Classification, Morphology, Molecular Pathogenesis, and Outcome of Premalignant Lesions of the Pancreas

Pittman, Meredith E.; Rao, Rema; Hruban, Ralph H.

doi:10.5858/arpa.2016-0426-ra

Cited by 41 publications

(48 citation statements)

References 78 publications

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“…Low-grade PanINs are common and incidentally observed in the general populations over the age of 50 [8,9]. In contrast, high-grade PanINs are frequently found in association with PDACs [5,8,10,11,12]. Low-grade PanINs express MUC5AC and MUC6, while high-grade PanINs express MUC1.…”

Section: Paninmentioning

confidence: 99%

“…GNAS mutations are the second most common and occur in approximately 40-79% of IPMNs [53,54,55,56], and this can be used to differentiate IPMNs from other pancreatic cystic lesions including MCNs, solid pseudopapillary neoplasms, and serous cystic neoplasms [10]. RNF43 mutations are detected in 14-38% of IPMNs [53,55,56,57].…”

Section: Ipmnmentioning

confidence: 99%

“…1N, O) [5]. Cytological features alone are not sufficient to differentiate MCNs from IPMNs because of their cytological similarities [10]. The presence of subepithelial ovarian-type stroma is a pathognomonic feature of MCN, which differentiate MCNs from IPMNs [10].…”

Section: Mcnmentioning

confidence: 99%

“…Cytological features alone are not sufficient to differentiate MCNs from IPMNs because of their cytological similarities [10]. The presence of subepithelial ovarian-type stroma is a pathognomonic feature of MCN, which differentiate MCNs from IPMNs [10]. The genetic alterations found in MCNs are not specific to them and overlap with those in IPMNs and PDACs, which include KRAS , TP53 , SMAD4 , and CDKN2A/p16 mutations [79].…”

Section: Mcnmentioning

confidence: 99%

“…Ovarian-type stroma is decreased or destroyed in high-grade MCNs or at the site of invasion [82,87,88]. Risk factors for combining of invasive components are large size, presence of a solid portion, and thickening of septations on radiological findings, and intracystic solid nodules with papillary structures, and severe nuclear atypia on pathological findings [10,82,89,90]. …”

Section: Mcnmentioning

confidence: 99%

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Precursor Lesions of Pancreatic Cancer

Kim

Hong

2018

Oncol Res Treat

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Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. Although the treatment modalities are improving, the prognosis of PDAC continues to be poor. Therefore, early detection of PDAC or its precursor lesions may be the best way to improve patient survival. PDACs have several different precursor lesions, including pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), intraductal tubulopapillary neoplasms (ITPNs), intraductal oncocytic papillary neoplasms (IOPNs), and mucinous cystic neoplasms (MCNs). PanINs cannot be identified using imaging modalities, while the other lesions are radiologically detectable. These precursor lesions are categorized based on structural and cytological atypia as low-grade and high-grade lesions. We discuss recent updates regarding histopathological and molecular pathological overviews of PDAC precursor lesions. Better understanding of such lesions may contribute to earlier detection of PDAC or its precursor lesions and improve PDAC patient survival.

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Section: Paninmentioning

confidence: 99%

Section: Ipmnmentioning

confidence: 99%

Section: Mcnmentioning

confidence: 99%

Section: Mcnmentioning

confidence: 99%

Section: Mcnmentioning

confidence: 99%

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Precursor Lesions of Pancreatic Cancer

Kim

Hong

2018

Oncol Res Treat

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Downregulation of 5‐hydroxymethylcytosine is an early event in pancreatic tumorigenesis

Fujikura

Alruwaii

Haffner

et al. 2021

The Journal of Pathology

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Epigenetic alterations are increasingly recognized as important contributors to the development and progression of pancreatic ductal adenocarcinoma. 5‐hydroxymethylcytosine (5hmC) is an epigenetic DNA mark generated through the ten‐eleven translocation (TET) enzyme‐mediated pathway and is closely linked to gene activation. However, the timing of alterations in epigenetic regulation in the progression of pancreatic neoplasia is not well understood. In this study, we hypothesized that aberrant expression of ten‐eleven translocation methylcytosine dioxygenase 1 (TET1) and subsequent global 5hmC alteration are linked to early tumorigenesis in the pancreas. Therefore, we evaluated alterations of 5hmC and TET1 levels using immunohistochemistry in pancreatic neoplasms (n = 380) and normal ducts (n = 118). The study cohort included representation of the full spectrum of precancerous lesions from low‐ and high‐grade pancreatic intraepithelial neoplasia (n = 95), intraductal papillary mucinous neoplasms (all subtypes, n = 129), intraductal oncocytic papillary neoplasms (n = 12), and mucinous cystic neoplasms (n = 144). 5hmC and TET1 were significantly downregulated in all types of precancerous lesion and associated invasive pancreatic ductal adenocarcinomas compared with normal ductal epithelium (all p < 0.001), and expression of 5hmC positively correlated with expression of TET1. Importantly, downregulation of both 5hmC and TET1 was observed in most low‐grade precancerous lesions. There were no clear associations between 5hmC levels and clinicopathological factors, thereby suggesting a common epigenetic abnormality across precancerous lesions. We conclude that downregulation of 5hmC and TET1 is an early event in pancreatic tumorigenesis. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Pancreatic Adenocarcinoma: Current Status in Diagnostic Methods, Surgical Techniques, Complications, and Short/Long-Term Survival

Muñoz

Martin

Tuñón

et al. 2023

Recent Innovations in Surgical Procedures of Pancreatic Neoplasms

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Classification, Morphology, Molecular Pathogenesis, and Outcome of Premalignant Lesions of the Pancreas

Abstract: - Our understanding of the molecular alterations that lead from pancreatic precursor lesion to invasive carcinoma continues to evolve. These advances aid clinicians in their treatment decisions and researchers in their search for actionable, druggable targets.

Cited by 41 publications

References 78 publications

Precursor Lesions of Pancreatic Cancer

Precursor Lesions of Pancreatic Cancer

Downregulation of 5‐hydroxymethylcytosine is an early event in pancreatic tumorigenesis

Pancreatic Adenocarcinoma: Current Status in Diagnostic Methods, Surgical Techniques, Complications, and Short/Long-Term Survival

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