1. Title: pancreatic cysts and neoplasms.
Objectives: to
1. Identify congenital cysts.
2. Describe pseudocysts.
3. Explain cystic neoplasms.
4. Study pancreatic adenocarcinoma.
5. Outline pancreatoblastoma.

2. Pancreatic cysts:
 A variety of cysts can arise in pancreas.
 Most are non-neoplastic pseudocysts ,
but congenital cysts and neoplastic cystic tumors
also occur.
 Unilocular cysts tend to be benign.
 Multilocular cysts are more often neoplastic and
possibly malignant.

3. CONGENITAL CYSTS:
 Result from anomalous development of
pancreatic ducts.
 Those in kidney, liver, and pancreas frequently
coexist in polycystic disease .
 Range from microscopic lesions to 3 to 5 cm in diameter.
 Lined by duct type cuboidal epithelium, or
by completely attenuated cell layer.
 Enclosed in thin fibrous capsule and filled with
clear-to-turbid mucoid or serous fluid.

4. PSEUDOCYSTS:
 Localized collections of necrotic-hemorrhagic
material rich in pancreatic enzymes.
 Lack epithelial lining (hence the prefix "pseudo").
 account for 75% of cysts in pancreas.
 Usually arise after an episode of acute
pancreatitis, often in setting of chronic
alcoholic pancreatitis.
 Traumatic injury to abdomen can also give rise to
pseudocysts.
 Many spontaneously resolved, may become secondarily
infected, and larger pseudocysts may compress or
even perforate into adjacent structures.

5. Morphology:
 Range in size from 2 to 30 cm in diameter.
 Usually solitary, may be situated within substance of
pancreas, or more commonly attached to surface of
pancreas and involve peripancreatic tissues .
 Composed of central necrotic-hemorrhagic material rich in
pancreatic enzymes , surrounded by nonepithelial-lined
fibrous walls.
Pancreatitis with pseudocyst formation.
pseodocyst is walled off by fibrotic tissue with hemorrhage.

6. Neoplasms:
 A broad spectrum of exocrine neoplasms
can arise in pancreas.
 May be cystic or solid ; benign or malignant.
Cystic neoplasms:
 Only 5% to 15% of all pancreatic cysts are neoplastic.
 Cystic neoplasms make up fewer than 5% of all
pancreatic neoplasms.
 While serous cystadenoma are entirely benign;
mucinous cystic neoplasms can be benign, border line
malignant, or malignant.

7. Serous cystadenomas:
 Benign cystic neoplasms lined by low-cuboidal cells,
and contain clear, thin, straw-colored fluid (serous fluid).
 They account for about 25% of all cystic neoplasms
of pancreas.
 Arise twice as often in women as in men.
 Typically present in seventh decade of life.
 Non specific symptoms such as abdominal pain,
and palpable abdominal masses.

8. Pancreatic serous cyst adenoma- microscope
Pancreatic serous cyst adenoma:
gross specimen clearly demonstrates
microcystic nature of tumor (arrow).

9. Mucinous cystic neoplasms:
 Mostly arise in women, in contrast to serous type
can be benign, borderline malignant, or malignant.
 Usually arise in body or tail of pancreas and
present as painless, slow-growing masses.
 Cystic spaces are filled with thick tenacious mucin,
and lined by columnar mucinous epithelium with
intervening dense stroma.
 Benign mucinous cystadenomas lack significant
cytologic or architectural atypia.

10.  Borderline ones show significant cytologic and
architectural atypia , but no tissue invasion.
 Malignant cases have associated tissue invasion.
pancreatic mucinous cystic neoplasms,
note mucin-filled cystic cavities.

11. Pancreatic carcinoma:
 Infiltrating ductal adenocarcinoma of pancreas,
commonly known as "pancreatic cancer“.
 Fourth leading cause of cancer death preceded by lung,
colon, and breast cancers.
 5-year survival rate is dismal, less than 5%.
Precursors to Pancreatic Cancer:
 There is a progression in pancreas from:
non-neoplastic epithelium ; to noninvasive lesions in
small ducts and ductules ; to invasive carcinoma.
 These precursor lesions are called
“Pancreatic Intraepithelial Neoplasias" (PanINs).

12.  PanIN - invasive carcinoma sequence is supported by:
o PanINs often found adjacent to infiltrating carcinomas.
o Isolated case reports of patients with PanINs later on
developed invasive pancreatic cancer.
o Genetic alterations in PanINs are similar to those
present in invasive cancers.

13. Molecular Carcinogenesis:
 Like all cancers, pancreatic cancer is fundamentally
a genetic disease .
 Multiple genes are often altered in pancreatic cancer:-
K-RAS:
o Oncogene, present on chromosome 12 P.
o Most frequent altered oncogene in pancreatic cancer.
o Activated by point mutation in 80% to 90% of cases.

14. p16:
o Tumor suppressor gene ( chromosome 9 P).
o Most frequently inactivated tumor suppressor gene.
o Inactivated in 95% of cases.
o Gene product (p16 protien) plays a critical role
in control of cell cycle.
SMAD4:
o Tumor suppressor gene (chromosome 18q).
o Inactivated in 55% of cases.
o Also known as DPC4.

15. o Normal function of SMAD4 is to suppress growth
and promote apoptosis.
o SMAD4 rarely inactivated in other cancer types.
p53:
o Tumor suppressor gene (chromosome 17p).
o Inactivated in 50% to 70% of cases.
o The gene product is a nuclear DNA-binding protein
that acts both as cell cycle checkpoint, and as
inducer of cell death (apoptosis).

16. Epidemiology, Etiology :
 Is primarily disease of elderly, 80% of cases
occurring between age 60 and 80.
 More common in blacks than whites, and slightly more
common in individuals of Jewish decent.
 The strongest environmental influence is smoking.
 Consumption of diet rich in fats also implicated.
 Chronic pancreatitis and diabetes mellitus are
associated with increased risk .

17.  Familial clustering of pancreatic cancer has been reported.
 Number of inherited genetic syndromes are recognized
to increase the risk :-
o Hereditary nonpolyposis colorectal cancer .
o Hereditary breast and ovarian cancer.
o Familial atypical multiple mole melanoma syndrome.
o Hereditary pancreatitis.
o Peutz-Jeghers syndrome.

18. Morphology:
Grossly: hard, stellate, gray-white, poorly defined masses.
Microscopically:
 No difference between carcinomas of head, and
those of body and tail.
 The appearance is that of moderately to poorly
differentiated adenocarcinoma forming abortive tubular
structures, or cell clusters ; and exhibiting aggressive
deeply infiltrative growth pattern.
 Dense fibrous stroma accompanies tumor invasion.

19.  The malignant glands are
atypical, irregular, small, and bizarre; and
are lined by anaplastic cuboidal-to-
columnar epithelial cells.
 Well-differentiated tumors are the exception.

20. Less common variants of pancreatic cancers:
 Acinar cell carcinomas: show prominent acinar cell
differentiation, including formation of zymogen granules
and production of exocrine enzymes including trypsin and
lipase.
 Adenosquamous carcinomas: have focal squamous
differentiation in addition to glandular differentiation.
 Undifferentiated carcinomas: they contain large
multinucleated osteoclast-like giant cells.

21. General Features:
 60% arise in head , 15% in body, and 5% in tail ;
in 20% there is diffuse involvement of entire pancreas.
 Two features characteristic of pancreatic cancer:
o Highly invasive.
o Intense non-neoplastic host reaction composed
of fibroblasts, lymphocytes, and extracellular matrix
(called "desmoplastic response").
 Most carcinomas of head obstruct common bile duct
and cause jaundice.

22.  In contrast, carcinomas of body and tail do not
impinge on biliary tract and hence remain silent
for some time.
 Pancreatic cancers often extend through retroperitoneal
space entrapping adjacent nerves.
 Occasionally invade spleen, adrenals, vertebral column,
transverse colon, and stomach.

23.  Peripancreatic, gastric, mesenteric, omental,
and portahepatic lymph nodes are frequently involved.
 Liver is often enlarged owing to metastatic deposits.
 Distant metastases principally to lungs and bones.
Clinical Features:
 Remain silent until their extension impinges on
other structures.
 Pain is usually first symptom, but by the time
pain appears are usually beyond cure.

24.  Obstructive jaundice in most cases of carcinoma of head.
 Weight loss, anorexia, malaise and weakness are
signs of advanced disease.
 Migratory thrombophlebitis known as
Trousseau sign occurs in 10% of patients due to
elaboration of platelet-aggregating factors and
procoagulants from tumor or its necrotic products.

25. Diagnosis:
 K-RAS oncogene is mutated in 90% of cases.
 Serum levels of tumor markers (carcinoembryonic
antigen and CA19-9) are elevated.
 Several imaging techniques:
Endoscopic US and CT scan:- for diagnosis and
performance of percutaneous needle biopsy.

26. PANCREATOBLASTOMA:
 Rare neoplasms, occur primarily in children
aged 1 to 15 years.
 Have distinct microscopic appearance with
squamous islands admixed with undifferentiated cells.
 They are malignant neoplasms, although survival may be
better than that for pancreatic ductal adenocarcinomas.

27. Summary:
1. Pancreatic cysts: pseudocysts , congenital cysts,
and cystic neoplasms.
2. Cystic neoplasms: Serous cystadenomas
and Mucinous cystic neoplasms.
3. Infiltrating ductal adenocarcinoma of pancreas
is fourth leading cause of cancer death.
4. Less common variants : acinar cell ca. ,
adenosquamous ca. , and undifferentiated ca.
5. Pancreatoblastoma: rare neoplasms, occur primarily
in children.

28. Questions:
1. Write short assay on molecular carcinogenesis
of pancraetic cancer?
2. Discuss briefly pseudocyst of pancreas?
THANK YOU