43 Pathology Lecture 2024 Malignancies Liver Pancreas Gallbladder PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn TurningPoint ID: GIHEPPathL5 Malignancies of Liver, Pancreas a...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn TurningPoint ID: GIHEPPathL5 Malignancies of Liver, Pancreas and Gallbladder, Gallstones and Pancreatitis Course: Pathology Lecturer: Dr Clive Kilgallen Date: 2nd October 2024  LEARNING OUTCOMES Classify liver tumours and demonstrate an understanding of their relative frequency Describe Hepatocellular carcinoma Define cholangiocarcinoma Describe how pancreatic cancer presents and discuss its diagnosis and treatment Discuss the frequency and significance (or otherwise) of finding gallstones Define acute cholecystitis List the causes and effects of extra hepatic bile duct obstruction Discuss the common causes and presentation of acute pancreatitis and chronic pancreatitis AN APPROACH TO LIVER TUMOURS Non-neoplastic versus neoplastic  Non-neoplastic lesions can mimic neoplasms  Cysts, haemangiomas, regenerative tumour-like lesions, abscesses: US, CT, MR + context diagnostic Benign versus malignant neoplasms Primary versus secondary malignancies Consider different types of primary neoplasm  Depending on tissue type of origin, e.g. for malignancies: carcinoma, possibly of different types, sarcomas of different types, lymphoma etc. But focus/highlight commoner entities  PRIMARY LIVER TUMOURS Benign Hepatic adenoma (= liver cell adenoma, anabolic steroids and oral contraceptive pill (OCP)) Bile duct adenoma (rare) Haemangioma Malignant Hepatocellular carcinoma (=liver cell carcinoma, hepatoma, HCC) Intrahepatic cholangiocarcinoma (=intrahepatic bile duct adenocarcinoma) Haemangiosarcoma (textbook rarity)  SECONDARY TUMOURS/LIVER METASTASES Commonest ‘liver tumour’ in Europe/N America Carcinoma - primary in GI tract, lung, breast Other malignancies can infiltrate liver  e.g. lymphoma, leukaemia Metastases may obstruct bile flow  Early: few symptoms/effects, Alk Phos raised  Late: rising bilirubin, jaundice Generally poor prognosis Identify primary site of origin - treatment Surgery for isolated colorectal metastases IMMUNOHISTOCHEMISTRY IS USED IN LIVER METASTASIS HISTOLOGY CK20, CDX2 - Large intestine TTF1 - Lung S100, Melan A, HMB, SOX10 - Melanoma WHAT IS IN THIS IMAGE? A. Cirrhosis B. Metastases to liver GROSS APPEARANCE OF METASTASES (SECONDARIES) TO LIVER Multiple pale deposits are metastases (don’t confuse with cirrhosis, not diffuse change)  HEPATOCELLULAR CARCINOMA Europe/North America relatively uncommon East and SE Asia/Africa common Associated with cirrhosis/chronic hepatitis (>90%) Can occur in non-cirrhotic fibrotic HBV livers Single mass or multifocal, may have vascular invasion Metastases not as usual as in some other tumour types Presentation High incidence areas - co-presents with or precedes cirrhosis, in relatively young patients Low incidence areas - decompensation of cirrhosis, 3% HCC/yr, vague/changing symptoms  HEPATOCELLULAR CARCINOMA Diagnosis Radiology: US, specific contrast-enhanced CT and/or MRI protocols Assessment of nodules in cirrhosis, >1cm or enlarging Alpha-fetoprotein (AFP): ‘tumour marker’ Biopsy rarely necessary Screening High risk patients (compensated cirrhosis), every 6/12 US AFP blood test – alone not specific/sensitive enough Prevention Treatment of cause of underlying chronic liver disease? Prevention of chronic liver disease (HBV vaccination)  HEPATOCELLULAR CARCINOMA Treatment Resection if early OLT Local ablative treatments: radiofrequency, arterial chemo- embolization Prognosis – depends on: Stage Degree of liver function impairment Co-morbidity Typically poor but in selected cases 5 year survival of 50% Aetiology Cirrhosis (HBV/HCV/HFE > other causes cirrhosis?) Chronic HBV directly oncogenic? Aflatoxins - fungal contaminants of food stores  GROSS APPEARANCE OF HEPATOCELLULAR CARCINOMA MICROSCOPIC APPEARANCE OF HCC Tumour cells resemble hepatocytes but show pleomorphism  CHOLANGIOCARCINOMA Adenocarcinoma arising from bile duct epithelium  Intrahepatic or extrahepatic location Commonest site at hilum of liver  Klatskin tumour = obstructing bifurcation of CHD Intrahepatic cholangiocarcinoma a minority of primary liver malignancy (10%) Associations: PSC  Rare: chronic fluke infestation, congenital biliary abnormalities Diagnosis difficult and often late, outcome poor Selected cases – surgical resection Typically, palliate obstruction with stent placement CHOLANGIOCARCINOMA IMAGE  PANCREAS Retroperitoneal location 2 components, embryologically distinct Exocrine 98%: makes digestive enzymes Endocrine: islets of Langerhans, hormones Exocrine composed of glandular acini grouped into lobules Exocrine secretions drain via ducts, joining to form pancreatic duct  HISTOLOGY OF NORMAL PANCREAS Small pancreatic duct (centre) surrounded by exocrine pancreatic glandular acini. Pale collection of cells (left centre) is islet of Langerhans  PANCREATIC TUMOURS Exocrine pancreas Malignant: pancreatic (ductal) adenocarcinoma Other less common tumours, sometimes cystic May be benign or have intermediate behaviour Some recognised as precursors to pancreatic ca Endocrine Pancreatic neuroendocrine tumours rare Behaviour difficult to predict Classified by hormone type produced Hormone may cause clinical symptoms Association with parathyroid hyperplasia and pituitary adenomas in inherited MEN type 1 syndrome  PANCREATIC CARCINOMA Adenocarcinoma, arising from pancreatic ducts Common: 5th/6th by rank of cancer deaths M>F, 80% >60 years 60-70% from head, rest from body & tail Spread  Direct local: peritoneum (vessels, nerves), duodenum, CBD = ‘locally advanced’  Lymph nodes or to liver (50% metastatic at diagnosis) Risk factors (relatively weak)  Smoking, DM, chronic pancreatitis  Family history (5%)  PANCREATIC CARCINOMA Symptoms Typically symptomatic only with advanced disease Easily missed Anorexia, weight loss Painless obstructive jaundice (tumours in head) Vague abdominal pain, may radiate to back Rare: palpable mass, thrombotic tendency  Migratory thrombophlebitis = Trousseau’s sign Diagnosis CA 19-9 serum marker for pancreatico-biliary cancer  Not useful in diagnosis, used for response/relapse assessment Imaging (US, CT, EUS), FNA cytology via EUS Avoid unnecessary invasive investigation in majority  PANCREATIC CARCINOMA Prognosis 5 year survival M, older age group Presents late, vague symptoms, outlook poor Clinical problem: gall bladder “polyps” often identified at US  Question is: could they be neoplasms of the gall bladder (adenomas or carcinomas)?  If small/non-progressive, likely to be harmless non- neoplastic cholesterol “polyps” CAUSES OF EXTRAHEPATIC BILE DUCT OBSTRUCTION Gallstones in common bile duct Tumour  Adenocarcinoma of pancreas  Extra-hepatic bile duct adenocarcinoma Benign stricture (post-operative or PSC) Mass outside CBD/CHD compressing duct  Mirizzi syndrome (external compression from stone in neck/cystic duct of GB)  Primary tumour or metastases in lymph nodes  EXTRAHEPATIC BILE DUCT OBSTRUCTION Courvoisier’s law – historic interest only Investigation  US shows dilated ducts above obstruction  Cause may need investigation by MRCP or EUS  May perform ERCP for diagnosis if treatment also considered Treatment is decompression +/- treat cause  Stones  ERCP with sphincterotomy +/- stone removal  CBD exploration at surgery (laparoscopic or open) Structure: stent Tumour: stent  Stenting usually via ERCP  ASCENDING (ACUTE) CHOLANGITIS Infection in static, obstructed bile High fever, pain, jaundice = Charcot’s triad Add hypotension, altered mental state = Reynolds’ pentad Requires urgent decompression  HEPATIC ABSCESS Biliary tract disease a/w ascending infection commonest cause Seeding from systemic sepsis may sometimes be the cause Historically, common cause was spread via portal vein from intra-abdominal sepsis Drain and antibiotics (Amoebic abscess)  ACUTE PANCREATITIS Acute inflammation of pancreas 10-20/million, mortality ?5% (higher if severe) Single or recurrent attacks Pathogenesis  Premature (intra-pancreatic) activation of pancreatic enzymes  Once initiated, irreversible cascade (auto-digestion)  May trigger systemic inflammatory response syndrome (SIRS) if severe Obstructing stone at lower end CBD causes reflux of bile/concentration of pancreatic juices Alcohol direct toxic effect MECHANISM OF PANCREATITIS  SEVERITY OF ACUTE PANCREATITIS Mild acute pancreatitis (80% cases) Self limiting disease Interstitial oedematous acute pancreatitis on imaging, non-necrotizing Severe acute pancreatitis (20% cases) Necrotizing inflammation of pancreas and surrounding tissue (peri-pancreatic fat)  EFFECTS OF SEVERE ACUTE PANCREATITIS Systemic inflammatory response syndrome  Hypovolaemia, hypotension, ARDS, acute renal failure, disseminated intravascular coagulation (DIC) Hypocalcaemia, hyperglycaemia, ileus Local complications  Extensive necrosis (acute necrotic collection), risk secondary infection  Later: pseudocyst, fistula Mortality a/w acute pancreatitis two phases  First week (50%) a/w SIRS and complications  Second week (50%) a/w necrosis and sepsis  CAUSES OF ACUTE PANCREATITIS Gallstones – 50% men and women Alcohol – a very common case also Post-ERCP (5%) Idiopathic (10%) - biliary microlithiasis Miscellaneous uncommon causes (5%)  Trauma, ischaemia, major surgery  Drugs, viral  Hypercalcaemia, hyperlipidaemia  Hereditary pancreatitis  DIAGNOSIS OF ACUTE PANCREATITIS Symptoms Epigastric pain, may radiate into back ‘Acute abdomen’, seen by surgeons If severe: differential diagnosis - MI, ruptured AAA, perforated or ischaemic abdominal organ Blood tests Blood amylase higher than 3X normal Amylase short half life Lipase used in future? If equivocal, ?radiology Try and identify cause, avoid immediate laparotomy  CHRONIC PANCREATITIS Patchy, irreversible fibrosis, ongoing inflammation Pancreatic function impaired (exocrine>endocrine) Distortion of ductal system  Strictures, dilatation and cysts behind strictures, pancreatic ductal stones Causes: Alcohol Idiopathic Childhood causes including cystic fibrosis CF more typically a/w pancreatic insufficiency due to damage but without clinical ‘chronic pancreatitis’  CHRONIC PANCREATITIS Symptoms: Pain (dull, epigastric, radiating to back) Weight loss Steatorrhoea and malabsorption Secondary diabetes mellitus Treatment: Analgesia (opiates), enzyme supplements Diagnosis: Difficult, sometimes diagnosis of exclusion Amylase not useful Tests of pancreatic function not routine Imaging in advanced disease  PANCREATIC PSEUDOCYST Collection of pancreatic fluid in disrupted tissue in or adjacent to pancreas Defined wall but not a true cyst (no epithelial lining) Causes: acute or chronic pancreatitis, pancreatic surgery or trauma Complications: pain/pressure, infection, erosion with fistula or blood vessel damage Aspirate or drain by endoscopy or surgery  END OF LECTURE