Pancreatic Pseudocyst

Composed of necrotic debris encased by fibrous walls of granulation tissue, this is to wall off necrotic
debris (hemorrhagic liquefactive fat necrosis, pancreatic enzymes (diameter from 2 cm to 30 cm)
typically located in peripancreatic tissues such as the lesser omental sac or the retroperitoneum
between the stomach and transverse colon or liver. They are usually solitary, attached to the surface of
the gland

They are sometimes called false cysts because they do not have a true epithelial lining, and instead is
lined by fibrin and granulation tissue, with typical changes of chronic inflammation.

Cross-section revealing a poorly defined cyst with a necrotic brownish wall.

Rupture is associated with release of enzymes into the abdominal cavity and hemorrhage.

Chronic pancreatitis (irreversible impairment in pancreatic function)

Characterized by

Extensive parenchymal fibrosis

reduced number and size of acini
variable dilation of the pancreatic ducts (can be extreme dilatation)
visible calcified ductal concretions, sometimes eosinophilic
ductal epithelium may be atrophied or hyperplastic or exhibit squamous metaplasia
long standing inflammation with chronic inflammatory infiltrate around remaining lobules and
ducts
remaining islets of Langerhans become embedded in the sclerotic tissue and may fuse and
appear enlarged; eventually they also disappear (relative sparing of the islets of Langerhans)
appear hard on gross evaluation
Exocrine pancreas destruction. In its late stages, the endocrine parenchyma also is lost.

A. Extensive fibrosis and atrophy has left only residual islets ( left ) and ducts ( right), with a sprinkling of
chronic inflammatory cells and acinar tissue.
B. A higher-power view demonstrating dilated ducts with inspissated eosinophilic concretions n a
patient with chronic pancreatitis.
Causes

Alcohol abuse (Middle-aged men)

- Alcohol transiently increases pancreatic exocrine secretion and contraction of the sphincter
of Oddi (the muscle regulating the tone at the ampulla of Vater).
- Alcohol also has direct toxic effects on acinar cells, including induction of oxidative stress
(free radicals) in acinar cells, which leads to membrane damage and lipid accumulation, and
subsequent expression of chemokines like interleukin-8 (IL-8), which recruits mononuclear
inflammatory cells.
- Oxidative stress also promotes the fusion of lysosomes and zymogen granules with resulting
acinar cell necrosis, inflammation, and eventually parenchymal fibrosis.
- Chronic alcohol ingestion results in the secretion of protein-rich pancreatic fluid, which leads
to the deposition of inspissated protein ductal plugs (concretions) and obstruction of small
pancreatic ducts.
Long-standing pancreatic duct obstruction (e.g., by pseudocysts, calculi, neoplasms, or pancreas
divisum)
Tropical pancreatitis, a poorly characterized heterogeneous disorder seen in Africa and Asia,
with a subset of cases having a genetic basis
Hereditary pancreatitis due to mutations in the pancreatic trypsinogen gene ( PRRS1 ), or the
SPINK1 gene encoding a trypsin inhibitor
Cystic fibrosis
caused by mutations in the CFTR gene; the CFTR proteinalso is expressed in pancreatic ductal
epithelium, and CFTR mutations decrease bicarbonate secretion and increase the viscosity of
the secretions, thereby promoting protein plugging.
Malnutrition
Autoimmune disorder

In contrast with acute pancreatitis, a variety of profibrogenic cytokines, such as transforming growth
factor- (TGF-), connective tissue growth factor, and platelet derived growth factor, are secreted in
chronic pancreatitis.

These cytokines induce the activation and proliferation of periacinar myofibroblasts (pancreatic stellate
cells), which deposit collagen and are instrumental in the pathogenesis of fibrosis.

Autoimmune Pancreatitis

IgG4-related autoimmune pancreatitis is a multisystem disease and may be one manifestation of IgG4-
associated fibrosing disorders). Recognition of autoimmune pancreatitis in both its forms is important,
because it can mimic pancreatic cancer and also because it responds to steroid therapy.

This distinct form of chronic pancreatitis that is characterized by one of two morphologic patterns:

(1) striking infiltration of the pancreas by lymphoplasmacytic cells, many of which are positive for
IgG4, accompanied by a swirling fibrosis and venulitis (lymphoplasmacytic sclerosing
pancreatitis), or
(2) a duct-centric mixed infiltrate composed of neutrophils, lymphocytes and plasma cells, often
obliterating the ductal epithelium (idiopathic duct centric pancreatitis).
Pancreatic neoplasms

Pancreatic exocrine neoplasms can be cystic orsolid. Some tumors are benign, others are among the
most lethal of all malignancies.

Cystic Neoplasms

Only 5% to 15% of all pancreatic cysts are neoplastic. Cystic tumors constitute less than 5% of pancreatic
neoplasms; they typically occur as painless, slow-growing masses.

Serous cystadenoma

Typically seen in women older than 60 years; these are usually solitary, well-circumscribed nodules with
a central stellate scar without atypia. They are composed of numerous 1- to 3-mm small cysts lined by a
glycogen-rich cuboidal epithelium and containing serous, watery clear straw colored fluid. These are
almost always benign and resection is curative.

Most serous cystadenomas carry somatic mutations of the von Hippel-Lindau ( VHL ) tumor suppressor
gene, the product of which binds to hypoxia-inducible factor 1 alpha (HIF1 alpha) and results in its
degradation.

Mucinous cystic neoplasm

These multiloculated cystic neoplasms are filled with thick mucinous material; the cysts are lined by
mucin-producing columnar cells within a dense cellular stroma resemble that of the ovary. Almost 95%
occur in women, and most arise as slow-growing painless masses in the body or tail of the gland. Based
on the degree of cytologic and architectural atypia in the lining epithelium, noninvasive mucinous cystic
neoplasms are classified as harboring low-grade, moderate, or severe dysplasia. One third of these
lesions harbor an invasive adenocarcinoma. Distal pancreatectomy for noninvasive cysts typically is
curative, even in the setting of severe dysplasia.

Intraductal papillary mucinous neoplasm (IPMN): These are intraductal mucin-producing neoplasms,
more common in men than women. Most arise in the head of the gland, and 10% to 20% are multifocal.
They differ from mucinous cystic neoplasms by lacking an associated dense stroma and by involving a
larger pancreatic duct, but they have a similar malignant potential. Solid-pseudopapillary tumor: These
round and well-circumscribed neoplasms have solid and cystic regions; they occur mainly in young
women and cause abdominal discomfort due to their large size. These tumors are associated with
activating mutations of b-catenin. Although some are locally aggressive, complete resection is usually
curative.