Liver / Pancreas
Taiwanese pathology site
Good place to go to practice
Pancreas
Photo Library of Pathology
U. of Tokushima
Title: Exocrine Pancreas
Date & Time: Thursday, March 2, 2012 at 9 AM
Lecturer: The Pathology Team
QUIZBANK Pancreas (all except #'s 1-8)
|
|
|
|
|
|
|
|
|
|
|
|
|
NORMAL PANCREAS
I'm tired of all this nonsense about beauty being only skin-deep. That's deep enough. What do you
want -- an adorable pancreas?
Eat when you can.
Sleep when you can.
Don't touch the pancreas.
{25019} normal pancreas, the white hamburger
{14887} normal pancreas, trichrome; no blue, so no
dense fibrous tissue in the healthy pancreas.
{12463} islets of Langerhans (no, IZZ-lett is not really an acceptable pronunciation);
H&E stain
Unqualified, disease of the pancreas ("pancreatitis", "pancreatic tumor", "pancreatic cancer", etc.) means disease of the exocrine pancreas. The plural of "pancreas" is "pancreata".
| You are already familiar with the gross and microscopic structure, and the physiology, of the exocrine and endocrine pancreas. |
|
Because of its lobulated texture, many surgeons and pathologists call the pancreas "the hamburger".
Remember that the islands make up about 15% of the organ's weight, and that they are concentrated in the tail.
Fatty ingrowth is common in the normal pancreas, and this fat can undergo fat necrosis.
The exocrine pancreas has great functional reserve, and no symptoms will occur until 85% or so of the gland is gone.
To keep your pancreas healthy, your digestive enzymes must not be activated until they reach the duodenum! Ordinarily, trypsinogen is activated only on contact with enterokinase (from the duodenal mucosa), and trypsin in turn activates the other enzymes.
Immunostaining the cells of the pancreas is now routine whenever there is a question about the nature of a pancreatic mass; this is common and you'll see these in reports (Cancer 66: 2134, 1990):
acinar... trypsin, lipase
ductal... carbonic anhydrase, CEA-125, or just plain old mucin from the pre-immunostain era
islet... somatostatin, chromogranin, of course specific hormones
The embryonic pancreas arises from the duodenum as two buds.
* Embryologists: The "dorsal bud" contributing the bulk of the organ, all that is drained by the duct of Wirsung; the ventral bud contributes the small portion drained by the "duct of Santorini".
The anatomy of the pancreatic ducts is variable. Don't worry about this unless you are a surgeon.
In a few % of autopsies, one or more pancreatic choristomas are found somewhere in the gut. These are confusing when found, but probably cause no problems.
An "annular pancreas" is wrapped around the duodenum, and gets blamed for obstruction.
{49140} annular pancreas; sideways, liver on left, pancreas extends across duodenum and gall bladder
The adult organ varies widely in size ("Big Robbins"'s 60-140 gm seems reasonable). Anatomists talk about "head, body, and tail", which are visible with a little imagination; you may even hear about a "neck".
THE PANCREAS IN SYSTEMIC DISEASE
You remember that cystic fibrosis is a dread, common disease that causes atrophy of the pancreatic acini and malabsorption (actually, maldigestion). It's now clear that some mutant CFTR homozygotes have normal sweat chloride studies and only pancreatic damage ("chronic pancreatitis" -- Gut 52-S2: S-31, 2003; NEJM 339: 645, 1998; Dig. Dis. Sci. 45: 2007, 2000; Chest 126: 1215, 2004).
{00044} cystic fibrosis; trichrome stain,
showing dilated ducts plugged with good, and absent acini
{20204} hemochromatosis; Prussian Blue stain
{24505} hemochromatosis, gross, one's a Prussian blue
{24506} hemochromatosis, rusty color
{38848} hemochromatosis, rusty color. Scar tissue is white.
ACUTE
PANCREATITIS ("soapsuds"; "chicken soup"; the classic term "rum belly" seems no longer in use; NEJM 330: 1998, 1994;
Lancet 361: 1446, 2003 also describes chronic cases;
update Lancet 371: 143, 2008; inflammatory mediation Surg. Clin. N.A. 87:
1325, 2007)
{39802} acute pancreatitis. Feels as bad as it looks.
{49232} ditto. Black area is a big hematoma.
Hemorrhagic pancreatitis
Urbana Atlas of Pathology
This is defined as inflammation of the exocrine pancreas with damage to the acinar cells.
While "Big Robbins" distinguishes "acute interstitial-edematous" and "acute hemorrhagic-necrotizing", these probably describe varying degrees of severity of the same underlying process, and there's no longer much discussion. With imaging, we're coming to recognize milder cases of pancreatitis than in the past. "Big Robbins" is also simply wrong to say acute pancreatitis is "by no means common"; it is one of the most common severe intra-abdominal processes in adults, accounting for 240,000 annual admissions in the US (Ann. Surg. 250: 712, 2009 -- a Dutch study in which "probiotic bacteria" for acute pancreatitis were a catastrophic failure).
Whatever the etiology in a specific case, pancreatitis is perpetuated by release of activated digestive enzymes into the organ and surrounding tissues. Intracellular activation of trypsinogen is the essential lesion; trypsin is presently credited with activating the other enzymes, as well as kallikrein (remember that?). Whatever abnormally activates trypsinogen must be the cause of pancreatitis.
* Minimally-invasive drainage for necrotizing pancreatitis seems as good as or maybe better than the classic open "necrosectomy". See NEJM 362: 1491, 2010.
CHRONIC PANCREATITIS (Lancet 377: 1184, 2011) is a misnomer for pancreatic insufficiency and/or pain that probably is caused by a previous episode of acute pancreatitis.
Because of its nature, any injury to the acinar cells will release digestive enzymes (trypsin, elastases, other proteases, amylases, lipases, phospholipase) and result in more extensive damage.
"Idiopathic hereditary pancreatitis" often results from a mutant trypsinogen gene (PRSS1, Lancet 354: 42, 1999; Gut 44: 259, 1999). Also common is a mutated pancreatic protease inhibitor (SPINK1 antitrypsin: Gut 53: 723, 2004; Gut 50: 687, 2002).
The clinical diagnosis of pancreatitis is generally made on the basis of finding damage to the pancreatic acinar cells, i.e., by finding an elevated blood amylase and/or lipase.
Pitfall: About 1% of humankind has "macroamylasemia", a "large amylase" molecule (i.e., one bound to an autoantibody) that is cleared abnormally slowly via the kidney (i.e., the urinary amylase is not increased even though the serum amylase may be extremely high). This accounts for many mistaken diagnoses of pancreatitis by the unwary.
Pitfall: About a third of folks who have (usually milder) pancreatitis on imaging have normal amylases. Lipase stays up longer.
What damages the exocrine pancreas? The list in "Big Robbins" is worth remembering:
Very heavy drinking (not exactly the same thing as "alcoholism"...) is the most important cause of pancreatitis in the U.S., and many extreme alcoholic debauches end this way, and it is likely to be severe.
How alcoholic excesses cause pancreatitis is remains mysterious.
Old thinking focused on malfunctions of the sphincter of Oddi, allowing reflux of enterokinase and/or other noxious stuff; and/or increased production of secretin in the gut.
Experimental choline deficiency scrambles transport of proenzymes within acinar cells; they end up activating one another. Binge drinkers don't keep a good, balanced diet....
* Your lecturer predicts that when the real cause of alcoholic pancreatitis is found, it will be a physicochemical change in the subcellular membranes that causes intra-cellular activation of pro-enzymes.
Cholelithiasis accounts for a large minority of cases of pancreatitis.
Gallstones are thought to cause pancreatitis:
(1) by lodging in the common bile duct and blocking the pancreatic duct, producing back-pressure which pushes enzymes from the duct back into the interstitium, and/or;
(2) by damaging the sphincter of Oddi, allowing backwash of enterokinase and/or cell poisons such as lysolecithin into the pancreas.
In the absence of a really solid stone, biliary sludge (i.e., many tiny particles in suspension, preventing flow of bile) was a long-unrecognized cause of pancreatitis (NEJM 326: 589, 1992). Indeed, the smaller the gallstone, the more pancreatitis risk: Arch. Int. Med. 157: 1674, 1997.
Less common are:
Trauma (i.e., a steering-wheel injury, or a poke at surgery)
Something bad in the general area, notably a perforated gastric ulcer
Viruses (i.e., mumps
,
cytomegalovirus;
herpes simplex
Arch. Path. Lab. Med. 127: 231, 2003)
Worms (clonorchis, ascaris)
Ischemia (i.e., horrible atherosclerosis)
Vasculitis (i.e., rickettsial disease, polyarteritis nodosa, etc.)
Drugs (most notably big doses of morphine)
Hyperlipidemia (types I and V; figure that one out!)
Hypercalcemia (no one knows why; * possibly it activates trypsinogen Gastroent. 109: 239, 1995; or * prevents the zymogens from leaving the acinar cells, eventually getting them digested Am. J. Surg. 169: 167, 1995)
Certain CFTR carriers: NEJM 339: 645 & 653, 1998.
Following cardiopulmonary bypass (from calcium chloride in the resuscitation solution? NEJM 325: 382, 1991)
Drugs. Glucocorticoids, ddI, pentamidine, and azathioprine (Am. J. Gastro. 98: 1305, 2003) are famous.
Uremia (i.e., renal failure)
Heredity (see below)
Scorpion sting (only Tityus trinitatis, the Trinidad scorpion)
* Pancreas divisum (i.e., failure of the two buds to fuse, with Santorini's duct awkwardly draining the body and tail) affects 3-10% of people and is touted as an additional "cause of pancreatitis" because most of the pancreas drains through the smaller duct. If this really causes pancreatitis, it is uncommon (Int. J. Pancr. 5: 317, 1989).
* Autoimmune exocrine pancreatitis ("lymphoplasmacytic sclerosing pancreatitis") is an autoimmune disease that's being recognized more often nowadays: Arch. Surg. 140: 1104, 2005; Arch. Path. Lab. Med. 129: 1148, 2005; Ann. Surg. 237: 853, 2003; Modern Path. 20: 23, 2007; imaging studies Radiology 260: 428, 2011. Future pathologists: Look for inflammation centered around the ducts ("type I"), or lots of lymphoytes and plasma cells ("type II"). Pathlogy update: Gastroenterology 139: 140, 2010. Autoimmune pancreatitis with pseudocyst: Arch. Path. Lab. Med. 131: 16, 2007. How and when to treat: Gut 56: 1719, 2007; Br. J. Surg. 94: 1067, 2007.
Cannabis / cannabinoids as a treatment for both the pain and the pathophysiology of acute pancreatitis (Gastroent. 132: 1968, 2007). Very carefully reasoned, and with an experimental model. Watch this one.
Patients present with abdominal and/or back pain, fever and shock; the latter are probably due to contamination of the bloodstream by foul products of autodigestion.
In addition to hyperamylasemia, patients may have obstructive jaundice (understandable!), hypocalcemia ("from all that fat necrosis calcifying", and/or some substance that depresses the parathyroid glands), and/or elevated blood glucose.
They may develop duodenal obstruction, ARDS, and/or acute tubular necrosis of the kidney (more about the last one under "Kidney").
Physical diagnosticians: Here are ominous signs. Pancreatic enzymes flowing along the falciform ligament produce hemorrhage and necrosis of the anterior abdominal wall around the umbilicus ("Cullen's sign" -- Cullen was an obstetrician actually described this first in ruptured ectopic pregnancy). Check the left flank, too ("Grey Turner's sign", after George Grey Turner, the British surgeon).
* Future pathologists: A few days after death, the autolyzing pancreas, though normal in life, may look intensely hemorrhagic. Don't be fooled. Microscopic views will clarify the issue.
At surgery ("close him back up") or autopsy ("a familiar finding"), acute pancreatitis is unmistakable.
In the acute process, the pancreas undergoes proteolysis (proteases) and lipolysis (lipase), eventually with hemorrhage (elastases damage vessels). Not surprisingly, this produces considerable acute inflammation (neutrophils, edema, and so forth).
Ascites in these patients is ugly brown and often has globules of fat floating on its surface, like on chicken soup. Of course, it is loaded with amylase.
Long considered not to be a surgeon's disease, a few brave surgeons are resecting necrotic pancreas and peripancreatic tissues. Stay tuned on the outcomes -- there's no controlled studies yet (J. Am. College Surg. 209: 712, 2009). Other surgeons are taking the approach of operating only the worst cases, and then only with drainage, and then after letting healing start (Gastroent. 141: 254, 2011).
You are already familiar with fat necrosis ("saponification", etc.) The dead cells may fill with amorphous debris and/or calcify (calcium complexes with free fatty acids) heavily enough to have caused hypocalcemia. Grossly, fat necrosis looks and feels much like chalk.
Even years later, spots of old calcified enzymatic fat necrosis may stud the omentum (though the polys are gone after the acute phase). Finding a few flecks of fat necrosis at autopsy is of no significance, and could be agonal (i.e., the result of the ischemic death-throes of the pancreas). Lots of fat necrosis is very suspicious for previous pancreatic injury.
|
|
{08339} enzymatic fat necrosis, gross; it is the
chalky granular stuff. The background is hemorrhagic pancreatitis.
{08342} enzymatic fat necrosis, microscopic;
left upper corner
{08348} enzymatic fat necrosis, microscopic
Oddly, these patients can also have fat necrosis at sites remote from the pancreas, i.e., under the skin.
The mix of processes gives the acute case a variegated pattern of blacks, browns, reds, yellows, and off-whites.
After the acute phase is over, liquefied areas may be surrounded by fibrous tissue, producing a pseudocyst ("pseudo" because there is no interior epithelial lining). If they become infected while forming, a pancreatic abscess results. The biggest pseudocysts replace the lesser sac, which was autodigested.
{49233} pseudocyst; spleen at right. Hollow and filled with fluid.
It is worth remembering that the duodenum can become obstructed in pancreatitis.
Future radiologists: Look for a paralyzed segment of bowel ("sentinel loop") near the sick pancreas.
"Chronic pancreatitis" probably is the result of scarring from one or more episodes of pancreatitis, which have perhaps not been obvious clinically. It's also common in the hereditary pancreatitis syndromes.
It is usually seen in chronic problem drinkers, as a pain syndrome associated with nerve involvement and/or dilatation of the duct. Surgery for the latter helps: NEJM 356: 676, 2007.
On imaging / endoscopy, the pancreatic duct is often dilated ("scar contracts"), but in the relatively common and hard-to-diagnose "small duct chronic pancreatitis" (Ann. Surg. 244: 940, 2008), the big duct looks normal but the patient is every bit as sick.
There is loss of acinar cells (later, even the islets are gone), atrophy of some of the remaining cells, and dense fibrous tissue; as noted scar contraction is likely to dilate the ducts at least at some level.
Grossly, this produces a small, firm, white pancreas.
* Squamous metaplasia of the ducts may occur, perhaps because the cells are seeing so much more irritating material.
Pathologists also look for calcifications ("chronic calcifying pancreatitis"). These may be either (1) calcified fat necrosis, or (2) "pancreatic calculi", dystrophic-calcified lumps of protein in the pancreatic duct. The protein is assumed to be some digestive thing, though it has eluded precise characterization.
* Many people think that "protein plugs", their production somehow stimulated by alcohol excess, "cause" acute alcoholic pancreatitis. This is unlikely, since the histology of chronic alcoholic pancreatitis is different from the obstructive lesion (Am. J. Gastroent. 85: 271, 1990). See below.
* To make things more difficult, the mysterious "tropical pancreatitis" that is endemic especially in parts of India, features dilated ducts with calculi as its principal lesion. The genetics are just now being worked out; causes include mutations in secretory trypsin inhibitor and in cathepsin B (Gut 555: 1270, 2006).
The scarring may produced unorganized-appearing glands, which the unwary pathologist may mistake for cancer.
Future pathologists: Sometimes it is very hard to tell well-differentiated adenocarcinoma from scarring here. Clues to cancer included mitotic figures, necrotic debris, incomplete lumens, and widely-variable nuclear sizes (4:1 or more); today's pathologist may also stain for k-ras mutations (Am. J. Clin. Path. 105: 321, 1996), and other genes (p53, more arcane ones Am. J. Clin. Path. 117: 755, 2002; even on fine-needle aspirates).
* Most recently, positive staining of a fine-needle aspirate for MUC4 or mesothelin or maspin seems to be very good evidence of malignancy, while positive staining for clusterin-beta seems fairly good evidence that the process is benign (Am. J. Clin. Path. 126: 572, 2006). Smad4 says "benign" as well (Arch. Path. Lab. Med. 131: 556, 2007). Likewise, in sections mesothelin stains almost all cancers and no "chronic pancreatitis" or normal pancreas cases (Am. J. Clin. Path. 124: 838, 2005, from the NIH).
* Equally impressive results with S100P, which seems sensitive and specific for pancreatic cancer (Am. J. Clin. Path. 129: 81, 2008).
* And cytology itself is notoriously insensitive, especially when the lesion presents as a pancreatic and/or biliary stricture (the cells are stuck in a desmoplastic stroma and don't shed... what everyone already knew: Am. J. Clin. Path. 128: 272, 2007). Molecular biology seems to be taking over (Gastroent. 131: 1064, 2006; JAMA 297: 1901, 2007; telomerase Surgery 143: 113, 2008).
{49234} chronic pancreatitis; pale white is scar
{08853} chronic pancreatitis; extensive scarring
{20279} chronic pancreatitis in an alcoholic, nice protein plug
{46283} chronic pancreatitis with calculi
{49230} burned out alcoholic chronic pancreatitis, with calculi;
the tube along the bottom is the splenic artery, twisting in and out
In the late stages, patients can expect to have malabsorption (actually, maldigestion -- steatorrhea, weight loss), and perhaps a pseudocyst. The worst problem that many of these people have is chronic severe pain from involvement of the sensory nerves around the celiac plexus.
As you must have noticed, there is little justification for calling this "chronic pancreatitis", except that it may be chronically painful. This misnomer was canonized in the Marseilles-Rome criteria of 1988 (Scand. J. Gastroent. 24: 641, 1989).
Chronic obstructive pancreatitis, a slightly different entity from the above, follows obstruction of the pancreatic duct (gallstone, surgeon's mishap). In this situation, there is selective atrophy of acini around the head of the pancreas. Surgeons can repair the ampulla if that is the problem.
* Exactly how the cells die remains obscure; there are conflicting animal models (apoptosis vs. inflammation/necrosis): Gastroenterology 110: 875, 1996.
Future pathologists: Here's how to distinguish these two entities (after World. J. Surg. 14: 2, 1990):
| Chronic alcoholic | Chronic obstructive |
| Lobules unevenly scarred | All lobules in an area involved equally |
| Protein plugs in small ducts | Few or no protein plugs |
| Perineural chronic inflammation | Normal nerves |
NON-MALIGNANT MASSES
With today's imaging studies, we are finding more and more "incidentalomas" in the pancreas. Most are benign, but it's probably best to work all of them up (Am. J. Surg. 195: 329, 2008).
* Simple cysts of the pancreas are relatively rare. They are seen (in a minority of cases) in two anti-oncogene-deletion syndromes (Von Hippel-Lindau, adult polycystic kidney disease).
Pancreatic pseudocysts (see above) are common after acute pancreatitis from alcoholism or trauma or any other cause.
Benign tumors of the exocrine pancreas are uncommon. They are almost always some variant of adenoma. "Solid pseudopapillary neoplasm", a tumor mostly of young women, is poorly-understood both in terms of origin and outcome ("coffee bean nuclei, lights up with antitrypsin, and maybe some big hyaline globulines" -- Arch. Path. Lab. Med. 133: 1989, 2009). Serous cystadenomas ("microcystic serous adenomas") are the most common and are uniformly benign. Leave it to the pathologist to decide whether a particular tumor has malignant potential (classic paper Cancer 71: 82, 1993; update 114: 102, 2008).
PANCRETAIC INTRAEPITHELIAL NEOPLASIA ("precancer", "PanIN"), always along a portion of the ductal system is seen often enogh to deserve your notice. Of course, you'll see it only at autopsy or in pancreas removed for some other reason. Future pathologists only: The in-situ evolution of pancreatic cancer has been well-studied. See Arch. Path. Lab. Med. 118: 227, 1994; update Arch. Path. Lab. Med. 129: 1398, 2005; Gut 57: 1555, 2008. Most recent update Arch. Path. Lab. Med. 133: 375, 2009.
Grade I and II lesions are common, present in perhaps 50% of older folks if you look really hard.
Distinguishing these lesions from invasive cancer on fine needle aspiration can probably be done: Am. J. Clin. Path. 129: 115. 2008. Prognosticating the tumor based on histology, duct size, and CA19-9 to decide treatment: Am. J. Surg. 194: 304, 2007.
{49238} cystadenoma of the pancreas; has been cut in half and opened; spleen at right
CANCER OF THE PANCREAS ("cank of the pank", "the dismal disease", etc.; Lancet 378:607, 2011; Disease-A-Month 50: 545, 2004)
This dread cancer accounts for about 5% of U.S. cancer deaths; the incidence has tripled in the past 50 years "because of smoking and chemicals" (I wonder).
The large majority of cancers of the pancreas are adenocarcinomas arising from the ducts ("ductal adenocarcinoma". Most are desmoplastic (Am. J. Surg. 194: S-84, 2007).
Like adenocarcinomas anywhere else, you can spot them because they make little glands and/or are secretory-product (i.e., mucin)-positive.
Your workup will start with endoscopy. Obviously-malignant cells from the pancreatic duct permit a confident diagnosis, but only one pancreatic cancer patient in five has these. We are now doing fluorescent in-situ hybridization on these cells to look for aneuploidy, which is a pretty good sign of cancer and more sensitive than morphology: Am. J. Clni. Path. 136: 442, 2011. The rest of your patients with suspected pancreatic cancer will get fine-needle aspiration biopsies. Some of these will return false-negative results. If there's an obvious mass on imaging or the pancreatic duct is dilated, think about getting another "FNA" (Dig. Dis. Sci. 55: 1161, 2010).
* Truly hardcore future pathologists will want to read about MUC4 as a stainable marker for pancreatic neoplasia, especially as it grows nastier: Am. J. Clin. Path. 117: 791, 2002. Two useful markers by fluorescent in-situ hybridization are trisomy 7 and trisomy 3 (Gastroent. 131: 1064, 2006).
{08851} adenocarcinoma of pancreas;
no normal pancreas on the slide; some glands are more anaplastic than
others;
{26003} adenocarcinoma of pancreas; mucin-producer
(pale apical cytoplasm, sharp borders)
|
|
Pancreatic cancers
Histopathology
Wikimedia Commons
Future pathologists and surgeons: Cancer of the pancreas and "chronic pancreatitis" (i.e., old scarring) are hard to tell apart. A certain percentage of false-positive diagnoses of cancer of the pancreas, and a certain number of Whipple procedures for those without cancer of the pancreas, is acceptable: Br. J. Surg. 81: 585, 1994.
* For some reason, it is not uncommon to see real osteoclasts and even osseous metaplasia here (J. Clin. Path. 47: 372, 1994; Arch. Path. Lab. Med. 120: 306, 1996); these are still carcinomas.
| Risk factors include (1) smoking (3x the normal risk), (2) exposure to chemicals (the disease is supposedly more common among both chemists and garage workers), (3) hereditary pancreatitis (huge risk), and (4) some of the anti-oncogene deletion syndromes. (5) Obesity is also supposed to be an independent risk factor that somehow promotes the growth (Surgery 146: 258, 2009). |
 |
"Big Robbins" links it to the notable carcinogens naphthylamine and benzidine, and the hoopla over nitrosamines in food was related to their link to cancer of the pancreas in experimental animals.
Questionable risk factors include alcohol consumption, high-fat diet ("cholecystokinin must be a promoter"; tough to believe if you think pancreatic acinar cells don't ordinarily divide), coffee drinking, obesity, smokeless tobacco, second-hand smoke, and pernicious anemia. All of these are now pretty much discredited (see for example Cancer 67: 2664, 1991; the coffee crock discredited Cancer Epidem. 10: 429, 2001, several others uniformly negative). The Texans at M.D. Anderson, who we may think know plenty about smokeless tobacco, found no link either with this or with second-hand smoking (Cancer 109: 2547, 2007.)
Anti-oncogene deletion syndromes placing people at excess risk for pancreatic cancer include BRCA2 (breast-and-ovary), the Lynch hereditary nonpolyposis coli cancer syndromes (hMSH2, hMLH1 -- reaffirmed JAMA 302: 1790, 2009), Peutz-Jegher's (STK1/LKB1; Big Robbins' claim of a x130 increased risk can't be right), and the p16/CDKN2A pancreatic cancer/melanoma syndrome (NEJM 350: 2623, 2004).
Hereditary pancreatitis in particular (see above) gives at least a 40% risk of getting pancreatic cancer (Med. Clin. N.A. 84: 719, 2000 -- whether the pancreatic cancers that killed three of Jimmy Carter's siblings were really familial remains unknown).
* Concerns about exposure to particular pesticides keep coming up, but the whole business remains very soft -- the ones that "mutate k-ras in lab animals" aren't the ones that "are associated with a 5x increased risk of cancer of the pancreas in workers", etc., etc. To become confused, see Env. Health Perspect. 111: 724, 2003; Lancet 354: 2125, 1999.
Whatever the environmental "cause", most (or maybe all) cancers of the exocrine pancreas have mutated k-ras at hot-spot codon 12. This can be detected on fine-needle aspirate material, and by PCR in pancreatic fluid (Cancer 73: 1589, 1994; Am. J. Path. 144: 889, 1994) or stool (ooh, Cancer Res. 54: 3568, 1994) or smears (Am. J. Clin. Path. 105: 257 & 321, 1996). Smoking seems to cause this mutation (Cancer 85: 326, 1999).
The distribution of cancers in "Big Robbins" is reasonable:
60% head
15% body
5% tail
20% too late to tell
Patients come in with back pain (why?), jaundice, weight loss, epigastric pain, GI upsets, depression (very typical, and poorly understood), and/or migratory thrombophlebitis ("Trousseau's other sign"; the mechanism of the distinctive paraneoplastic problem is unknown).
The size of the cancer depends on the stage at which it is detected. Those in the head may be found early because they produce jaundice. Those in the body and tail will be detected late.
There's a serum tumor marker, CA-19-9 (Gut 35: 707, 1994). Others exist, including CA 125. None has come into use for screening, though for following the disease they may have value. Update Arch. Surg. 141: 968, 2006.
Grading system based on cell morphology predicts who will probably be dead by 6 months vs. who might survive for a year or more: Am. J. Clin. Path. 124: 697, 2005.
Future surgeons: Courvoisier's law states that a distended gall bladder in a patient with obstructive jaundice means cancer (pancreas, common bile duct). Obstruction due to a gallstone in the common bile duct will not result in a distended gallbladder, because the gallbladder would be heavily scarred-up from years of cholelithiasis. This works most of the time, though you would never rely on it.
Gung-ho surgeons may try to resect a tumor in the head of the pancreas ("Whipple procedure"). For the pylorus-sparing technique see J. Am. Col. Surg. 178: 443, 1994; for the Hopkins study, which hails 11 cures out of 201 surgeries as an enormous improvement, see Ann. Surg. 221: 721, 1995. Desperate diseases require desperate remedies).
Today, a surgeon may perform a total pancreatectomy for a cancer not in the head
of the pancreas These patients often have diabetes, and the cause is insulin resistance. This now appears to be due to
massive production of amylin (IAPP; NEJM 330: 313, 1994; Gastroenterology 114:
130, 1998); probably the amylin is produced by the islets
in response to one or more factors produced
by the tumor itself (J. Clin. Endo. Metab. 85: 1232, 2000). This probably
explains the well-known "link" between pancreatic cancer and diabetes, and it now appears that only
new-onset (i.e., less than three years) diabetes is a "risk factor" (NEJM 331: 81, 1994).
* A recent British euthanasia case involved intractable pain from cancer of the pancreas: Lancet 335:
719, 1990 ("not guilty"; in my opinion this is a triumph of humanity and common sense; you may
disagree).
Adenocarcinoma of the pancreas typically metastasizes to lymphatics, and blood-borne metastases to the liver are typically massive.
"Pancreatic adenocarcinoma, among the most lethal human malignancies, is resistant to current chemotherapies." Gastroent. 139: 598, 2010.
* INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM is a low-grade pancreatic cancer notorious for being multifocal (Am. J. Surg. 198: 709, 2009). This creates a nightmare for the surgeon attempting to save some of the pancreas, while the pathologist performs numerous intra-operative frozen sections (Cancer 107: 2567, 2006; Ann. Surg. 242: 774, 2005; Cancer 107: 2567, 2006). Prognosis based on histopathology: Ann. Surg. 246: 644, 2007; Gut 60: 509 & 1712, 2011; and lymph node status (Ann. Surg. 251: 477, 2010). Fine-needle diagnosis: Am. J. Clin. Path. 129: 67, 2008. Only one in ten has an invasive lesion; surgeons examine the gland meticulously, monitor glucose tolerance (if it worsens, it may warn of an invasive cancer... remember why), and monitor serum CA 19-9 (Ann. Surg. 251: 70, 2010.
* MUCINOUS CYSTIC NEOPLASM OF THE PANCREAS is an uncommon entity almost involving the tail of a woman's pancreas. After much study and worry, there's a large series and they seem benign (Ann. Surg. 247: 571, 2008). Making the distinction from intraductal papillary mucinous neoplasm isn't always easy (Arch. Path. Lab. Med. 135: 264, 2011; cytopathology for distinguishing various mucinous cystic lesions Ann. Surg. 254: 977, 2011.
* ACINAR CARCINOMA OF THE PANCREAS makes up about 1% of pancreatic caners. Most often it affects young adults. It presents stippled cells that stain for trypsin, amylase, lipase, and chymotrypsin, and often elaborates lipase into the blood (which may produce subcutaneous fat necrosis) and/or elaborate proteases into the blood, causing arthritis (a "zebra" to remember). Molecular genetics: Am. J. Path. 160: 953, 2002. A very large series confirms that it is a relatively indolent disease, and much more likely to be cured than common pancreatic adenocarcinoma (Surgery 144: 141, 2008).
* PANCREATOBLASTOMA is a tumor, usually seen in children, resembling embryonic pancreas. There are often morules of squamous cells recalling squamous pearls or meningothelium; however the tumor stains for exocrine and endocrine pancreatic markers (J. Clin. Path. 49: 952, 1996). This cancer is aggressive.
|
|
Pancreas
Hemorrhagic pancreatitis
Cancer of the pancreas
Eurytremiasis, the pancreatic fluke