Pancreatic specimens from SPINK1 patients with a 7-to-15-year history of abdominal pain. The pancreata demonstrated increasing loss of acinar cell epithelium and intralobular ducts, which coincided with intralobular, interlobular and perilobular fibrosis (A and B). Ductal ectasia, squamous metaplasia and intraductal concretions were also present (C). The periphery of the pancreas was remarkable for complete loss of acinar and ductal epithelium, but preservation of islets of Langerhans and surrounding nerves (D). In addition, while the majority of patients were heterozygous for SPINK1, 3 patients were SPINK1 homozygotes with reported abdominal pain between 8.1 to 10 years and their pancreata exhibited similar histopathologic features as their SPINK1 heterozygous counterparts with ductal ectasia and intraductal concretions (E) and both intralobular and interlobular fibrosis (F).