Micrograph of<unk>  ductal adenocarcinoma (the most common type of<unk> , H&E stain Precancer Micrographs of normal pancreas,<unk>  intraepithelial neoplasia (precursors to<unk>  carcinoma) and<unk>  carcinoma. H&E stain Exocrine cancers are thought to arise from several types of precancerous lesions within the pancreas, but these lesions do not always progress to cancer, and the increased numbers detected as a byproduct of the increasing use of CT scans for other reasons are not all treated. Apart from<unk>  serous cystadenomas, which are almost always benign, four types of precancerous lesion are recognized. The first is<unk>  intraepithelial neoplasia. These lesions are microscopic abnormalities in the pancreas and are often found in autopsies of people with no diagnosed cancer. These lesions may progress from low to high grade and then to a tumor. More than 90% of cases at all grades carry a faulty KRAS gene, while in grades 2 and 3, damage to three further genes – CDKN2A (p16), p53, and SMAD4 – are increasingly often found. A second type is the intraductal papillary mucinous neoplasm (IPMN). These are macroscopic lesions, which are found in about 2% of all adults. This rate rises to about 10% by age 70. These lesions have about a 25% risk of developing into invasive cancer. They may have KRAS gene mutations (40–65% of cases) and in the GNAS Gs alpha subunit and RNF43, affecting the Wnt signaling pathway. Even if removed surgically, a considerably increased risk remains of<unk>  developing subsequently. The third type,<unk>  mucinous cystic neoplasm (MCN), mainly occurs in women, and may remain benign or progress to cancer. If these lesions become large, cause symptoms, or have suspicious features, they can usually be successfully removed by surgery. A fourth type of cancer that arises in the pancreas is the intraductal tubulopapillary neoplasm. This type was recognised by the WHO in 2010 and constitutes about 1–3% of all<unk>  neoplasms. Mean age at diagnosis is 61 years (range 35–78 years). About 50% of these lesions become invasive. Diagnosis depends on histology, as these lesions are very difficult to differentiate from other lesions on either clinical or radiological grounds. Invasive cancer The genetic events found in ductal adenocarcinoma have been well characterized, and complete exome sequencing has been done for the common types of tumor. Four genes have each been found to be mutated in the majority of adenocarcinomas: KRAS (in 95% of cases), CDKN2A (also in 95%), TP53 (75%), and SMAD4 (55%). The last of these is especially associated with a poor prognosis. SWI/SNF mutations/deletions occur in about 10–15% of the adenocarcinomas. The genetic alterations in several other types of<unk>  and precancerous lesions have also been researched. Transcriptomics analyses and mRNA sequencing for the common forms of<unk>  have found that 75% of human genes are expressed in the tumors, with some 200 genes more specifically expressed in<unk>  as compared to other tumor types. PanNETs The genes often found mutated in PanNETs are different from those in exocrine<unk> . For example, KRAS mutation is normally absent. Instead, hereditary MEN1 gene mutations give rise to MEN1 syndrome, in which primary tumors occur in two or more endocrine glands. About 40–70% of people born with a MEN1 mutation eventually develop a PanNet. Other genes that are frequently mutated include DAXX, mTOR, and ATRX.
Pancreatic cancer
Autoimmune pancreatitis
Liver cancer
Duodenal cancer
Gallbladder cancer
Periampullary cancer
Kang cancer
Small intestine cancer