Pathology Flashcards
What is a polyp?
A protrusion above an epithelial surface
Classify the vast amount of polyps in the large bowel
Benign, epithelial and neoplastic
Differential diagnosis of a colonic polyp
Adenoma
Serrated polyp
Polypoid carcinoma
Other
Three macroscopic appearances of removed colonic polyps
Pedunculated
Sessile
Flat
Explain adenoma of the colon
Benign tumours of the colon. Not yet invasive, and do not metastasise. All dysplastic = must be removed
Adenoma-Carcinoma Sequence
Normal epithelium -> mutations to APC -> small adenoma -> further mutation e.g. k-ras -> large adenoma -> chromosomal mutations e.g. p53 -> Invasive adenocarcinoma
Why remove all adenomas?
They are premalignant
Removal of adenomas by…?
Endoscopy
Surgery
Primary treatment of Adenocarcinoma
Surgical removal of colon/rectum for staging
What kind of tumours are majorly found in the large bowel?
Malignant Adenocarcinomas
Colorectal Carcinoma - Dukes Staging
Dukes A = Confined by muscular propria
Dukes B = Through muscular propria
Dukes C = Metastatic to lymph nodes
Left Sided Colorectal Carcinoma
75%
P/R Bleeding
Altered Bowel Habit
Obstruction
Right Sided Colorectal Carcinoma
25%
Anaemia
Weight Loss
Colorectal carcinoma - Gross appearance
Varied =
Polypoid
Stricturing
Ulcerating
Colorectal carcinoma - Histopathological appearance
Typical adenocarcinoma
Colorectal carcinoma - Local invasion
Mesorectum, peritoneum, other organs
Colorectal carcinoma - Lymphatic spread
Mesenteric nodes
Colorectal carcinoma - Haematogenous spread
Liver, distant sites
Inherited Colorectal Carcinoma - HNPCC
Late onset (50/60s)
Inherited Colorectal Carcinoma - FAP
Early onset (teens) >100 polyps Mutation to FAP gene Tumours throughout colon Adenocarcinoma NOS Desmoid tumours & thyroid carcinomas
Diverticular Disease - Histopathology
Out-pouchings of mucosa
These are at increased risk of bursting and releasing septic contents into the abdominal cavity
Diverticular Disease - Complications
Inflammation Rupture Abscess Fistula Massive Bleeding
Ischaemia of the Large Bowel - Endoscopic View
Diffusely ulcerated and erythematous mucosa
Ischaemia of the Large Bowel - Histopathology
Withering of crypts
Smudging of lamina propria
Fewer chronic inflammatory cells
Ischaemia of the Large Bowel - Aetiology
CVS disease, A Fib, Embolus, Atherosclerosis (usually IMA), Shock, Vasculitis
Ischaemia of the Large Bowel - Clinical Context
Elderly
Left sided
Segmental on endoscopy
Ischaemia of the Large Bowel - Complications
Massive Bleeding
Rupture
Stricture
Antibiotic-Induced “Pseudomembranous” Colitis - Endoscopic View and Gross Appearance
Speckled, spotted appearance
Patchy, yellow membranous exudate on mucosal surface
Antibiotic-Induced “Pseudomembranous” Colitis - Histopathology
Explosive fibrinopurulent exudate on surface (volcano lesions)
Antibiotic-Induced “Pseudomembranous” Colitis - Causes
Patients in broad spectrum of antibiotics - C Diff proliferates
Toxins A and B attack endothelium and epithelium, causing mini-infarcts along the membrane
Antibiotic-Induced “Pseudomembranous” Colitis - Symptoms
Massive diarrhoea and bleeding
Antibiotic-Induced “Pseudomembranous” Colitis - Treatment
Flagyl/Vancomycin
May need colectomy
May be fatal
Collagenous Colitis - Appearance
Endoscope = Normal Histology = Increase in thickness of sub epithelial collagen
Collagenous Colitis - Clinically
Watery diarrhoea
Normal endoscopy
History of causative drugs
Lymphocytic Colitis - Appearance
Endoscope = Normal Histology = Normal architecture, but massive increase in intraepithelial lymphocytes
Lymphocytic Colitis - Clinically
Watery diarrhoea
Normal endoscopy
Raise possibility of Coeliac disease
Radiation Colitis - Endoscopy Appearance
Red, angry bowel
Radiation Colitis - Histology
Bizarre stream cells
Bizzarre vessels
Radiation Colitis - Cause
History of cervical/prostate cancer
Radiation therapy damaged cells
Acute (infective) Colitis _ Endoscopy Appearance
Very red
Very ulcerated
Very inflamed
Acute (infective) Colitis - Histology
Busy epithelium but not crypt irregularity
Florid diffuse acute cryptitis
Acute (infective) Colitis - Causes
Infection
Rarely: Drugs, ischaemia, endoscopy prep.
Acute (infective) Colitis - Diagnosis
Stool sample culture
Normal Appearance of the Liver
Light, tan in colour
Smooth regular surface
Pathogenesis of Liver Disease
Insult to hepatocytes
Inflammation
Fibrosis
Cirrhosis
Causes of Acute Onset of Jaundice
Viruses
Alcohol
Drugs
Bile duct obstruction
Histological Appearance of Paracetamol Poisoning
Confluent necrosis produce massive acute necrosis and liver failure
(lots of hepatocyte death)
Consequences of Acute Liver Failure
Complete recovery
Chronic liver disease
Death from liver failure
Pre-Hepatic Jaundice
Too much harm to break down
Haemolysis of any cause
Haemolytic anaemias
Unconjugated billrubin
Hepatic Jaundice
Liver cells injured or dead Acute liver failure Alcoholic hepatitis Cirrhosis (decompensated) Bile duct loss Pregnancy Conjugated jaundice
Post-Hepatic Jaundice
Biel cannot escape into the bowel Congenital biliary atresia Gallstones blocking CBD Strictures of CBD Tumours
Appearance of a Cirrhotic Liver
Nodular, craggy, scarred
Histological Appearance of Cirrhosis
Bands of fibrosis separating regenerative nodules of hepatocytes
Loss of function of hepatocytes due to alteration of hepatic microvasculature
Complications of Cirrhosis
Portal hypertension =
Oesophageal varices
Caput medusa
Rectal varices
Ascites
Liver Failure
Alcoholic Liver Disease - Pathology Influenced By
Extent of the alcohol abuse
Individual factors
Pathogenesis of Alcoholic Liver Disease
Increased peripheral release of fatty acids
Increased synthesis of fatty acids within the liver cells
Acetaldehyde, a product of alcohol metabolism, is probably responsible for liver cell injury (manifested by the formation of Mallory’s hyalin)
Increased collagen synthesis by fibroblasts
Appearance of Alcoholic Fatty Liver - Days
Yellow
Greasy
Histological Appearance of Alcoholic Fatty Liver - Days
Fat vacuoles appear clear in hepatocytes
Histological Appearance of Alcoholic Fatty Liver - Heavy Drinking Weeks to Months
Accumulation of bile
Hepatocytes with thick dark pink cytoplasm
Accumulation of neutrophils
Histological Appearance of Alcoholic Fatty Liver - Heavy Drinking Months to Years
Collagen played down around cells
Collagen appears blue
Appearance of Alcoholic Cirrhosis
Micro-nodular cirrhosis with abundant white scarring
Histological Appearance of Alcoholic Cirrhosis
Bands of fibrosis separating regenerative nodules
Alcoholic Liver Disease - Outcome
Cirrhosis Portal hypertension Malnutrition Hepatocellular carcinoma Social disintegration
Non-Alcoholic Steatohepatitis
Non-drinkers
Pathologically identical to alcoholic liver disease
Occurs in patients with diabetes, obesity, hyperlipidaemia
May lead to fibrosis and cirrhosis
Increasing incidence
Common causes of viral hepatitis
Hep A, B, C, E
Rarer causes of viral hepatitis
Hep D Epstein-Barr virus Yellow fever virus Herpes Simplex virus Cytomegalovirus
Hepatitis A - Histological Appearance
Death of hepatocytes
Directly cytopathic
No immunological phase
Chronic Viral Hepatitis -Histological Appearance
Visible immune cells are damaging the liver
Dense portal chronic inflammation (erodes the border)
Interface hepatitis (piecemeal necrosis)
Fibrosis forms bridges between different portal areas (bridges filled with collagen)
Cirrhosis
Not distinguishable from other chronic hepatitis causes
Hepatits B - Outcomes
Fulminant acute infection (death) Chronic hepatitis Cirrhosis Hepatocellular carcinoma Asymptomatic (carrier)
Hepatitis C - Outcomes
Chronic hepatitis
Cirrhosis
Causes of Chronic Hepatitis
Viruses = Hep B and C
Drug induced
Autoimmune =
Primary biliary cirrhosis/cholangitis
Autoimmune hepatitis
Primary sclerosing cholangitis
Primary Biliary Cirrhosis - Aetiology and Clinical
Rare autoimmune disease, unknown aetiology
Associated with autoantibodies to mitochondria
Females (90%)
Biopsy is to stage disease or diagnose uncertain cases
Outcome is unpredictable
Primary Biliary Cirrhosis - Histological Appearance
Chronic portal inflammation
Inflamed bile ducts
Granulomas around bile ducts
Cirrhosis
Primary Biliary Cholangitis - Pathogenesis
If untreated, bile duct loss leads to cholestasis liver injury, inflammation, fibrosis and cirrhosis
Autoimmune Hepatitis - Clinical
Commoner in females
Associated with other AI
Chronic hepatitis pattern
May have triggers, including some drugs
Autoimmune Hepatitis - Histological Appearance
Numerous plasma cells
Autoantibodies to smooth muscle, nuclear or LKM
Raised IgG
Chronic Drug-Induced Hepatitis - Clinical
Similar features to all other types of chronic hepatitis
May trigger an autoimmune hepatitis
Chronic active process
Many causes
General Points about Drugs and the Liver
Innumerable drugs can damage the liver
May be dose related or idiosyncratic
Can cause hepatitis, granulomas, fibrosis, necrosis, failure, cholestasis or cirrhosis
Can mimic any liver disease
Primary Sclerosing Cholangitis - Clinical
Chronic inflammatory process affecting intra- and extra-hepatic bile ducts
Leads to pericardial fibrosis, duct destruction, jaundice and fibrosis
Associated with UC
More common in males
Increased risk of malignancy in bile ducts and colon
Primary Sclerosing Cholangitis - Histological Appearance
Periductal onion-skinning fibrosis
Loss/damage of bile ducts
Storage Disease - Types
Haemochromatosis
Wilsons Disease
Alpha-1-Antitrypsin Deficiency
What is haemochromatosis?
Excess iron within the liver
Primary Haemochromatosis - Causes
Genetic condition Inherited autosomal recessive condition Gene defect very complex Exces absorption of iron from intestine, abnormal iron metabolism Worse in homozygotes, men
Primary Haemochromatosis - Histological Appearance
Iron accumulates in hepatocytes
Iron confirmed by Perls Stain
Primary Haemochromatosis - Clinical
Iron deposited in liver, assymptomatic for years
Eventually deposited in portal connective tissue and stimulates fibrosis
Cirrhosis if not treated
Predisposes to carcinoma
Also causes diabetes, cardiac failure and impotence
Secondary Haemochromatosis - Causes
Iron overload from diet
Transfusions
Iron therapy
Haemochromatosis - Outcomes
Depends on genetics, therapy (venesection), cofactors like alcohol
Cirrhosis
Hepatocellular carcinoma
Wilson’s Disease
Inherited autosomal recessive disorder of copper metabolism
Copper accumulates in liver and brain (basal ganglia)
Kayser-Fleischer rings at corneal limbus
Low serum caeruloplasmin
Causes chronic hepatitis and neurological deterioration
Alpha-1-Antitrypsin Deficiency
Inherited autosomal recessive disorder of production of an enzyme inhibitor
Causes empysema and cirrhosis
Cytoplasmic globules of unsecreted globules of protein in liver cells
Tumours of the Liver
Primary (rare)
Hepatocellular adenoma
Hepatocellular carcinoma (Hepatoma)
Secondary (common)
Multiple
Metastases from colon, pancreas, stomach, breast, lung and others
Hepatocellular Adenoma
Benign
Females
May become large - can rupture or bleed
Most remain asymptomatic
Hepatocellular Carcinoma
Rare in Europe
Associated with Hep B, Hep C, Cirrhosis, PBC, PSC
Usually presents as mass, pain, obstruction
usually advanced unless discovered incidentally
Poor prognosis
Hepatocellular Carcinoma - Histopathological Types
Hepatocyte = Malignant tumour of liver cells Cholangio = Malignant tumour of bile ducts
What is Cholelithiasis?
Gallstones
Defined as hard stone-like or gravel-like material formed within the biliary system most commonly the gallbladder
What is normal bile made from?
Micelles of cholesterol, phospholipid, bile salts and bilirubin
Where is normal bile stored and how is it released?
Stored and concentrated in gallbladder, released by common cystic duct into the 2nd part of the duodenum through common bile duct and Ampulla of Vater
Pathogenesis of Cholesterol Gallstones
Gallstones form when there is an imbalance between the ratio of cholesterol to bile salts, disrupting micelle formation
Free crystallisation on micelle surface
Risk Factors for Cholesterol Gallstones
Cholesterol excess in bile Female Obesity Diabetics Genetic
Pathogenesis of Pigment Gallstones
Excess bilirubin cannot be solubilised in bile salts
Tend to be black
Risk Factors for Pigment Gallstones
Excess bilirubin
Due to excess haemolysis
e.g. Haemolytic anaemia
Pathogenesis of Gallstones
Gallbladder pH and mucosal glycoproteins may be contributory factors
Infection and inflammation of biliary lining
Most gallstones are a mixture (mixed stones)
Pure cholesterol and pure pigment stones do occur
Calcium carbonate stones do occur
Pathology of Gallstones
Acute Cholecystitis Chronic Cholecystitis Mucocoele Empyema Carcinoma Ascending Cholangitis Obstructive Jaundice Gallstone Ileus Acute Pancreatitis Chronic Pancreatitis
What is cholecystitis?
Inflammation of gallbladder
Usually associated with gallstones
Acute or chronic
Common
Acute Cholecystitis
Gallstones obstructing outflow of bile
Initially sterile, then becomes infected
May cause empyema, rupture, peritonitis
Causes intense adhesions within 2-3 days
Acute Cholecystitis - Appearance
Gross = Red, haemorrhage, mixed gallstones embedded in pus Histology = Acute inflammation indicated by neutrophils
Chronic Cholecystitis
Associated with Gallstones
May develop insidiously or after bouts of acute cholecystitis
Galbladder wall is thickened but not distended
Chronic Cholecystitis - Appearance
Gross = Mixed stones and thickened gallbladder wall due to fibrosis Histology = Chronic inflammation and Rokitansky-Aschoff sinuses
What do stones in the common bile duct cause?
Obstructive jaundice
Carcinoma of the Gallbladder
Rare Adenocarcinoma Associated with gallstones Local invasion of liver Poor prognosis
Carcinoma of Bile Ducts (Cholangiocarcinoma)
Rare
Associated with Ulcerative Colitis and Primary Sclerosing Cholangitis
Presents with obstructive jaundice
Adenocarcinoma
What is a Klatskin Tumour?
Cholangiocarcinoma at bifurcation of hepatic ducts
Cholangiocarcinoma - Histology Appearance
Densely packed call glands in a fibrous stroma
What is Pancreatitis?
Inflammation of the pancreas
May be acute or chronic (overlap exists between the two)
Acute Pancreatitis - Clinical
Adults (rare in children)
Sudden onset severe abdominal pain
Patients may be severely shocked
Elevated serum amylase
Acute Pancreatitis - Aetiology
Alcohol Cholelithiasis Shock Mumps Hyperparathyroidism Hypothermia Trauma Iatrogenic (post ERCP)
Acute Pancreatitis - Pathogenesis
Bile reflux, duct obstruction due to stone damage to sphincter of Oddi all cause pancreatic duct epithelial injury
Loss of protective barrier allows autodigestion of pancreatic acini
Release of lytic pancreatic enzymes proteases and lipases
Intra- and peripancreatic fat necrosis (lipases)
Tissue destruction and haemorrhage (proteases)
Appearance of Acute, Mild Pancreatitis
Focal areas of necrosis
Appearance of Acute, Moderate Pancreatitis
Intrapancreatic fat necrosis (may bind large amounts of calcium)
Appearance of Acute, Severe Pancreatitis
Complete pancreatic destruction with haemorrhage and fat necrosis
What is a Pancreatic Pseudocyst?
Fleshy pseudocyst complicating pancreatitis
Acute Pancreatitis - Histological Appearance
Large areas of pancreas and fat necrosis
Acute Pancreatitis - Complications
Death Shock Pseudocyst formation Abscess formation Hypocalcemia Hyperglycaemia
What is Chronic Pancreatitis?
Relapsing disorder may develop insidiously or following bouts of acute pancreatitis
Chronic Pancreatitis - Aetiology
Alcohol Cholelithiasis Cystic fibrosis Hyperparathyroidism Familial
Chronic Pancreatitis - Pathology
Replacement of pancreas by chronic inflammation and scar tissue
Destruction of exocrine acini and islets
Gross Appearance of Chronic Pancreatitis
Fibrotic and necrotic
Inflammation and fibrosis can mimick a tumour in the head of the pancreas
Chronic Pancreatitis - Histological Appearance
Exocrine pancreas is replaced by chronic inflammation and fibrosis (first)
Carcinoma of Pancreas
Adenocarcinoma
Aetiology Unknown
Weak associated with smoking, diabetes, familial pancreatitis
Poor prognosis (pancreas is intimately related to many important structures. Also, resistant to most forms of chemo)
Gross Appearance of Adenocarcinoma of Head of Pancreas
Can invade duodenal wall
Can constrict the common bile duct
How can Carcinoma of the Tail of the Pancreas spread?
By direct invasion of the spleen
Adenocarcinoma of Pancreas - Histological Appearance
Irregular abortive glands in a dense stroma
Adenocarcinoma of Pancreas - Spread
Direct spread to other organs e.g. duodenum, stomach, spleen
Spread to local lymph nodes
Haematogenous spread to the liver
