High‐grade Pan IN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer
Abstract
Aims: This study aimed to identify the pathological features of high‐grade Pan IN that presents with imaging‐detectable abnormalities. Methods and results: Ten cases of isolated, main‐duct, high‐grade Pan IN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with two being associated with extensive upstream duct dilatation (>5 mm in diameter). Pancreatic juice cytology suggested adenocarcinoma in all seven cases examined. In resected specimens, high‐grade Pan IN was present chiefly in the main pancreatic duct, with longitudinal extension ranging between 3 and 40 mm in length (median = 18 mm). In four cases, in which hypoechoic or hypovascular masses were observed on imaging, radiopathology correlations suggested that they represented parenchymal atrophy and subsequent fibrosis around affected ducts, but not invasive malignancy. On immunohistochemistry, the loss of p16 expression was found in five (50%), p53 overexpression in two (20%) and loss of SMAD 4 expression in none (0%). KRAS mutations were detected in nine cases, with two dominant clones being found in three by ultrasensitive droplet digital polymerase chain reaction, suggesting the genetic heterogeneity of dysplastic cells composing individual lesions. Mutant GNAS was also observed in one case. Conclusions: Isolated high‐grade Pan IN may present with pancreatic duct stenosis. Therefore, intensive investigations including pancreatic juice cytology will be required for patients with unexplained pancreatic duct stenosis. The abnormal expression of p53 and SMAD 4 is infrequent, while GNAS may be mutated in premalignant lesions mainly affecting the main pancreatic duct, similar to KRAS.
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In a study of 10 patients with high-grade pancreatic intraepithelial neoplasia, localized pancreatic duct stricture was found in all patients.
“In a study of the imaging findings of 10 patients with high-grade pancreatic intraepithelial neoplasia, as the premalignant lesion, localized pancreatic duct stricture was found in all patients (30).”
From Suspicious findings observed retrospectively on CT imaging performed before the diagnosis of pancreatic cancer (2023) · cites this paper as [30]
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- Authors
- Yokode, M., Akita, M., Fujikura, K., Kim, M., Morinaga, Y., Yoshikawa, S., Terada, T., Matsukiyo, H., Tajiri, T., Abe‐Suzuki, S., Itoh, T., Hong, S., & Zen, Y.
- Affiliations
- Kobe City Medical Center West Hospital (JP)
- Kobe University (JP)
- Asan Medical Center (KR)
- Nagaoka Red Cross Hospital (JP)
- Fukui-ken Saiseikai Hospital (JP)
- Toho University Ohashi Medical Center (JP)
- Tokai University Hachioji Hospital (JP)
- Corresponding author
- Hong, Seung‐Mo
- Zen, Yoh
- ORCID
- Venue
- Histopathology
- Publisher
- Wiley
- Published
- 2018-05-30
- Volume
- 73
- Issue
- 2
- Pages
- 247-258
- ISSN
- 0309-0167 (ISSN-L)
- 1365-2559
- OpenAlex
- W2799853953
- Cited by
- 44
- References
- 25
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 1 · 2021: 4 · 2020: 6 · 2019: 9 · 2018: 3
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Histopathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15K08345, 18H02630)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Keywords
- main pancreatic duct stenosis, pancreatic duct dilatation, pancreatic juice cytology, KRAS mutation, GNAS mutation, p53 overexpression, SMAD4 loss, p16 loss, pancreatic fibrosis, premalignant pancreatic lesions, genetic heterogeneity
- MeSH terms
- Aged, Carcinoma in Situ, Chromogranins, Constriction, Pathologic, Female, Humans, Male, Middle Aged, Mutation, Pancreatic Ducts, Pancreatic Neoplasms, Biomarkers, Tumor, Proto-Oncogene Proteins p21(ras), GTP-Binding Protein alpha Subunits, Gs, Carcinoma, Pancreatic Ductal, Early Detection of Cancer
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