Pathology part 2 (Cancer, liver, pancreas) Flashcards
What is Peutz-Jeghers syndrome?
- Small dark coloured spots on lips, nostrils, anus
- Develop polyps (hamartomatous) in colon
- Increased risk of GI cancers and breast
- Autosomal dominant
What syndromes are associated with hamartomatous polyps in the colon?
- Peutz-Jeghers
- Juvenile polyposis synrdrome
Name the generally nonneoplastic polyps?
- Hamartomatous polyps (peutz-jeghers, juvenile polyposis)
- Hyperplastic polyps (most common)
- Inflammatory pseudopolyps (IBD)
- Mucosal polyps (clinically insignificant)
- Submucosal polyps (lipomas, leiomyomas, fibromas)
What noneoplastic polyp is associated with IBD?
Inflammatory pseudopolyps
What is the most common polyp?
Hyperplastic
What are mucosal polyps?
- Small, usually < 5 mm
- They look similar to normal mucosa
- Clinically insignificant
What types of growths are submucosal polyps?
- May be lipomas, leiomyomas and other lesions
Where are hyperplastic polyps most commonly found?
Rectosigmoid
What can hyperplastic polyps develop into?
Serrated polyps and more advanced lesions
Via what pathway do adenomatous polyps arise?
Neoplastic, via chromosomal instability pathway with mutations in APC and KRAS
What do adenomatous polyps arise with?
Usually asymptomatic, may present with occult bleeding
What has a greater malignant potential tubular or villous histology?
Villous more malignant than tubular (tubulovillous in between)
- Villous histology is villainous
How do serrated polyps develop?
- Neoplastic
- Characterised by CpG island methylator phenotype (CIMP; cytosine base followed by guanine, linked by a phosphodiester bond)
- Defect may silence MMR gene (DNA mismatch repair) expression
- Mutations lead to mucrosatellite instability and mutations in BRAF
What do serrated polyps look like on biopsy?
‘Saw-tooth’ pattern of crypts on biopsy
What percetage colorectal cancers are caused by serrated polyps?
20% of cases of sporadic CRC
FAP is what kind of mutation, on what gene and in what location?
- Autosomal dominant
- APC tumour suppressor gene
- Chromosome 5q21-22
When do polyps arise in FAP?
Thousands arise all throughout colon after puberty, rectum always involved
How is FAP treated?
- Prophylactic colectomy as 100% progress to CRC
What is Gardner syndrome?
- FAP + osseus and soft tissue tumours (eg osteomas of skull or mandible)
- Congenital hypertrophy of retinal pigment epithelium
- Impacted/supernumerary teeth
What is turcot syndrome?
Turcot - Turban
- FAP or Lynch +
- Malignant CNS tumour (medulloblastic, glioma)
What is Juvenile polyposis syndrome?
- Aut dominant
- Children < 5 years old
- Numerous hamartomatous polyps
- Increased risk of CRC
What genes are affected in Lynch syndrome?
- MLH1, MSH2
- Mismatch repair genes
- Microsatellite instability
What cancers are assocaited with Lynch syndrome?
- 80% progress to CRC
- Proximal colon always involved
- Associated with endometrial, ovarian and skin cancers
What is a useful tumour marker to predict recurrent colorectal cancer?
CEA tumor marker (should not be used for screening)
What percentage of colon cancer patients have a FH?
25%
Where is colon cancer most common / least common?
Rectosigmoid > Ascending > Descending
What is hematochezia?
Fresh blood in stools
What bacterial infection is associated with colon cancer?
S bovis (gallolyticus) bacteremia/endocarditis or as an acute episode of diverticulitis
What are the signs of colon cancer in the ascending colon?
- Occult bleeding
- Exophytic mass
- iron deficiency anemia
- Weight loss
What are the signs of colon cancer in the descending colon?
- Infiltrating mass
- Partial obstruction
- Colicky pain
- Hematochezia
What are risk factors for colon cancer?
- Adenomatous and serrated polyps
- Familial cancer syndromes
- IBD
- Tobacco
- Processed meat + low fiber diet
Mutations in APC and FAP (chromosomal instability pathway)cause cancer via what sequence?
Adenoma-carcinoma sequence
What causes CRC via the serrated polyp pathway?
Microsatellite instability pathway
- Mutations or methylation of mismatch repair genes (eg MLH1/Lynch)
The serrated polyp (Lynch) CRC pathway usually leads to CRC where?
- Right-sided CRC
How can NSAIDs be chemopreventive?
Overexpression of COX-2 has been linked to CRC
Molecular pathway
LEARN
What patients may experience spontaneous bacterial peritonitis?
Patients with cirrhosis and ascites
What organisms may cause spontaneous bacterial peritonitis?
- E. coli, Klebsiella (gram -ves most common)
- Streptococcus
What is Reye syndrome?
- Childhood hepatic encephalopathy
- VZV or influenza treated with aspirin
Reye of sunSHINE
- Steatosis of liver/hepatocytes
- Hypoglycemia
- Hepatomegaly
- Infection
- Not awake (coma)
- Encephalopathy
- Vomitting
Describe how aspirin actually causes on a microscopic level Reye syndrome?
- Aspirin metabolites decrease Beta-oxidation by reversible inhibition of mitochondrial enzymes (changes to mitochondrial abnormalities)
What are 3 main stages of alcoholic liver disease?
- Hepatic steatosis
- Alcoholic hepatitis
- Alcoholic cirrhosis
What can be seen in hepatic steatosis?
Macrovesicular fatty change that may be reversible with alcohol cessation
What can be seen in alcoholic hepatitis?
- Swollen and necrotic hepatocytes with neutrophilic infiltration
- Mallory bodies (intracytoplasmic eosinophilic inclusions of damaged keratin filaments)
What can be seen in alcoholic cirrhosis?
- Sclerosis around central vein may be seen in early disease
- Regenerative nodules surrounded by fibrous bands in response to chronic liver injury -> portal hypertension, end-stage liver disease
What may be associated with autoimmune hepatitis?
- Positive antinuclear, anti-SM and anti-liver/kidney microsomal antibodies
What can be seen on histology in autoimmune hepatitis?
Portal and periportal lymphoplasmacytic infiltrate
What may trigger hepatic encephalopathy?
- Increased NH3 production and absorption (due to GI bleed, constipation, infection)
- Decreased NH3 removal (due to renal failure, diuretics, nypassed hepatic blood flow post-TIPS)
How is hepatic encephalopathy treated?
- Lactulose (Increased NH4+ generation)
- Rifaximin (Decreased NH3-producing gut bacteria)
What are the different types of liver tumour?
- Hepatic hemangioma (most common)
- Focal nodular hyperplasia (asymptomatic)
- Hepatocellular carcinoma (primary malignant tumour)
- Hepatic angiosarcoma (rare malignant tumour of endothelial origin)
- Metastases
What are the signs of focal nodular hyperplasia?
- Females 35-50
- Hyperplastic reaction of hepatocytes to an abherrant dystrophic artery
- Marked by central stellate scar
- Asymptomatic usually
What bug may lead to hepatocellular carcinoma?
Aspergillus’ aflatoxin
What may be the signs of hepatocellular carcinoma?
- Anorexia, jaundice, tender hepatomegaly, decompensation of previously stable cirrhosis
- Budd-Chiari syndrome
How can hepatocellular carcinoma spread?
Hematogenously
How is hepatocellular carcinoma diagnosed?
- Increased alpha-fetoprotein
- US or contrast CT/MRI
- Biopsy
What is hepatic adenoma linked to?
- Rare, benign tumour
- Linked to OCP and anabolic steroid use
- May regress or spontaneously rupture (abdo pain + shock)
What are some of the sources of malignant liver tumours?
- GI
- Breast
- Lungs
Rarely solitary metastases
What may cause nutmeg liver (mottled appearence)?
Budd-Chiari syndrome
What can alpha1 antitrypsin deficiency cause in liver on histology?
Misfolded gene product protein aggregates in hepatocellular ER -> cirrhosis with PAS positive globules in liver
What may cause neonatal jaundice?
- Lower activity of UDP gluconyltransferase (physiological clears up by itself)
- Biliary atresia (pediatric liver transplantation)
What causes biliary atresia?
- Fibro-obliterative destruction of bile ducts -> cholestasis
What are the 4 hereditary hyperbilirubinemia syndromes?
- Gilbert syndrome
- Crigler-Najjar syndrome type 1
- Dubin-Johnson syndrome
- Rotor syndrome
All autosomal recessive
What enzyme is decreased in Gilbert syndrome?
UDP-gluconyltransferase
What causes Crigler-Najjar syndrome?
Absent UDP-gluconyltransferase
How is Crigler-Najjar syndrome treated?
- Plasmapheresis, phototherapy
- Liver transplant is curative
Type 2 crigler-Najjar syndrome which is less severe can be treated with what?
Phenobarbital which increases liver enzyme synthesis
What causes Dubin-Johnson syndrome?
- Conjugated hyperbilirubinemia due to defective liver excretion
- Dark/black liver due to impaired excretion of epinephrine metabolites, benign
What causes causes Rotor syndrome?
- Similar to Dubin-Johnson but milder
- Liver looks Regular (not black)
- Impaired hepatic storage of conjugated bilirubin
What is th defect in Wilson disease?
- Hepatocyte copper-transporting ATPase
- ATP7B gene, chromosome 13
What is Wilson disease treated with?
- Chelation with penicillamine or trientine
- Oral zinc
- Liver transplant in acute liver failure
Hamosiderin (iron) can be identified with what?
- Prussian blue stain on biopsy
- Liver MRI
How is Haemochromatosis treated?
- Phlebotomy
- Iron chelation with:
- Deferasirox, deferoxamine, deferipone
How is PBC (primary biliary cholangitis) treated?
Ursodiol
What disease is associated with primary sclerosing cholangitis?
- Ulcerative colitis
- Increases risk of cirrhosis, cholangiocarcinoma and gallbladder cancer
PSC has what signs?
- Onion skin bile duct fibrosis
- Alternating strictures and dilation with beading of intra and extrahepatic bile ducts on ERCP, MRCP
What antibodies can be increased in PSC?
- Positive for MPO-ANCA/p-ANCA
- Increased IgM
PBC has what signs in the blood?
- Anti-mitochondrial antibody
- Increased IgM
Describe pigment stones and what they are made from?
- Black: Ca2+, bilirubinate, hemolysis, radiopaque
- Brown: Radiolucent, infection
What is choledocholithiasis?
Presence of gallstone(s) in the common bile duct
What is acalculous cholecystitis caused by?
Gallbladder stasis, hypoperfusion, CMV infection, critically ill patients
What is Charcot triad?
- Jaundice
- Fever
- RUQ pain
What is Reynolds pentad?
- Jaundice
- Fever
- RUQ pain
- Altered mental status
- Shock
What is Porcelain gallbladder?
Calcified gallbladder due to chronic cholecystitis, usually found incidentally on imaging
What can porcelain gallbladder predispose to?
Gallbladder cancer (likely adenocarcinoma) - Prophylactic cholecystectomy recommended
What cacn be seen on histology of cholangiocarcinoma?
Infiltrating neoplastic glands associated with desmoplastic stroma
What tumour marker is associated with pancreatic adenocarcinoma?
CA 19-9 tumor marker (also CEA, less specific)
