Pancreas and Gallbladder Pathology PDF

Pancreas and gallbladder pathology Jin Guo MD 1/2025  Objectives: By the end of the lecture, the students should be able to recognize and discuss the clinicopathologic and diagnostic features of: Pancreas pathology – Acute and chronic pancreatitis – Neo...

Pancreas and gallbladder pathology Jin Guo MD 1/2025  Objectives: By the end of the lecture, the students should be able to recognize and discuss the clinicopathologic and diagnostic features of: Pancreas pathology – Acute and chronic pancreatitis – Neoplasms – Congenital Anomalies Agenesis, pancreas divisum, annular pancreas, ectopic pancreas – Cystic Fibrosis Gallbladder pathology – Cholecystitis, cholelithiasis, gallbladder ca Case 38-year-old man who has abused alcohol his entire adult life experienced a gradual onset of pain in his upper abdomen that radiated to his back following an episode of binge drinking. The pain persisted for several hours and worsened each time that he ate. Nausea and repeated episodes of vomiting. The pain grew more intense and on PE there is intense pain upon palpation of the upper left quadrant.  Lab findings WBC 19.1 TGs: 511 (0-149) Ca: 7.9 (8.4-10.2) ALT:10 (8-48) AST:9 (7-55) AP:79 (45-115) Cr 3.2 (baseline 1.2) Amylase: 804 (0-100) Lipase: 2211 (0-60)  Imaging studies Ultrasonography – enlarged pancreas with decreased echogenicity and distinct border CT – diffuse enlargement of the pancreas with non-uniform density  Acute pancreatitis Acute inflammatory process of the pancreas – edema (edematous pancreatitis) – hemorrhagic necrosis (necrotizing pancreatitis) Most common middle age Men > women Can be life threatening  Acute pancreatitis Abdominal pain (LUQ or midepigastrum) – Pain radiates to back, sudden onset – Described as severe, deep piercing pain – Aggravated by eating – Not relieved by vomiting Pathophysiology – inappropriate activation of pancreatic enzymes causing autodigestion of pancreatic parenchyma and damage to the peripancreatic tissues and vascular network  Acute pancreatitis - causes Mechanical – Gallstones (>45%), pancreatic mass, ampullary stenosis or mass, duodenal stricture or obstruction Toxic – Alcohol (>35%), methanol, steroids, scorpion venom Metabolic – Hyperlipidemia, hypertriglyceridemia, hypercalcemia Trauma – Blunt or penetrating, ERCP, s/p abdominal surgery Miscellaneous - Infection, Vascular, Congenital, Genetic 10% unknown causes  Acute pancreatitis 200,000 US hospital admission yearly 20% have a severe course and increased mortality Severe course – Systemic complications Shock, DIC, Pulm. Insufficiency/ARDS – Local complications Pseudocyst, Necrosis, Abscess, Pseudoaneurysm, Splenic vein thrombosis  The diagnosis of acute pancreatitis is largely a clinical one based on physical signs and symptoms as well as serum levels of pancreatic enzymes and radiologic findings. Hemorrhagic and necrotizing pancreatitis  Acute pancreatitis Hemorrhage and necrosis Normal fat nccrosis  Acute pancreatitis hemorrhage fat necrosis fat necrosis What causes fat necrosis? Lipase released in AP digests fat cells releasing free fatty acids. Free fatty acids saponify with calcium salts to form soaps. Hypocalcaemia as a result.  parenchymal necrosis hemorrhage fat necrosis Acute pancreatitis  Acute pancreatitis necrosis of pancreatic parenchyma acute inflammatory cells necrotic fat cells inflammatory cells  Acute pancreatitis - complications Pseudocyst – collections of pancreatic juice, usually rich in digestive enzymes, that are enclosed by a non epithelialized wall composed of fibrous and granulation tissue Pancreatic abscess Pseudoaneurysm Splenic vein thrombosis Pseudocyst Pseudocyst Chronic pancreatitis extensive scarring with fibrosis loss of more exocrine pancreas with more residual islet cells  Chronic pancreatitis Continuous inflammatory disease of the pancreas characterized by irreversible morphologic changes of both the parenchyma and ducts; typically coupled with permanent loss of function and/or pain normal intense scarring and fibrosis of parenchyma  Chronic pancreatitis 10-15/100,000 population in western countries Typical age 35-55 50% mortality over 20-25 years Etiologies – Alcohol: 60-70% of all cases in developed countries – Obstruction of the pancreatic duct – Pancreas divesum, post traumatic strictures, tumors – Cystic fibrosis (CFTR mutations) – Autoimmune – Hypercalcemia – Hyperlipidemia – Idiopathic  Chronic pancreatitis Abdominal pain – Diffuse and localized to the upper abdominal region; worse after meals, also nocturnal symptoms. Weight loss – Early, decreased caloric intake secondary to the fear and anticipation of abdominal pain. – Later, pancreatic insufficiency due to malabsorption. – Diabetes mellitus develops when more than 80% of the gland has been destroyed. – Steatorrhea occurs when over 90% of pancreatic function lost.  Summary - acute and chronic pancreatitis Autodigestion, edema, hemorrhage, Irreversible parenchymal damage, necrosis, fat necrosis, inflammatory cell progressive parenchymal fibrosis, infiltrates, saponification, hypocalcemia, chronic malabsorption, pseudocysts. diabetes mellitus. Case A 48 yo male who presented with complaints of abdominal discomfort and “generally feeling ill” Symptoms persisted, and ultimately developed jaundice with markedly elevated LFTs An abdominal ultrasound confirmed biliary dilatation and enlargement in HOP Follow up CT scan confirmed mass in HOP, 4.5x2.5 cm, with dilation of the intrahepatic and pancreatic ducts Biopsy of pancreas was performed  Infiltrative irregular glands Ductal adenocarcinoma normal  Diagnosis: ductal adenocarcinoma arising from the head of the pancreas Staging CT scans revealed no evidence for metastatic disease, therefore, patient was referred to surgical oncology for consideration of Whipple procedure Ductal adenocarcinoma  benign Chronic pancreatitis normal Ductal adenocarcinoma: Infiltrative irregular complex glands; cytologic atypia; desmoplastic stromal change Ductal adenocarcinoma  Pancreatic cancer Estimated 44,000 new cases, 37,000 deaths every year 4th leading cause of cancer-related death in US Mortality rate closely follows incidence rate due to poor prognosis Incidence rare before the age of 45, however, sharply rises thereafter Higher in men than women More in blacks compared to the general population  Pancreatic cancer - pathophysiology Arise from both exocrine and endocrine portions of the pancreas 95% develop in the exocrine pancreas – ductal epithelium, acinar cells, connective tissue and lymphatic tissue 5-10% of patients with pancreatic carcinoma have some genetic predisposition Inherited disorders: – Hereditary pancreatitis, hereditary breast/ovarian cancer, multiple endocrine neoplasia, familial atypical multiple mole melanoma syndrome, HNPCC, FAP/Gardner syndrome, Peutz-Jeghers syndrome  Pancreatic cancer Head of pancreas, 60% – Obstruction of the bile duct to the small intestine, associated with jaundice, pruritus, and/or vomiting Body/tail of the pancreas, 20% – Upper abdominal/back pain, weight loss (usually substantial, 30-50lb) and fatigue The pain may be intermittent, worse with eating, and usually associated with a poor prognosis In general, 90% of the time, the tumor has already metastasized outside the pancreas Risk Factors: Age, Chronic pancreatitis, Tobacco, DM, Hereditary predisposition, Obesity/Diet Serum tumor markers - elevated CA 19-9, CEA Ductal adenocarcinoma infiltrating tumor glands - adenocarcinoma Ductal adenocarcinoma - cribriform growth Ductal adenocarcinoma – marked cytologic atypia and nuclear pleomorphism perineural invasion metastatic carcinoma  Other pancreatic neoplasms Benign – Serous cystadenoma Benign, borderline or malignant – Mucinous cystic neoplasm almost always arise in women usually in the body or tail of the pancreas – Intraductal papillary mucinous neoplasm more frequently in men more frequently involve the head of the pancreas Serous cystadenoma Pancreatic mucinous cystadenoma intraductal papillary mucinous neoplasm Case A 45-year-old obese native American woman with mid-epigastric pain, nausea, vomiting and fever; multiple occasions over last 6 months Steady but cramping pain lasting several hours, sometimes with radiation to the right subscapular area. A few episodes could be clearly related to eating. Chills, fever, nausea and vomiting. Icteric eyes, tender abdomen in the right upper quadrant, especially on deep inspiration.  Laboratory results: White blood cell count 15,000/µL AST 85 U/L ALT 100 U/L Alkaline phosphatase 240 U/L (45 to 115) Total bilirubin 3.5 mg/dl (0.1 to 1.2) Amylase 750 U/L Lipase 200 U/L  An abdominal ultrasound exam showed stones in the gallbladder and dilation of the hepatic and common bile ducts and pancreatic duct. ERCP demonstrated obstruction of the distal portion of the common bile duct near the ampulla of Vater, due to an impacted stone. Attempts to remove the stone via the endoscope were unsuccessful. Surgery was scheduled. Cholelithiasis with acute and chronic cholecystitis  Chronic cholecystitis Normal Ulcerative hemorrhagic cholecystitis  Aggregates of histiocytes Cholesterolosis Black calcium bilirubinate stones: seen in cirrhosis, chronic hemolytic anemia, bacterial contamination of the biliary tree and chronic parasitic biliary infections Combination of cholesterol and bilirubinate stone Adenocarcinoma – complex glands with cytologic and nuclear atypia; mitosis  Summary Acute pancreatitis – Edema, hemorrhage, necrosis, fat necrosis, neutrophils Chronic pancreatitis – Sclerosis of parenchyma, irregularly sized remaining ducts and islets Pancreatic ductal carcinoma – Complex glands, deeply infiltrative growth pattern, cytologic and nuclear atypia Cholecystitis, cholelithiasis, gallbladder ca