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Scientifically reviewed by: Michael A. Smith, MD
Illustration indicating the location of the pancreas
Figure 1. Location of the Pancreas. Credit: BruceBlaus, CC BY-SA 4.0, via Wikimedia Commons

The pancreas is an organ in the upper abdominal cavity that has both endocrine and exocrine functions. Its exocrine functions are to make digestive enzymes, and its endocrine role is to make insulin and glucagon for glucose metabolism. The pancreas is surrounded by the stomach, small intestine, liver, and spleen, and is subdivided into a head, body, and tail. The head is very close to the small intestine and connects to it via the pancreatic duct, and the tail is near the spleen. The cell types that make up the pancreas are primarily ductal cells, acinar cells, and islet cells—any of which can give rise to a tumor, as well as primitive cells.12

Pancreatic cancer develops from previously normal cells through a build-up of genetic mutations, either inherited or arising when cells are dividing.4 As the cancer evolves, these genetic mutations can alter the appearance of cells. Several precursor lesions (discussed below) are recognized which, if left untreated, would be expected to develop into pancreatic cancer. These precursor lesions may also be present within or near pancreatic cancer and can be identified on biopsy and surgical resection.

Diagram of the various parts of the pancreas
Figure 2. The Pancreas. Credit: OpenStax College. CC BY 3.0, via Wikimedia Commons

Exocrine Pancreatic Cancers

As in other organs of the body, pancreatic neoplasms, or abnormal tissue masses, can be benign or malignant. Of all pancreatic neoplasms, approximately 85% are ductal adenocarcinoma and its subtypes.13 Ductal adenocarcinoma forms from ductal cells which, along with acinar cells, make up the exocrine pancreas. Over 95% of pancreatic cancers originate from the exocrine pancreas.12 Because of its frequency, the term “pancreatic cancer” generally refers to ductal adenocarcinoma; this meaning will be used throughout this text, and ductal adenocarcinoma is the main topic of this protocol.

The majority (60‒70%) of ductal adenocarcinomas arise in the head of the pancreas, with about 15% in the body and 15% in the tail.4 Those arising in the head of the pancreas tend to present earlier because they block a main duct via which bile leaves, resulting in jaundice and epigastric pain. When surgically removed, ductal adenocarcinomas average 3-5 cm in size and show invasion of surrounding tissue. The cancer can also invade nerves, blood vessels, and lymphatics within the pancreas. Direct extension to nearby organs and larger blood vessels outside of the pancreas is common.12

There are several types of pancreatic cancer that look and behave differently but are still considered to be ductal in origin. Adenosquamous carcinoma has at least 30% squamous cells and has a worse prognosis than ductal adenocarcinoma. Undifferentiated/anaplastic carcinoma has little to no resemblance to normal ductal cells and is a highly aggressive cancer with extremely poor survival rates. A type with a better prognosis is colloid/mucinous carcinoma. In this form, large amounts of mucin—a gel-like fluid that is made by normal glands and some adenocarcinomas—are secreted into the surrounding tissue. Most colloid/mucinous carcinomas form in association with intraductal papillary mucinous neoplasms (described below).4

Precursor Lesions

Pancreatic intraepithelial neoplasia (PanIN) is a non-invasive lesion composed of abnormal ductal cells. The lesions arise in small pancreatic ducts and are too small to be detected by imaging studies. As a non-invasive lesion, PanIN cannot spread to other parts of the body, but may progress over time and eventually become ductal adenocarcinoma. The changes in the appearance of cells can be graded into low-grade PanIN and high-grade PanIN.12

Intraductal papillary mucinous neoplasms (IPMNs) are another category of precursor lesion. Unlike PanIN, which are very small lesions in small ducts, IPMNs are larger and grow in the main pancreatic duct or its smaller branches. The location is relevant because co-existing cancer is found in about 70% of main pancreatic duct IPMNs versus only 25% of those arising inside branches.4

Mucinous cystic neoplasms (MCNs) are precursor lesions that appear as cysts and so must be distinguished from benign pancreatic cysts. One study found that about 25% of surgically resected pancreatic cysts are MCNs.14 Of MCNs resected, approximately 18% have been found to have co-existing cancer.15 Diagnosis of MCN requires surgical excision with examination by a pathologist.12 Recognition of pancreatic cysts on abdominal imaging offers one of the few opportunities for early intervention in the prevention and early diagnosis of pancreatic cancer.4

Non-Ductal Exocrine Pancreatic Cancers

A few non-ductal cancers can arise in the exocrine pancreas and are much less common than ductal cancers.

As previously described, the exocrine pancreas includes not just ductal cells but also acinar cells. Cancers arising from this cell type are calledacinar cell carcinoma and mixed acinar carcinomas. These are rare cancers, representing only 1‒2% of all adult pancreatic neoplasms, and 15% of pancreatic neoplasms in the pediatric population.16

Pancreatoblastoma arises from primitive cells and can have different appearances. Although rare in adults, it is the most common pancreatic neoplasm in children, comprising about 25% of all cases.16

Finally, solid pseudopapillary neoplasm is a low-grade cancer that represents 2‒5% of all pancreatic cancers; it is not well-understood what cell it arises from.16

Endocrine Pancreatic Cancers

Cancers of the endocrine pancreas fall under the general category of pancreatic endocrine neoplasms (PENs), which include insulinomas and glucagonomas. Due to their unpredictable behavior, prognosis can be difficult to determine. They may be functioning (secreting hormones and thus giving rise to related symptoms) or non-functioning. While many small PENs can be cured with surgical resection, larger (>2 cm) tumors have a worse prognosis; of this group, 50‒80% ultimately recur or spread to other parts of the body.16