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CASE 18Section CSevilla, AllanTulas, UlyssesRulla, Carissa CamilleSalbino, KrizziaSagorsor, Hazel MaeTabula, Greyzielle GisellaWarren, Hope

PATIENTS PROFILE51 year old maleComplains of pruritus and abdominal pain-(+) radiation to his backWeight loss of 15kg over the past 4 months

Urine: darkStools: clay-coloredSmoker: 60 pack-yearsHeavy alcohol drinker(+) multiple prior bouts of pancreatitis

PE:Cachectic male with scleral icterus, hepatomegaly and palpable gall bladderMass: 8cm in size, located in the mid-epigastric region

Lab tests:Direct bilirubin: 20mg/dL

TransaminasesElevatedPTNormal CA 19-9Elevated

CT scan and Ultrasound: Mass in the head of the pancreas and dilated intrahepatic bile ducts

ERCP: Abrupt cut-off the main pancreatic duct

UGIS: Narrowing of the lumen of the duodenum

1. What is the most likely diagnosis? (Justify)Pancreatic carcinoma

Pancreatic CarcinomaPatient Etiology: Cigarette Smoking :strongest environmental influenceIncreased risk with Chronic pancreatitis Smoker: 60 pack years

(+) multiple prior bouts of pancreatitisClinical Features:PainObstructive jaundice

Weight loss

Serum levels of enzymes & antigens (e.g. CA19-9 antigen & carcinoembryonic antgen) often elevatedAbdominal painScleric icterus, dark-colored urine, clay-colored stools, pruritusWeight loss of 15kg over the past 4 monthsCA19-9 elevated

2. What mechanisms are involved in the development of this disease?Precursor to Pancreatic Cancer: PanINsMolecular CarcinogenesisInherited Predisposition to Pancreatic Cancer

Precursor to Pancreatic CancerThese precursor lesions are called Pancreatic Intraepithelial Neoplasias PanINsPanINs are supported by the following observations:The distribution of PanINs within the pancreas parallels that of invasive cancerPanINs are often found in Pancreatic parenchyma adjacent to infiltrating carcinomaIsolated case reports: Individuals with PanINs later developed an invasive pancreatic cancer

Epithelial cells in PanINs show dramatic TELOMERE SHORTENINGPredispose lesion to accumulation of progressive chromosomal abnormalitiesDevelopment of an invasive Carcinoma

Mechanisms in the development of the diseasePrecursor to Pancreatic Cancer: PanINsMolecular CarcinogenesisInherited Predisposition to Pancreatic Cancer

Molecular CarcinogenesisKRASCDKN2ASMAD4p53Methylation abnormalitiesGene ExpressionOther Genes

Molecular Carcinogenesis

Mechanisms in the development of the diseasePrecursor to Pancreatic Cancer: PanINsMolecular CarcinogenesisInherited Predisposition to Pancreatic Cancer

Inherited predisposition to Pancreatic Cancer

3. What structural changes in the pancreas are seen in this disease?50% of patients with carcinoma of the head of the pancreas: Marked distention of the biliary tree and most develop jaundice

MicroscopicallyModerately to poorly differentiated adenocarcinoma forming abortive tubular structures or cell clustersShows an aggressive, deeply, infiltrative growth pattern

Invasive CA: Presence of DENSE STROMAL FIBROSISPerineural invasion: Presence of proclivityAlso involves lymphatic and large vesselMalignant glands:Poorly formedLined by pleomorphic cuboidal-to-columnar epithelial cells

Variants:- Adenosquamous carcinomas: focal squamous differentiation + glandular differentiation- Undifferentiated carcinomas: large multinucleated osteoclast-like giant cells

4. What is the prognosis of this disease?2008: approximately 37,000 Americans diagnosed with Pancreatic CA virtually all of them will die from their disease5-year survival rate is dismal, LESS THAN 5%