The normal pancreas is a large mixed exocrine and endocrine gland, with acinar cells arranged around ducts in lobular units. The acinar cells secrete digestive enzymes in precursor form, which travel to the duodenum via the ducts. Normal ducts are low cuboidal epithelium, and the acinar cells are wedge-shaped granular pink and purple cells (Figure 10.1). Scattered among them are the islets of Langerhans, which show typical neuroendocrine cytology and are arranged in little nests. The pancreas is shaped like a J, with the head forming the base of the J and the uncinate process the hook. The head is nestled in the curve of the duodenum near the major papilla. The distal common bile duct runs through the head of the pancreas and joins the main pancreatic duct to form the ampulla just before entering the duodenum (Figure 10.2).

The Whipple procedure is, at minimum, a pancreaticoduodenectomy , which may or may not also include pylorus of the stomach and the gallbladder. In the pylorus-preserving Whipple, the simplest version, you receive the segment of duodenum from just past the pylorus to about 20 cm beyond the ampulla of Vater. Usually it is only the head of the pancreas that accompanies the Whipple specimen; if the tail is also involved by tumor, you may get the total pancreas and spleen. A resection of only the tail is a distal pancreatectomy and comes with attached spleen but no duodenum.

Margins are the most complicated element of the Whipple specimen, so a word on general margin strategy and nomenclature is in order. In any specimen, not just the pancreas, there are two principal types of margin: shave (also called tangential or en face) and perpendicular. If you consider a loaf of bread, with the inked margin represented by the crust, a shave margin would be the heel of the loaf, in which one entire surface is covered with crust. This type of margin is sectioned parallel to the inked surface, and therefore the entire block is a margin; the presence of any tumor, regardless of ink, is a positive margin. The shave margin is best used when: (1) you need to evaluate the entire margin, not just a representative cross section, and (2) the presence of tumor within 1 mm of the ink is considered a positive margin, even if the tumor doesn’t actually touch the inked surface. The ends of hollow structures, like the colon, stomach, ureter, etc., are almost always sampled by shave margin , as you can see the entire circumference of the ring on one or two slides.

The perpendicular margin, on the other hand, is represented by a slice of bread in the middle of the loaf. In this slice, there is only crust around the edge of the bread. In a perpendicular margin, the margin is only positive if tumor extends to the ink; tumor away from the inked surface is irrelevant. A related concept is the radial margin, in which you slice a round specimen into pizzalike slices, and only the outer rim of pizza crust is a true margin. The perpendicular margin is used if you want to get a precise measurement of how close the tumor is to the margin, as you can see the relationship of tumor to ink on the slide. Edges that are very close to solid tumors are usually sampled by perpendicular margin. The downside is that like a single slice of bread, a perpendicular margin is only a representative sample, unless you are submitting the entire tumor. Therefore, you are relying on your ability to grossly identify the point at which the tumor is closest to the margin.

Now back to the Whipple. There are five principal margins that are usually sampled on frozen section (Figure 10.2). The first is the pancreatic margin, called the pancreatic neck (where the pancreas is transected). This is usually taken as a shave margin . There is no neck margin on a total pancreatectomy. The second margin is the common bile duct margin, which is a shave of the bile duct stump. This ensures that cancer is not tracking up the bile duct toward the liver. The third is the uncinate (retroperitoneal) margin . This is the edge of the short end of the J, and it represents the place where the pancreas sits against the retroperitoneum. This surface is inked, and you take one representative perpendicular margin. Cancer on the slide is okay, as long as it does not touch ink. As this tissue abuts major vessels and nerves, the surgeon often cannot resect additional tissue if this is positive, but it has prognostic and therapeutic implications. The fourth and fifth margins are the proximal and distal duodenal margins, taken as shave margins. It is rare for these sections to contain tumor.

Most Whipple procedures are performed for a pancreatic mass seen radiologically. There may be no prior biopsy of tumor available. For this reason, it is useful to include a slide of tumor, often adjacent to the uncinate margin, at the time of frozen section so that you can compare funny looking cells on the margins to the morphology of the tumor itself.

Chronic pancreatitis is a common finding in a resected pancreas. The damage done to the pancreas by chronic obstruction, as with a mass, causes diffuse fibrosis, atrophy of the acinar units, reactive changes, and disruption of the normal architecture, all of which can mimic carcinoma. One of the hardest tasks (especially on frozen section) is differentiating reactive pancreatic ducts from well-differentiated infiltrating adenocarcinoma, the most common pancreatic malignancy. Some tips include the following: