracholecystic Papillary Neoplasms Are Distinct From Papillary Gallbladder Cancers

Abstract

Although intracholecystic papillary neoplasms (ICPNs) have been increasingly recognized, their features remain unclear because of the lack of standardized definition. This study aimed to elucidate clinicopathologic and genetic features of ICPNs using stringent diagnostic criteria. On the basis of the recently proposed criteria, gallbladder neoplasms showing delicate papillary growth were diagnosed as ICPNs, while polypoid papillary adenocarcinomas arranged in a complex architecture were categorized as papillary gallbladder cancers (GBCs). Clinicopathologic features were compared among ICPNs (n=7), papillary GBCs (n=24), and nonpapillary GBCs (n=44). Whole-exome and validation Sanger sequencing was also conducted. Gross mucin hypersecretion was detected in 3/7 ICPNs (43%), 1/24 papillary GBCs (4%), and 1/44 nonpapillary GBCs (2%) (P<0.001). All patients with ICPN lacked lymphovascular invasion and nodal metastasis, while these features were occasionally observed in patients with papillary or nonpapillary GBC (13% to 59%). ICPNs were less advanced than papillary and nonpapillary GBCs (P<0.001) with all cases of ICPNs being recurrence-free. Whole-exome and Sanger sequencing identified somatic mutations in STK11 (a causative gene of Peutz-Jegher syndrome; n=3), CTNNB1 (n=2), and APC (a gene of familial adenomatous polyposis; n=1) in ICPNs, while those alterations were exceptional in papillary and nonpapillary GBCs. ICPNs more commonly showed cytoplasmic and/or nuclear expressions of β-catenin than papillary and nonpapillary GBCs. In conclusion, the histology-based classification of gallbladder papillary neoplasms is useful for identifying ICPNs that share clinicopathologic features with the pancreatic counterpart. ICPNs meeting the criteria were genetically distinct from papillary and nonpapillary GBCs, with STK11, CTNNB1, and APC being identified as major driver genes for ICPNs.

Intracholecystic Papillary Neoplasm Arising in A Patient with Pancreaticobiliary Maljunction: A Case Report

“…Table 1 Evaluation for the mutation and expression status of the epithelium exposed to the pancreatobiliary re ux. Besides the present case, only two cases of ICPN in the presence of PBM have been reported (8,21).…”

“…According to Akita et al, there was no signi cant difference in the relationship with PBM between the three groups of patients with ICPN, papillary gallbladder cancer (GBC), and nonpapillary GBC. In Akita et al's report no concrete evidence suggesting PBM as a cause of ICPN was available (8). In another case reported by Meguro et al (21), the AMY level of the bile juice in the gallbladder was not elevated, possibly due to the dilution by mucin produced from the ICPN.…”

“…According to recent study by Akita et al (8) suggesting the speci c contribution of the activated Wnt/βcatenin pathway in the tumorigenesis of ICPNs, expression of β-catenin was also evaluated ( Table 1).…”

Intracholecystic papillary neoplasm arising in a patient with pancreaticobiliary maljunction: A case report

“…We performed KRAS gene mutation analyses and IHC examination on p53 protein to evaluate whether the genetic alterations in the biliary tract, which had been affected by pancreatobiliary re ux, were also recognized in the ICPN. According to recent study by Akita et al (8) suggesting the speci c contribution of the activated Wnt/βcatenin pathway in the tumorigenesis of ICPNs, expression of β-catenin was also evaluated (Table 1). Table 1.…”

“…The CD and EHBD were covered by epithelium with low-grade atypia. By referring to previous studies concerning gene expression on the biliary tract epithelium exposed to the pancreatobiliary re ux as was summarized in Table 1 (8,(10)(11)(12)(13), KRAS gene mutation, and the expressions of p53 protein as well as β-catenin were assessed in the tissues from three sites as the follows: tumor cells of ICPN, background mucosa of gallbladder surrounding the ICPN, and epitheliums of EHBD. Analyses for gene mutations in codon 12/13, 59/51, 117, and 146 of the KRAS gene were performed by SRL, Inc. (Shinjuku, Japan), and IHC was performed to evaluate expression of p53 protein and β-catenin ( Fig.…”