Intraductal papillary bile duct adenocarcinoma and gastrointestinal stromal tumor in a case of neurofibromatosis type 1

Lee, Jung Min; Lee, Jae Min; Hyun, Jong Jin; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Jeen, Yoon Tae; Chun, Hoon Jai; Lee, Hong Sik; Kim, Chang Duck; Kim, Joo Young

doi:10.3748/wjg.v24.i4.537

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…(2) Other diseases: IPNB and gastrointestinal stromal tumor and neurofibromatosis type 1 were found in a case of neurofibromatosis type 1 [ 61 ]. There have also been rare cases of IPNB in liver cirrhosis patients [ 62 ].…”

Section: Clinical Features Epidemiology and Imaging And Endoscopimentioning

confidence: 99%

Intraductal Papillary Neoplasm of Bile Duct: Updated Clinicopathological Characteristics and Molecular and Genetic Alterations

Nakanuma

Uesaka

Kakuda

et al. 2020

JCM

113

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Intraductal papillary neoplasm of the bile duct (IPNB), a pre-invasive neoplasm of the bile duct, is being established pathologically as a precursor lesion of invasive cholangiocarcinoma (CCA), and at the time of surgical resection, approximately half of IPNBs show stromal invasion (IPNB associated with invasive carcinoma). IPNB can involve any part of the biliary tree. IPNB shows grossly visible, exophytic growth in a dilated bile duct lumen, with histologically villous/papillary neoplastic epithelia with tubular components covering fine fibrovascular stalks. Interestingly, IPNB can be classified into four subtypes (intestinal, gastric, pancreatobiliary and oncocytic), similar to intraductal papillary mucinous neoplasm of the pancreas (IPMN). IPNBs are classified into low-grade and high-grade based on lining epithelial features. The new subclassification of IPNB into types 1 (low-grade dysplasia and high-grade dysplasia with regular architecture) and 2 (high-grade dysplasia with irregular architecture) proposed by the Japan–Korea pathologist group may be useful in the clinical field. The outcome of post-operative IPNBs is more favorable in type 1 than type 2. Recent genetic studies using next-generation sequencing have demonstrated the existence of several groups of mutations of genes: (i) IPNB showing mutations in KRAS, GNAS and RNF43 belonged to type 1, particularly the intestinal subtype, similar to the mutation patterns of IPMN; (ii) IPNB showing mutations in CTNNB1 and lacking mutations in KRAS, GNAS and RNF43 belonged to the pancreatobiliary subtype but differed from IPMN. IPNB showing mutation of TP53, SMAD4 and PIK3CA might reflect complicated and other features characterizing type 2. The recent recognition of IPNBs may facilitate further clinical and basic studies of CCA with respect to the pre-invasive and early invasive stages.

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Section: Clinical Features Epidemiology and Imaging And Endoscopimentioning

confidence: 99%

Intraductal Papillary Neoplasm of Bile Duct: Updated Clinicopathological Characteristics and Molecular and Genetic Alterations

Nakanuma

Uesaka

Kakuda

et al. 2020

JCM

113

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“…It has also been reported that individuals with NF1 may have an increased susceptibility to other neoplasms [ 13 ]. Recent studies have suggested that NF1 may also play a role in breast tumors [ 23 ], colorectal cancer [ 24 ], pancreatic ductal adenocarcinoma [ 25 ], gastrointestinal stromal tumor (GIST), and neoplasm of the bile duct [ 26 ]. Despite these findings, it remains unclear how NF1 contributes to the pathogenesis of these malignancies, and its role in GBC remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

The oncogenic role of NF1 in gallbladder cancer through regulation of YAP1 stability by direct interaction with YAP1

et al. 2023

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Background Gallbladder cancer (GBC) is the most prevalent and invasive biliary tract malignancy. As a GTPase-activating protein, Neurofibromin 1 (NF1) is a tumor suppressor that negatively regulates the RAS signaling pathway, and its abnormality leads to neurofibromatosis type 1 (NF-1) disease. However, the role of NF1 playing in GBC and the underlying molecular mechanism has not been defined yet. Methods A combination of NOZ and EH-GB1 cell lines as well as nude mice, were utilized in this study. mRNA expression and protein levels of NF1 and YAP1 were evaluated by quantitative real-time PCR (qRT-PCR), western blot (WB), and immunohistochemistry (IHC). In vitro and in vivo assays were performed to explore the biological effects of NF1 in NOZ and EH-GB1 cells via siRNA or lv-shRNA mediated knockdown. Direct interaction between NF1 and YAP1 was detected by confocal microscopy and co-immunoprecipitation (Co-IP), and further confirmed by GST pull-down assay and isothermal titration calorimetry assay (ITC). The stability of proteins was measured by western blot (WB) in the presence of cycloheximide. Results This study showed that a higher level of NF1 and YAP1 was found in GBC samples than in normal tissues and associated with worse prognoses. The NF1 knockdown impaired the proliferation and migration of NOZ in vivo and in vitro by downregulating YAP1 expression. Moreover, NF1 co-localized with YAP1 in NOZ and EH-GB1 cells, and the WW domains of YAP1 specifically recognized the PPQY motif of NF1. The structural modeling also indicated the hydrophobic interactions between YAP1 and NF1. On the other hand, YAP1 knockdown also impaired the proliferation of NOZ in vitro, phenocopying the effects of NF1 knockdown. Overexpression of YAP1 can partially rescue the impaired proliferation in NF1 stably knockdown cells. In mechanism, NF1 interacted with YAP1 and increased the stability of YAP1 by preventing ubiquitination. Conclusions Our findings discovered a novel oncogenic function of NF1 by directly interacting with YAP1 protein and stabilizing YAP1 to protect it from proteasome degradation in NOZ cells. NF1 may serve as a potential therapeutic target in GBC.

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Cystic intraductal papillary neoplasms with infiltrating carcinoma of the intrahepatic bile duct

Zhao

Pan

et al. 2020

Medicine

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Introduction: Intraductal papillary neoplasms of the bile duct (IPNB) is a kind of rare disorder with low incidence but high misdiagnosis due to untypical symptoms and non-specific laboratory indicators. Herein, we report a case of cystic type IPNB with infiltrating carcinoma of the intrahepatic bile duct presented as a single giant cystic mass of the liver. Patient concerns: A 51-year-old woman was admitted due to right upper abdominal discomfort for 10 months. Physical examination indicated no specific finding. Laboratory tests showed that serum total bilirubin and carcinoembryonic antigen level was mildly elevated. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) of abdomen indicated a giant lobulated cystic lesion involving the left, right and the caudate lobes of liver. There were multiple small nodules of different sizes with papillary or coral reef-like pattern protruding into the cystic lumen from the inner wall. Diagnosis: The patient was diagnosed as malignant tumors of intrahepatic bile duct. Interventions: She received radical resection of the lesion by hepatectomy. Outcomes: The postoperative pathological examination revealed an IPNB with infiltrating carcinoma of the intrahepatic bile duct. This patient had an uneventful postoperative recovery and was discharged on day 21 post-surgery. Until 35 months after surgery, there is no recurrence or metastasis. Conclusion: The CT and MRI can show certain morphologic features including the segmental cystic dilatation of intrahepatic bile ducts and the pathological details of papillary tumors inside the lesion. Cystic IPNB with infiltrating carcinoma of the intrahepatic bile duct can be treated with surgery.

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Intraductal papillary bile duct adenocarcinoma and gastrointestinal stromal tumor in a case of neurofibromatosis type 1

Cited by 4 publications

References 18 publications

Intraductal Papillary Neoplasm of Bile Duct: Updated Clinicopathological Characteristics and Molecular and Genetic Alterations

Intraductal Papillary Neoplasm of Bile Duct: Updated Clinicopathological Characteristics and Molecular and Genetic Alterations

The oncogenic role of NF1 in gallbladder cancer through regulation of YAP1 stability by direct interaction with YAP1

Cystic intraductal papillary neoplasms with infiltrating carcinoma of the intrahepatic bile duct

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