Abstract

Simple SummaryPancreatic ductal adenocarcinoma (PDAC) is typically associated with an extremely poor prognosis; however, small PDAC tumors show good prognosis. High-grade pancreatic intra-epithelial neoplasia (PanIN), which precedes invasive PDAC, is a primary target for improving the prognosis of PDAC. However, detection of high-grade PanIN without invasive carcinoma by existing imaging modalities is difficult because the lesions are only microscopically detectable. Recent studies have reported the characteristics of imaging findings associated with localized high-grade PanIN and the usefulness of serial pancreatic-juice aspiration cytologic examination as a method to confirm the pre-operative histopathology. In this review, we aimed to clarify recent clinical findings regarding detection of localized high-grade PanIN, which may contribute to improvement of the prognosis of patients with PDAC.Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions, such as pancreatic intra-epithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). The prognosis of high-grade precancerous lesions, including high-grade PanIN and high-grade IPMN, without invasive carcinoma is good, despite the overall poor prognosis of PDAC. High-grade PanIN, as a lesion preceding invasive PDAC, is therefore a primary target for intervention. However, detection of localized high-grade PanIN is difficult when using standard radiological approaches. Therefore, most studies of high-grade PanIN have been conducted using specimens that harbor invasive PDAC. Recently, imaging characteristics of high-grade PanIN have been revealed. Obstruction of the pancreatic duct due to high-grade PanIN may induce a loss of acinar cells replaced by fibrosis and lobular parenchymal atrophy. These changes and additional inflammation around the branch pancreatic ducts (BPDs) result in main pancreatic duct (MPD) stenosis, dilation, retention cysts (BPD dilation), focal pancreatic parenchymal atrophy, and/or hypoechoic changes around the MPD. These indirect imaging findings have become important clues for localized, high-grade PanIN detection. To obtain pre-operative histopathological confirmation of suspected cases, serial pancreatic-juice aspiration cytologic examination is effective. In this review, we outline current knowledge on imaging characteristics of high-grade PanIN.

Highlights

  • The incidence of pancreatic cancer (PC) has been increasing worldwide, and PC has the seventh most frequent cause of cancer-related mortality, with more than 432,000 deaths per year [1]

  • pancreatic intra-epithelial neoplasia (PanIN) lesions, high-grade PanIN lesions found in pancreatic ducts unrelated to intraductal papillary mucinous neoplasm (IPMN), should be associated with the development of concomitant invasive Pancreatic ductal adenocarcinoma (PDAC) coexisting with IPMN [104]

  • Another study retrospectively reviewed patients with PanIN who underwent pancreatectomy for non-IPMN and non-PDAC; the findings showed that 2.2% of patients had high-grade PanIN lesions [108]

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Summary

Introduction

The incidence of pancreatic cancer (PC) has been increasing worldwide, and PC has the seventh most frequent cause of cancer-related mortality, with more than 432,000 deaths per year [1]. The 5-year survival rate of patients with high-grade precancerous lesions (mainly high-grade PanIN and IPMN with high-grade dysplasia without accompanying invasive carcinoma; Union for the International Cancer Control stage 0 PC [carcinoma in situ]) [8,10] is over 85%. High-grade PanIN is difficult to detect without an associated invasive PDAC. High-grade PanIN is rarely found in large-scale screening studies of patients with a strongly related family history or with PDAC-associated gene mutations [20,21,22,23,24,25,26,27,28]. High-grade dysplasia is related to a high risk of progression into invasive carcinoma and requires surgical management [8,10,36]

Genetic Features
Chronic Pancreatitis
IPMN with High-Grade Dysplasia
High-Grade PanIN Associated with IPMN
Other Pancreatic Diseases
Aging Pancreas
Indirect Imaging Characteristics of High-Grade PanIN
Focal PPA
Hypoechoic Changes Around the MPD
Other Newer Imaging Modalities
Pre-Operative Histopathological Diagnosis of High-Grade PanIN
Challenges in Diagnosis and Follow-Up
Limitation of High-Grade PanIN Diagnosis
Findings
Conclusions
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