Diseases of the Gallbladder, Extrahepatic Biliary Tract and Pancreas

            Last updated: October 1, 2015

            Objectives, vocabulary, Power Point presentation

           

Extrahepatic biliary tract and gallbladder

 

Gallbladder, congenital anomalies:

-          Absent (agenesis)

-          Duplicated/accessory

-          Septate/bilobed

-          Diverticular

-          Aberrant locations (malplaced), most commonly embedded in the liver (arrest of normal migration during gestation from intrahepatic position to the normal superficial location)

-          Folded fundus (Phrygian cap, gallbladder size larger than gallbladder fossa)

-          Malformations are often clinically silent; some predispose to stone formation; of importance for the surgeon particularly when taking a laparoscopic approach

 

 

Biliary atresia:

-          Complete obstruction of the biliary tree

-          Manifest within the first 3 months of life

-          Accounts for about one third of infants with neonatal cholestasis (see Digestive Pathology lecture #4)

-          If left untreated, secondary biliary cirrhosis develops within 3 to 6 months

-          Accounts for 50-60% of children referred for liver transplantation

-          Is the most common cause of death from liver disease in early childhood

-          Two forms proposed:

o       Fetal (up to 20% of cases)

-          Aberrant development

-          Associated with abnormalities resulting from defective establishment of laterality of thoracic and abdominal organs, including situs inversus, congenital heart disease, malrotation

o       Perinatal (more common)

-          Normal development followed by an inflammatory injury leading to fibrosis and obliteration

-          A perinatal viral infection followed by an abnormal immune response in a genetically-predisposed host is suspected

-          Types:

o       Type I:  Common bile duct atresia, with patent proximal ducts

o       Type II: hepatic duct atresia, with patent (IIa) OR obliterated (IIb) cystic and common bile ducts

-          Both types I and II are amenable to surgical correction by biliary-enteric anastomosis

o       Type III (majority of cases): complete extrahepatic biliary atresia (including right and left hepatic ducts)

-          Managed with hepatoportoenterostomy (Kasai procedure): The bile ducts are transected at the porta hepatis and a segment of small intestine is connected at that point; minute residual patent bile ducts present at the porta hepatis may allow sufficient bile drainage into the intestine (with this procedure, about one third of the patients avoid liver transplantation, one third require transplantation within a year and one third after one year)

 

Choledochal cysts

-          Congenital dilatations or diverticula of the bile ducts

-          Most often identified before age 10

-          More frequent in females, up to 4:1

-          Types:

o       Single segmental cylindrical dilatation of the common bile duct; the most common type (80-90%)

o       Diverticulum

o       Choledochocele (dilatation of the distal common bile duct which bulges into the duodenal lumen)

o       Multiple cystic dilatations of the bile ducts, extrahepatic and intrahepatic

o       Multiple cystic dilatations only of  intrahepatic bile ducts (corresponds to Caroli disease, see Digestive Pathology lecture #6)

-          May cause:

o       Neonatal cholestasis

o       Recurrent biliary colic and/or jaundice

o       Pancreatitis (when located at the distal end of the common bile duct)

-          Predispose to:

o       Calculus formation (choledocholithiasis)

o       Inflammation, stenosis

o       Pancreatitis

o       Cholangiocarcinoma

-          Treatment: excision with biliary-enteric anastomosis

 

 

2.  Cholelithiasis

-          Calculi (stones) in the gallbladder (gallstones)

-          Present in 10-20% of the population

-          >80% are silent

-          May cause pain in the right upper quadrant/epigastrium

o       Constant or

o       Postprandial (particularly after fat-rich meals) subsiding gradually in 1 to 5 hours

o       May radiate to the right scapular region in the back

o       May associate nausea and vomit

-          When solitary or few, stones tend to be large, round or oval

-          When multiple, they may be faceted (molded) and their size decreases in proportion to their number

-          Very small stones, called “gravel”, are more likely to escape the gallbladder and produce biliary obstruction

-          Thick bile is called sludge, may also cause obstruction

-          Gallstones may contain different amounts of:

o       Cholesterol (yellow)

o       Calcium bilirubinate (green-black)

o       Calcium carbonate (gray-white)

-          Gallstones can be classified as:

o       Pure, only one component

o       Mixed (the majority, 80%), more than one component blended together

o       Combined (pure nucleus, mixed shell)

-          Gallstones are also classified as:

o       Cholesterol stones (80%), those made predominantly of cholesterol crystals, are pale yellow when pure or yellow-green/yellow-gray when mixed

o       Pigmented stones, those made predominantly of calcium bilirubinate, are brown or jet black

-          Pure cholesterol stones are radiolucent (invisible on plain X-ray films)

-          Mixed and combined stones become radiopaque (visible) depending on their content of calcium

-          Cholesterol stones nucleation:

o       In the bile, cholesterol is rendered soluble by aggregation with phospholipids and bile acids (the balance of cholesterol, phospholipids and bile acids  is known as the lithogenic index)

o       Nucleation (crystallization) of cholesterol is promoted by supersaturation of bile with cholesterol and by microprecipitates of inorganic or organic calcium salts

-          Risk factors for cholesterol stones are associated with excess cholesterol secretion in relation to phospholipids and bile acids, resulting in an increased lithogenic index:

o       Native Americans, Hispanics, Americans of Northern European descent

o       Being over age 55

o       Female sex, oral contraceptives containing estrogen, estrogen replacement therapy, pregnancy

o       Obesity

o       Rapid weight reduction (as after gastric bypass surgery)

o       Hyperlipidemia

o       Some cholesterol-lowering medications may increase the risk (fibrates, by increasing the cholesterol concentration and decreasing the bile acid concentration in the bile), others may decrease the risk (statins, by decreasing cholesterol synthesis)

o       Disorders of bile acids metabolism (decreasing the concentration of bile acids in bile)

o       Ileal dysfunction or bypass (as in Crohn disease), compromise the enterohepatic circulation of bile acids decreasing their concentration in bile)

o       Gallbladder stasis (as with diabetic autonomic neuropathy), hypomotility promotes nucleation

o       Family history

o       Genetic predisposition:

§         Cholesterol transporter ABCG5/G8 mutation: cholesterol hypersecretion

§         CYP7A1 mutation: deficiency in the synthesis of bile acids from cholesterol

§         MDR3 mutation: defective phospholipid export pump in the canalicular membrane

-          Pigmented stones are associated with elevated unconjugated bilirubin levels

-          Risk factors for pigmented stones:

o       Asian populations

o       Hemolytic disorders (unconjugated hyperbilirubinemia)

o       Bacterial colonization of the biliary tree (bacterial glucuronidases increase levels of unconjugated bilirubin)

o       Parasitic colonization of the biliary tree (Ascaris lumbricoides, Opisthorchis viverrini, Clonorchis sinensis), unknown mechanism, the parasites may be a source of stone nucleation

 

 

3.  Cholesterolosis

-          Accumulation of cholesterol esters in foamy histiocytes within the lamina propria

-          Grossly the gallbladder is studded by minute bright yellow flecks (strawberry gallbladder)

-          Related to cholesterol hypersecretion but not necessarily to hypercholesterolemia

-          Clinically inconsequential

 

 

4.  Cholecystitis

-          Inflammation of the gallbladder, may be acute or chronic

-          Almost always seen in association with gallstones, otherwise it is designated as acalculous cholecystitis

 

Acute cholecystitis

-          Acute calculous cholecystitis

o       90% result from obstruction of the gallbladder neck or the cystic duct by gallstones, biliary gravel (small stone fragments) or biliary sludge (thick bile)

-          Acute acalculous cholecystitis; it is thought to result from:

o       Ischemia (cystic artery is an end-artery with no collateral circulation making the gallbladder susceptible to ischemia), conditions associated with dehydration and shock:

§         Postoperative status

§         Postpartum status

§         Severe trauma

§         Severe burns

§         Sepsis and other causes of shock

o       Prolonged absence of oral feeding resulting in lack of cholecystokinin-induced gallbladder contraction, bile stasis

o       Primary bacterial infection of the gallbladder

§         Diabetes, immunosuppression, HIV/AIDS

-          Symptoms:

o       Right upper quadrant/epigastric pain, persist more than 6 hours

o       Murphy’s sign: patient asked to breath out, examiner’s hand presses on the right hypochondrial area, patient is asked to breath in; if gallbladder is inflamed, inspiration is inhibited by pain

o       Nausea, vomiting

o       Mild fever

o       Mild to moderate leukocytosis

o       High fever, chills and jaundice or hyperbilirubinemia are not characteristic of acute cholecystitis; when present, they may indicate cholangitis (obstruction and inflammation of the common bile duct, a major medical emergency, see below)

o       Symptoms of acalculous cholecystitis are more insidious, not necessarily referred to the gallbladder, obscured by the underlying condition, may be overlooked and, therefore, there is a high risk of gangrene and perforation

-          Attack usually subsides within few days, recurrence is common

-          Up to 25% require immediate surgical intervention

 

Chronic cholecystitis

-          Cholelithiasis is present in over 90%, most gallbladders removed for gallstones have chronic cholecystitis

-          Obstruction is not always found

-          May be acalculous

-          Causes recurrent episodes of right upper quadrant or epigastric pain, with or without nausea and vomit as described with cholelithiasis

-          Microscopically the inflammation dominated by lymphocytes and plasma cells

-          Fibrosis in more advanced cases

-          Outpouchings of the mucosa (called Rokitansky-Aschoff sinuses) may be seen

-          Porcelain gallbladder: Excessive dystrophic calcification of the wall, reportedly associated with a markedly increased incidence of cancer; however, this association is not as strong as previously estimated or it is non-existent

 

Complications of cholecystitis:

-          Choledocholithiasis, cholangitis (see below)

-          Sepsis

-          Perforation, abscess, peritonitis

-          Cholecystenteric fistula (fistula between the gallbladder and the intestine).  It may allow the passage of gallstones into the intestine and gallstone ileus: intestinal obstruction secondary to the impaction of a large gallstone.  It also allows the passage of air and bacteria into the biliary tree

 

5.  Choledocholithiasis

-          The presence of stones within the common bile duct

-          Most originate in the gallbladder

-          Stones may also form within the bile duct:

o       Associated with choledochal cysts, bacterial and parasitic infections (ascaris, trematodes)

-          Obstruction may cause:

o       Pain and jaundice

o       Cholangitis

o       Secondary biliary cirrhosis

o       Pancreatitis (if occlusion is at the level of the ampulla)

 

6.  Cholangitis

-          Inflammation of the biliary tract

-          Results most commonly from:

o       Choledocholithiasis

o       Other causes of obstruction: indwelling catheters, strictures, tumors, parasites, acute pancreatitis

-          Enteric Gram negatives colonize the obstructed or disrupted bile ducts (ascending infection)

-          Clinical findings, the Charcot triad:

o       Fever, chills

o       Right upper quadrant pain

o       Jaundice, hyperbilirubinemia

-          Is a medical emergency, may respond to prompt antibiotic therapy but usually requires endoscopic biliary drainage or surgical evacuation

-          May result in:

o       Hepatic abscesses

o       Sepsis

 

7.  Neoplasms

 

Gallbladder adenomas

-          Rare

-          Similar to colonic adenomatous polyps may have a tubular, tubulovillous or villous architecture (see Digestive Pathology lecture #3)

-          Are lined by gastric-type (pyloric/foveolar), intestinal-type or biliary-type epithelium

-          May develop dysplasia, have malignant potential

 

Gallbladder cancer

-          Most are adenocarcinomas

-          Relatively infrequent

-          Risk factors:

o       History of gallstones (the strongest risk factor)

o       Obesity

o       Female sex, multiparity

o       Old age

o       In the US, higher rates in: Native Americans, Hispanics, Korean and Chinese

o       Chronic infections:  S. typhi and S. parathyphi, Helicobacter bilis, Helicobacter pylori, trematodes

o       Anomalous pancreatobiliary junction (abnormal junction of the common bile duct and pancreatic duct that allows regurgitation of pancreatic juice into the gallbladder), associated with chronic inflammation and gallbladder carcinoma in Japan

-          Clinical features:

o       Preoperative diagnosis is exceptional

o       Symptoms are those associated with cholelithiasis

-          Dismal survival

 

Carcinoma of extrahepatic bile ducts

-          Most are adenocarcinomas; have abundant fibrous stroma, similar to cholangiocarcinoma

-          Slightly more frequent in men

-          Older individuals

-          As with cholangiocarcinoma, association with:

o       Primary sclerosing cholangitis, inflammatory bowel disease

o       Choledochal cysts

o       Trematodes (clonorchiasis, opisthorchiasis)

-          Specific subtypes:

o       Peri-ampullary carcinomas, generally small (cause rapid obstruction and jaundice)

o       Klatskin tumors, developing in the hepatic duct: between the junction of the cystic duct and the confluence of the right and left hepatic ducts

-          50% to 60% of cholangiocarcinomas are perihilar (Klatskin) tumors, 20 to 30% are distal, 10% are intrahepatic

-          Clinical features:

o       Progressive jaundice

o       Painless palpable gallbladder (Courvoisier’s sign, jaundice with painless palpable gallbladder is most likely due to a neoplasm –pancreas, common bile duct, ampulla– than to a gallstone; with gallstones the gallbladder most often is inflamed/tender and/or fibrotic/contracted/not palpable)

o       Most are not resectable

o       Short survival

 

 

 

The Pancreas

 

Exocrine pancreas: cystic fibrosis, covered in genetics lectures

Endocrine pancreas: non-tumoral conditions covered in endocrinology lectures

           

1.  Congenital anomalies

-          Pancreas divisum

o       Embryologically, the pancreas arises from the fusion of dorsal and ventral primordia

o       The dorsal primordium gives rise to the majority of the gland and the accessory duct

o       The ventral primordium gives rise to the posterior inferior portion of the head and the main duct

o       In pancreas divisum, the dorsal and ventral duct systems fail to fuse properly

o       As a consequence, the bulk of the pancreas drains through the smaller accessory duct (minor papilla)

o       May predispose to chronic pancreatitis but this association has been questioned

-          Annular pancreas

o       Partial or complete ring of pancreas encircling the second portion of the duodenum

o       Causes symptoms of duodenal obstruction early in life, symptoms of pancreatitis in adults

o       May be associated with other congenital anomalies particularly pancreas divisum (29%)

o       Associated with pancreatitis and pancreatic adenocarcinoma

-          Ectopic/accessory pancreas

o       Stomach, duodenum, jejunum, Meckel diverticulum, ileum, mesentery

o       May cause localized inflammation and bleeding, tumors

-          Congenital cysts

o       Anomalous development of the pancreatic ducts

o       Association with autosomal dominant polycystic kidney disease and von Hippel-Lindau disease

 

 

2.  Pancreatitis

           

Acute pancreatitis

-          Biliary obstruction (gallstones, biliary sludge) and alcoholism account for 80% of cases

o       Gallstones, 3:1 female to male

o       Alcohol, 6:1 male to female

-          Cryptogenic (idiopathic), 10-20%, many of these cases may be caused by biliary sludge (a thick suspension of cholesterol or calcium bilirubinate granules)

-          Other causes:

o       Hypertriglyceridemia

o       Hypercalcemia, hyperparathyroidism

o       Drugs (thiazide diuretics, and many others)

o       Blunt trauma, surgical trauma, instrumentation (as in endoscopic retrograde cholangiopancreatography -ERCP)

o       Ischemia: shock, embolism, vasculitis

o       Infections: mumps

o       Congenital anomalies:

-          Pancreas divisum, annular pancreas, choledochocele (see above)

o       Mutations in cationic trypsinogen (PRSS1) and serine protease inhibitor Kazal type 1 (SPINK1) and  cystic fibrosis (CFTR) genes (see below)

o       Periampullary tumors

-          Pathogenesis

o       Defense mechanisms

-          Most pancreatic enzymes are secreted as inactive proenzymes

-          Proenzymes are activated by trypsin

-          In turn trypsin is secreted as a proenzyme (trypsinogen) activated in the small bowel by enteropeptidase (also called enterokinase), avoiding intrapancreatic activation of other proenzymes

-          Furthermore, pancreatic acinar and ductal cells secrete trypsin inhibitors such as serine protease inhibitor Kazal type 1

-          Lipase is secreted in its active form (does not require cleavage by trypsin); however, for optimal enzymatic function it requires colipase, a protein cofactor which in turn is secreted by the pancreas as a proenzyme (procolipase) that does require activation by trypsin in the intestinal lumen.

o       Pancreatitis occurs when normal defense mechanisms are deranged, particularly by the inappropriate intrapancreatic activation of trypsin

o       Alcohol

-          Increases secretion of protein-rich pancreatic fluid, deposition of inspissated protein plugs in pancreatic ducts

-          Contraction of sphincter of Oddi

-          Direct toxic effect

o       Pancreatic duct obstruction (impaction of gallstones, biliary gravel or sludge in the ampulla, choledochocele, neoplasms)

o       Direct acinar injury (viruses, drugs, trauma, ischemia)

o       Hereditary pancreatitis:

-          Mutations in the cationic trypsinogen (PRSS1) gene produce a cleavage-resistant trypsin

-          Mutations of the serine protease inhibitor Kazal type 1 (SPINK1) gene inactivates an essential pancreatic trypsin inhibitor

-          Cystic fibrosis CFTR gene mutations cause abnormal bicarbonate secretion (in cystic fibrosis there is also compromise of the chloride-dependent fluid transport that result in inspissated secretions causing obstruction of pancreatic ducts)

-          Morphology:

o       Inflammation

o       Fat (enzymatic) necrosis

o       Released fatty acids combine with calcium to form insoluble salts (dark precipitate seen on H&E stains)

o       Destruction of the parenchyma and vessels with hemorrhage

-          Clinical features:

o       Attacks precipitated by

-          Alcoholic binge

-          Overeating

-          Opiates and other drugs that increase the tone of the sphincter of Oddi

o       Epigastric pain, stabbing, often severe, often referred to the upper back

o       Jaundice may be present if there is concomitant obstruction of the bile duct

o       Hemorrhagic exudates seen as

-          Periumbilical ecchymosis: Cullen’s sign

-          Flank ecchymosis: Turner’s sign

o       Nodules of subcutaneous fat necrosis in extremities

-          Laboratory findings:

o       Marked elevation of amylase

o       Followed by elevation of lipase

o       Hypocalcemia, results from precipitation of calcium salts with free fatty acids

o       Hyperglycemia, due to compromised insulin production

o       Leukocytosis

o       Electrolyte disturbances

-          Therapy

o       Total restriction of food and oral fluids (pancreatic resting)

o       Supportive therapy

-          5% mortality

-          Complications

o       Disseminated intravascular coagulation

o       Acute respiratory distress syndrome

o       Shock, acute renal failure

o       Pancreatic pseudocyst (see below)

o       Abscess, sterile or infected (infection of the dead pancreatic tissue is an important cause of mortality)

o       Splenic/portal venous thrombosis, one of the causes of portal hypertension (see Digestive Pathology lecture #6)

 

 

Pancreatic pseudocysts

-          Walled-off collection of debris and fluid rich in pancreatic enzymes

-          The wall lacks epithelial lining, is made of fibrous and granulation tissue

-          Usually solitary

-          Arise after episodes of acute pancreatitis, particularly with alcohol-induced pancreatitis and in patients with chronic pancreatitis with acute exacerbations

-          May be caused by trauma (blunt, penetrating or operative)

-          May retain a communication with the ductal system

-          May

o       Resolve spontaneously

o       Become infected

o       Compress adjacent structures (splenic vessels, portal vein, bile ducts)

o       Erode into adjacent vessels causing abundant bleeding

o       Rupture

 

 

Chronic pancreatitis

-          May present as repeated bouts of acute pancreatitis

-          Shared pathogenesis with acute pancreatitis:

o       Alcoholism, the most common cause

o       Long-standing pancreatic duct obstruction (gallstones, neoplasms)

o       Pancreas divisum

o       Tropical pancreatitis: attributed to malnutrition

o       Hereditary pancreatitis: genetic mutations (see above)

o       Autoimmune pancreatitis (see below)

o       Idiopathic, up to 40%, a growing number shown to be caused by mutation in hereditary pancreatitis genes

-          Morphology

o       Grossly:

§         Fibrosis

§         Atrophy

§         Dilated ducts, some with calcified concretions (calculi)

o       Microscopically:

§         Fibrosis

§         Chronic inflammation

§         Acinar loss (constant)

§         Islets of Langerhans loss also occurs, although the islets may become prominent due to greater acinar loss, they may also fuse appearing enlarged

§         Dilatation of pancreatic ducts, some contain protein plugs and calcifications

§         Ductal epithelium may be atrophic, hyperplastic or show squamous metaplasia

-          Clinical features

o       Repeated attacks of acute pancreatitis

o       Lipase and amylase may fail to elevate if a substantial portion of the acinar parenchyma has disappeared

o       Constant abdominal and back pain

o       May be silent until pancreatic insufficiency (malabsorption) and/or diabetes develop

o       Plain films may show pancreatic calcifications

o       Pancreatic cancer:

§         With hereditary pancreatitis, 40% lifetime risk

 

 

Autoimmune pancreatitis

-          Distinct form of chronic pancreatitis characterized by:

o       Periductal inflammation with abundant IgG4-secreting plasma cells

o       Periductal fibrosis and ductal narrowing

o       Response to steroid treatment

-          Autoimmune pancreatitis is a manifestation of IgG4-related disease which also involves bile ducts, gallbladder, and many other organ systems

-          Often presents with obstructive jaundice, mimicking pancreatic cancer

-          The majority of patients are men older than 50 (unlike most autoimmune diseases)

 

 

3.  Pancreatic neoplasms

 

Cystic neoplasms

-          Fewer than 5% of all pancreatic neoplasms

-          Most cystic lesions of the pancreas are pseudocysts, only 5 to 15% are neoplastic

-          Serous cystadenomas

o       Microcystic (composed of numerous small cysts)

o       Clear, thin, straw-colored fluid contents

o       Lined by low cuboidal epithelium

o       More common in women

o       Almost always benign, rare serous cystadenocarcinomas

-          Mucinous cystic neoplasms

o       Macrocystic (composed of relatively few large cysts)

o       Thick, mucinous fluid contents

o       Lined by tall columnar epithelium

o       Arise almost exclusively in women

o       Can be benign or malignant

-          Intraductal papillary mucinous neoplasms

o       Arise in the main pancreatic ducts

o       Intraductal proliferation of mucinous cells arranged in a papillary pattern

o       Mucin accumulation leads to cystic dilatation of the ducts

o       10 to 20% are multifocal

o       More common in men

o       Can also be benign or malignant

 

4. Pancreatic (ductal) adenocarcinoma

-          Fourth leading cause of death in men and women

-          Not among the 10 most frequent cancers in men, ninth in incidence among women

-          5-year survival rate < 5%

-          Incidence and mortality

o       Greater in men than in women

o       Greater in blacks than in whites

o       Greater in the Acadiana region of Louisiana (Caucasians and African Americans)

-          Risk factors

o       Smoking

o       High-protein, high-fat diets

o       Chronic pancreatitis, diabetes (difficult to sort out if they are the cause or the effect of the disease)

o       Hereditary pancreatitis

o       Alcohol

o       Exposure to chemicals (gasoline products, pesticides)

o       Hereditary nonpolyposis colorectal cancer (Lynch syndrome)

o       BRCA2 gene mutation, also associated with hereditary breast and ovarian cancer

o       Peutz-Jeghers syndrome (LKB1 gene)

o       p16/CDKN2A gene mutation in 95% of the cases

o       KRAS gene mutation in 80% to 90% of cases

-          Pancreatic cancer is preceded by pancreatic intraepithelial neoplasia (dysplasia in the pancreatic ducts)

-          The progression from intraepithelial neoplasia of increasing severity to invasive carcinoma coincides with the accumulation of genetic and epigenetic events; a process analogous to the multiple-hit progression observed in colorectal carcinogenesis

-          Location:

o       60% arise in the head

o       20% diffusely

o       15% in the body

o       5% in the tail

-          Microscopically:

o       Adenocarcinoma that recapitulates the ductal epithelium

o       Two peculiarities:

§         High invasiveness (perineural invasion, lymphatic invasion)

§         Desmoplastic (fibrotic, scirrhous, hard)

-          Clinical findings

o       Pain

o       Constitutional symptoms: anorexia, malaise, fatigue, weight loss

o       Obstructive jaundice

§         Courvoisier’s sign (jaundice with palpable non-tender gallbladder is most likely due to a neoplasm –pancreas, common bile duct, ampulla– and not to a gallstone)

o       Migratory thrombophlebitis (Trousseau sign), occurs in about 10%, due to elaboration by the tumor of platelet-aggregating factors and other procoagulants

-          Fewer than 20% are resectable

-          Tumor markers: elevation of CA19-9, and carcinoembryonic antigen

o       Not specific or sensitive

o       Used for follow-up after diagnosis has been established (as to detect recurrence after surgery)

 

5. Pancreatic endocrine neoplasms (islet cell tumors)

-          Account for only 2% of all pancreatic neoplasms

-          May elaborate hormones, but some are non-functional

-          Are morphologically similar to carcinoid tumors:

o       Grossly: yellow, red-brown

o       Microscopically: uniform, monotonous cells

o       May invade adjacent organs and metastasize

-          May be associated with Multiple Endocrine Neoplasia type 1 syndrome (MEN 1), hyperplasia or adenomas in:

o       Adrenal cortex

o       Pancreatic islets

o       Parathyroid

o       Pituitary

-          Gene responsible for MEN 1 encodes for protein menin

 

Beta-cell tumors (insulinoma)

-          The most common type

-          May cause attacks of severe hypoglycemia

o       Whipple triad:

-          Fatigue, confusion, stupor, coma, convulsions

-          Hypoglycemia, glucose < 50 mg/dL

-          Attacks precipitated by fasting or exercise and relieved by feeding or by the intravenous administration of glucose

-          Many are asymptomatic

-          Only about 10% invade locally and/or metastasize

-          Usually small (< 2 cm) and encapsulated

 

G-cell tumors (gastrinomas)

-          Cause the Zollinger-Ellison Syndrome

o       Hypergastrinemia

o       Multiple peptic ulcers (gastric, duodenal, jejunal), unresponsive to therapy

o       Diarrhea, may be the presenting symptom

-          Located in the “gastrinoma triangle”: duodenum, pancreas and peripancreatic soft tissues

-          Over half locally invasive or have metastasized at the time of diagnosis

 

Alpha-cell tumors (glucagonomas)

-          Cause the glucagonoma syndrome:

o       Mild diabetes

o       Necrolytic migratory erythema

o       Anemia

o       Deep vein thrombosis

o       Tendency to develop overwhelming infections

-          Seen mostly perimenopausal and postmenopausal women

-          Approximately 50% have metastases at the time of diagnosis

 

Other endocrine neoplasms:

-          Somatostatinoma (Delta-cell tumors), may present with diabetes

-          VIPomas (vasoactive intestinal peptide), may present with secretory diarrhea

-          Carcinoids

-          Tumors producing more than one hormone

Slides reviewed:

96. HB-12 Gallbladder - Acute Cholecystitis 
97. 
HB-13 Gallbladder - Carcinoma

73. P-1   Acute Hemorrhagic Pancreatitis
74. 
P-2   Chronic Pancreatitis
75. 
P-3   Atrophy
76. 
P-4   Hyalinization of Islet of Langerhans
77. 
P-5   Adenocarcinoma
78. 
P-6   Islet Cell Adenoma

 

 

https://www.pathology.med.umich.edu/slides/search.php?collection=McKenna&dxview=show

 

36196 Autoimmune pancreatitis IgG4-related

33205 Pancreatic neuroendocrine neoplasm

44207 Pancreatic neuroendocrine neoplasm IHC

35140 Mucinous cystic neoplasm