GIT Pathology Lab 4
Fatty metamorphosis of liver, gross
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This liver is slightly enlarged and has a pale yellow appearance, seen both on the capsule and
cut surface. This uniform change is consistent with fatty metamorphosis (fatty change).
GIT Pathology Lab 4
Fatty metamorphosis of liver, gross
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2
This is a larger liver with more pronounced fatty change. Such fatty change is most often
"nutritional" in etiology when diet is poor in protein and/or when fatty acid metabolism is
deranged and/or when liver cell function is impaired.
GIT Pathology Lab 4
Fatty metamorphosis of liver, microscopic
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3
Here are lipid vacuoles within hepatocytes in a case of macrovesicular steatosis (fatty
change). The lipid accumulates when lipoprotein transport is disrupted and/or when fatty acids
accumulate. Alcohol (ethanol), the most common cause, is a hepatotoxin that interferes with
mitochondrial and microsomal function in hepatocytes, leading to an accumulation of lipid.
GIT Pathology Lab 4
Non-alcoholic fatty liver disease, microscopic
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4
This is the histologic appearance of hepatic macrovesicular steatosis (fatty change). The lipid
accumulates in the hepatocytes as vacuoles. These vacuoles have a clear appearance with
H&E staining. The most common cause of fatty change in developed nations is alcoholism.
However, other causes can lead to a condition termed non-alcoholic fatty liver (NAFL) disease.
In developing nations, kwashiorkor in children is one cause. Diabetes mellitus, obesity,
metabolic syndrome, and severe gastrointestinal malabsorption are additional causes.
GIT Pathology Lab 4
Non-alcoholic steatohepatitis, liver, trichrome
stain, microscopic
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5
The term non-alcoholic fatty liver (NAFL) has been applied to the appearance of fatty liver in
patients without a history of alcoholism. NAFL can be seen with diabetes mellitus. NAFL can
be reversible, but in some cases it proceeds to fibrosis, called steatohepatitis (NASH), and
even cirrhosis. There is variable inflammation. This trichrome stain demonstrates blue-staining
collagen extending from the centrilobular region at the right.
GIT Pathology Lab 4
Macronodular cirrhosis of liver, gross
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6
Ongoing liver damage with liver cell necrosis followed by fibrosis and hepatocyte regeneration
results in cirrhosis. This produces a nodular, firm liver. The nodules seen here are larger than
3 mm and, hence, this is an example of "macronodular" cirrhosis.
GIT Pathology Lab 4
Macronodular cirrhosis of liver, gross
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7
Here is another example of macronodular cirrhosis. Viral hepatitis (B or C) is the most common
cause for macronodular cirrhosis. Wilson's disease and alpha-1-antitrypsin deficiency also can
produce a macronodular cirrhosis.
GIT Pathology Lab 4
Macronodular cirrhosis of liver, gross
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8
Here is another example of macronodular cirrhosis. The fibrosis and the loss of the normal
architecture of liver lobules leads to obstruction of portal venous blood flow. This results in
portal hypertension, one of the most serious consequences of cirrhosis. Portal hypertension
leads to ascites, splenomegaly, and to esophageal varices.
GIT Pathology Lab 4
Micronodular cirrhosis of liver, gross
•
9
This is an example of a micronodular cirrhosis. The regenerative nodules are quite small,
averaging less than 3 mm in size. The most common cause for this is chronic alcoholism. The
process of cirrhosis develops over many years.
GIT Pathology Lab 4
Micronodular cirrhosis and fatty change of liver,
gross
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10
Here is another example of micronodular cirrhosis. Note that the liver also has a yellowish hue,
indicating that fatty change (also caused by alcoholism) is present.
GIT Pathology Lab 4
Micronodular cirrhosis and fatty change of liver,
gross
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11
A close-up view of a micronodular cirrhosis in a liver with fatty change demonstrates the small,
yellow nodules. Micronodular cirrhosis may also be seen with Wilson's disease, primary biliary
cirrhosis, and hemochromatosis.
GIT Pathology Lab 4
Micronodular cirrhosis and fatty change of liver,
gross
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12
The regenerative nodules of liver in this case of micronodular cirrhosis are 3 mm in size or
smaller. The pale tan color is due to fatty change.
GIT Pathology Lab 4
Cirrhosis of liver, microscopic
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13
Microscopically with cirrhosis, the regenerative nodules of hepatocytes are surrounded by
fibrous connective tissue that bridges between portal tracts. Within this collagenous tissue are
scattered lymphocytes as well as a proliferation of bile ducts.
GIT Pathology Lab 4
Micronodular cirrhosis and fatty change of liver,
microscopic
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14
Micronodular cirrhosis is seen along with moderate fatty change. Note the regenerative nodule
surrounded by fibrous connective tissue extending between portal regions.
GIT Pathology Lab 4
Mallory's hyaline, liver, microscopic
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15
At high magnification can be seen globular red hyaline material within hepatocytes. This is
Mallory's hyaline, also known as "alcoholic" hyaline because it is most often seen in
conjunction with chronic alcoholism. The globules are aggregates of intermediate filaments in
the cytoplasm resulting from hepatocyte injury.
GIT Pathology Lab 4
Alcoholic hepatitis, microscopic
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16
Mallory's hyaline is seen here, but there are also neutrophils, necrosis of hepatocytes, collagen
deposition, and fatty change. These findings are typical for acute alcoholic hepatitis. Such
inflammation can occur in a person with a history of alcoholism who goes on a drinking "binge"
and consumes large quantities of alcohol over a short time.
GIT Pathology Lab 4
Caput medusae of skin with portal hypertension,
gross
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17
Portal hypertension results from the abnormal blood flow pattern in liver created by cirrhosis.
The increased pressure is transmitted to collateral venous channels. Sometimes these
venous collaterals are dilated. Seen here is "caput medusae" which consists of dilated
veins seen on the abdomen of a patient with cirrhosis of the liver.
GIT Pathology Lab 4
Esophageal varices with portal hypertension, gross
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A much more serious problem produced by portal hypertension results when submucosal
veins in the esophagus become dilated. These are known as esophageal varices. Varices are
seen here in the lower esophagus as linear blue dilated veins. There is hemorrhage around
one of them. Such varices are easily eroded, leading to massive gastrointestinal hemorrhage.
GIT Pathology Lab 4
Splenomegaly with portal hypertension, gross
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One of the most common findings with portal hypertension is splenomegaly, as seen here. The
spleen is enlarged from the normal 300 grams or less to between 500 and 1000 gm. Another
finding here is the irregular pale tan plaques of collagen over the purple capsule known as
"sugar icing" or "hyaline perisplenitis" which follows the splenomegaly and/or multiple episodes
of peritonitis that are a common accompaniment to cirrhosis of the liver.
GIT Pathology Lab 4
Cholestasis of liver, microscopic
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The yellowish-green accumulations of pigment seen here are bile. Most often this is due to
extrahepatic biliary tract obstruction. However, bile may also accumulate in liver (called
cholestasis) when there is hepatocyte injury.
GIT Pathology Lab 4
Cholestasis of liver, microscopic
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21
Small brown-yellow bile plugs are seen here in canaliculi. The total serum bilirubin is increased
and the patient demonstrates jaundice (icterus) by physical examination. The easiest place to
see this is on the sclerae of the eyes. With obstruction or liver cell injury, the direct bilirubin is
greater than indirect (unconjugated) bilirubin. With excess RBC destruction (as with
hemolysis), the indirect bilirubin is greater.
GIT Pathology Lab 4
Hemangioma of liver, gross
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This is a benign hemangioma of the liver just beneath the capsule. Perhaps one person in 50
has such a neoplasm, which is typically just an incidental finding, since most are 1 cm or less.
They can sometimes be multiple.
GIT Pathology Lab 4
Hepatic adenoma, liver, gross
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Shown here is a well-circumscribed neoplasm that is arising within the liver. This is an hepatic
adenoma.
GIT Pathology Lab 4
Hepatic adenoma, cut surface, liver, gross
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The cut surface of the liver reveals the hepatic adenoma. Note how well circumscribed it is.
The remaining liver is a pale yellow brown because of fatty change from chronic alcoholism.
GIT Pathology Lab 4
Hepatic adenoma, liver, microscopic
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25
Normal liver tissue with a portal tract is seen on the left. The hepatic adenoma is on the right
and is composed of cells that closely resemble normal hepatocytes, but the neoplastic liver
tissue is composed of disorganized hepatocyte cords and does not have a normal lobular
architecture.
GIT Pathology Lab 4
Hepatocellular carcinoma, liver, gross
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Here is an hepatocellular carcinoma. Such liver cancers arise in the setting of cirrhosis.
Worldwide, viral hepatitis is the most common cause, but in the U.S., chronic alcoholism is the
most common cause. The neoplasm is large and bulky and has a greenish cast because it
contains bile. To the right of the main mass are smaller satellite nodules.
GIT Pathology Lab 4
Hepatocellular carcinoma with satellite nodules,
liver, gross
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The satellite nodules of this hepatocellular carcinoma represent either intrahepatic spread of
the tumor or multicentric origin of the tumor.
GIT Pathology Lab 4
Hepatocellular carcinoma, liver, gross
•
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Here is another hepatocellular carcinoma, which has a greenish yellow hue. One clue to the
presence of such a neoplasm is an elevated serum alpha-fetoprotein (AFP). AFP is normally
produced by fetal liver, but not adult liver. Such intrahepatic masses may also focally obstruct
the biliary tract and lead to the finding of an elevated serum alkaline phosphatase.
GIT Pathology Lab 4
Hepatocellular carcinoma, liver, microscopic
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The malignant cells of this hepatocellular carcinoma (seen mostly on the right) are well
differentiated and interdigitate with normal, larger hepatocytes (seen mostly at the left).
GIT Pathology Lab 4
Hepatocellular carcinoma, liver, microscopic
•
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Note that this hepatocellular carcinoma is composed of liver cords that are much wider than
the normal liver plate that is two cells thick. There is no discernable normal lobular
architecture, though vascular structures are present.
GIT Pathology Lab 4
Hepatocellular carcinoma with necrosis and
hemorrhage, liver, microscopic
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31
At the right is an area of necrosis and hemorrhage in this hepatocellular carcinoma. Liver cell
carcinomas are very prone to necrosis and hemorrhage. In fact, hemorrhage from such an
hepatocellular carcinoma at the liver capsule may lead to hemoperitoneum.
GIT Pathology Lab 4
Cholangiocarcinoma, liver, gross
32
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The white mass with a few satellite nodules seen here in the liver is a cholangiocarcinoma.
Cholangiocarciomas occur less frequently than hepatocellular carcinomas. Identifiable risk
factors for cholangiocarcinoma can be similar to those for hepatocellular carcinoma. Viral
hepatitis B and C are more strongly associated with hepatocellular carcinoma, though they
have been reported with cholangiocarcinoma. Chronic alcoholism has been reported as a risk
in both. The most common risk factor for cholangiocarcinoma in the U.S. is primary sclerosing
cholangitis.
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Cholangiocarcinomas are more common in parts of the world in which persons can be infected
with trematodes (liver flukes) such as Clonorchis sinensis. Clinically, cholangiocarcinomas
resemble hepatocellular carcinomas. They are rarely diagnosed early, so the prognosis is
often poor.
GIT Pathology Lab 4
Cholangiocarcinoma, liver, microscopic
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The carcinoma at the left has a glandular appearance that is most consistent with a
cholangiocarcinoma. A liver cancer may have both hepatocellular as well as cholangiolar
differentiation. Cholangiocarcinomas do not make bile, but the cells do make mucin, and they
can be almost impossible to distinguish from metastatic adenocarcinoma on biopsy or fine
needle aspirate.
GIT Pathology Lab 4
Metastatic adenocarcinoma, liver, gross
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34
Note the numerous mass lesions that are of variable size. Some of the larger ones
demonstrate central necrosis. The masses are metastases to the liver. The obstruction from
such masses generally elevates alkaline phosphatase, but not all bile ducts are obstructed, so
hyperbilirubinemia is typically not present. Also, the transaminases are usually not greatly
elevated.
GIT Pathology Lab 4
Metastatic adenocarcinoma, liver, gross
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Here is a liver with metastatic adenocarcinoma. Note the serrated edges of the metastases
and the prominent central necrosis seen in the larger nodules. Of all neoplasms involving the
liver, metastases are the most common, because the liver is a good place for neoplastic cells
to grow. Metastases are usually multiple throughout the liver.
GIT Pathology Lab 4
Metastatic adenocarcinoma, liver, gross
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Here are liver metastases from an adenocarcinoma primary in the colon, one of the most
common primary sites for metastatic adenocarcinoma to the liver.
GIT Pathology Lab 4
Metastatic adenocarcinoma, liver, microscopic
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Microscopically, metastatic infiltrating ductal carcinoma from breast is seen on the right, with
normal liver parenchyma on the left.
GIT Pathology Lab 4
Viral hepatitis, liver, gross
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Grossly, there are areas of necrosis and collapse of liver lobules seen here as ill-defined areas
that are pale yellow. Such necrosis can occur with hepatitis.
GIT Pathology Lab 4
Viral hepatitis, liver, gross
•
39
The necrosis and lobular collapse is seen here as areas of hemorrhage and irregular furrows
and granularity on the cut surface of the liver.
GIT Pathology Lab 4
Viral hepatitis B, liver, low power microscopic
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40
Viral hepatitis leads to liver cell destruction. A mononuclear inflammatory cell infiltrate extends
from portal areas and disrupts the limiting plate of hepatocytes which are undergoing necrosis,
the so-called "piecemeal" necrosis of chronic active hepatitis. In this case, the hepatitis B
surface antigen (HbsAg) and hepatitis B core antibody (HbcAb) were positive.
GIT Pathology Lab 4
Viral hepatitis B, liver, high power microscopic
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41
Individual hepatocytes are affected by viral hepatitis. Viral hepatitis A rarely leads to signficant
necrosis, but hepatitis B can produce a fulminant hepatitis with extensive necrosis. A large pink
cell undergoing "ballooning degeneration" is seen below the right arrow. At a later stage, a
dying hepatocyte is seen shrinking down to form an eosinophilic "councilman body" below the
arrow on the left. Other hepatocytes are swollen and have granular pink cytoplasm.
GIT Pathology Lab 4
Viral hepatitis C, liver, high power microscopic
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42
This is a case of viral hepatitis C, which in half of cases leads to chronic liver disease. The
extent of chronic hepatitis can be graded by the degree of activity (necrosis and inflammation)
and staged by the degree of fibrosis. In this case, necrosis and inflammation are prominent,
and there is some steatosis as well. Regardless of the grade or stage, the etiology of the
hepatitis must be sought, for the treatment may depend upon knowing the cause, and chronic
liver diseases of different etiologies may appear microscopically and grossly similar.
GIT Pathology Lab 4
Viral hepatitis C, liver, low power microscopic
43
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This is a case of viral hepatitis C which is at a high stage with extensive fibrosis and
progression to macronodular cirrhosis, as evidenced by the large regenerative nodule at the
center right. The screening laboratory test for this form of viral hepatitis is the hepatitis C
antibody test. Hepatitis C accounts for most (but not all) cases formerly called "non-A, non-B
hepatitis". In addition to this serologic test PCR and genotyping can be performed.
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Nucleic acid sequencing identifies of six common HCV types (1a,b-5) which have different
clinical courses and responsiveness to alpha interferon therapy. Infection with HCV type 1b or
4 leads to more severe liver disease, faster progression to chronic hepatitis, and less
responsiveness to interferon therapy. Type 1a, 2, 3, and 5 infections have a more favorable
prognosis. Type 2 and 3 infections may be treated with shorter therapeutic regimens.
GIT Pathology Lab 4
Viral hepatitis with collapse, liver, Trichrome stain,
microscopic
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44
This trichrome stain demonstrates the collapse of the liver parenchyma with viral hepatitis. The
blue-staining areas are the connective tissue of many portal tracts that have collapsed
together.
GIT Pathology Lab 4
Acute pancreatitis, gross
•
45
This is an example of acute pancreatitis. The pancreas is swollen and does not show the
typical tan, lobulated architecture. Instead, it has areas of hemorrhagic necrosis that appear as
blotchy black red areas at the mid right of the photograph.
GIT Pathology Lab 4
Acute pancreatitis, gross
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46
Here is a more florid example of acute pancreatitis. The stomach is reflected superiorly and
the spleen can be seen at the far upper right. The pancreas is swollen and has areas of
hemorrhage. The serum amylase and serum lipase are often elevated with acute pancreatitis.
GIT Pathology Lab 4
Pancreatic pseudocyst
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47
This tissue is hardly recognizable as pancreas because a large pancreatic pseudocyst has
formed. Seen here at autopsy is the opened pseudocyst extending from hilum of liver at the
left to the spleen at the right of the photograph. It has an irregular red to brown to black inner
surface. The mortality from acute and chronic pancreatitis and their complications is not
insignificant.
GIT Pathology Lab 4
Acute pancreatitis with fat necrosis, high power
microscopic
•
48
Microscopically, acute pancreatitis has necrosis of pancreatic parenchyma (lower left) with
acute inflammation and fat necrosis (right and upper part of photograph). Fat necrosis appears
grossly as tan-yellow flecks of soft material within and on the surface of pancreas as well as on
mesentery.
GIT Pathology Lab 4
Acute pancreatitis, high power microscopic
•
49
The neutrophilic infiltrates of acute pancreatitis can be seen here with early fat necrosis of
several steatocytes. Severe acute abdominal pain is often present. The serum amylase and
lipase are typically elevated.
GIT Pathology Lab 4
Acute pancreatitis, low power microscopic
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50
At low power, the extent of the necrosis with acute pancreatitis is seen here. The mid-lower
portion of the photograph also demonstrates hemorrhage that is typical of this process. Many
cases of acute pancreatitis are associated with biliary tract lithiasis in which a gallstone
traverses the common bile duct to impact into the ampulla of Vater, resulting in pancreatic duct
obstruction (when the pancreatic duct and common bile duct merge prior to the ampulla).
GIT Pathology Lab 4
Acute hemorrhagic pancreatitis, high power
microscopic
•
51
At high magnification, acute inflammation with necrosis and hemorrhage is seen with residual
pancreatic acini in a case of acute hemorrhagic pancreatitis.
GIT Pathology Lab 4
Acute pancreatitis with fat necrosis, gross
•
52
Yellow-tan foci of fat necrosis are visible throughout the pancreas seen here which has been
sectioned in half. There is some edema, but no hemorrhage in this case of mild acute
pancreatitis. In addition to gallstones, causes for acute pancreatitis include viral infections,
drugs, marked hypertriglyceridemia, hypercalcemia, toxins, and blunt abdominal trauma.
GIT Pathology Lab 4
Acute pancreatitis with fat necrosis and
hemorrhage, high power microscopic
•
53
Microscopically, the fat necrosis consists of steatocytes (adipocytes) that have lost their nuclei
and whose cytoplasm has a granular pink appearance. Some hemorrhage is seen at the left in
this case of acute pancreatitis.
GIT Pathology Lab 4
Chronic pancreatitis, low power microscopic
•
54
Microscopically, this low power photomicrograph demonstrates scattered chronic inflammatory
cells in a collagenous stroma, with a few remaining islets of Langerhans, in a case of
chronic pancreatitis. Chronic alcoholism is a common cause for this condition, but longstanding obstruction of the pancreatic duct from gallstones or masses may produce
inflammation. Some cases may be related to germ line mutations in the PRSS1 and SPINK1
genes.
GIT Pathology Lab 4
Chronic pancreatitis, low power microscopic
•
55
Seen here is chronic pancreatitis in which the pancreatic parenchyma has been nearly
replaced by pink collagenous connective tissue. About all that remains are islets of
Langerhans. Chronic pancreatitis may sometimes be severe enough even to lead to
malabsorption from loss of the acinar parenchyma or to diabetes mellitus from loss of islets of
Langerhans.
GIT Pathology Lab 4
Adenocarcinoma of head of pancreas, gross
•
56
An adenocarcinoma of the head of the pancreas is shown here obstructing the pancreatic duct.
This may well have produced the clinical finding of "painless jaundice" in this patient.
Adenocarcinomas at this site have a very poor prognosis, even if a Whipple procedure is done,
as shown here, since the cancer is often at a high stage.
GIT Pathology Lab 4
Adenocarcinoma of head of pancreas, gross
•
57
This adenocarcinoma of the pancreas is very extensively infiltrative, sparing only the uncinate
process at the lower left center. Chronic biliary tract obstruction from this mass produced
icterus (jaundice) in the patient, and marked by the green color of the liver after formalin
fixation at autopsy. The tumor invades into the hilum of liver, and small metastases to liver are
also present.
GIT Pathology Lab 4
Adenocarcinoma of pancreas, low power
microscopic
•
58
At low power there is an adenocarcinoma of the pancreas seen at the left, with normal
pancreas at the right. A risk factor for pancreatic adenocarcinoma is smoking. There is a
weaker association with diabetes mellitus and chronic pancreatitis.
GIT Pathology Lab 4
Adenocarcinoma of pancreas, medium power
microscopic
•
59
The appearance of an adenocarcinoma of the pancreas is seen at medium magnification. Just
to the left of center can be seen perineural invasion by the neoplasm, which is composed of
very irregular glands. Involvement of the nerves can lead to the intense, constant pain typical
for infiltrative malignant neoplasms.
GIT Pathology Lab 4
Adenocarcinoma of pancreas, high power
microscopic
•
60
At high magnification, the microscopic appearance of an adenocarcinoma of the pancreas is
seen. At the left can be seen normal pancreatic acini, but the neoplasm is composed of
small irregular glands.
GIT Pathology Lab 4
Adenocarcinoma of pancreas, high power
microscopic
At high magnification, this adenocarcinoma of the pancreas has very poorly differentiated
glands and extensive desmoplasia (production of collagenous stroma). Typical mutations found in
pancreatic adenocarcinomas include K-RAS (present in many adenocarcinomas), p16, p53 (present
in many carcinomas), and SMAD4.
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