12-2 Pathology of the Pancreas (Liver Path 7) Flashcards
What are the 2 main functional components of the pancreas (excluding ducts and other conducting stuff)?
Exocrine and Endocrine pancreas
What is the exocrine pancreas? How much of the pancreas does it take up, and what does it do?
Exocrine pancreas constitutes 80% to 85% of the organ
composed of acinar cells that
secrete enzymes needed for digestion. (~1.5L of secretions)
How much of the pancreas is taken up by the other functional component, the endocrine pancreas? What does it make?
Endocrine pancreas is composed of about 1 million clusters of cells, the islets of Langerhans.
Islet cells secrete insulin, glucagon and somatostatin and constitute only 1% to 2% of the organ.
Pancreatic development frequently gives rise to congenital variations in pancreatic anatomy. What is the most common anomaly?
Pancreas divisum is the most common congenital anomaly of the pancreas where there is a failure of fusion of the fetal duct systems of the dorsal and ventral pancreatic primordia leaving most of the pancreas being drained by a limited duct system.
Explain how the most common congenital anomaly of the pancreas, pancreas divisum, is different from normal anatomy of the pancreas.
Normal pancreas - pancreas is efficiently drained by the main pancreatic duct, the duct of Wirsung. This joins the common bile duct just proximal to papilla of Vater. The accessory pancreatic duct drains the rest of the pancreas, and has it’s own minor papilla.
Pancreas divisum - most of the pancreas is drained through a limited duct system into the minor papilla
In addition to pancreas divisum, what other common congenital anomalies of the pancreas exist?
•Annular pancreas can be associated with duodenal obstruction
•
•Ectopic pancreas - sites: Stomach, duodenum, jejunum, ileum are sites of ectopic pancreas usually very small or microscopic
•
•Agenesis (very rare)
What is this image of a normal pancreas trying to show?
2 main fxn’al domains of the pancreas
- endocrine pancreas are the clusters of smaller cells (Islets of Langerhan) that stain lightly, and make up a minority of total mass
- exocrine is the larger, darker staining, majority of cells that secrete digestive enzymes that go into the duodenum just proximal to pancreas
What functional part of the pancreas does the blood supply go to first?
Much of the blood coming to the pancreas goes to the islets first, then to the acinar cells
What do alpha and beta cells do?
The alpha- and beta-cells regulate the usage of glucose through the production of glucagon and insulin, respectively.
What leads to DM1?
Autoimmune destruction of islet beta cells triggered by a virus or some other factor, leads to Type 1 diabetes mellitus
How are digestive enzymes secreted from the pancreas? What is the stimulus, and how are they secreted?
Enzymatic secretion is mediated by stimulants such as secretin, a hormone released from the duodenum by the introduction of gastric acid, cholecystokinin (CCK), released by the presence of dietary fat, amino acids, hydrochloric acid, and acetylcholine, which is produced as a response to the sensory aspects of feeding and to the physical effects of chewing and swallowing. Upon binding of specific receptor sites on the acinar membrane with CCK or acetylcholine, the zymogen granules migrate to the apex of the acinar cell, where they are extruded into the central ductal lumen
Why does this pic of normal pancreatic tissue have a bunch of cells that look grainy?
Depicts pancreatic acinar cells
These cells have basally located nuclei and numerous zymogen granules at their apical pole. They also have abundant endoplasmic reticulum in the basal portion of the cytoplasm. These cells will secrete their granule contents into the lumen of the duct, which will carry the enzymes out of the pancreas and to the duodenum
When you picture an SEM photograph of pancreatic acinar cells secreting zymogens, what does it look like?
Something like this:
have basally located nuclei and numerous zymogen granules at their apical pole. They also have abundant endoplasmic reticulum in the basal portion of the cytoplasm. These cells will secrete their granule contents into the lumen of the duct, which will carry the enzymes out of the pancreas and to the duodenum
Why are so many pancreatic enzymes synthesized and stored as zymogens?
•Pancreatic enzymes such as trypsinogen are synthesized and stored in an inactive form, and are activated upon release into the lumen of the duodenum via the action of enterokinases.
•
Premature activation of these enzyme precursors results in autodigestion of the surrounding tissues and triggers an inflammatory chain response
What is acute pancreatitis?
Autodigestion of the pancreas by its own enzymes (inappropriate activation of digestive proenzymes)
What is the autodigestion process in acute pancreatitis often initiated by?
•initiated by:
–Alcohol (65% in US)
–Pancreatic duct obstruction (calculi) (20%)
–Drugs (furosemide, associated with HIV treatment)
–Vascular injury (ischemia)
–Infections (viruses including mumps)
–Hereditary factors (Hereditary pancreatitis)
–Hypercalcemia
What is the mortality rate for acute pancreatitis?
~10% on average
When does alcoholic pancreatitis occur?
•In people with alcoholic pancreatitis, the symptoms of acute pancreatitis often occur one to three days after an alcohol binge or after stopping drinking.
What is hereditary pancreatitis?
•Hereditary pancreatitis characterized by recurrent attacks of severe acute pancreatitis beginning in childhood and the development of chronic pancreatitis. Trypsin appears to be resistant to self inactivation. Increased risk for cancer (25-40%)
How is acute pancreatitis treated?
•Acute pancreatitis can be treated by medical management including supportive care with fluid replacement, pain relief and reduction of pancreatic secretions by avoidance of food.
What is the progression and prognosis of acute pancreatitis?
- Most attacks of acute pancreatitis do not lead to complications, and most people recover uneventfully with medical care.
- A small proportion of people have a more serious illness that requires intensive medical care.
What contributes to the development and recurrence of pancreatitis?
A complex combination of genetic, environmental, and metabolic factors contribute to the development and recurrence of acute and chronic pancreatitis
–Multiple lines of evidence indicate that premature activation of trypsin in acinar cells damages the cells causing inflammatory response recognize clinically as acute pancreatitis
–Many different genetic factors affect acinar cell function, bile duct function, trypsin inactivation and intensity of a immune response in the pancreas
What is the peak age range for acute pancreatitis?
•Peak age range for initial episode is 35 to 44 yrs
What serum components are helpful in making a dx of acute pancreatitis? How accurate are they?
- Serum amylase rises within 6 to 12 hours of the onset of acute pancreatitis. (Moderate sensitivity, high specificity)
- Serum lipase rises within 4 to 8 hours of onset of acute pancreatitis (high sensitivity and specificity)
What are the SSXs of acute pancreatitis?
What is required to make a DX of acute pancreatitis?
Two of the following three are required to make a diagnosis:
- (1) typical abdominal pain
- (2) threefold or more elevation of pancreatic enzyme values in the blood
- (3) inflammation of the gland on computed tomography (CT) scan or magnetic resonance imaging (MRI) scan.
What are the 3 types of pathology you’ll see in histology of acute pancreatitis?
acute interstitial pancreatitis
acute necrotizing pancreatitis
hemorrhagic pancreatitis
What is the pathology associated with acute interstitial pancreatitis?
–Interstitial edema, and focal areas of fat necrosis in peri-pancreatic fat
What is the pathology associated with acute necrotizing pancreatitis?
–Necrosis of acinar and ductal tissues as well as islets of Langerhans
What is the pathology associated with hemorrhagic pancreatitis?
•Hemorrhagic pancreatitis
–Extensive parenchymal necrosis accompanied by dramatic hemorrhage within the pancreas
What are the basic alterations behind the pathology of acute pancreatitis?
The basic alterations are
(1) microvascular leak and edema
(2) fat necrosis
(3) acute inflammation
(4) destruction of pancreatic parenchyma
(5) destruction of blood vessels and interstitial hemorrhage
What’s this?
Acute pancreatitis
fat necrosis on right
residual acini with inflammation and fibrosis on left
What’s this?
Acute pancreatitis
fat necrosis - light area on top
Ca++ deposits - small purple area next to fat necrosis
Earl fat necrosis - bottom left
Inflammation and fibrosis - middle
What does this pancreas show?
Acute hemorrhagic pancreatitis - Cut surface of pancreas displaying edematous pancreas with diffuse focal hemorrhage ( reddish black discoloration)
What’s this?
What’s this?
Acute hemorrhagic pancreatitis
due to autolysis of pancreatic tissue caused by escape of enzymes into the
substance, resulting in hemorrhage into the parenchyma and surrounding tissues
What’s this?
Acute pancreatitis - this cross section of teh pancreas shows yellow specks in the fat (red arrows), consistent with fat necrosis. Sometimes fat necrosis is chalky white with calcium. (saponification)
What’s this?
Described by Grey Turner in 1920 as a sign of hemorrhagic pancreatitis, flank ecchymoses are caused by blood tracking subcutaneously from a retroperitoneal or intraperitoneal source.
How often does recurrent acute pancreatitis lead to chronic pancreatitis?
only a subset of patients
What initiates chronic pancreatitis?
•Can be initiated by recurrent acute pancreatitis -> myofibroblast stellate cell activation
What happens when the exocrine pancreas gets fibrosed?
•Irreversible destruction of exocrine parenchyma with fibrosis ->
destruction of endocrine parenchyma ->
insulin-dependent diabetes
When is loss of exocrine fxn clinically apparent?
loss of ~85-90% of the exocrine gland
What are the general categories of causes of chronic pancreatitis?
Alcohol
Repeat acute pancreatitis
Obstruction
Metabolic
What are the causes of chronic pancreatitis, and what is the incidence?
- Alcohol abuse 70-80% of cases
- Repeat episodes of acute pancreatitis (10-20%)
- Obstruction of the pancreatic duct by calculi or neoplasms
- Metabolic
–Primary hyperparathyroidism
–Hyperlipidemia
–Renal transplantation
–Cystic fibrosis
What is the gold standard for dx of chronic pancreatitis?
histology
In addition to tissue biopsy, what other diagnostic techniques work for dx of chronic pancreatitis?
- Demonstrating a reduction in bicarbonate in a duodenal aspirate after secretin stimulation
- Endoscopic retrograde cholangiopancreatography (ERCP) shows abnormal pancreatic ductal system
- Presence of chunky intrapancreatic calcifications on plain radiographs (minority of cases)
When is a biopsy generally performed for chronic pancreatitis? Why?
Biopsy is impractical in most situations and usually performed when mass lesion is present
What’s this?
Chronic pancreatitis with extensive pancreatic calcification
- creates opacities on radiograph
What’s this? How is it different from autoimmune pancreatitis?
Chronic pancreatitis - dense interlobular fibrosis with preserved zones of acinar cells between the septa
•In comparison to autoimmune pancreatitis, the stroma is relatively acellular and lacks an inflammatory infiltrate.
What’s this?
Chronic pancreatitis
extensive fibrosis with ductal structures and atrophic acini in lobular configuration
What’s this?
autoimmune pancreatitis
- Need to have lots of pink collagen with lots of autoimmune cells infiltrating
- autoimmune, T cell mediated
What’s this?
A needle core biopsy from a patient with autoimmune pancreatitis
Summarize the complications of pancreatitis - name 8.
- Pleural effusions
- Pancreatic pseudocyst
- Diabetes
- Fat malabsorption (steatorrhea, decreased vit K)
- Ascites
- Stones in pancreatic duct
- Pancreatic Calcification
- Pain from perineural fibrosis
What’s this?
Pancreatic pseudocyst arising from the head of the pancreas.
Pseudocysts are the result of pancreatitis.
Liquified tissue within.
What’s this?
•Gross appearance of a cystic serous cystadenoma. The lesion is well circumscribed and composed of small cysts and separated by thin, translucent septa.
What’s this?
Serous cystadenoma
Each small cyst is lined by a flattened layer of epithelium.
What’s this?
Serous Cystadenoma
Each small cyst is lined by a flattened layer of epithelium.
Cytologically, the lining cells have small, uniform, hyperchromatic nuclei.
What’s this?
Mucinous cystadenoma
What’s this?
Mucinous cystadenoma
Cystic spaces lined by tall columnar mucin containing cells
What’s this?
Intraductal Papillary Mucinous Neoplasm (IPMN)
The pancreatic ducts are significantly dilated with extensive involvement by tumor cells of the main pancreatic ducts and cystic dilation of branch ducts.
What’s this?
IPMN
. At low power, the ducts are filled with complex papillary projections lined by tall columnar, mucinous epithelial cells.
Can see papillary fronds along with arborization (fronds connect and look like a tree)
What’s this? What are the 2 names for this entity?
Intraductal Papillary Mucinous Cystadenoma (IPMN)
low grade dysplasia
IPMNs with low-grade dysplasia are also called intraductal papillary mucinous adenomas
What’s this?
IPMN - moderate dysplasia
Moderate dysplasia – loss of mucin, bigger nuclei with hyperchromatic nuclei and more chromatin
What’s this?
IPMN - high grade dysplasia
high-grade dysplasia are called intraductal papillary mucinous carcinoma in situ.
What are the primary and secondary effects/complications/signs of pancreatic carcinoma?
Primary:
metastases to lung, liver, peritoneum
pancreatic carcinoma
abdominal pain (perineural lymphatic invasion)
Secondary:
Weight loss
Obstructive jaundice
Courvoisier gallbladder
Migratory thrombophlebitis
What’s Courvoisier gallbladder?
Enlarged, palpable gallbladder with jaundice
- indicative of chronically elevated intragallbladder pressure, usually from neoplasm
What’s this?
Obstruction of common bile duct via an invasive ductal carcinoma of head of pancreas
This gross specimen shows a tumor mass of the head of the pancreas, seen in the center of the photo, surrounded by duodenum, resected together as part of a Whipple procedure for pancreatic adenocarcinoma. Head of Pancreas cancer frequently obstructs the common bile duct
What’s this?
Invasive ductal carcinoma of the pancreas
- moderately differentiated
What’s this?
Invasive ductal carcinoma of the pancreas
- poorly differentiated
What’s this?
Acinar cell carcinoma of the pancreas
What’s this?
Acinar cell carcinoma of the pancreas
- At high power, the acinar structures of an acinar cell carcinoma are evident, with pinpoint lumina and basally located nuclei.
- Prominent nucleoli are also a characteristic feature.
What’s this?
Acinar cell carcinoma of pancreas
Immunohistochemical staining for trypsin in acinar cell carcinomas
What’s this?
Pancreatoblastoma
- Squamoid nests are the histologic hallmark of pancreatoblastomas.
- Epithelial tumor that exhibits acinar differentiation and often a lesser degree of neuroendocrine and ductal differentiation
What’s this?
pancreatic neuroendocrine tumor
- The well-differentiated pancreatic neuroendocrine tumor has a histologic appearance that is typical of neuroendocrine tumors, with nests (A) and trabeculae (B) of relatively uniform epithelial cells separated by scant fibrovascular stroma.
- Cytologically, the tumor has the typical salt-and-pepper chromatin pattern of neuroendocrine tumors (C), and mitoses and necrosis are inconspicuous.
