Pathology analysis reveals that dysplastic pancreatic ductal lesions are frequent in patients with hereditary pancreatitis

Clin Gastroenterol Hepatol. 2010 Feb;8(2):206-12. doi: 10.1016/j.cgh.2009.09.009. Epub 2009 Sep 16.

Abstract

Background & aims: Hereditary pancreatitis (HP) is a risk factor for pancreatic adenocarcinoma. We performed a retrospective, multicenter study to characterize and evaluate the frequency of pancreatic intraepithelial neoplasia (PanIN) and to describe the characteristics of fibrosis in pancreatic surgical specimens from patients with HP.

Methods: Samples from partial pancreatectomies (n = 13) of patients with HP complications (n = 12; 7 males; mean age, 24 y; 1 patient underwent 2 surgeries over 16 years) were analyzed by histologic and immunohistologic analyses; patients with suspected or proven pancreatic adenocarcinoma were excluded. HP diagnosis was confirmed by analysis of PRSS1 mutations. Dysplastic lesions were described according to the PanIN classification.

Results: Eleven patients were found to have the R122H mutation in PRSS1 and 1 patient was found to have the N29I mutation in PRSS1. Fifty-one PanIN lesions were observed in 10 specimens (77%): PanIN lesions 1a, 1b, 2, and 3 were observed in 8, 5, 8, and 5 specimens, respectively. The median number of PanIN lesions was 3.5 for each specimen. The density of the lesions was 2.6 per 10 cm(2). The size of lesions was greater than 0.5 mm in 55% of the samples. Two patients with PanIN-3 developed pancreatic cancer, 18 months and 44 years after surgery.

Conclusions: PanIN lesions are frequent, severe, and occur early in the course of HP. Among patients with PanINs, 50% had PanIN-3 lesions. Pancreatectomy could be considered as a prophylactic against pancreatic cancer in patients with high-grade dysplasia.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Carcinoma in Situ / epidemiology*
  • Carcinoma, Pancreatic Ductal / epidemiology*
  • Child
  • Child, Preschool
  • Female
  • Genetic Diseases, Inborn / complications*
  • Humans
  • Male
  • Middle Aged
  • Pancreatectomy
  • Pancreatic Ducts / pathology*
  • Pancreatic Neoplasms / epidemiology*
  • Pancreatitis / complications*
  • Retrospective Studies
  • Trypsin / genetics
  • Young Adult

Substances

  • PRSS1 protein, human
  • Trypsin