General Pathology (Laboratory) / Pancreas 2013

O
w

M
e
n
g

/

M
e
d
i
c
i
n
e

2
0
1
5

1

ACUTE PANCREATITIS
Acute pancreatitis is reversible pancreatic
parenchymal injury associated with
inflammation.
autodigestion of the pancreatic substance by
inappropriately activated pancreatic enzymes
inappropriate activation of trypsinogen is an
important triggering event in acute pancreatitis
first 24 hours ----> marked elevation of serum
amylase levels
within 72 to 96 hours ----> rising serum lipase
level
Hypocalcemia: from precipitation of calcium
soaps in necrotic fat
Mechanisms

1. Pancreatic duct obstruction.
Gallstones or biliary sludge impacted in
the region of the ampulla of Vater can
raise intrapancreatic ductal pressure
and lead to the accumulation of
enzyme-rich fluid in the interstitium.
Lipase
- one of the few enzymes secreted in
an active form
- cause local fat necrosis
- Injured tissues, periacinar
myofibroblasts, and leukocytes
release proinflammatory cytokines
including IL-1, IL-6, tumor necrosis
factor, platelet-activating factor,
and substance P ----> local
inflammation & interstitial edema
through a leaky microvasculature
- Edema ----> further compromise
local blood flow ----> vascular
insufficiency & ischemic injury to
acinar cells.

2. Primary acinar cell injury
most clearly involved in the
pathogenesis of acute pancreatitis
caused by:
- certain viruses (e.g., mumps)
- drugs
- direct trauma to the pancreas
- pancreatitis following ischemia or
shock

3. Defective intracellular transport of
proenzymes within acinar cells
normal acinar cells: digestive enzymes
and lysosomal hydrolases are
transported in separate pathways.
pancreatic proenzymes: inappropriately
delivered to the intracellular
compartment containing lysosomal
hydrolases ----> proenzymes are then
activated ----> lysosomes disrupted ---->
activated enzymes released
Morphology
wide areas of lightly stained structure less areas
----> shadowy outlines of fat cells
ranges from trivial inflammation and edema to
severe extensive necrosis and hemorrhage
basic alterations:
1) microvascular leakage causing edema
2) necrosis of fat by lipolytic enzymes
3) acute inflammation
4) proteolytic destruction of pancreatic
parenchyma
5) destruction of blood vessels and subsequent
interstitial hemorrhage
acute interstitial pancreatitis
- milder form
- mild inflammation, interstitial edema, and
focal areas of fat necrosis in the substance
of the pancreas and in peripancreatic fat
Fat necrosis
- from enzymatic activity of lipase
- released fatty acids combine with calcium
to form insoluble salts that impart a
granular blue microscopic appearance to
the fat cells
acute necrotizing pancreatitis
- severe form
- acinar and ductal tissues as well as the islets
of Langerhans are necrotic
- Vascular injury can lead to hemorrhage into
the parenchyma of the pancreas
- pancreatic substance shows areas of red-
black hemorrhage interspersed with foci of
yellow-white, chalky fat necrosis
- Foci of fat necrosis may also be found in
extra-pancreatic collections of fat, such as
General Pathology (Laboratory) / Pancreas 2013


O
w

M
e
n
g

/

M
e
d
i
c
i
n
e

2
0
1
5

2

the omentum and the mesentery of the
bowel, and even outside the abdominal
cavity, such as in the subcutaneous fat
- peritoneal cavity contains a serous, slightly
turbid, brown-tinged fluid in which globules
of fat (derived from the action of enzymes
on adipose tissue)
hemorrhagic pancreatitis
- more severe
- extensive parenchymal necrosis is
accompanied by dramatic hemorrhage
within the substance of the gland


SCLEROSIS OF ISLETS OF LANGERHANS

large patches of fibrosis
some islets within these areas of fibrosis


CYSTIC FIBROSIS

bi-allelic inherited mutations in the cystic
fibrosis transmembrane conductance regulator
(CFTR) gene
decrease bicarbonate secretion by pancreatic
ductal cells
protein plugging ----> chronic pancreatitis
disorder of ion transport in epithelial cells that
affects fluid secretion in exocrine glands and the
epithelial lining of the respiratory,
gastrointestinal, and reproductive tracts
abnormally viscous secretions ----> obstruct
organ passages ---->
- chronic lung disease secondary to recurrent
infections
- pancreatic insufficiency
- steatorrhea
- malnutrition
- hepatic cirrhosis
- intestinal obstruction
- male infertility

Morphology
ducts are dilated and plugged with eosinophilic
mucin, and the parenchymal glands are atrophic
and replaced by fibrous tissue
nonclassic cystic fibrosis
- quite mild and does not seriously disturb
their growth and development.
Severe pancreatic involvement ---> impairs
intestinal absorption because of the pancreatic
achylia ---> malabsorption stunts development
and post-natal growth.
mucus secretion defect ----> defective
mucociliary action, obstruction of bronchi and
bronchioles, & crippling fatal pulmonary
infections
sweat glands are morphologically unaffected
milder cases: accumulations of mucus in the
small ducts with some dilation of the exocrine
glands
more severe cases
- usually seen in older children or adolescents
- ducts are completely plugged ----> atrophy
of the exocrine glands & progressive fibrosis
- Atrophy of the exocrine portion of the
pancreas may occur ----> leaving only the
islets within a fibrofatty stroma
- loss of pancreatic exocrine secretion
impairs fat absorption
- avitaminosis A ----> squamous metaplasia of
the lining epithelium of the ducts in the
pancreas, which are already injured by the
inspissated mucus secretions
- thick viscid plugs of mucus may also be
found in the small intestine of infants ---->
small-bowel obstruction, known as
meconium ileus.

PANCREATIC ADENOCARCINOMA

Infiltrating ductal adenocarcinoma of the
pancreas: pancreatic cancer
precursor lesions: pancreatic intraepithelial
neoplasias (PanINs)
cigarette smoking

Morphology
clusters of moderately differentiated glandular
structures infiltrating the stroma
parenchyma is replaced by fibrous tissue
60% arise in the head of the gland
15% in the body
5% in the tail
20% the neoplasm diffusely involves the entire
gland.
usually hard, stellate, gray-white, poorly defined
masses
General Pathology (Laboratory) / Pancreas 2013


O
w

M
e
n
g

/

M
e
d
i
c
i
n
e

2
0
1
5

3

ductal adenocarcinomas: Recapitulate to some
degree normal ductal epithelium by forming
glands and secreting mucin
Two features:
- highly invasive (even early invasive
pancreatic cancers extensively invade
peripancreatic tissues)
- elicits an intense non-neoplastic host
reaction composed of fibroblasts,
lymphocytes, and extracellular matrix
(called a desmoplastic response).
Most carcinomas of the head of the pancreas
- obstruct the distal common bile duct as it
courses through the head of the pancreas
----> marked distention of the biliary tree
in about 50% of patients with carcinoma
of the head of the pancreas ----> jaundice.
carcinomas of the body and tail
- do not impinge on the biliary tract and hence
remain silent for some time.
- may be quite large and most are widely
disseminated by the time they are discovered.
often grow along nerves and invade into the
retroperitoneum.
can directly invade the spleen, adrenals,
vertebral column, transverse colon, and
stomach
Peripancreatic, gastric, mesenteric, omental,
and portahepatic lymph nodes are frequently
involved
Distant metastases occur, principally to the liver,
lungs, and bones.
Microscopically, there is no difference between
carcinomas of the head of the pancreas and
those of the body and tail of the pancreas.
moderately to poorly differentiated
adenocarcinoma forming abortive tubular
structures or cell clusters and showing an
aggressive, deeply infiltrative growth pattern
Dense stromal fibrosis accompanies the invasive
cancer, and there is a proclivity for perineural
invasion within and beyond the organ.
Lymphatic and large vessel invasion are also
commonly seen.
The malignant glands are poorly formed and are
usually lined by pleomorphic cuboidal-to-
columnar epithelial cells.
Less common variants of pancreatic cancer:
- adenosquamous carcinomas
- colloid carcinoma
- hepatoid carcinoma
- medullary carcinoma
- signet-ring cell carcinoma, undifferentiated
carcinoma
- undifferentiated carcinomas with
osteoclast-like giant cells.
Adenosquamous carcinomas: focal squamous
differentiation in addition to glandular
differentiation
undifferentiated carcinomas: may contain large
multinucleated osteoclast-like giant cells.