Pancreas:

1. Congenital anomalies of pancreas.

2. Pancreatic cysts.
3. Acute and chronic pancreatitis.
4. Pancreatic cancer.

By:
Dr. Jawhar Tahir Omer
M.B.ch.B / F.I.C.Path.
 Congenital anomalies of pancreas:
1. Agenesis:
 Very rare, pancreas is totally absent (agenesis).
 Germ line mutation in IPF1 (PDX1) gene on chromosome 13.
 Incompatible with life.
2. Pancreas Divisum:
• Clinically significant, caused by failure of duct systems of
dorsal and ventral primordia to fuse.
• As a result, the bulk of the pancreas (formed by the dorsal
pancreatic primordium) drains into the duodenum through
the small-caliber minor papilla .
• The duct of Wirsung in persons with divisum drains only a
small portion of the head of the gland through the papilla of
Vater.
 Accumulated pancreatic secretions predispose to chronic
pancreatitis.
 3. Annular Pancreas:
 Develops when the bifid ventral pancreatic primordium or
bud forms a band-like ring that encircles the second portion
of duodenum.
 Presents with signs and symptoms of duodenal obstruction
such as gastric distention and projectile vomiting.
4. Ectopic Pancreas:
 Found in 2% of routine postmortem examination.
 2% of islet cell tumors arise in ectopic pancreatic tissue.
 Favored sites are stomach and duodenum, followed by
jejunum and ileum;
 Usually located in submucosa.
 Histologically: pancreatic acini , occasionally islets.
 May forms a sessile mass.
 May cause pain from localized inflammation, or
rarely mucosal bleeding.
Summary of pancreatic cysts:

• Congenital cysts and serous cystadenoma are lined by

cuboidal cells
• Pseudocysts  no epith lining , instead fibrin-lined
• Mucinous cystic neoplasm  columnar mucinous

• Serous cystadenoma -- >benign

• Mucinous  benign , borderline , malignant
• Unilocular cysts  benign
• Multilocular cysts  malignant

• congental cysts are Filled with serous or mucoid fluid.

• Pseudocysts filled with necrotic-hemorrhagic matrials with
pancriatic enzymes
• Serous cystadenoma filled with serous
• Mucinous cystic neoplasms filled with mucus
 Pancreatic cysts:
No epithelial lining
 Most are non-neoplastic pseudocysts;
but congenital cysts and cystic neoplasms also occur.
 Unilocular cysts tend to be benign;
while Multilocular cysts are more often malignant.
Congenital Cysts: Arise from pancreatic
ducts
 Result from anomalous development of pancreatic ducts.
 Range from microscopic lesions to 3-5 cm in diameter.
 Lined by cuboidal epithelium, or by attenuated cell layer.
 Filled with serous or mucoid fluid.
 Those in kidney, liver, and pancreas coexist in polycystic disease
 Pseudocysts:

 Lack epithelial lining (hence the prefix "pseudo").

Most common
 Account for 75% of cysts in pancreas.
 They are localized collections of necrotic-hemorrhagic
material rich in pancreatic enzymes, surrounded by
non-epithelial lined fibrous wall..
 Result from :
1. Usually arise after an episode of acute pancreatitis.
2. Traumatic injury to abdomen(pancreas) could be the cause.
 Clinically:
1. Many spontaneously resolved,
2. may become secondarily infected,
3. the larger one may compress or even perforate into
adjacent structures.
 Morphology:
o Size: from 2 to 30 cm in diameter.
o Usually solitary and attached to surface of pancreas;
but may be situated within the substance of pancreas.
o Composed of central necrotic-hemorrhagic material rich
in pancreatic enzymes, surrounded by non-epithelial lined
fibrous wall.
(The cyst lacks a true epithelial lining and instead is lined 
by fibrin)

Stroma of the cyst

 Cystic neoplasms:
Serous cystadenoma: In otherthey
organs it couldbenign
are mostly be malignant but in pancreas

 Benign, Lined by low-cuboidal cells, and contain clear serous fluid

Mucinous cystic neoplasms:
 Can be benign, borderline, or malignant.
 Filled with thick tenacious mucin, and lined by columnar
mucinous epithelium.
 Benign cysts: lack cytological or architectural atypia.
 Borderline cysts: show cytological and architectural atypia,
but no tissue invasion.
 Malignant cysts: have associated tissue invasion.
Atypia in the epithelial line
Pancreatitis:
Acute pancreatitis:
 Reversible lesion. Because there is no fibrosis
 Pathogenesis:
o Pancreatic enzymes present in acinar cells in proenzyme
form and have to be activated.
In pancreatic acinar cells
o Lysosomal hydrolases permitting proenzyme activation,
and local release of activated enzymes.
Or due to injury to pancreatic acini and release of enzymes
 Causes:
1. Gall stones: pancreatic duct obstruction.
2. Alcoholism: primary acinar cell injury.
3.Trauma. Causing injury to acini

4.Hereditary. Like cystic fibrosis

 Second type of necrosis is parynchmal
necrosis( acinar necrosis)when there loss of
pancreatic tissue

 Morphology:
o Gross:
 Swollen edematous, with
hemorrhagic and necrotic yellow
nodules (represent fat necrosis).
 Chalky white foci due to calcium
deposition in fat necrosis
areas (calcium soap).
o Microscope:
1. Fat necrosis by lipolytic enzymes.
2. Parenchymal (acini) necrosis by Proteolytic enzymes.
3. Acute inflammatory reaction.
4. Edema by microvascular leakage.
5. Destruction of blood vessels with interstitial hemorrhage.
 Diagnosis:
o Marked elevation of serum amylase and elevated serum
lipase level.
o Hypocalcaemia: result from precipitation of calcium soaps.
o Direct visualization of enlarged inflamed pancreas by
radiographic means.
Chronic pancreatitis:
 Irreversible.
 Inflammation of pancreas with destruction of exocrine
pancreas and fibrosis.
 In late stages: destruction of endocrine pancreas.
 Pathogenesis: Four hypotheses:
1. Ductal obstruction by concretions. Very small tiny stones
2. Toxic-metabolic: alcohol.
3. Oxidative stress: alcohol-induced free radicals.
4. Necrosis-fibrosis: hereditary pancreatitis by autolysis-
-resistant trypsin molecules.
Activation and ihibtion of inhibitors
 Morphology:
o Gross:
- pancreas is hard,
- visible calcified concretions.
- dilated ducts
o Microscope:
- Acini destruction and reduction in number,
- dilation of pancreatic ducts,
- chronic inflammatory cells infiltration.
- parenchymal fibrosis,
 Diagnosis:
1. Mild-to-moderate elevations of serum amylase. Could be normal
2. Elevation in serum alkaline phosphatase level.
3. Visualization of calcifications within pancreas by CT scan and
US.
4. Hypoalbuminemia and hypoalbuminemic edema from
malabsorption caused by pancreatic exocrine insufficiency.
Due to decrease in enzymes required for protein absorption
 Pancreatic cancer: Arising from pancreatic ducts (exocrine portion)
 Pancreatic adenocarcinoma is fourth leading cause of cancer
death preceded only by lung, colon, and breast cancers.
 5-years survival rate is less than 5%.
 Precursor lesions to Pancreatic Cancer:
o There is a progression from non-neoplastic epithelium,
 noninvasive lesions in small ducts and ductules
(PanINs) invasive carcinoma.
o These precursor lesions are called:
“Pancreatic Intraepithelial Neoplasias" (PanINs).
Severe dysplasia,
Mild dysplasia Moderate dysplasia, carcinoma in situ atyp

Pancreatic ducts
Pancreatic ducts
Pancreatic ducts
 Gene Chromosomal  Type of Gene Percentage 
Region of Carcinoma 
with Genetic 
Alteration

K-RAS 12P Altered oncogene 80-90% of cases

the most frequent

P16 9P inactivated tumor 95% of cases

suppressor gene the most frequent

SMAD4 (DPC4) 18q inactivated tumor 55% of cases

suppressor gene

P53 17p inactivated tumor 50-70% of cases

suppressor gene
 Molecular Carcinogenesis: Multiple genes are often altered
in pancreatic cancer:- Chromosome
Petit=small
12 small arch
o K-RAS: Oncogene (12P), it’s the most frequent altered
oncogene in pancreatic cancer (80-90% of cases).
o P16: Tumor suppressor gene (9P), it’s the most frequent
inactivated tumor suppressor gene (95% of cases).
o SMAD4 (DPC4): Tumor suppressor gene (18q),
inactivated in 55% of cases.
o P53: Tumor suppressor gene (17p), inactivated in 50-70%
of cases. P=short arm
Q=long
arm
 Morphology:
o Grossly: hard, stellate, gray-white, poorly defined masses.
o
Most of them
Microscopically:
 Moderate to poorly differentiated adenocarcinoma.
 Well-differentiated tumors are the exception.
 Dense fibrous stroma (desmoplastic stroma).
 Diagnosis:
o Gene study: K-RAS oncogene is mutated in 80-90% of cases.
o Serum levels of tumor markers:
Carcino Embryonic Antigen (CEA) and CA19-9 are elevated.
o Several imaging CA=Carbohydrate antigen (not specific because it present in colon
CA and other neoplastic conditions and also non neoplastic)

techniques:
Endoscopic US and CT scan for diagnosis and performance
of needle biopsy.
 Epidemiology, Etiology, clinical course :
o Most cases occur between age 60 and 80 years.
o More common in blacks than whites, and in Jewish decent.
o Risk factors:
- smoking,
- diet rich in fats,
- Chronic pancreatitis
- diabetes mellitus.
The features will be late in the

Early jaundice body and tail

o 60% of cases arise in head, 15% in body, and 5% in tail ;
and in 20% there is diffuse involvement.
o Two characteristic features:
 Highly invasive. Reaction of the pancreatic tissue

 Desmoplastic stroma: intense non-neoplastic host

reaction composed of fibroblasts, lymphocytes, and
extracellular matrix.
o Most carcinomas of head obstruct the common bile duct
and cause jaundice;
o in contrast, carcinomas of body and tail remain silent for
some time.
o The cancer often extend through retroperitoneal space
entrapping adjacent nerves.
o Local invasion to surrounding organs (stomach, spleen);
and regional L.N’s involvement
o Distant metastases principally to lungs and bones.
Less common variants of pancreatic cancers:

 Acinar cell carcinomas:

- show prominent acinar cell differentiation, includin
- formation of zymogen granules
- and production of exocrine enzymes including trypsin and lipase

Metaplasia
 Adenosquamous carcinomas: have focal squamous
differentiation in addition to glandular differentiation.

 Undifferentiated carcinomas: they contain

large multinucleated giant cells.
 Acinar cell ca. Adenosquamous ca.

Squamous

Undifferentiated ca.