Outcomes of surgery for 2010 WHO classification-based intraductal papillary neoplasm of the bile duct: Case–control study of a single Japanese institution's experience with special attention to mucin expression patterns

Harada, Fumi; Matsuyama, Ryusei; Mori, Rintaro; Kumamoto, Takafumi; Morioka, Daisuke; Taguri, Masataka; Yamanaka, Shōji; Endo, Itaru

doi:10.1016/j.ejso.2018.10.532

Cited by 21 publications

(12 citation statements)

References 33 publications

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“…The prognosis of IPNB as well as invasive carcinoma derived from IPNB has been consistently better than that of conventional CCA [ 155 , 156 , 157 , 158 , 159 , 160 ]. Invasive IPNB showed poor survival compared with non-invasive IPNB [ 1 , 38 ].…”

Section: Common Precursors Of the Biliary Tractmentioning

confidence: 99%

Pathologies of Precursor Lesions of Biliary Tract Carcinoma

Nakanuma

Kakuda

Sugino

et al. 2022

Cancers

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Carcinomas and precursor lesions of the biliary tract belong to a spectrum of pancreatobiliary neoplasms that share common histology and cell lineages. Over the past two decades, preinvasive precursors to biliary tract carcinomas (BTCs) have been identified such as high-grade biliary intraepithelial neoplasm (high-grade BilIN), intraductal papillary neoplasm of bile duct (IPNB) and intracholecystic papillary neoplasm of the gallbladder (ICPN). While a majority of these precursors may arise from the biliary tract mucosa, some originate from the peribiliary glands and Rokitansky-Aschoff sinuses in the walls of the biliary tract. High-grade BilIN is a microscopically identifiable intraepithelial neoplasm of the biliary tract, whereas IPNB and ICPN are grossly visible intraductal or intraluminal preinvasive neoplasms in the bile duct and gallbladder, respectively. These neoplasms show characteristic histologic features according to four cell lineages and two-tiered grading, and show intraepithelial spreading to the surrounding mucosa and involve non-neoplastic glands in the walls of the biliary tract. These precursors are not infrequently associated with stromal invasion, and high-grade BilIN, in particular, are frequently identified in the surrounding mucosa of BTCs. Taken together, it seems likely that progression from these precursors to invasive carcinoma is a major process in biliary carcinogenesis.

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Section: Common Precursors Of the Biliary Tractmentioning

confidence: 99%

Pathologies of Precursor Lesions of Biliary Tract Carcinoma

Nakanuma

Kakuda

Sugino

et al. 2022

Cancers

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“…The IPNB subtype (gastric, intestinal, pancreatobiliary, or oncocytic) is often considered a counterpart to intraductal papillary mucinous neoplasms in the pancreas [9][10][11]. Immunohistochemistry can help to determine the immunophenotype, and our findings of positive MUC1 and MUC5AC expression supported a diagnosis of the pancreatobiliary type (Fig.…”

Section: Discussionmentioning

confidence: 76%

Lung metastases from intraductal papillary neoplasm of the bile duct: a case report

et al. 2020

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Background Intraductal papillary neoplasm of the bile duct (IPNB) is considered a pre-cancerous biliary lesion and/or an early cancer lesion, although its classification remains unclear. The 2019 revised edition of the World Health Organization Classification of Tumors of the Digestive System proposed type 1 and type 2 as new classification categories, and meta-analyses and/or multi-center cohort studies are beginning to be reported. However, treatment for IPNB recurrence and metastasis remains unclear. Case presentation A 60-year-old man who was referred to our hospital after a suspected liver tumor was diagnosed using abdominal ultrasonography. Imaging findings revealed an irregularly shaped tumor in segment 5 (S5) of the liver (size 20 mm). The S5 lesion was suspected as IPNB, and segmentectomy was performed. The pathological findings revealed invasive carcinoma derived from IPNB, and immunohistochemistry revealed positive expression of MUC1, MUC5AC, and MUC6, but negative expression of CDX2 and MUC2. At 9 months after the surgery, computed tomography revealed a tumor in the right bile duct, which was diagnosed as liver recurrence of IPNB, and right hepatectomy was performed. The histopathological findings were the same as for the first resected specimen (i.e., IPNB). At 45 months after the second surgery, computed tomography revealed nodules in both lungs, which were diagnosed as lung metastases from IPNB and resected in two separate procedures. The pathological findings were metastatic carcinoma from IPNB for both lung lesions. The patient is currently alive and undergoing adjuvant chemotherapy (S-1), which was initiated 64 months after the first resection and 12 months after resection of the lung metastases. Conclusion We encountered a rare case of lung metastases from IPNB, which were diagnosed immunohistologically. Because IPNB is generally a slow-growing tumor, resection may be feasible for IPNB recurrence and/or metastasis, which may be detected during long-term follow-up. Thus, even if resection is performed for primary IPNB, additional surgical treatment may be feasible in this setting.

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“…Based on IHC analysis of mucin expression, human IPNBs can be classified into four subtypes, including the pancreatobiliary (MUC1+MUC5AC ± MUC6ÀMUC2À), gastric (MUC1-MUC5 AC+MUC6+MUC2À), intestinal (MUC5AC-MUC6ÀMUC2+), and oncocytic (H&E stain morphology-dependent) types (Harada et al, 2019;Nagtegaal et al, 2019;Sasaki et al, 2013). We found gastric and pancreaticobiliary types of IPNBs in Dox+ and TAA+Dox+ iFGF10 mice, respectively (Figure S6).…”

Section: Fgf10 Concomitant With Inflammation Accelerated Ipnb Progressionmentioning

confidence: 82%

“…Curative resection, including BD resection and partial liver resection, is the mainstay of treatment in patients with IPNBs. IPNBs are considered premalignant and preinvasive lesions, even in LGD (Harada et al, 2019;Uemura et al, 2021;Vibert et al, 2010); thus, lesion resection is recommended and performed in the clinical setting. Moreover, resection is recommended because of the recurrent episodes of cholangitis and obstructive jaundice caused by mucin production (Ohtsuka et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of FGF10-ERK signal activation suppresses intraductal papillary neoplasm of the bile duct and its associated carcinomas

et al. 2021

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Evidence regarding intraductal papillary neoplasm of the bile duct (IPNB) as a type of precancerous lesion of cholangiocarcinoma is limited. Moreover, a reproducible in vivo model is lacking, and IPNB pathogenesis remains unclear. Here, we use a doxycycline-inducible tetracycline (Tet)-on mice model to control fibroblast growth factor 10 (FGF10) expression, which regulates branching and tubule formation. FGF10-induced IPNB mimics the multifocal and divergent human IPNB phenotypes via the FGF10-FGF receptor 2 (FGFR2)-RAS-extracellular-signal-regulated kinase (ERK) signaling pathway. A paracrine/autocrine growth factor is sufficient to initiate and maintain IPNB originating from the peribiliary glands, including biliary stem/progenitor cells. With Kras G12D , p53, or p16 mutations or both, Fgf10-induced IPNB shows stepwise carcinogenesis, causing associated invasive carcinoma. Fgf10-induced papillary changes and progression are suppressed by the inhibition of the FGF10-FGFR2-RAS-ERK signaling pathway, demonstrating that the signal is a therapeutic target for IPNB and associated carcinoma.

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Outcomes of surgery for 2010 WHO classification-based intraductal papillary neoplasm of the bile duct: Case–control study of a single Japanese institution's experience with special attention to mucin expression patterns

Cited by 21 publications

References 33 publications

Pathologies of Precursor Lesions of Biliary Tract Carcinoma

Pathologies of Precursor Lesions of Biliary Tract Carcinoma

Lung metastases from intraductal papillary neoplasm of the bile duct: a case report

Inhibition of FGF10-ERK signal activation suppresses intraductal papillary neoplasm of the bile duct and its associated carcinomas

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