Title: pancreatic cysts and neoplasms.Objectives: to1. Identify congenital cysts.2. Describe pseudocysts.3. Explain cystic neoplasms.4. Study pancreatic adenocarcinoma.5. Outline pancreatoblastoma.
Pancreatic cysts: A variety of cysts can arise in pancreas. Most are non-neoplastic pseudocysts ,but congenital cysts and neoplastic cystic tumorsalso occur. Unilocular cysts tend to be benign. Multilocular cysts are more often neoplastic andpossibly malignant.
CONGENITAL CYSTS: Result from anomalous development ofpancreatic ducts. Those in kidney, liver, and pancreas frequentlycoexist in polycystic disease . Range from microscopic lesions to 3 to 5 cm in diameter. Lined by duct type cuboidal epithelium, orby completely attenuated cell layer. Enclosed in thin fibrous capsule and filled withclear-to-turbid mucoid or serous fluid.
PSEUDOCYSTS: Localized collections of necrotic-hemorrhagicmaterial rich in pancreatic enzymes. Lack epithelial lining (hence the prefix "pseudo"). account for 75% of cysts in pancreas. Usually arise after an episode of acutepancreatitis, often in setting of chronicalcoholic pancreatitis. Traumatic injury to abdomen can also give rise topseudocysts. Many spontaneously resolved, may become secondarilyinfected, and larger pseudocysts may compress oreven perforate into adjacent structures.
Morphology: Range in size from 2 to 30 cm in diameter. Usually solitary, may be situated within substance ofpancreas, or more commonly attached to surface ofpancreas and involve peripancreatic tissues . Composed of central necrotic-hemorrhagic material rich inpancreatic enzymes , surrounded by nonepithelial-linedfibrous walls.Pancreatitis with pseudocyst formation.pseodocyst is walled off by fibrotic tissue with hemorrhage.
Neoplasms: A broad spectrum of exocrine neoplasmscan 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 allpancreatic neoplasms. While serous cystadenoma are entirely benign;mucinous cystic neoplasms can be benign, border linemalignant, or malignant.
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 neoplasmsof 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.
Mucinous cystic neoplasms: Mostly arise in women, in contrast to serous typecan be benign, borderline malignant, or malignant. Usually arise in body or tail of pancreas andpresent as painless, slow-growing masses. Cystic spaces are filled with thick tenacious mucin,and lined by columnar mucinous epithelium withintervening dense stroma. Benign mucinous cystadenomas lack significantcytologic or architectural atypia.
Borderline ones show significant cytologic andarchitectural atypia , but no tissue invasion. Malignant cases have associated tissue invasion.pancreatic mucinous cystic neoplasms,note mucin-filled cystic cavities.
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 insmall ducts and ductules ; to invasive carcinoma. These precursor lesions are called“Pancreatic Intraepithelial Neoplasias" (PanINs).
PanIN - invasive carcinoma sequence is supported by:o PanINs often found adjacent to infiltrating carcinomas.o Isolated case reports of patients with PanINs later ondeveloped invasive pancreatic cancer.o Genetic alterations in PanINs are similar to thosepresent in invasive cancers.
Molecular Carcinogenesis: Like all cancers, pancreatic cancer is fundamentallya 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.
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 rolein control of cell cycle.SMAD4:o Tumor suppressor gene (chromosome 18q).o Inactivated in 55% of cases.o Also known as DPC4.
o Normal function of SMAD4 is to suppress growthand 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 proteinthat acts both as cell cycle checkpoint, and asinducer of cell death (apoptosis).
Epidemiology, Etiology : Is primarily disease of elderly, 80% of casesoccurring between age 60 and 80. More common in blacks than whites, and slightly morecommon in individuals of Jewish decent. The strongest environmental influence is smoking. Consumption of diet rich in fats also implicated. Chronic pancreatitis and diabetes mellitus areassociated with increased risk .
Familial clustering of pancreatic cancer has been reported. Number of inherited genetic syndromes are recognizedto 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.
Morphology:Grossly: hard, stellate, gray-white, poorly defined masses.Microscopically: No difference between carcinomas of head, andthose of body and tail. The appearance is that of moderately to poorlydifferentiated adenocarcinoma forming abortive tubularstructures, or cell clusters ; and exhibiting aggressivedeeply infiltrative growth pattern. Dense fibrous stroma accompanies tumor invasion.
The malignant glands areatypical, irregular, small, and bizarre; andare lined by anaplastic cuboidal-to-columnar epithelial cells. Well-differentiated tumors are the exception.
Less common variants of pancreatic cancers: Acinar cell carcinomas: show prominent acinar celldifferentiation, including formation of zymogen granulesand production of exocrine enzymes including trypsin andlipase. Adenosquamous carcinomas: have focal squamousdifferentiation in addition to glandular differentiation. Undifferentiated carcinomas: they contain largemultinucleated osteoclast-like giant cells.
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 composedof fibroblasts, lymphocytes, and extracellular matrix(called "desmoplastic response"). Most carcinomas of head obstruct common bile ductand cause jaundice.
In contrast, carcinomas of body and tail do notimpinge on biliary tract and hence remain silentfor some time. Pancreatic cancers often extend through retroperitonealspace entrapping adjacent nerves. Occasionally invade spleen, adrenals, vertebral column,transverse colon, and stomach.
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 onother structures. Pain is usually first symptom, but by the timepain appears are usually beyond cure.
Obstructive jaundice in most cases of carcinoma of head. Weight loss, anorexia, malaise and weakness aresigns of advanced disease. Migratory thrombophlebitis known asTrousseau sign occurs in 10% of patients due toelaboration of platelet-aggregating factors andprocoagulants from tumor or its necrotic products.
Diagnosis: K-RAS oncogene is mutated in 90% of cases. Serum levels of tumor markers (carcinoembryonicantigen and CA19-9) are elevated. Several imaging techniques:Endoscopic US and CT scan:- for diagnosis andperformance of percutaneous needle biopsy.
PANCREATOBLASTOMA: Rare neoplasms, occur primarily in childrenaged 1 to 15 years. Have distinct microscopic appearance withsquamous islands admixed with undifferentiated cells. They are malignant neoplasms, although survival may bebetter than that for pancreatic ductal adenocarcinomas.
Summary:1. Pancreatic cysts: pseudocysts , congenital cysts,and cystic neoplasms.2. Cystic neoplasms: Serous cystadenomasand Mucinous cystic neoplasms.3. Infiltrating ductal adenocarcinoma of pancreasis fourth leading cause of cancer death.4. Less common variants : acinar cell ca. ,adenosquamous ca. , and undifferentiated ca.5. Pancreatoblastoma: rare neoplasms, occur primarilyin children.
Questions:1. Write short assay on molecular carcinogenesisof pancraetic cancer?2. Discuss briefly pseudocyst of pancreas?THANK YOU