1. Pancreatic Disorder

2. Pancreas
• The pancreas is a gland organ participating both in the
digestive and in the endocrine system.
• As endocrine:
– producing several important hormones including insulin,
glucagon and somatostatin.
• As exocrine:
– Secreting pancreatic juice containing digestive enzymes that
pass to the small intestine.
– Enzymes: trypsin, chymotrypsin, aminopeptidase,
elastase, amylase, lipase, phopholipases and
nucleases.

3. Development

4. 5 weeks embryo end of 6th
week
• The pancreas is developed in two parts, a dorsal and a ventral.
• The former arises as a diverticulum from the dorsal aspect of the duodenum a short distance
above the hepatic diverticulum, and, growing upward and backward into the dorsal
mesogastrium, forms a part of the head and uncinate process and the whole of the body and tail
of the pancreas.
• The ventral part appears in the form of a diverticulum from the primitive bile-duct and forms the
remainder of the head and uncinate process of the pancreas. The duct of the dorsal part
(accessory pancreatic duct) therefore opens independently into the duodenum, while that of the
ventral part (pancreatic duct) opens with the common bile-duct.

5. Coarsely lobulated, elongated, lies transversely across the abdomen
and extends from the duodenum to the splenic hilum.
Three parts: head with the uncinate process, body and tail.
Duodenum
Splenic hilum

6. Anterior aspect: directly in contact with the posterior wall of the stomach
Posterior: extends to the inferior vena cava
: superior mesenteric vessels
: splenic vein
: left kidney

7. Pancreatic ducts
• Main pancreatic duct
– Duct of Wirsung
– Ends in the papilla or ampulla of vater in
conjunction with the common bile duct.
• Accessory pancreatic duct
– Duct of Santorini
– Opens independently into a minor duodenal
papilla

8. Pancreatic ducts
• Both ducts are joined by numerous anastomostic connections.
• When this is not the case and the duct of Santorini becomes the
principal drainage – result to a condition called – pancreas divisum

9. Histology
Two separate components: Exocrine & Endocrine
– Exocrine portion
• Constitute 80-85% of the organ
• Made up of numerous small glands or acini
• Lining cells: columnar to pyramidal cells radially
oriented about the gland circumference
ACINI

10. Endocrine portion
• Mainly represented by the Langerhan’s islet
• Constitute 1%-2% of the adult pancreas
• Main cell types:
B cells - insulin secreting (2/3 -3/4 of cell population)
A cells - glucagon secreting (1/5 -1/4 of cell population)
D cells - somatostatin secreting (small in number)
PP cells - pancreatic polypeptide secreting cells
(scarce and located at the periphery)
Islet of Langerhans

11. Congenital Anomalies
• Annular pancreas
– Rare embryologic abnormality in which the
ventral primordium fails to rotate properly.
– Down syndrome is a predisposing condition
for this anomaly.
Duct originates anteriorly
Courses to the right over the duodenum,
then posteriorly to the left of the duodenum
passing near the common duct
Finally, joining the pancreatic duct.

12. Congenital Anomalies
• Gross:
– There is encirclement of the duodenum by
pancreatic parenchyma -> may lead to
constriction of the duodenal lumen.
• Microscopic:
– Contains a large number of PP cells in its
many irregularly shaped islets.

13. Heterotopic pancreas
• Frequent congenital anomaly
• Sites:
– Duodenum (particularly the 2nd
portion)
– Stomach
– Jejunum
– Ileum
– Meckel’s diverticulum
– Gastric and intestinal diverticula
– Gall bladder
– Bile ducts
– Large bowel
– Spleen (usually within or beneath the capsule)
– Omentum
– Abdominal wall

14. Pancreatitis
• Acute pancreatitis
– Acute onset of abdominal pain resulting from enzymatic necrosis
and inflammation of the pancreas.
• 80% of cases associated with biliary tract disease and
alcoholism.
• Gallstone present in 35% to 60%
• Less common causes:
– Infections with mumps, coxsackieviruses, and Mycoplasma
pneumoniae
– Acute ischemia induced by vascular thrombosis, embolism,
vasculitis
– Drugs – thiazide diuretics, azathioprine, estrogens,
sulfonamides, furosemide, methyl dopa, procainamide
– Occlusion of pancreatic ducts by Ascaris and Clonorchis
sinensis.

15. Morphology
The morphologic change stems directly from the
action of activated pancreatic enzymes that
are released into the pancreatic substance.
1. Microvascular leakage, to cause edema.
2. Necrosis of fat by lipolytic enzyme.
3. Acute inflammatory reaction.
4. Proteolytic destruction of pancreatic substance.
5. Destruction of blood vessels with subsequent
interstitial hemorrhage.

16. Chronic pancreatitis
• Characterized by repeated bouts of mild to moderate
pancreatic inflammation, with continued loss of pancreatic
parenchyma and replacement by fibrous tissues.
• Etiologic factors:
– Obstruction of the ductal system by carcinoma or stones
– Alcoholism
– Hyperparathyroidism (as a result of hypercalcemia)
– Polyarteritis nodosa
– Mumps, Tb, sarcoidosis

17. Morphology
• Gross:
– Gland is hard, sometimes with dilated ducts and
grossly visible calcified concretions.
– Pseudocyst formation is common.
• Microscopic:
– Fibrosis.
– Reduced number and size of acini.
– Relative sparing of the islets of Langerhans.
– Variable obstruction of pancreatic ducts of all sizes.
– Chronic inflammatory infiltrates around lobules usually
present.

18. Cysts
• Congenital cysts
– Believe to result from anomalous development of
pancreatic ducts.
– Cysts range from 3 to 5 cm in diameter.
– Lined by glistening, duct type cuboidal epithelium or a
completely attenuated cell layer, enclosed in a thin
fibrous capsule filled with a clear to turbid, mucoid or
serous fluid.

19. Cysts
• Pseudocyts
– Localized collection of pancreatic secretions
that develop after inflammation of the
pancreas.
– Gross: wall is thick and irregular
– Microscopic: devoid of lining epithelium
• Complication: perforation and hemorrhage

20. TUMORS

21. Ductal Adenocarcinoma
• General and Clinical Features
– Ductal adenocarcinoma of the exocrine pancreas
comprises about 85% of all cases of pancreatic
malignancy.
– Cases have been reported in workers exposed to
B-naphthylamine or benzidine
– Cigarette smoking has also been cited as a risk
factor.

22. Ductal Adenocarcinoma
• General and Clinical Features
– About 10% of pancreatic cancers show familial
aggregation consistent with genetic susceptibility.
– Chronic pancreatitis is positively associated with an
increased risk for pancreatic cancer, cause and effect
relationship is difficult to ascertain.

23. Ductal Adenocarcinoma
• General and Clinical Features
– Most patients are elderly
– With slight male preponderance (1.6:1 ratio)
– Because of its strategic location in relation to the
extrahepatic bile ducts, carcinoma of the head of the
pancreas usually causes progressive jaundice that is
associated with pain in at least half of the patients;
however the diagnosis in most cases is made when
the tumor is relatively large (5 cm) and has extended
beyond the pancreas (85% of the cases).

24. Ductal Adenocarcinoma
General and Clinical Features
• Carcinoma of the body and tail grow insidiously and has
already metastasized at the time of diagnosis.
• Several diagnostic tests to detect early stage of
pancreatic ca:
– CT scan - nuclear magnetic resonance
– Celiac angiography - sonography
– Endoscopic retrograde cholangiopancreotography (ERCP)
– Selenomethionine scan - duodenal aspiration
– Serum test: monoclonal antibodies against various cancer-
related antigens:
• SPan1
• CA 19-9

25. Location and Gross Features
• Pancreatic carcinoma is located in the head of the
pancreas in 2/3 of cases.
• 1/3 either body or tail.
• 20% of cases there are multiple tumors
• Gross:
– Most are poorly delineated and firm.
– Yellowish gray cut surface.
– Rarely undergoes massive cystic degeneration.

26. Location and Gross Features
• Duodenal wall is invaded by direct extension in ¼ of the
tumors arising from the pancreatic head.
• Extrapancreatic extension is common and when
extensive, it may be difficult to determine whether the
tumor is of pancreatic in origin.
• Pancreatic ducts if involved – frequently become greatly
dilated and plugged with necrotic tumor.
• The non-neoplastic pancreas distal to the tumor may
show extensive atrophy, chronic inflammation and
fibrosis plus ductal dilatation.

27. Microscopic features
• Pancreatic duct adenocarcinoma are graded
microscopically:
– Well-differentiated
– Moderately differentiated
– Poorly differentiated

28. Microscopic features
• Well-differentiated tumors:
– Can be extremely difficult.
– Attention to cytologic details.
– LPO:
• Glands are well formed, large lumen and are lined
by one or few layers of cylindrical or cuboidal
epithelium.
• Irregular shape and distribution of the glands and
peculiar desmoplastic stroma.
• Note: overall low power view may not be
particularly suggestive of carcinoma.

29. Microscopic features
• Well-differentiated tumors:
– HPO:
• Lining epithelium will show one or more features indicative of
malignancy:
– Marked nuclear pleomorphism
– Loss of polarity
– Prominent nucleoli
– Mitotic activity
• Vascular invasion particularly veins – seen in ½ of
tumors.
• Perineural invasion – present in 90% of cases is an
additional important diagnostic sign.

30. Caution:
– Benign epithelial inclusions in the pancreatic
nerves.
– Perineural extension of islet cells which can
occur in chronic pancreatitis.

31. PanIN
• Pancreatic Intraepithelial Neoplasia
– Carcinoma-in-situ / Atypical hyperplasia
– Believed to be precursors of Invasive ductal
adonocarcinoma

32. Histochemical and
Immunohistochemical Features
• Most pancreatic ductal carcinomas are positive for
mucin stains.
• Immunohistochem:
– (+) reactivity to keratin (not much of a diagnostic help)
– EMA (epithelial membrane antigen)
– CEA - Tn / sialosyl-Tn antigens
– CA 19-9 - DF3 antigen (mammary-type apo-mucin)
– DU-PAN2 - M1 and cathepsin
– YPan-1 - pepsinogen II
– Span-1 - villin

33. Question
• Are these histochemical and immunohistochemical
studies sufficient to confirm the diagnosis of
Pancreatic adenocarcinoma?

34. • NO
• Unfortunately, ducts in cases of chronic
pancreatitis also exhibit immunoreactivity
for most of these markers, thus
diminishing their utility.

35. Molecular Genetic Features
• Structural rearrangement or loss of genes:
– 1p, 3p, 6p, 8p and 17p – important in pancreatic
carcinogenesis
– Mutations or accumulation of p53 – detected in half of
the cases
– Mutation of the K-ras oncogene in 95% of cases
– Inactivation of p16 in over 95% of cases
– Overexpression of HER2 / neu oncogene in
approximately ½ of the cases

36. • DPC4 suppressor gene
– Inactivated in approximately half of pancreatic ductal
carcinomas
– NEVER inactivated in benign conditions.
– Therefore:
• The immunohistochemical absence of this protein
product in the ductal epithelium of a pancreatic
biopsy specimen is strongly suggestive of
carcinoma.

37. Other Microscopic Types
• Adenosquamous carcinoma
• Oncocytic carcinoma
• Clear cell carcinoma
• Hepatoid carcinoma
• Signet ring carcinoma
• Mucinous (colloid carcinoma)

38. Endocrine Tumors
• General and clinical features
– Traditionally designated as islet cell tumors
– Some books – pancreatic endocrine neoplasm
– Most common in adults
– Few reported cases in children and newborn.

39. Morphologic Features
• Body and tail – most common location
• Gross:
– Pinkish cast resembling spleen or congested lymph
node.
– Do not have well-defined capsule.
– Long standing tumors – large amount of fibrous
tissues and may contain calcium and bone.
– Some may be predominantly cystic in appearance.

40. Morphologic Features
• Histologic:
– Usually composed of small, relatively uniform
cuboidal cells with centrally located nuclei and
acidophilic or amphophilic finely granular cytoplasm.
– Patterns:
• Solid - any cell type
• Gyriform - Beta and alpha cell type
• Glandular - G or VIP cells
• Nondescript
G - Gamma cells; VIP – vasoactive intestinal peptide

41. Morphologic Features
• Stroma:
– Highly vascular
– Some cases – abundant hyaline material separates
the tumor into scattered nests
– Amyloid may be encountered paticularly in insulin
producing neoplasm

42. Unusual features of pancreatic endocrine tumors:
a. mucin production
b. black pigmentation – due to lipofuscin-type granules
c. clear cell – tends to occur in tumors associated with
von Hippel-Lindau disease and may mimic renal cell ca
d. vacuolation – accumulation of cytoplasmic lipid
e. psammomma body formation
f. rhabdoid features
g. sarcomatoid transformation – include presence of
skeletal muscle cells.

43. Specific Types
• Beta cell tumors
– Most common
– When functioning – referred to as insulinoma
– Occur in adults – incidence equal in both sexes
– Whipple Triad: characteristic of Beta cell tumor
consists of:
• Mental confusion, fatigue and convulsion
• Fasting blood glucose below 50 mg%
• Relief of symptoms by the administration of
glucose

44. Specific Types
• Beta cell tumors
– Over 90% - solitary
– Located within the substance of the pancreas
– 2% - seen in adjacent areas
– 70% - measure 1.5 cm or less
• Microscopically:
– May grow in solid or gyriform pattern.
– Glands are usually absent.

45. Specific Types
• Beta cell tumors
– Immunohistochemically
• lesser degree of reactivity for insulin than the
normal beta cells.
• Amylin – can be used for detection
Amylin
Amylin is a peptide of 37 amino acids, which is also secreted by the
beta cells of the pancreas.
Some of its actions:
inhibits the secretion of glucagon;
slows the emptying of the stomach;
sends a satiety signal to the brain.

46. Specific Types
• Beta cell tumors
– Only 7% to 10% - are malignant
– Evidence of infiltration and metastases
– Associated clinically with more pronounced
hypoglycemia.
– Treatment: SURGICAL

47. Specific Types
• Alpha cell Tumor
– Two distinct types:
• Those associated with glucagonoma syndrome
• Those not associated with glucagonoma syndrome

48. Alpha cell tumor
• Those associated with glucagonoma syndrome
(Glucagonomas)
– Usually solitary and large
– Nondescript microscopic pattern
– Few cells positive for glucagon immnuhistochemically
(caused by abnormalities in the biosynthesis of
glucagon)
• Not associated with glucagonoma syndrome
– Multiple and small
– Gyriform pattern of growth
– Strongly immunoreactive for glucagon
– Nearly always benign

49. Specific Types
• G-cell tumors
– Referred to as Gastrinoma
– Due to excessive production of gatrin
– Can produce Zollinger-Ellison syndrome
– Tumors often found in pancreas, duodenum and
gastric antrum
– Diarrhea – seen in 1/3 of patients as a result of
excessive gastric secretion
– Immunocytochemical studies: will show presence of
gastrin production by tumor cells.

50. Specific Types
• G-cell tumors
• Treatment of choice:
– Removal of the target organs – total gastrectomy
– Solitary non-metastasizing tumors - excision

51. Specific Types
• VIP-producing tumors
– Associated with a diarrheogenic or cholera-like
syndrome in the absence of gastric hypersecretion
– Due to vasoactive intestinal polypeptide (VIP)
– Immunocytochem: absence of gastrin production
– Tumors also contain:
• PP – pancreatic polypeptide
• calcitonin
• Alpha chain of hCG

52. Specific Types
• Delta cell tumors
– Seem generally nonfunctioning at the clinical level
– Produces somatostatin (growth hormone inhibiting
hormone)
– Patient presentation: somatostatinoma syndrome
• Diabetes
• Cholecystolithiasis
• Steatorrhea
• Indigestion
• Hypochlorhydria
• Occasionally anemia

53. • Zollinger–Ellison syndrome
– is a triad of gastric acid hypersecretion
– severe peptic ulceration
– non-beta cell islet tumor of pancreas (Gastrinoma).
• In this syndrome increased levels of the hormone
gastrin are produced, causing the stomach to produce
excess hydrochloric acid. Often the cause is a tumor (
gastrinoma) of the duodenum or pancreas producing the
hormone gastrin. Gastrin then causes an excessive
production of acid which can lead to peptic ulcers in
almost 95% of patients.
• Gastric hyperacidity with gastric, duodenal and jejunal
ulcers.

54. • Somatostatin – growth hormone inhibiting
hormone

55. Question:
• One of the following is not a poduct of the
endocrine function of the pancreas.
–A. Insulin
–B. Glucagon
–C. Amylase
–D. Somatostatin

56. Question:
The uncinate process of the pancreas is part
of which of the ff?
A. Head
B. Body
C. Tail
D. None of the above

57. Question:
Which of the following is not true?
A. The posterior portion of the pancreas is in
direct contact with the stomach.
B. The head of the pancreas is in close proximity
with the 2nd
portion of the duodenum.
C. The pancreas traverse across the abdomen.
D. The tail ends near the splenic hilum.

58. Question:
The pancreatic duct that opens directly to
the duodenum:
A. Duct of Warsung
B. Bile duct
C. Duct of Santorini
D. All of the above

59. Question
Which of the following has the highest cell
population in the Islet of Langerhans’?
A. A cells
B. B cells
C. D cells
D. PP cells

60. Question
True with annular pancreas:
A. Originates from the ventral bud.
B. Originates from the dorsal bud.
C. Encircle first posteriorly to the right of the
duodenum.
D. Joins the bile duct to form the common bile
duct.

61. Question:
• This is not true with ectopic pancreatic
tissue.
A. Function normally as the pancreas.
B. Could also develop neoplasm.
C. Most common location is the duodenum.
D. Development is via the aberrant rotation of
the ventral bud.

62. Question
• The ff. are morphologic changes seen in
acute pancreatitis except:
A. Edema as a result of microvascular leak.
B. Fibrosis
C. Presence of acute inflammatory cells
D. Proteolytic destruction of the pancreatic substance.

63. Question
• Which is true regarding chronic pancreatitis?
A. Edema as a result of microvascular leak.
B. Fibrosis
C. Presence of acute inflammatory cells
D. Proteolytic destruction of the pancreatic substance.