Intraductal Tubulopapillary Neoplasms of the Pancreas Distinct From Pancreatic Intraepithelial Neoplasia and Intraductal Papillary Mucinous Neoplasms

Yamaguchi, Hiroshi; Shimizu, Michio; Ban, Shinichi; Koyama, Isamu; Hatori, Takashi; Fujita, Izumi; Yamamoto, Masakazu; Kawamura, Shunji; Kobayashi, Makio; Ishida, Kazuyuki; Morikawa, Takanori; Motoi, Fuyuhiko; Unno, Michiaki; Kanno, Atsushi; Satoh, Kennichi; Shimosegawa, Tooru; Orikasa, Hideki; Watanabe, Tomoo; Nishimura, Kazuhiko; Ebihara, Yoshiro; Koike, Naoto; Furukawa, Toru

doi:10.1097/pas.0b013e3181a162e5

Cited by 193 publications

(254 citation statements)

References 29 publications

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“…4 Male sex, large tumor size, increased mitosis, and high Ki-67 proliferative index, but not age, are associated with a higher risk of invasive growth. 4,13 Therefore, one study 4 proposed that imagingguided core needle biopsy followed by Ki-67 immunohistochemical staining, together with imaging to determine the tumor size, should be used to stratify the risk of invasion before surgery. Rare cases of death from multiple ITPN liver metastases have been reported.…”

Section: Prognosis and Treatmentmentioning

confidence: 99%

“…Nevertheless, close clinical follow-up is considered essential to detect early recurrence. Fortunately, the prognosis of ITPN-associated invasive carcinoma is much better than that of traditional pancreatic 4 Kloppel et al, 6 Yamaguchi et al, 13 Reid et al, 28 Amato et al, 29 Urata et al, 36 Esposito et al, 38 Wu et al, 39 and Furukawa et al 40 ductal adenocarcinoma, even in patients with recurrent and metastatic disease. 6 The 5-year survival is more than 30%.…”

Section: Prognosis and Treatmentmentioning

confidence: 99%

“…[4][5][6][7][8][9][10] It was actually first recognized by Japanese investigators in the mid 1990s and then was proposed to be named intraductal tubular carcinoma by the Japan Pancreas Society in 2002. 11,12 In 2009, Yamaguchi et al 13 proposed renaming this entity as intraductal tubulopapillary neoplasm. It accounts for less than 1% of all pancreatic exocrine neoplasms and approximately 3% of intraductal pancreatic neoplasms.…”

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confidence: 99%

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Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective

Rooney

Shi

2016

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Intraductal tubulopapillary neoplasm (ITPN)is a rare intraductal epithelial neoplasm of the pancreas recently recognized as a distinct entity by the World Health Organization classification in 2010. It is defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. The diagnosis can be challenging owing to morphologic overlap with other intraductal lesions and its rarity. While recent advances in molecular genetic studies of ITPN have provided new tools to facilitate clinical diagnosis, the limited number of cases has yielded limited follow-up data to guide management.Objective.-To provide a clinical, pathologic, and molecular update on ITPN with respect to clinical presentation, imaging findings, histopathologic features, differential diagnosis, biological behavior, molecular characteristics, and treatment options.Data Sources.-Analysis of the pertinent literature (PubMed) and authors' research and clinical practice experience based on institutional and consultation materials.Conclusions.-Clinical presentation, imaging findings, histopathology, immunohistochemistry studies, molecular characteristics, prognosis, and treatment options of ITPN are reviewed. Important differential diagnoses with other intraductal neoplasms of the pancreas-especially intraductal papillary mucinous neoplasm-using histopathologic, molecular, and immunohistochemical studies, are discussed. Despite the recent progress, more studies are necessary to assess the biology and genetics of ITPN for a better understanding of the prognostic factors and treatment options.(Arch Pathol Lab Med. 2016;140:1068-1073; doi: 10.5858/arpa.2016-0207-RA) T he intraductal neoplasms of the pancreas are defined by the current 4th edition of the World Health Organization (WHO) classification as macroscopic epithelial neoplasms with ductal differentiation that grow in the pancreatic ductal system. The 2 entities included in this category are intraductal papillary mucinous neoplasm (IPMN) and intraductal tubulopapillary neoplasm (ITPN). Note that intraductal lesions with nonductal differentiation, such as acinar cell carcinoma, are not included in this category. Interestingly, before the current WHO classification, intraductal neoplasms of the pancreas were classified into 3 groups: IPMN, pancreatic intraepithelial neoplasia (PanIN), and intraductal tubular neoplasm.1,2 Intraductal tubular neoplasm was then further classified into intraductal tubular adenoma and intraductal tubular carcinoma, with intraductal tubular adenoma considered as the precursor of intraductal tubular carcinoma.3 Both IPMN and ITPN can be either cystic or solid-mass forming. The distinction between the intraductal neoplasms and PanIN is that PanIN is microscopic. On the contrary, by definition, both IPMN and ITPN are grossly and radiographically detectable lesions with an arbitrary minimal size criterion of 1 cm. Intraductal tubulopapillary neoplasms can have variable componen...

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Section: Prognosis and Treatmentmentioning

confidence: 99%

Section: Prognosis and Treatmentmentioning

confidence: 99%

mentioning

confidence: 99%

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Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective

Rooney

Shi

2016

Archives of Pathology &Amp; Laboratory Medicine

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“…It has also been speculated that a novel type of biliary intraductal neoplasm with a predominantly tubular architecture may be analogous to intraductal tubulopapillary neoplasm of the pancreas. 30 This issue should be clarified in the future.…”

Section: Discussionmentioning

confidence: 99%

Cholangiocarcinoma with intraductal tubular growth pattern versus intraductal papillary growth pattern

et al. 2016

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Intraductal neoplasms of the bile duct are macroscopically characterized by exophytic or polypoid growth patterns and have a favorable prognosis. Although some tumors with a predominantly tubular microscopic pattern have been reported, they have not been well characterized clinicopathologically. The purpose of the present study was to compare the newly recognized cholangiocarcinoma with an intraductal tubular growth pattern and cholangiocarcinoma with an intraductal papillary growth pattern and to investigate the pathological and prognostic significance of the former. This study analyzed 161 patients with tumors with exophytic or polypoid growth patterns from a large series of 733 cholangiocarcinoma cases surgically resected from January 1998 to May 2013. The study patients were divided into two groups: those whose tumors showed a predominantly tubular growth pattern (n = 52) and those whose tumors exhibited a predominantly papillary growth pattern (n = 109). Tubular growth pattern was associated with combined vascular resection and the absence of macroscopic mucin. Several histological indexes were significantly higher for the tubular growth pattern than the papillary one, including tubular adenocarcinoma, depth of invasion, microscopic lymphatic invasion, venous invasion, perineural invasion, and necrosis. Although the survival curves overlapped (P = 0.693), the rate of liver metastasis was significantly higher for the tubular growth pattern than for the papillary one (P = 0.012). Genomic DNA analysis focusing on somatic mutations in codons 12 and 13 of KRAS and codon 600 of BRAF revealed only one (4%) KRAS and no BRAF mutation among the 25 tubular cases examined. In conclusion, the tubular growth pattern exhibited differences in some histologic indexes, in addition to a higher hepatic metastasis rate and a lower KRAS mutation frequency, compared with the papillary growth pattern, but no difference in prognosis was observed. The distinctiveness of this tubular neoplasm should be further examined in the future.

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“…in models of pancreatic, breast and colon cancers, Smad4 was shown to activate the molecular mechanisms regulating tumor cell migration and invasion (12)(13)(14). However, there are only limited available data regarding whether TGF-β1-Smad4 is involved in the invasion and metastasis of Hcc.…”

Section: Introductionmentioning

confidence: 99%

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

Ji¹

2010

Mol Med Rep

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Abstract. Hepatocellular carcinoma (Hcc) is a highly malignant cancer characterized by rapid progression, easy metastasis and frequent recurrence. Previous studies have shown that the Smad4 signaling pathway plays an important role in the cell growth and apoptosis of Hcc. However, the effect of Smad4 signaling on the invasion and migration of Hcc cells remains unclear. The present study aimed to examine the effects of the transforming growth factor (TGF)-β1-Smad4 signaling pathway on the migration of Hcc cells. lentiviral vectors expressing mirna against Smad4 were constructed to block the expression of Smad4 in Hcc cells, and transwell units were used to investigate the invasive potential of SMMc-7721 cells before and after TGF-β1 treatment. mrna levels of matrix metalloproteinase (MMP)-2 and -9 were analyzed by reverse-transcription Pcr, and concentrations of vascular endothelial growth factor (VeGF), p-JnK, p-p38 and p-erk1/2 proteins were analyzed by Western blotting. The results indicate that TGF-β1 induced cellular invasion in the SMMc-7721 cells. These effects were almost completely blocked by the knockdown of Smad4. reverse-transcription Pcr and Western blot analysis revealed that MMP-2, VeGF, p-JnK and p-p38 were up-regulated by the silencing of Smad4, while the expression of MMP-9 and p-erk1/2 was not affected by Smad4 silencing with or without TGF-β1 stimulation. These findings suggest that TGF-β1-induced SMMc-7721 cell invasion by the up-regulation of MMP-2 and VeGF is Smad4-dependent. The activation of MMP-2 and VeGF may be an important mechanism by which Smad4 is involved in metastasis. TGF-β1-Smad4 signaling may regulate SMMc-7721 cell migration through the activation of the MaPK pathway.

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Intraductal Tubulopapillary Neoplasms of the Pancreas Distinct From Pancreatic Intraepithelial Neoplasia and Intraductal Papillary Mucinous Neoplasms

Cited by 193 publications

References 29 publications

Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective

Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective

Cholangiocarcinoma with intraductal tubular growth pattern versus intraductal papillary growth pattern

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

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