path liver and biliary tract - formatted

Question 1

1. 28.APRIL02 Which of the following IS LEAST correct in regards to hepatocellular carcinoma (HCC)?
2. HCC accounts for 90% of all primary liver cancers
3. The global distribution of HCC is strongly linked to prevalence of hepatitis B infection
4. In the cirrhotic liver HCC may arise within dysplastic nodules
5. HCC may have unifocal, multifocal or diffuse growth patterns, all of which have a propensity to vascular invasion
6. Fibrolamellar carcinoma, as distinct variant of HCC, is associated with a less favourable prognosis

Answer 1

Answer: Fibrolamellar carcinoma, a distinct variant of HCC, is associated with a less favourable prognosis (LEAST CORRECT)

ROBBINS: HCC
- 85% of cases occur in countries with high rates of chronic HBV infection
- highest incidences of HCC: Southeast china, Korea, Taiwan, sub-saharan Africa. peak incidence in 20-40 years old, 50% without evidence of cirrhosis.
- in western countries, HCC increasing due to Hep C epidemic. Rarely manifests before 60 years old, 90% of cases have evidence of established cirrhosis.
- male > female globally.

Most important underlying risk factors for HCC
- HBV, HCV
- alfatoxin, alcohol.
Other risk factors
- herediatary hemochrombtosis, alpha-1 anti-trypsin.
- wilsons
- metabolic syndrome associated with obesity, DM, NAFLD.

High-grade dysplastic nodules are probably the most important pathway for emergence of HCC in viral hepatitis and alcoholic liver disease.

Overall, HCC may appear grossly as
1) unifocal (large) mass
2) multifocal, widely distributed nodules
3) diffusely infiltrative cancer.

Fibrolamellar carcinoma accounts for 5% of HCC. 85% occur under the age of 35 years, m=f. No predisposing factors.

5. Fibrolamellar carcinoma, as distinct variant of HCC, is associated with a less favourable prognosis

HCC
• Overall, death occurs in 6/12 (30% 5 yr survival) → cachexia, GI or oesophageal variceal bleeding, liver failure with hepatic coma
Fibrolamellar Variant
• Often resectable
• 60% 5 yr survival

Question 2

2. 16.02.47 FNA of a liver lesion shows atypia of the hepatocytes. This is consistant with ?
3. Well-differentiated HCC
4. FNH
5. Adenoma
6. Niemann-Pick Dz
7. Alcoholic cirrhosis and fatty change

Answer 2

1. Well-differentiated HCC
   *AJL - precursor lesions for HCC show either large cell change or small cell change (which are as the name suggests larger or smaller than the typical hepatocyte).

Note : Well Differntiated HCC is principally distinguished from borderline foci/nodules, from which it may arise (nodule in a nodule), by a nuclear density greater than twice normal and by mild but definite nuclear atypia (hyperchromasia, irregular nuclear contours)

Question 3

3. 16.03.59 Staging hepatocellular carcinoma, portal nodes negative, NEXT MOST LIKELY SITE ?
4. Bone
5. Lungs
6. Adrenals
7. Brain
8. Spleen

Answer 3

Answer: Lungs

FROM ROBBINS
The natural course of HCC involves progressive enlargement of the primary mass until it disturbs hepatic function or metastasises to the lungs or other sites.

FROM STATDX
Complications
- Spontaneous rupture and massive hemoperitoneum
- IVC invasion with tumor embolism to lungs
- Metastases (adrenals and lungs most common).

FROM DAHNERT
Metastases to:
- lung (most common 8%)
- adrenal, lymph nodes, bone.

Question 4

4. 16.02.39 Commonest cause of HCC worldwide?
5. Aflatoxin
6. Hep B or C
7. Alcohol
8. Great escape food

(*AJL added some options to aid in learning. Feel free to edit the question better)

Answer 4

• Internationally, the common causes of HCC are hepatitis B, hepatitis C, and aflatoxin exposure (in that order)
• Alcohol is most common cause in western countries

Question 5

5. 29.APRIL02 A patient has isolated segmental dilatation of their intrahepatic biliary ducts on CT scan. Which of the following histories would be most likely to-suggest primary sclerosing cholangitis?
6. A 15-year history of severe ulcerative colitis in a 45-year-old male
7. A 5-year history of severe Crohn’s colitis in a 15-year-old female
8. A 30-year history of Type 1 diabetes in.a 50-year-old female with end stage renal failure
9. A 45 year old female with a history of pernicious anaemia and rheumatoid arthritis
10. A 7-year-old boy with a history of an inherited cystic renal disease.

Answer 5

1. A 15-year history of severe ulcerative colitis in a 45-year-old male

• Commonly seen in association with IBD, particularly chronic UC, which coexists in approximately 70% (conversely, PSC occurs in 4% of UC)
• 3rd – 5th decades
• M:F 2:1

Question 6

6. 30.APRIL02 A 32-year-old man with weight loss for investigation has a 3 cm non-specific hepatic nodule on CT. Fine needle aspirates are non-diagnostic and a core biopsy is performed. The report describes; “ abnormal spindle cells lining cleft-like dilated jagged vascular spaces. These lack an endothelial lining and are surrounded by similar spindle cells.” The most likely diagnosis is:
7. A cavernous haemangioma of the liver
8. A capillary haemangioma of the liver
9. Metastatic Kaposi Sarcoma
10. Metastatic angiosarcoma
11. Glomangioma of the liver (hepatic glomus tumour)

Answer 6

Answer: Metastatic Kaposi Sarcoma

FROM ROBBINS
Cavernous hemangioma
- Unencapsulated, infiltrative borders
- large, cavernous blood-filled vascular spaces separated by connective tissue storm.

Capillary hemangioma
- Thin-walled capillaries with scant storm.

Kaposi Sarcoma
- dilated, jagged vascular channels lined and surrounded by plump spindle cells.

Angiosarcoma
- all degrees of differentiation can be seen, from plump, atypical endothelial cells forming vascular channels, to wildly undifferntiated tumor with a solid spindled appearance and no discernible blood vessels that may be difficult to distinguish from carcinomas and melanomas.

Glomus (Glomangioma)
- arising form modified smooth muscle cells of the glomus bodies. most common in digits.

Question 7

7. 18.APRIL02 Which of the following is the LEAST likely pattern of spread/invasion seen with carcinoma of the gallbladder?
8. Extension along the cytic duct into the biliary tree
9. Invasion of the portal vein/ IVC
10. involvement of the porta hepatic lymph nodes
11. Peritoneal seeding
12. Pulmonary metastases

Answer 7

2. Invasion of the portal vein/ IVC

• By the time these neoplasms are discovered, most have invaded the liver centrifugally, and many have extended
o cystic duct and adjacent bile ducts
o porta hepatic lymph nodes
o peritoneum
o gastrointestinal tract
o lungs

Question 8

8. 19.APRIL02 Which of the following is the LEAST likely to be a clinical manifestation of primary hemochromatosis;
9. Arthritis
10. Loss of libido
11. Cardiac arrhythmias
12. Haematuria
13. Polyuria /polydipsia

Answer 8

Answer: Hematuria

FROM ROBBINS
Principle manifestations of classic hemochrombtosis include
- hepatomegaly
- abdominal pain
- abnormal skin pigmentation in sun exposed areas
- deranged glucose homeostasis/diabetes due to destruction of pancreatic islets
- cardiac dysfunction (arrhythmias, cardiomyopathy)
- atypical arthritis.

In some patients, the presenting complaint is hypogonadism (amenorrhoea in females, impotence and loss of libido in males). This sis secondary to a derangement in the HPA resulting in reduced GNTH and testosterone levels.

Question 9

9. 20.APRIL02 Recognised morphological appearances in acute fulminant hepatitis DO NOT include which of the following?
10. Involvement of the whole liver
11. Patchy random areas of hepatic necrosis
12. Massive loss of liver substance
13. Sparring of the subcapsular hepatocytes
14. Wrinkling/ folding of the hepatic capsule

Answer 9

4. Sparring of the subcapsular hepatocytes

Question 10

10. 21.APRIL02 A member of your staff receives a needle stick injury. They are initially seronegative but seroconvert after exposure and six months later have HbsAg, (without HbeAg, HBV DNA or anti-HBc) on blood test. These results are best summarised as;
11. Successful eradication of Hepatitis B but with impaired immune response; persisting rise of infection
12. Successful eradication of Hepatitis B with normal immune response/ immunity
13. A carrier state but without definite persisting replication / liver damage
14. A carrier state with likely persisting replication / liver damage
15. Chronic hepatitis by definition

Answer 10

Answer: A carrier state but without definite persisting replication/liver damage

ROBBINS
Chronic hepatitis is defined as symptomatic, biochemical, or serologic evidence of continuing or relapsing hepatic disease for more than 6 months.

A “carrier” is an individual who harbors and can transmit an organism, but has no manifest symptoms. It can be interpreted to mean
1) individuals who carry one of the viruses but have no liver disease
2) those who harbor one of the viruses and have non-progressive liver damage
Both are free of symptoms of disability.

IN the case of HBV, an often used term is the so called “healthy carrier”. Defined as:
- individual with HBsAG but without HBeAg
- the presence of anti-HBe
- normal aminotransferases, low/undetectable serum HBV DNA.

The questions state that 6 months on the patient has HBsAg. HBeAg/HBV DNA, anti-HBc are either not included in the bloods or negative. Therefore 3 is the most likely answer.

Question 11

11. A 60-year-old male has no cirrhosis but has imaging features suggesting post hepatic venous obstruction. The three most common causes of this in Western societies, in no particular order, are:
12. Severe right-sided heart failure, Budd Chiari Syndrome and constrictive pericarditis
13. Severe right-sided heart failure, Budd Chiari Syndrome, and mesothelioma
14. Budd Chiari Syndrome, mesothelioma and constrictive pericarditis
15. Budd Chiari Syndrome, constrictive pericarditis, and fibrosing mediastinitis
16. Idiopathic, Budd Chiari Syndrome and constrictive pericarditis

Answer 11

Answer: Severe right-sided heart failure, Budd Chiari syndrome, constrictive pericarditis

FROM ROBBINS
Components of both left and right sided heart failure can contribute to passive hepatic congestion.

FROM STATDX: Passive hepatic congestion etiology
- Congestive heart failure
- constrictive pericarditis
- pericardial effusion
- cardiomyopathy.

Budd Chiari Syndrome
- Primary: venous outflow membranous
- Secondary: Thrombotic (many causes).

Question 12

12. 23.APRIL02 Characteristic macroscopic appearances of focal nodular hyperplasia include;
13. A bile-stained homogenous mass, with a well-defined pseudocapsule
14. A poorly encapsulated mass with dense scar containing abundant bland collagen and fibroblasts.
15. A poorly encapsulated mass with a central scar containing areas of fibromuscular hyperplasia, lymphocytic infiltrate and bile duct proliferation.
16. A well encapsulated mass with areas of haemorrhage, necrosis and scar formation.
17. A poorly defined heterogenous bile stained mass, typically adjacent to the porta.

Answer 12

3. A poorly encapsulated mass with a central scar containing areas of fibromuscular hyperplasia, lymphocytic infiltrate and bile duct proliferation.

Question 13

13. 16.03.57 Patient sent with liver ultrasound, mother has primary biliary cirrhosis – which is TRUE?
14. Patient has 50% of having it
15. 20% chance based on epidemiology (increased but not sure if 20%)
16. more likely to have it if father has it
17. Has same risk as general population

Answer 13

Answer: 20% chance based on epidemiology

FROM ROBBINS
PBC primarily a disease of middle-aged women, with a female predominance of 9:1.
Peak incidence 40-50 years.
Prevalent in Northern European countries.
Family members of PBC patients have an increase risk for development of the disease

FROM STATDX
- Also known as Primary biliary cholangitis
- PBC not inherited in any recessive/dominant pattern
- 1,000x greater prevalence in families with 1 affected member.

FROM UPTODATE
Prevalence between 19-402 cases per million

Therefore if you take then mean of 200 cases per million, at 1000x the population, roughly 20%.

Question 14

14. 16.02.48 Fatty liver of pregnancy is ?
15. A benign self-limiting condition
16. Associated with a spectrum of clinical significance including death
17. Associated with abnormality of transaminases only

Answer 14

2. Associated with a spectrum of clinical significance including death

• Spectrum from mild hepatic dysfunction to hepatic failure, coma, and death
• Usually 3rd TM
• 20-40% present with co-existent preeclampsia
• Heterozygous deficiency of enzyme causing defect in mitochondrial fatty acid oxidation in high proportion of mothers

Question 15

15. 16.03.58 Acute acalculous cholecystitis which is UNLIKELY?
16. Post partum
17. HIV postive
18. TPN
19. Amyloid
20. Post surgical

Answer 15

Answer: Amyloid (only reported in 5 cases in the literature)

ROBBINS
Acute calculus cholecystitis is thought to result from schema.
It occurs in patient who are hospitalised for unrelated conditions. Risk factors include
1) sepsis with hypotension and MSOF
2) immunosupression
3) major trauma and burns
4) diabetes mellitus
5) infections

A more indolent form of acute acalculous cholecystitis may occur in the setting of systemic vasculitis, severe atherosclerotic disease in the elderly, in patients with AIDS, and with biliary tract infection

STATDX: Risk factors
- major trauma, burn injuries
- major surgery
- sepsis, hypotension, mechanical ventilation
- immunosupression
- TPN & fasting
- DM, CAD, ESRF
- Childbirth
- Cholesterol emboli, vasculitis, medications
- severe weight loss.
- AIDS immunocompromised patients.

RADIOPAEDIA
- all above + viral infections including hep a-c, CMV, EBV, VZV, Zika, HIV.

Question 16

16. Sep03.02 CEA is least likely to be associated with:
17. cirrhosis
18. hepatitis
19. smoking
20. alcoholic cirrhosis
21. breast cancer
22. pancreatic cancer
23. RCC

Answer 16

Answer: RCC (least likely)

RADIOPAEDIA
Carcinoembryonic antigen. Primary significant is in CRC
- used routinely to detect post-op recurrence and metastatic disease. as well as response to treatment.

Elevated in the following malignancies
- Pancreatic adenocarcinoma
- Stomach cancer
- Cholangiocarcinoma
- Lung cancer
- Breast cancer
- Medullary thyroid cancer
- Ovarian cancer
- Sarcomas (rare)

Elevated in the following non-neoplastic causes
- UC & Crohns
- alcoholic pancreatitis
- Liver disease (cirrhosis, chemotherapy related liver injury, anaesthetic relative liver injury)
- COPD, lung infections
- hypothyroidism
- smoking.

Question 17

17. Sep03.19 Definition of chronic cholecystitis

Answer 17

Answer

STATDX
Definition: Chronic inflammatory infiltration of gallbladder wall, frequently associated with gallstones.
Intermittent obstruction of cystic duct causes chronic low-grade inflammatory infiltration of wall, which can lead to fibrosis and contraction

ROBBINS
Associated with cholelithiasis in >90% of cases.
E.coli and enterococci cultured from bile in 1/3 of cases.
Unlike acute cholecystitis, obstruction of gallbladder outflow not a requisite.

Morphology
Macro
- thickened GB wall
- normal size, enlarged, or shrunken.
- adhesions may be present
Micro
- outpouchings of mucosal epithelium through the wall (Rokitansky-Aschoff sinuses) may be quite prominent
- lymphocyte-predominant inflammatory infiltrate.

Question 18

18. Sep03.23 Liver cirrhosis patient. History of Ulcerative colitis. Post mortem showed a green mass 7cm in size. What is the most likely cause?
19. hepatocellular carcinoma
20. cholangiocarcinoma
21. adenoma
22. nodular regeneration

Answer 18

HCC

*LW:
Robbins states HCC may be pale or have a variable appearance depending on degree of differentiation: yellow when fatty change predominates or green when well differentiated malignant hepatocytes make abundant bile.
Thus in a cirrhotic patient a large green mass is favored to represent HCC.
UC is likely a distractor in this case.

Cholangiocarcinoma, tends to be small gray nodules, especially if extra hepatic. Larger if intra hepatic. Risk factors include PSC, which is associated with UC.

**LJS - agree

Nodular regeneration / regenerative nodules; occur in cirrhotic livers, but appear as paler than normal liver parenchyma.

Question 19

19. Sep03.46 Primary biliary cirrhosis

describe.

Answer 19

ROBBINS

PBC is an autoimmune disease characterised by non-suppurative inflammatory destruction of small and medium-sized intrahepatic bile ducts.

Epidemiology
- Median age 50 (30-70 range)
- 90% female (9:1)
- 1000x more likely to have if 1 family member has it, but no inheritance pattern.
Clinical course: progressive
Associated conditions
- Sjogrens (70%)
- Thyroid disease (20%)
- Scleroderma (5%)
Serology
- 95% AMA positive
- 50% ANA positive
- 40% ANCA positive
Radilogical findings: NAD
Duct lesion
- florid duct lesions and loss of small ducts only.

MORPHOLOGY
Gross
• Initially normal liver, eventually green + micronodular cirrhosis
Histology
• Best description = marked damage to portal tracts, followed by progressive damage to parenchyma, with changes of cholestasis

Question 20

21. 16.03.56 Choledochal cysts
22. If jaundiced implies secondary stricture
23. Primary abnormality is stricture with secondary dilatation proximal
24. presents 10-20’s
25. pain always means pancreatitis
26. females 80%

Answer 20

Answer: Females 80%

ROBBINS
Choledochal cysts are congenital dilations of the CBD. They present most often in children <10 years as jaundice +/- recurrent abdomen pain.
Only 20% of cases present symptomatically in adulthood.

Female-male ratio is 3-4:1.

Predisposed to stone formation, stenosis/stricture, pancreatitis, and obstructive biliary complications within the liver.
IN older patients, the risk of bile duct carcinoma is elevated.

Question 21

22. Sep03.89 Epidemiology and incidence of hepatoma

Answer 21

Answer:

More than 85% of cases occur in countries with high rates of chronic HBV infection.

Highest incidences of HCC are found in Asian countries (Chine, Korea, Taiwan) and sub-Saharan countries.

In these locales, vertical transmission occurs, and carrier state starts in infancy. Therefore, peak incidence of HCC in these areas is 20-40 years old. 50% of cases appear in absence of cirrhosis.
Additional risk factors in these areas is exposure to aflatoxin.

Western countries, HCC rarely manifests before 60 years old
90% of cases emerge after cirrhosis is established.
Male predilection (3-8:1)

Factors in hepatocarcinogenesis
- HBV, HCV
- Aflatoxin, alcohol
- Aflatoxin synergizes with HBV
- Alcohol synergizes with HBV/HCV and cigarette smoking
- Hereditary hemochromatosis
- Alpha-1 antitrypsin deficience
- Wilson’s disease (less so)
- Metabolic syndrome associated with obesity, DM, non-alcoholic fatty liver disease.

Question 22

23. Sep03.90 What is not a complication of Gallstones

Answer 22

ROBBINS

Complications
- Biliary colic
- Cholecystitis
- Empyema
- Perforation
- Fistulas
- Cholangitis
- Obstructive cholestasis
- Pancreatitis.
- Gallstone ileus/Bouveret syndrome
- Gallbladder carcinoma

Question 23

24. Psammoma bodies NOT SEEN in ?
25. primary liver cancer
26. thyroid cancer
27. meningioma
28. ovarian ca

Answer 23

Answer: primary liver cancer

RADIOPAEDIA
Definition: Round microscopic calcific collections i.e. form of dystrophic calcification.

Found in the following tumors
- Papillary thyroid carcinoma
- Papillary serous carcinoma of the endometrium
- Melanotic schwannoma
- Mengioma (WHO 1)
- Serous cystadenocarcinoma of the ovary
- Adenocarcinoma of the lung

Question 24

25. PATH2004 52yo male with ulcerative colitis and cirrhosis. A 7cm green tumour in the liver exists. What is the most likely diagnosis:
26. Cavernous haemangioma
27. Cholangiocarcinoma
28. HCC
29. Nodular regenerative hyperplasia
30. Hepatic adenoma

Answer 24

Answer: HCC (see below)

HCC
HCC may be pale or have a variable appearance depending on degree of differentiation: yellow when fatty change predominates or green when well differentiated malignant hepatocytes make abundant bile.

Cavernous haemangioma
- Soft red-blue mass composed of large cavernous vascular spaces, no bile pigment.

Cholangiocarcinoma
- have abundant fibrous stroma (desmoplasia) giving a firm gritty consistency. Bile pigment is not found within the cells (differentiated bile duct epithelium cannot secrete bile). Note that 4% of UC patients develop PSC, and this carries a 10-15% risk of cholangioCa (70% of those with PSC have UC).

Nodular regenerative hyperplasia
- diffuse non-fibrosing version of FNH, affects entire liver with spherical nodules of plump hepatocytes surrounded by rims of atrophic cells in the absence of fibrosis.

Hepatic adenoma
- typically occurs in women of childbearing age who have used OCP; may be pale, yellow-tan or bile-stained. Note: bile duct adenomas are almost never bile-stained.

Question 25

26. PATH2004 Hemochromatosis – least correct:
27. Homozygous recessive
28. Iron is directly toxic to host tissues
29. Cardiac arrhythmia cause of sudden death
30. Incidence of hepatoma is recessive
31. Patients with longstanding disease develop cirrhosis + hyperbilirubinemia

Answer 25

4. Incidence of hepatoma is recessive - F
5. PATH2004 Hemochromatosis – least correct: (GC)
6. Homozygous recessive - T - (a repeat recall was “autosomal recessive”). Most common form is an AR disease of adult onset caused by mutations in the HFE gene (located on short arm of chromosome 6). Two common mutations in the HFE gene: C282Y and H63D. Carrier frequency in Causasians of the C282Y mutation is 1 in 70, and homozygotes 1 in 200. Approx 80% of haemochromatosis pts are homozygous for the C282Y mutation.
7. Iron is directly toxic to host tissues - T - by the following mechanisms: lipid peroxidation by iron-catalyzed free-radial reactions; stimulation of collagen formation; direct interactions of iron with DNA.
8. Cardiac arrhythmia cause of sudden death - T - death may result from cirrhosis, HCC, or cardiac disease (dysfunction with arrhythmias, cardiomyopathy).
9. Incidence of hepatoma is recessive - F
10. Patients with longstanding disease develop cirrhosis + hyperbilirubinemia - T - iron accumulation - haemosiderin granules in cytoplasm of periportal hepatocytes (stain blue with Prussian blue) - progressive involvement of lobule, bile duct epithelium and Kupffer cell pigmentation - fibrous septa form - micronodular cirrhosis. High bilirubin is due to impaired secretion of conjugated bilirubin into bile.
    [Robbins; eMedicine]

Question 26

27. PATH2004 Which is not a feature of acute cholecystitis:
28. Jaundice
29. Right upper quadrant pain
30. Mild fever
31. Leukocytosis

Answer 26

1. Jaundice - F - conjugated hyperbilibinaemia suggests CBD obstruction.
2. PATH2004 Which is not a feature of acute cholecystitis: (GC)
3. Jaundice - F - conjugated hyperbilibinaemia suggests CBD obstruction.
4. Right upper quadrant pain - T - steady pain often radiating to right shoulder; colicky if stones in GB neck or in ducts. Murphy’s sign positive (arrest of inspiration on deep palpation of GB).
5. Mild fever - T
6. Leukocytosis - T
   Classic triad of acute cholecystitis: RUQ pain + fever + leukocytosis.
   Charcot triad of acute cholangitis: jaundice + RUQ pain + fever. Implies inflammation of the bile duct walls, caused by bacterial infection of the normally sterile lumen; most commonly due to choledocholithiasis (any cause of obstruction).
   [Robbins]
   • (–) Not sure if other option is more apprpriate but jaundice is rare (except in Mirrizi syndrome)
   • acute cholecystitis begins with progressive right upper quadrant or epigastric pain, frequently associated with mild fever, anorexia, tachycardia, diaphoresis, and nausea and vomiting. The upper abdomen is tender, but a distended tender gallbladder is not usually evident. Most patients are free of jaundice; the presence of hyperbilirubinemia suggests obstruction of the common bile duct. Mild to moderate leukocytosis may be accompanied by mild elevations in serum alkaline phosphatase values

Question 27

28. PATH2004 Regarding necrosis (cell death). Which of the following is MOST CORRECT:
29. Liquefaction necrosis is characteristic of ischaemic destruction of cardiac muscle
30. Councilman bodies in the liver in toxic or viral hepatitis is an example of apoptosis
31. The dead cell usually shows decreased eosinophilia
32. Caseous necrosis is encountered principally in the centre of the Aschoff nodule
33. Expansion of the nucleus of dead cells with unravelling of the chromatin is called pyknosis

Answer 27

2. Councilman bodies in the liver in toxic or viral hepatitis is an example of apoptosis – T – cell injury in certain viral diseases, eg viral hepatitis, in which apoptotic cells in the liver are known as Councilman bodies.
3. PATH2004 Regarding necrosis (cell death). Which of the following is MOST CORRECT: (TW)
4. Liquefactive necrosis is a characteristic of ischaemic destruction of cardiac muscle – F – coagulative necrosis. Implies preservation of basic outline of the coagulated cell for a span of at least some days. MI is an excellent example in which acidophilic, coagulated, anucleated cells may persist for weeks.
5. Councilman bodies in the liver in toxic or viral hepatitis is an example of apoptosis – T – cell injury in certain viral diseases, eg viral hepatitis, in which apoptotic cells in the liver are known as Councilman bodies.
6. The dead cell usually shows decreased eosinophilia – F – increased eosinophilia. Attributable in part to loss of the normal basophilia imparted by the RNA in the cytoplasm and in part to the increased binding of eosin to denatured intracytoplasmic proteins.
7. Caseous necrosis is encountered principally in the centre of an Aschoff nodule – F – Aschoff body (or nodule) is in rheumatic fever (foci of fibrinoid degeneration).
8. Expansion of the nucleus of dead cells with unravelling of the chromatin is called pyknosis – F – pynkosis: nuclear shrinkage and increased basophilia. Karyolysis: basophilia of chromatin may fade. Karyorrhexis: pnknotic or partially pnknotic nucleus undergoes fragmentation.

Question 28

29. PATH2004 What is not associated with clinical aspect of portal HT:
30. Ascites
31. Porto systemic shunts
32. Congestive splenomegaly
33. Pancreatitis
34. Hepatic encephalopathy

Answer 28

4. Pancreatitis - F
5. PATH2004 What is not associated with clinical aspect of portal HT: (TW)
6. Ascites - T - multifactorial.
7. Portosystemic shunts - T - shunts open with increasing portal venous pressures.
8. Congestive splenomegaly - T - venous congestion in visceral organs. Splenomegaly occurs as a result of increased splenic vein pressure.
9. Pancreatitis - F
   Hepatic encephalopathy - T - with shunting of blood, substances that are normally removed by liver pass into the general circulation and reach the brain.

Question 29

30. PATH2004 30 yo female US – 3cm Homogenous hypo echoic mass + CT Hypodense pre contrast and isodense in PV phase:
31. Adenoma
32. HCC
33. Fibrolamellar HCC
34. FNH
35. Hemangioma

Answer 29

4. FNH - T - hamartomatous malformation (contains hepatocytes, Kupffer cells, bile ducts without connection to biliary tree); well-circumscribed non-encapsulated nodular mass in a non-cirrhotic liver. 85% are <5cm. Multiple in 20% of cases.
   US: iso- / mildly hypo- / mildly hyperechoic, homogeneous. +/- hyperechoic central scar.
   NECT: iso- / slightly hypoattenuating and homogenous.
   CECT: transient enhancement in arterial phase, isodense on PV and delayed phases. If a central scar is present (50%), it will be hypodense on arterial, and enhance in delayed phase .
   MRI: T1 iso- / hypo, T2 slightly hyper- / isointense; central scar T1 hypo, T2 hyper or hypo (dpt on vascular channels and oedema); Primovist uptake on delayed phase (functional hepatocytes).

*LW: adenoma is also a possibility as descriptors provided are still not enough to be conclusive. One would expect the presence of a scar to be mentioned or delayed phase gadxetate to be mentioned to confirm or deny such lesions.
From a simple epi point of view adenoma most common benign lesion.

Question 30

31. PATH2004 Same 30 yo female has Hx of Breast Ca. Dx?
32. Met
33. Adenoma
34. FNH
35. HCC

Answer 30

1. Met - T - see below.
2. PATH2004 Same 30 yo female has Hx of Breast Ca. Dx? (GC)
3. Met - T - see below.
4. Adenoma
5. FNH - T - also isodense on PV but would need to consider mets in the first instance.
6. HCC

• Mets with abundant arterial blood flow may enhance vividly during arterial phase - these include mets from neuroendocrine, phaeo, carcinoid, breast, RCC, thyroid.
• In fact, these tumors are often most conspicuous during the hepatic arterial-predominant phase of enhancement, reflecting their increased arterial supply.
• During PV phase, the lesions may be isodense to liver and difficult to detect. Indeed, there is the occasional patient with a hypervascular primary tumor in whom metastases will be entirely missed unless arterial-phase imaging is performed. There is some debate as to which tumors are best imaged with the addition of arterial-phase imaging.
• Research suggests that mets from neuroendocrine tumors, including carcinoid & thyroid, are extremely hypervascular and are best seen during the hepatic arterial phase of enhancement.
• Other so-called hypervascular tumors may be less vascular, including mets from RCC, breast, and melanoma. In these tumors, the added value of the arterial phase is controversial, at least in terms of detection per se. [Evaluation of liver for metastatic disease; 2001 Medscape]

Question 31

32. PATH2004 Regarding hemochromatosis, which is least correct:
33. autosomal recessive
34. more common in females
35. accumulation is life long
36. effects are due to direct toxic effect of iron on cells
37. end stage cirrhosis and hyperbilirubinemia

Answer 31

2. more common in females - F - males predominate (5 to 7:1) with slightly earlier clinical presentation, partly because physiologic iron loss (menstruation, pregnancy) delays iron accumulation in women.
3. PATH2004 Regarding hemochromatosis which is least correct: (GC)
4. autosomal recessive - T - most common form is an AR disease of adult onset caused by mutations in the HFE gene (located on short arm of chromosome 6). Two common mutations in the HFE gene: C282Y and H63D. Carrier frequency in Causasians of the C282Y mutation is 1 in 70, and homozygotes 1 in 200. Approx 80% of haemochromatosis pts are homozygous for the C282Y mutation.
5. more common in females - F - males predominate (5 to 7:1) with slightly earlier clinical presentation, partly because physiologic iron loss (menstruation, pregnancy) delays iron accumulation in women.
6. accumulation is life long - T - starts from young age.
7. effects are due to direct toxic effect of iron on cells - T - by the following mechanisms: lipid peroxidation by iron-catalyzed free-radial reactions; stimulation of collagen formation; direct interactions of iron with DNA.
8. end stage cirrhosis and hyperbilirubinemia - T - iron accumulation - haemosiderin granules in cytoplasm of periportal hepatocytes (stain blue with Prussian blue) - progressive involvement of lobule, bile duct epithelium and Kupffer cell pigmentation - fibrous septa form - micronodular cirrhosis. High bilirubin is due to impaired secretion of conjugated bilirubin into bile.
   [Robbins; eMedicine]

Question 32

33. PATH2004 Which cell is responsible for excess collagen production in cirrhosis:
34. Ito cell
35. Kupffer cell
36. Hepatocyte
37. Lymphocyte
38. Macrophage

Answer 32

1. Ito cell - T - the hepatic stellate cell (previously called the lipocyte, Ito, fat-storing, or perisinusoidal cell) is the primary source of extracellular matrix in normal and fibrotic liver. These cells are located in subendothelial space of Disse. Stellate cells undergo a transition from a quiescent vitamin A-rich cell into proliferative, fibrogenic, and contractile myofibroblasts. Sinusoidal endothelial cells also play a role.

As the liver becomes fibrotic, significant changes occur in the extracellular matrix quantitatively and qualitatively. The total collagen content increases 3- to 10-fold. Increase in various collagens, glycoproteins, proteoglycans, and glycosaminoglycans. UTD

Question 33

2. Sep03.72 16 year old with a cystic and solid pancreatic mass. Most likely cause:
3. mucinous cystadenoma
4. mucinous cystadenocarcinoma
5. solid-cystic (papillary cystic) tumour

Answer 33

3. Solid cystic (papillary cystic) tumour - T - Pancreatic mass of low malignant potential with solid and cystic features. Well-demarcated large mass. Commonly in body and/or tail. <35yo. F>M 9.5x. African-Americans or other non-Caucasian groups.
4. Sep03.72 16 year old with a cystic and solid pancreatic mass. Most likely cause: (TW)
5. mucinous cystadenoma - F - mucinous cystic pancreatic tumor (mucinous macrocystic neoplasm, macrocystic adenoma, mucinous cystadenoma or cysadenocarcinoma). Thick-walled, uni-/multilocular low grade malignant tumor composed of large, mucin-containing cysts. Likes the body or tail of pancreas.F>M 9x. Mean age 50yo (20-95yo). 50% occur between ages 40-60yo.
6. mucinous cystadenocarcinoma – F – see option 1
7. Solid cystic (papillary cystic) tumour - T - Pancreatic mass of low malignant potential with solid and cystic features. Well-demarcated large mass. Commonly in body and/or tail. <35yo. F>M 9.5x. African-Americans or other non-Caucasian groups.

Question 34

3. Sep03.23 Liver cirrhosis patient. History of Ulcerative colitis. Post mortem showed a green mass 7cm in size. What is the most likely cause?
4. hepatocellular carcinoma
5. cholangiocarcinoma
6. adenoma
7. nodular regeneration

Answer 34

1. hepatocellular carcinoma - T - HCC can be green due to bile and is the most likely mass in a cirrhotic liver. Although IBD and PSC are associated and PSC can lead to frank cirrhosis, only 4% of IBD have PSC, and it is rare to get HCC with PSC.
2. Sep03.23Liver cirrhosis patient. History of Ulcerative colitis. Post mortem showed a green mass 7cm in size. What is the most likely cause? (TW)
3. hepatocellular carcinoma - T - HCC can be green due to bile and is the most likely mass in a cirrhotic liver. Although IBD and PSC are associated and PSC can lead to frank cirrhosis, only 4% of IBD have PSC, and it is rare to get HCC with PSC.
4. cholangiocarcinoma - F - increased risk of cholangiocarcinoma in primary sclerosing cholangitis (40-70% of PSC have IBD, however only 4% of IBD have PSC), however not a green tumor. CC is an adenocarcinoma arising from bile ducts (so don’t produce bile like hepatocytes). Gray-white and firm, rarely bile stained.
5. adenoma - F - young woman on OCP. Pale, yello-tan lesion, frequently bile-stained nodules. Not cirrhotic liver.
6. nodular regeneration - F - regenerative nodule occasionally up to 5cm. Similar in colour and texture to surrounding liver. may be pale of bile stained.

Cholangiocarcinoma is associated with chronic bile stasis / cholangitis due to autosomal dominant polycystic disease, choledochal cysts, congenital hepatic fibrosis, liver flukes (Clonorchis or Opisthorchis), Thorotrast, anabolid steroids, PSC, intrahepatic lithiasis.

Question 35

5. Sep03.02 CEA is least likely to be associated with:
6. colonic ca
7. lung ca
8. pancreatic ca
9. ?smoking

Answer 35

**SCS: Prior recall- included RCC, (hence favoured answer). The rest are true.

5. Sep03.02 CEA is least likely to be associated with: (TW)
6. colonic ca - T - considered the marker of choice, but has no role in detection and diagnosis (high false positive rate). Reported to be positive in 60-90% of colorectal ca
7. lung ca - T - much less consistently has CEA been described in other forms of cancer (other than Colon, pancreatic, gastric, and breast)
8. pancreatic ca - T - sensitivity 16-92%, specificity 49-93%. Reported to be positive in 50-80% of pancreatic ca.
9. smoking - T - Occasionally, levels of CEA are elevated in healthy smokers.

CEA is normally preent in the liver, pancreas, and gastrointestinal tract during fetal life, and in adolescence in small amounts in the colon and endodermal tissue. Smoking can falsely elevate serum values of CEA, as can various benign diseases such as hepatic disease, extraheaptic cholestasis, and myocardial infarction.

Question 36

6. Sep03.01 Alpha feto-protein is least likely to be associated with:
7. Cirrhosis
8. Hepatitis

Answer 36

1. Cirrhosis - F - this would potentially be true is making trying to make a link with HCC, but.. see below.

AFP = normal glycoprotein produced by fetal liver and yolk sac.
Serum concentration of AFP is elevated in patients with HCC.
Elevated serum AFP may also be seen in pregnancy, tumors of gonadal origin, and in patients with chronic liver disease without HCC such as acute or chronic viral hepatitis. AFP may be slightly higher in patients with cirrhosis due to hepatitis C.

Question 37

1. 52 yo male with UC and cirrhosis. A 7cm green tumor within the liver. What is the most likely diagnosis:
2. Cavernous haemangioma
3. Cholangiocarcinoma
4. HCC
5. Nodular regenerative hyperplasia
6. Hepatic adenoma

Answer 37

1. hepatocellular carcinoma - T - HCC can be green due to bile and is the most likely mass in a cirrhotic liver. Although IBD and PSC are associated and PSC can lead to frank cirrhosis, only 4% of IBD have PSC, and it is rare to get HCC with PSC.
2. 52 yo male with UC and cirrhosis. A 7cm green tumour within the liver. What is the most likely diagnosis: (TW)
3. hepatocellular carcinoma - T - HCC can be green due to bile and is the most likely mass in a cirrhotic liver. Although IBD and PSC are associated and PSC can lead to frank cirrhosis, only 4% of IBD have PSC, and it is rare to get HCC with PSC.
4. cholangiocarcinoma - F - increased risk of cholangiocarcinoma in primary sclerosing cholangitis (40-70% of PSC have IBD, however only 4% of IBD have PSC), however not a green tumor. CC is an adenocarcinoma arising from bile ducts (so don’t produce bile like hepatocytes). Gray-white and firm, rarely bile stained.
5. adenoma - F - young woman on OCP. Pale, yello-tan lesion, frequently bile-stained nodules. Not cirrhotic liver.
6. nodular regeneration - F - regenerative nodule occasionally up to 5cm. Similar in colour and texture to surrounding liver. may be pale of bile stained.

Question 38

2. 17yo girl complains of abdominal discomfort. 10cm mixed solid and cystic mass in her pancreas. What is the most likely?
3. Neuroblastoma
4. Solid cystic (papillary cystic) tumour
5. Mucinous cystadenoma
6. Mucinous cystadenocarcinoma
7. Microcystic adenoma

Answer 38

2. Solid cystic (papillary cystic) tumour - T - Pancreatic mass of low malignant potential with solid and cystic features. Well-demarcated large mass. Commonly in body and/or tail. <35yo. F>M 9.5x. African-Americans or other non-Caucasian groups.
3. 17yo girl complains of abdominal discomfort. 10cm mixed solid and cystic mass in her pancreas. What is the most likely? (TW)
4. Neuroblastoma – too old, rare
5. Solid cystic (papillary cystic) tumour - T - Pancreatic mass of low malignant potential with solid and cystic features. Well-demarcated large mass. Commonly in body and/or tail. <35yo. F>M 9.5x. African-Americans or other non-Caucasian groups.
6. Mucinous cystadenoma - F - mucinous cystic pancreatic tumor (mucinous macrocystic neoplasm, macrocystic adenoma, mucinous cystadenoma or cysadenocarcinoma). Thick-walled, uni-/multilocular low grade malignant tumor composed of large, mucin-containing cysts. Likes the body or tail of pancreas.F>M 9x. Mean age 50yo (20-95yo). 50% occur between ages 40-60yo.
7. Mucinous cystadenocarcinoma – F – see option 3
8. Microcystic adenoma - F - serous cystadenoma (glycogen-rich or micro-/macrocystic serious adenoma). Benign pancreatic tumor that arises from acinar cells. Honeycomb or sponge-like mass in pancreatic head (microcystic cystadenoma). Or as Steve Drew says “like the surface of a cut orange”. Mean age 65yo. Middle-aged & elderly. F>M 4x.

Question 39

3. Haemachromatosis; least correct:
4. Homozygous recessive
5. Iron is directly toxic to host tissue
6. Cardiac arrhythymia cause of sudden death
7. Incidence of hepatoma is recessive
8. Patients with long standing disease develop cirrhosis + hyperbilirubinaemia

Answer 39

4. Incidence of hepatoma is recessive - F
5. Haemochromatosis; least correct: (GC)
6. Homozygous recessive - T - (a repeat recall was “autosomal recessive”). Most common form is an AR disease of adult onset caused by mutations in the HFE gene (located on short arm of chromosome 6). Two common mutations in the HFE gene: C282Y and H63D. Carrier frequency in Causasians of the C282Y mutation is 1 in 70, and homozygotes 1 in 200. Approx 80% of haemochromatosis pts are homozygous for the C282Y mutation.
7. Iron is directly toxic to host tissue - T - by the following mechanisms: lipid peroxidation by iron-catalyzed free-radial reactions; stimulation of collagen formation; direct interactions of iron with DNA.
8. Cardiac arrhythymia cause of sudden death - T - death may result from cirrhosis, HCC, or cardiac disease (dysfunction with arrhythmias, cardiomyopathy).
9. Incidence of hepatoma is recessive - F
10. Patients with long standing disease develop cirrhosis + hyperbilirubinaemia - T - iron accumulation - haemosiderin granules in cytoplasm of periportal hepatocytes (stain blue with Prussian blue) - progressive involvement of lobule, bile duct epithelium and Kupffer cell pigmentation - fibrous septa form - micronodular cirrhosis. High bilirubin is due to impaired secretion of conjugated bilirubin into bile.
    [Robbins; eMedicine]

Question 40

6. Which does not cause chronic pancreatitis:
7. Alcohol
8. Cholelithiasis
9. Divisum
10. Hypercalcaemia
11. Hyperinsulinaemia

Answer 40

5. Hyperinsulinaemia

Predisposing factors
• More commonly middle-aged male alcoholic than gallstone disease
• Also hypercalcaemia and hyperlipoproteinaemia
• Structural anomaly - 12% (Pancreas divisum with anomalous duct system or stricture at Ampulla)
• Maybe familial - Familial hereditary pancreatitis - begins in childhood & predisposes to carcinoma in later years
• Nonalcoholic tropical pancreatitis
• Idiopathic - 40% - no recognizable predisposing factors
UTD: It is estimated that fewer than 5% of patients with pancreas divisum develop pancreatic symptoms. The low frequency of symptoms has created a controversy as to whether PD and its associated small minor papilla orifice are ever a cause of obstructive pancreatitis. There may be a group of patients with PD who are subject to recurrent bouts of seemingly idiopathic pancreatitis.

Question 41

7. What does not cause acute pancreatitis:
8. Alcohol
9. Cholelithiasis
10. Trauma
11. Haemochromatosis
12. ERCP

Answer 41

Answer: Hemochromatosis (does not cause acute pancreatitis).

Hemochromatosis can cause chronic pancreatitis via diffuse interstitial fibrosis and atrophy.

ROBBINS
Acute pancreatitis results from inappropriate release and activation of pancreatic enzymes, which destroy pancreatic tissue, & elicit an acute inflammatory reaction. Etiologies include:

Metabolic:
- alcoholism, hyperlipoproteinemia, hypercalcemia, drugs
Genetic
Mechanical
- gallstones, trauma, iatrogenic (ERCP)
Vascular
- shock, atheroembolism, vasculitis
Infections i.e. mumps

Another way of looking at ethology:
Duct obstruction
- Cholelithiasis, chronic alcoholism
Acinar cell injury
- Alcohol, drugs, trauma, schema, viruses, hypercalcemia
Defective intracellular transport
- Metabolic injury, alcohol, duct obstruction.

Question 42

8. 30 yo. Female US 3cm homogenous hypoechoic mass, CT hypodense pre contrast and isodense in PV phase:
9. Adenoma.
10. HCC
11. Fibrolamellar HCC
12. FNH
13. Haemangioma

Answer 42

4. FNH - T - hamartomatous malformation (contains hepatocytes, Kupffer cells, bile ducts without connection to biliary tree); well-circumscribed non-encapsulated nodular mass in a non-cirrhotic liver. 85% are <5cm. Multiple in 20% of cases.
   US: iso- / mildly hypo- / mildly hyperechoic, homogeneous. +/- hyperechoic central scar.
   NECT: iso- / slightly hypoattenuating and homogenous.
   CECT: transient enhancement in arterial phase, isodense on PV + delayed phases. If central scar present (50%), it will be hypodense on arterial & enhance in delayed phase .
5. 30 yo. Female US 3cm homogenous hypoechoic mass, CT hypodense pre contrast and isodense in PV phase: (GC)
6. Adenoma - F - solid heterogeneous mass of variable echogenicity, typically hyperechoic with hypoechoic rim, hypo areas if cystic/haemorhagic change within. Isoattenuating with areas of hypo/hyper if fat/necrosis/hmg. Arterially enhance, iso-/hypoattenuating on delayed.
7. HCC - F - variable echogenicity; hypodense (hyperdense in fatty liver); arterial enchancement, inhomogenously lower on PV, isodense on delayed.
8. Fibrolamellar HCC - F - US: mixed echogenicity, central hyperechoic scar in 1/3-2/3.
   NECT: low attenuation; may have capsular retraction (10%), calcs within scar, hmg/necrosis, satellite lesions, adenopathy, distant mets (lung peritoneum)
   CECT: enhancement of non scar portion is prominent & heterogeneous in arterial + PV phases; delayed enhancement of scar in 25%, may see enhanceing pseudocapsule (15%).
9. FNH - T - hamartomatous malformation (contains hepatocytes, Kupffer cells, bile ducts without connection to biliary tree); well-circumscribed non-encapsulated nodular mass in a non-cirrhotic liver. 85% are <5cm. Multiple in 20% of cases.
   US: iso- / mildly hypo- / mildly hyperechoic, homogeneous. +/- hyperechoic central scar.
   NECT: iso- / slightly hypoattenuating and homogenous.
   CECT: transient enhancement in arterial phase, isodense on PV + delayed phases. If central scar present (50%), it will be hypodense on arterial & enhance in delayed phase .
10. Haemangioma - F - variable echogenicity; typically low density on NECT with peripheral/centripetal enhancement and complete fill-in on delayed phase. [Dahnert]

Question 43

12. With regards to HCC, which is false:
13. > 95% 5 year survival

Answer 43

12. With regards to HCC, which is false: (TW)
13. > 95% 5 year survival - F - 5yr survival rates, based upon newer staging systems are: Stage I - 55%, Stage II - 37%, Stage III 16% (UTD).

*AJL - according to radiopaedia, TNM is not typically used for HCC as it does not give accurate prognostic information. Apparently most commonly used is BCLC. It looks at Lesions (size and number), vascular invasion, nodal spread/mets, Child-pugh score of liver disease and performance status of the patient (ADLs, exercise tolerance etc).

TNM (AJCC) staging:
Primary tumor (T):
• Tx - can’t assess;
• T0 - no evidence primary tumor;
• T1 - solitalry tumor no vascular infasion;
• T2 - vascular invasion, or multiple tumors <5cm;
• T3 - multiple >5cm or involving major branch portal or hepatic veins;
• T4 - direct invasion adjacne torgans other than GB, or with perforation of visceral peritoneum.
Regional lymph nodes (N)
• Nx - can’t assess regional nodes;
• N0 - no regional nodes
• N1 - regional nodal mets
Distant metastasis (M)
• Mx, M0, M1.
Stage - easier than most!
• Stage I - T1,
• Stage II - T2,
• Stage IIIA T3,
• Stage IIIB T4 (all N0, M0)
• Stage IIIC - N1. (any T, M0)
• Stage IV - M1. (any T, any N)

Question 44

14. Patient hep D positive, needle stick injury to staff member. Which is true:
15. No risk because staff member doesn’t have hep B
16. No such thing as Hep D
17. More at risk of Hep B

Answer 44

*AJL - Can only be infected with Hep D if you have previous or simultaneous Hep B therefore the patient also has Hep B and therefore the staff member is at increased risk of Hep B from the patient.

14. Patient hep D positive, needle stick injury to staff member. Which is true: (TW)
15. No risk because staff member doesn’t have hep B - F - patient with HDV must have HBV too, so risk of both.
16. No such thing as Hep D - F
17. More at risk of Hep B - T - couldn’t find numbers, but this would be true as potentially could contract either HBV, or HBV + HDV (superinfection), so overall increased risk of HBV.
    Hepatitis D can replicate autonomously, however the simultaneous presence of HBV is required for complete virion assembly and secretion.
    All individuals with HDV are always dually infected with HDV and HBV.
    Due to mechanisms unknown, HBV replication is suppressed in most HDV-infected individuals.
    Tansmission can be permucosal, percutaneous spread. IVDU, sexual.

Question 45

15. Which if the following is most likely to suggest primary Sclerosing cholangitis:
16. A 15 year hx of severe UC in a 45 yo male
17. A 5 year hx of severe Crohn’s colitis in a 15 yo female
18. A 30 year history of Type 1 DM in a 50yo female patient with ESRF
19. A 45 yo female with a history of pernicious anemia and RA
20. A 7 yo boy with a history of inherited cystic renal disease

Answer 45

1. A 15 year hx of severe UC in a 45 yo male - T - 50-70% of PSC have IBD (ulcerative colitis in the majority ~70%), and 4% of IBD have PSC. M>F 7:3. Mean age at diagnosis 40yo.
2. Which if the following is most likely to suggest primary Sclerosing cholangitis: (TW)
3. A 15 year hx of severe UC in a 45 yo male - T - 50-70% of PSC have IBD (ulcerative colitis in the majority ~70%), and 4% of IBD have PSC. M>F 7:3. Mean age at diagnosis 40yo.
4. A 5 year hx of severe Crohn’s colitis in a 15 yo female - F - UC > CD in association with PSC. See ans 1.
5. A 30 year history of Type 1 DM in a 50yo female patient with ESRF - F - not sure what they’re getting at with this combination. ?depositional ?amyloid ?aluminium etc..
6. A 45 yo female with a history of pernicious anemia and RA - F - RA associated with primary biliary cirrhosis (associated with autoimmune disorders).
7. A 7 yo boy with a history of inherited cystic renal disease - F - assoc with Caroli’s disease, and subsequently increased risk of cholangiocarcinoma.
   UTD: The true prevalence of UC in PSC is probably closer to 90%.

Question 46

16. Gauchers, hepatosplenomegaly:
17. This is consistent with Gauchers
18. Involves the heart

Answer 46

1. This is consistent with Gauchers - T - results from lack of the lysosomal enzyme glucosylceramidase and accumulation of glucosylceramide in mononuclear phagocytic cells. In the most common, type I variant, affected phagocytes become enlarged (Gaucher cells) and accumulate in the liver, spleen, and BM, causing HSM and bone erosion. Type II and III have variable neuronal involvement.

Question 47

17. Myelofibrosis, patient with hepatosplenomegaly:
18. Typical finding

Answer 47

Primary myelofibrosis / chronic idiopathic myelofibrosis = chronic myeloproliferative disorder. Get chronic myeloproliferation and atypical megakaryocytic hyperplasia. Secondary process of bone marrow fibrosis from nonclonal fibroblastic proliferation and hyperactivity induced by growth factors abnormally shed from clonally expanded megakaryocytes.
S&S: severe fatigue. Splenomagaly (marked). Hepatomegaly. Extramedullary hematopoiesis. Osteosclerosis. periostitis. Secondary gout.

Question 48

18. Epidemiology and incidence of hepatoma:
19. Hep B

Answer 48

Liver cancer 4x leading cause of cancer-related death in the world. The number of deaths / yr = incidence throughout world (ie: if you get it, you probably die from it).
High incidence regions: sub-Saharan Africa, China, Hong Kong, Taiwan.
Intermediate regions: western Europe, Thailand, indonesia, Jamaica(man), Haiti, New Zealand (Maoris), Alaska (Eskimos).
Low incidence regions: North/South America. Most of Europe and parts of Middle East.
Men > Female 4:1.
Majority of HCC’s occur in patients with chronic liver disease or cirrhosis. Men age 50-60yo, however in sub-Saharan Africa the mean age of presentation of HCC is decreasing (mean 33yo at presentation).
Risk Factors: HBV carrier state. HCV (~33% cases). Hereditary hemochromatosis, and cirrhosis of almost any cause. Environmental toxins (Aflatoxin, Betel nut chewing, contaminated drinking water [Microcystin algae]).

Question 49

19. Which doesn’t cause pancreatitis:
20. Divisum
21. Idiopathic
22. Hereditary
23. Rheumatic fever
24. Hypercalcaemia

Answer 49

4. Rheumatic fever - F - acute rheumatic fever [ARF] is a delayed, nonsuppurative sequela of a pharyngeal infection with gpA strep. Pharyngitis usually occurs 2-4wks before onset of ARF. Get arthritis, carditis, valvulitis, CNS involvement (Sydenham chorea), rash (subcut nodules, erythema marginatum).
5. Which doesn’t cause pancreatitis: (TW)
6. Divisum - T - but controversial. Robbins says up to 12% (pg 907), however now questionable. See below.
7. Idiopathic - T - idiopathic 10-20%
8. Hereditary - T - familial
9. Rheumatic fever - F - acute rheumatic fever [ARF] is a delayed, nonsuppurative sequela of a pharyngeal infection with gpA strep. Pharyngitis usually occurs 2-4wks before onset of ARF. Get arthritis, carditis, valvulitis, CNS involvement (Sydenham chorea), rash (subcut nodules, erythema marginatum).
10. Hypercalcaemia - T - endocrine/metabolic - hyperlipoproteinaemia, hypercalcaemia
    UTD: It is estimated that fewer than 5% of patients with pancreas divisum develop pancreatic symptoms. The low frequency of symptoms has created a controversy as to whether PD and its associated small minor papilla orifice are ever a cause of obstructive pancreatitis. There may be a group of patients with PD who are subject to recurrent bouts of seemingly idiopathic pancreatitis.

Question 50

21. 32 yo African with 5cm mass invading IVC, non cirrhotic liver, Which is the most likely?
22. HCC in early stages of Hep B
23. Atypical for HCC
24. In absence of alfatoxin exposure HCC would be unlikely
25. Cholangiocarcinoma should be considered
26. Leishmaniasis should be considered

Answer 50

Answer: In absence of aflatoxin exposure, HCC would be unlikely.

ROBBINS
Highest incidences of HCC in southeast China, Korea, Taiwan, sub-subharan countries.
In these countries, HBV is transmitted VERTICALLy and carrier states start in INFANCY.
Peak incidence between 20-40 years of age, and in almost 50% of cases, the amor appears in the absence of cirrhosis.

Therefore
- HCC in early stages of HBV is false as carrier states start in infancy.
- Atypical of HCC is false as this is a typical presentation in the demographic
- Cholangiocarcinoma should be considered is false as wrong age and would be late stage if IVC invasi
- Leishmaniasis should be considered is false as it causes hepatomegaly, can cause liver nodules.

Question 51

22. Cholangiocarcinoma – most likely sites of spread:
23. Haematogenous to bone (vert bodies commonly) lungs and brain
24. Lungs, peritoneum and lymph nodes
25. Haematogenous to lungs, liver and adrenal

Answer 51

Answer: Lungs, peritoneum, and Lymph nodes.

ROBBINS
Cholangiocarcinoma is the 2nd most common primary malignant tumor of the liver after HCC.
Is a malignancy of the biliary tree, arising within and outside the liver.
All risk factors cause chronic inflammation and cholestasis. Of note is infestation by liver flukes.
Extrahepatic forms include Klatskin tumors (50-60% of all cholangiocarinomas).

Intrahepatic cholangiocarcinoma occurs in the non-cirrhotic liver, and may track along the intrahepatic portal tract system creating a branching tumor within a portion of liver.

STATDX
Patterns of disease progression
- Local extension along bile duct
- Local infiltration of liver parenchyma
- Spread to regional lymph nodes; porta heaptis, paracelia, and peripancreatic lymph node
- Perineural spread
- Intraperiteonal spread
- Hematogenous spread (lungs, bones, vertebrae, adrenal glands, brain).

Question 52

23. ER / MRCP demonstrates irregular bile ducts, least likely cause:
24. Crohn’s
25. Hepatic artery injection with cytotoxins
26. SLE
27. Caroli’s
28. Biliary stone

Answer 52

3. SLE - F - primary biliary cirrhosis is associated with autoimmune disorders (RA, Hashimoto’s, Sjorgren’s, scleroderma, membranous GN, coeliac disease). However, an association between PBC and SLE is rare. There are case reports of SLE patients with autoimmune cholangiopathy [Liver 2002] or PSC [Digestive diseases 2004].
   *LW: agree SLE relatively rarely involves the liver and when it does gives a more hepatitic picture, rather than a biliary pitcture.
4. ER / MRCP demonstrates irregular bile ducts, least likely cause: (GC)
5. Crohn’s - T - PSC is strongly associated with IBD, although more commonly UC.
6. Hepatic artery injection with cytotoxins - T - hepatic a. infusion of chemo agents such as floxuridine for palliative therapy for pts with colorectal liver mets. High rate of extraction on first pass through the liver, producing an inflammatory fibrosing process about the portal triads that simulates PSC. Mechanism is either direct effect of treatment or ischaemia secondary to thrombosis of the intrahepatic arterial branches.
7. SLE - F - primary biliary cirrhosis is associated with autoimmune disorders (RA, Hashimoto’s, Sjorgren’s, scleroderma, membranous GN, coeliac disease). However, an association between PBC and SLE is rare. There are case reports of SLE patients with autoimmune cholangiopathy [Liver 2002] or PSC [Digestive diseases 2004].
8. Caroli’s - T - segmental saccular / fusiform / beaded dilatation of IHBDs that retain a communication with the biliary tree.
9. Biliary stone - T - ascending cholangitis secondary to stone, may mimic PSC.
   [Robbins; Dahnert; PSC RG 2000]

Question 53

24. Middle aged man with 5cm solid lesion in the tail of the pancreas / splenic hilum and enlarged coeliac lymph nodes; most likely diagnosis:
25. Lymphoma
26. Pancreatic adenoCa
27. Serous cystadenoma
28. Mucinous cystadenocarcinoma

Answer 53

2. Pancreatic adenoCa - T - males (2:1) >60yo.; size ranges from 2-10cm (40% are 4-6cm); advanced local disease or mets in 2/3 of pts at presentation (21% have localised disease with regional nodes - pancreaticosplenic, pancreaticoduodenal, SMA). This would be stage II disease (I confined to pancreas; II + regional nodes; III + distant spread).
3. Middle aged man with 5cm solid lesion in the tail of the pancreas / splenic hilum and enlarged coeliac lymph nodes; most likely diagnosis: (GC)
4. Lymphoma - F - lymphoma is in the differential, however, primary lymphoma arising in the pancreas and/or peripancreatic LNs is rare, accounting for ~1% of NHL and <0.7% of all pancreatic malignancies. [Pancreas 2004]
5. Pancreatic adenoCa - T - males (2:1) >60yo.; size ranges from 2-10cm (40% are 4-6cm); advanced local disease or mets in 2/3 of pts at presentation (21% have localised disease with regional nodes - pancreaticosplenic, pancreaticoduodenal, SMA). This would be stage II disease (I confined to pancreas; II + regional nodes; III + distant spread).
6. Serous cystadenoma - F - more common in females (4:1) >60yo.; 70% in head/neck; may be microcystic or unilocular (lobulated contour); amorphous calcification in 40%; central stellate scar in 15%.
7. Mucinous cystadenocarcinoma - F - more common in females (19:1) 40-60yo.; >90% in body/tail; macrocystic, thick-walled; eggshell calcification in 20%. CEA, CA15-3 may be raised.

Question 54

25. Intraductal mucinous pancreatic lesion – most typical:
26. No such type
27. Common in young girls
28. Common in pancreatic tail
29. Common in pancreatic head

Answer 54

4. Common in pancreatic head - T - head/neck&raquo_space; body/tail. Septated cystic lesion and communication with main duct via a narrow neck suggest a branch duct-type IPMN.
5. Intraductal mucinous pancreatic lesion – most typical: (GC)
6. No such type - F
7. Common in young girls - F - more common in older patients, M>F (in general).
8. Common in pancreatic tail - F
9. Common in pancreatic head - T - head/neck&raquo_space; body/tail. Septated cystic lesion and communication with main duct via a narrow neck suggest a branch duct-type IPMN.

Main duct IPMN may occur in a diffuse or segmental pattern.
Branch duct IPMN occurs in uncinate process&raquo_space; tail > body; usually communicates with main duct via a narrow neck; may have internal septations.
Spectrum: adenoma - borderline - in situ/invasive Ca
Features suggestive of invasive tumour:
- main duct involvement, marked dilatation of main duct, diffuse/multifocal involvement
- large mural nodule or solid mass, irregular thick wall.
Note that all are considered premalignant. A small lesion in the tail may be managed with distal pancreatectomy, cf. main duct or lesion in the head (Whipple’s).
[IPMN RG 2005]

Question 55

26. Causes of fatty change in liver: Which is false?
27. Smoking
28. DM
29. Pregnancy
30. Obesity
31. Hypoxia

Answer 55

1. Smoking

Insulin resistance has a key role in the development of hepatic steatosis, and potentially, steatohepatitis. Obesity and type 2 DM, conditions assoc with peripheral insulin resistance, are frequently observed in patients with NAFLD.
Obstructive sleep apnoea has been proposed to have a role in inducing inflammation in NAFLD. Chronic intermittent hypoxia (in mice) showed signs of liver injury and lipid peroxidation.
Acute fatty liver of pregnancy: microvesicular fatty infiltration of hepatocytes. Thought related to inherited enzyme deficiency in beta-oxidation.

Question 56

27. Capillary and cavernous haemangioms, which is true:
28. Giant haemangioma causes low platelets and bleeding tendency’
29. Cavernous better circumscribed than capillary
30. Capillary not a recognized entity in liver

Answer 56

Answer: Giant hemangioma causes low platelets and bleeding tendency (true)

ROBBINS
Capillary hemangiomas
- most common hemanigoma, found in skin, s/c tissue, mucous membranes, liver, spleen, kidneys.
- composed of thin-walled capillaries with scant stroma

Cavernous hemangiomas
- frequently involve deep structures and do not spontaneously regress.
- are a component of von Hippel-Lindau disease
- composed of large, dilated vascular channels, unencapsulated and infiltrative.

RADIOPAEDIA/STATDX
Giant hemangioma
- aka giant hepatic venous malformations
- atypical hepatic hemangioma >10 cm in diameter
- may contain areas of central necrosis/liquefaction, haemorrhage, peripheral calcification, fibrosis and thrombosis.
- complications include mass effect, Kasabach-Merritt syndrome, rupture with haemoperitoneum

Kasabach-Merritt syndrome
- hemangioma thrombocytompenia syndrome
- rare life-threatening disease found in infants in which a rapidly growing vascular tumor is responsible for thrombocytopenia, microagniopathic haemolytic anemia, and consumptive coagulopathy.

Question 57

28. Cystic Fibrosis: (multiple true)
29. Late onset recognized as ‘chronic’ pancreatitis
30. If significant liver disease, consider alternative diagnosis
31. Mg co factor for Cl channel
32. Does not present with liver disease

Answer 57

28. Cystic Fibrosis: (TW & GC)
29. Late onset recognized as ‘chronic’ pancreatitis - T - An increased prevalence of CFTR mutations has been observed in pts with idiopathic chronic and acute pancreatitis. With increased CFTR, get other abnormalities. Late presenters / non-classic CF tend to have some functioning CFTR cf classic CF (NEJM, UTD). “Idiopathic” chronic pancreatitis occurs in a subset of patients with pancreas-sufficient CF and is associated with recurrent abdominal pain with life-threatening complications. [Robbins]
30. If significant liver disease, consider alternative diagnosis - F - although may remain symptomatic till late in disease process, can lead to fibrosis and cirrhosis (esp. now with improved life expectancy). See ans 4.
31. Mg co factor for Cl channel - T - Regulation of the CFTR channel gating is unusually complex. It requires phosphorylation by protein kinase C and protein kinase A, and binding a hydrolysis of ATP in the presence of Mg2+ by the two nucleotide binding domains.
32. Does not present with liver disease - ?T - liver disease in CF can often be difficult to Dx as patients may remains asymptomatic until late in the disease process. In the liver CFTR is located in the biliary epithelium. Get thick tenacious bile with blockage if the intrahepatic bile ducts. Lead to progressive fibrosis and eventually cirrhosis.

Question 58

29. ?A liver mass
30. Involves portal / hepatic veins, choriocarcinoma most likely
31. HCC and cirrhosis can elevate AFP

Answer 58

2. HCC and cirrhosis can elevate AFP
3. ?A liver mass (TW)
4. Involves portal / hepatic veins, choriocarcinoma most likely - F - not most likely (mets, or HCC: 25-48% invade). Vascular encasement by tumor (mass-forming type) is common, but grossly visible intravascular tumor thrombosis is rare. Klatskin tumors (indirect signs) pressure effect / encasement / invasion / obliteration of portal vein and hepatic artery.
   *LW: potentially poor recall as questions states choriocarcinoma (i.e. reproductive germ cell) which can metastasize to liver and is vascular. While theme would suggest cholangiocarcinoma, which can invade but occurs later in disease> i.e. T2 stage.
5. HCC and cirrhosis can elevate AFP
   AFP is a glycoprotein that is normally produced during gestation by the fetal liver and yolk sac. Serum concentration of AFP is often elevated in patients with HCC, although the serum levels of AFP do not correlate well with other clinical HCC, such as size, stage, or prognosis. Not all tumors secrete AFP and serum concentrations are normal in up to 40% of small HCC.
   Elevated serum AFP occurs in pregnancy, with tumors of gonadal origin, and may be seen in patients with chronic liver disease without HCC such as acute or chronic viral hepatitis.
   AFP may be slight higher in patients with cirrhosis due to hepatitis C.

Question 59

30. Dilated pancreatic duct of uncinate process “? IPMN”; which is most likely in a middle aged female patient:
31. Good age
32. No such diagnosis, clinicians mean cystic
33. Bad age / site
34. Is a macroscopic diagnosis
35. Uncommon not to involve main duct

Answer 59

4. Is a macroscopic diagnosis - T - Following CT or abdo US, one or more additional tests such as ERCP, MRCP, EUS, pancreatoscopy are usually required to make the diagnosis. ERCP and pancreatoscopy for Dx benign from malignant tumors (UTD). To diagnose, must detect endoscopically or radiologically or see gross cyst or mass (Path outlines).
5. Dilated pancreatic duct of uncinate process “? IPMN”; which is most likely in a middle aged female patient: (TW)
6. Typical age - F - most commonly between ages 60-70. M>F for the more common main duct type of IPMN (75% IMPNs), however the branch type IMPNs occur in younger patients and involve uncinate process (~55yo).
7. No such diagnosis, clinicians mean cystic - F
8. Atypical site for age - F - although IPMNs usually involve main pancreatic duct, and majority in the head, IPMNs in younger patients arise in the uncinate process (~55yo).
9. Is a macroscopic diagnosis - T - Following CT or abdo US, one or more additional tests such as ERCP, MRCP, EUS, pancreatoscopy are usually required to make the diagnosis. ERCP and pancreatoscopy for Dx benign from malignant tumors (UTD). To diagnose, must detect endoscopically or radiologically or see gross cyst or mass (Path outlines).
10. Common not to involve main duct - F - IPMNs classified and main duct type and branch duct type. MDT comprise ~75% of all IMPNs.

Question 60

32. Cholangiocarcinoma with in-drawing of liver capsule, why, cause?
33. Peripheral venous infarction
34. Invasion of artery ?hepatic
35. Chronic biliary obstruction with atrophy
36. Cirrhosis

Answer 60

*LW:
“Capsular hepatic retraction found in approx. 20% cholangiocarcinomas, and is thought to be the result of prominent tumoral fibrous stroma, whereas segmental hepatic parenchymal atrophy is due to both chronic bile duct obstruction and portal invasion”.

Cholangiocarcinoma rare in cirrhosis, while peripheral cholangiocarcinoma commonly shows retraction.
Likely poor recall given above pathophysiology, as tumoral scar / fibrosis is cause of capsular retraction.
If was asking regarding hepatic atrophy then answer 3 would be most likely.

4. Cirrhosis - T

Cholangiocarcinoma is rare in cirrhosis. In rare cases, intrahepatic cholangiocarcinoma causes lobar or segmental atrophy when it invades and obstructs the corresponding portal vein.

Radiographics 2002: Frequently noted ancillary findings in peripheral cholangiocarcioma include capsular retraction and dilatation and thickening of the peripheral intrahepatic bule ducts (especially when associated with clonorchiasis - liver fluke).

Radiographics 2009: Cholangiocarcinoma arising from a cirrhotic liver may be surrounded by a fibrotic pseudocapsule, which is an unusual finding in a cholangiocarcinoma arising from a noncirrhotic liver. In such cases, capsular retraction is noted along the tumor surface. This capsular retraction may be seen in some HCC’s with cirrhotic stroma but is more suggestive of cholangiocarcinoma.

Question 61

33. Cholecystitis:
34. 70% at 80 years
35. Chronic form: can x3 wall thickness
36. GB Ca high?
37. 1% per year

Answer 61

4. 1% per year - T - … of patients with cholelithiasis become symptomatic.

*LW:
Robbins states wall is variably thickened, rarely to more than 3x normal. So technically can have wall thickness 3x normal but rare,

33. Cholecystitis: (GC)
34. 70% at 80 years - F - 30%
35. Chronic form: can x3 wall thickness - ?F - morphologic changes are extremely variable and sometimes minimal; mere presence of stones (even in absence of acute inflam) is often sufficient to make the diagnosis; GB may be contracted, normal size, or enlarged; mucosal ulceration s infrequent, submucos and subserosa often thickened from fibrosis.
36. GB Ca high - F - rarely there is extensive dystrophic calcification in the wall (porcelain GB); this has a markedly increased incidence of GB Ca.
37. 1% per year - T - … of patients with cholelithiasis become symptomatic.

Question 62

34. Caroli’s disease, which is least correct:
35. Hepatic fibrosis
36. Kidney → cysts
37. ?Mass in liver
38. Communicating cysts
39. Autosomal recessive

Answer 62

1. Hepatic fibrosis - F - Caroli disease involves large IHBDs, without fibrosis. Congenital hepatic fibrosis involves small ducts with fibrosed portal tracts (seen in, but not pathognomonic for, ARPKD). Caroli syndrome affects ducts at all levels, and is histologically identical to CHF.
   Histochemical studies of CHF and Caroli disease show considerable overlap. Some investigators have hypothesized they represent a spectrum of portal tract malformations (ie. ductal plate malformation), with one end being portal fibrosis with normal-calibre ducts (CHF) and the other end being pure ductal

**LJS:
Caroli syndrome = Caroli disease + hepatic fibrosis
Caroli disease belongs to spectrum of fibropolycystic liver disease, caused by in utero malformation of ductal plate. Congenital hepatic fibrosis is part of this spectrum. Caution with wording

Caroli’s disease, which is least correct: (GC)
1. Hepatic fibrosis - F - Caroli disease involves large IHBDs, without fibrosis. Congenital hepatic fibrosis involves small ducts with fibrosed portal tracts (seen in, but not pathognomonic for, ARPKD). Caroli syndrome affects ducts at all levels, and is histologically identical to CHF.
Histochemical studies of CHF and Caroli disease show considerable overlap. Some investigators have hypothesized they represent a spectrum of portal tract malformations (ie. ductal plate malformation), with one end being portal fibrosis with normal-calibre ducts (CHF) and the other end being pure ductal dilatation with no portal fibrosis (Caroli disease). [ARPKD RG 2000]
2. Kidney → cysts - T - associated with medullary sponge and infantile PCKD.
3. ?Mass in liver - T - increased risk for cholangiocarcinoma (7%); mass-forming subtype is most common (others: periductal infiltrating, intraductal).
4. Communicating cysts - T - communicating cavernous ectasia of intrahepatic ducts. Cysts of von Meyenburg complex (biliary hamartomas) and polycystic liver disease are non-communicating.
5. Autosomal recessive - T - results from the arrest/derangement of the normal embryologic remodeling of ducts.
Clinical features reflect recurrent bouts of cholangitis due to bile stasis, including recurrent attacks of RUQ pain, fever, and, more rarely, jaundice.
Imaging studies show intrahepatic saccular or fusiform dilated cystic structures of varying sizes that communicate with the biliary tree. The “central dot sign” is considered highly suggestive of Caroli disease; produced by enhancing portal branches surrounded by cystic alterations of the IBHDs. Intraluminal biliary calculi may be demonstrated as well. [Pancreatic & Biliary congenital anomalies RG 2006]
Added options 4 and 5, changed Qu to “least correct”

Question 63

1. Small cyst in the tail of a pancreas of a male, most likely:
2. serous tumour
3. mucinous tumour
4. intraductal papillary mucinous tumour
5. adenocarcinoma
6. pseudocyst

Answer 63

**LJS - without any other info (age, prior hx pancreatitis, evidence chronic pancreatitis, size of cyst) I would probably go side branch IPMN. This is what we report in practice all the time.

*LW: ongoing theme of agreement, without any other discriminators, I would favor side branch IPMN. Technically pseudocyst is a walled off fluid collection most commony outside the pancreatic parenchyma with a defined wall. IPMNs although most common in head, do also occur in the tail, with variable gender predominance either slightly male or equal depending on geography.

5. pseudocyst - T - most common and most frequently encountered unilocular cystic lesion. A unilocular cyst in a patient with a clinical hx of pancreatitis is almost always a pseudocyst. Supportive fx: pancreatic inflam, atrophy or calcs; dilatation of / calculi in thin-walled duct.
   [Dahnert; Cystic pancreatic lesions RG 2005]
6. Small cyst in the tail of a pancreas of a male, most likely: (GC)
7. serous tumour - F - more common in females (4:1) >60yo.; 70% in head/neck; may be microcystic or unilocular (lobulated contour); amorphous calcification in 40%; central stellate scar in 15%.
8. mucinous tumour - F - more common in females (19:1) 40-60yo.; >90% in body/tail; macrocystic, thick-walled; eggshell calcification in 20%. CEA, CA15-3 may be raised.
9. intraductal papillary mucinous tumour - F - more common in elderly M>F, and in head/neck (in general). Main duct IPMN may occur in a diffuse or segmental pattern - the latter may appear as a cyst in the body/tail with normal remaining parenchyma. Branch duct IPMN occurs in uncinate process&raquo_space; tail > body; may manifest as a unilocular cyst - septations and communication with main duct via a narrow neck suggest IPMN. Note that although all are considered premalignant, a small lesion in the tail may be managed with distal pancreatectomy cf. a lesion in the head (Whipple’s).
10. adenocarcinoma - F - more common in males (2:1) >60yo. but usually solid, scirrhous (hypovascular). A post obstructive pseudocyst may be seen in a minority.
11. pseudocyst - T - most common and most frequently encountered unilocular cystic lesion. A unilocular cyst in a patient with a clinical hx of pancreatitis is almost always a pseudocyst. Supportive fx: pancreatic inflam, atrophy or calcs; dilatation of / calculi in thin-walled duct.
    [Dahnert; Cystic pancreatic lesions RG 2005]

Question 64

2. HCC and HBV, which is false:
3. Arise de novo
4. Earlier in children
5. 1/3 in non cirrhotic liver
6. fibrolamellar not associated with HBV

Answer 64

1. Arise de novo - F - pathogenesis remains uncertain; in most cases, HCC develops from small-cell, high-grade dysplastic nodules in cirrhotic livers. HBV causes chronic hepatitis in 4% of patients; of these, cirrhosis develops in 20-30%. The risk of HCC is 0.02% per year for chronic hep B, and 2.5% per yr when cirrhosis has developed. Note that neither HBV or HCV contain oncogenes; tumorigenic capacity probably relates to their capacity to cause continuing cell death, chronic inflammation, and regeneration.
2. HCC and HBV, which is false: (GC)
3. Arise de novo - F - pathogenesis remains uncertain; in most cases, HCC develops from small-cell, high-grade dysplastic nodules in cirrhotic livers. HBV causes chronic hepatitis in 4% of patients; of these, cirrhosis develops in 20-30%. The risk of HCC is 0.02% per year for chronic hep B, and 2.5% per yr when cirrhosis has developed. Note that neither HBV or HCV contain oncogenes; tumorigenic capacity probably relates to their capacity to cause continuing cell death, chronic inflammation, and regeneration.
4. Earlier in children - T - highest incidences of HCC are found in Asian and African countries in which HBV is transmitted vertically. In these instances, the carrier state begins in infancy and produces a high rate of chronic infection. HCC (of all causes) is the second most common paediatric hepatic malignancy, occurs in children >5yo. (most common is hepatoblastoma, <3yo).
5. 1/3 in non cirrhotic liver - T - only 10-20% of all HCC occurs in non cirrhotic livers, except for some groups of African blacks, where about 40% of HCCs are found in otherwise normal livers. The age of these pts is lower than with cirrhotic livers, with a peak in the 3rd decade. Aetiology remains unclear; suggested that oestrogens play a role. Other possible factors include ethanol abuse, hep B, pesticides, environmental toxins and cigarettes. [Malignant Liver Tumours, Y.Fong 2003].
6. fibrolamellar not associated with HBV - T - distinctive clinicopathologic variant of HCC; occurs in young adults (20-40yo. M=F). No association with cirrhosis or other risk factors (no known RFs).

Question 65

3. GB cancer - which is most correct:
4. 5 year survival less than 10%
5. <1% associated with gallstones
6. involve the lateral wall
7. lymphatic is the most common mode of spread

Answer 65

1. 5 year survival less than 10% - T - dismal prognosis, with 5YS of around 5%. Mets in 75% at time of dx.
2. GB cancer - which is most correct: (GC)
3. 5 year survival less than 10% - T - dismal prognosis, with 5YS of around 5%. Mets in 75% at time of dx.
4. <1% associated with gallstones - F - gallstones are present in 60-90% of cases. But Ca occurs in only 1% of patients with gallstones.
5. involve the lateral wall - F - infiltrating more common (cf. exophytic), usually appears as a poorly defined area of diffuse thickening and induration of GB wall that may cover several square cm’s or involve the entire GB. Majority occur in fundus (60%), body 30%, neck 10%.
6. lymphatic is the most common mode of spread - F - direct extension - to liver, duodenum, colon, pancreas… Reasons: thin GB wall with only a single muscle layer, no substantial lamina propria, perimuscular connective tissue is continuous with the interlobular CT of liver. Lymphatic spread and intraperitoneal seeding are common > haematogenous > neural > intraductal.

Question 66

4. HCC – not sure what the question is.
5. Beta-hCG
6. Alcohol
7. Cyclosporine
8. AFP

Answer 66

4. AFP

AFP is a glycoprotien that is normally produced during gestation by the fetal liver and yolk sac. Serum concentration of AFP is often elevated in patients with HCC, although the serum levels of AFP do not correlate well with other clinical HCC, such as size, stage, or prognosis. Not all tumors secrete AFP and serum concentrations are normal in up to 40% of small HCC.
Elevated serum AFP occurs in pregnancy, with tumors of gonadal origin, and may be seen in patients with chronic liver disease without HCC such as acute or chronic viral hepatitis.
AFP may be slight higher in patients with cirrhosis due to hepatitis C.

Question 67

5. Rheumatoid arthritis and auto-immune hepatitis
6. non-dilated ducts and acute hepatitis

Answer 67

5. Rheumatoid arthritis and auto-immune hepatitis (TW)
6. non-dilated ducts and acute hepatitis - T - see below.
   Autoimmune hepatitis is a chronic hepatitis of unknown aetiology characterised by immunologic and autoimmunologic features (remember PBC AMA, PSC ANCA, AIH ASMA and ANA).
   Histo is nonspecific: portal mononuclear cell infiltrate; piecemean necrosis which essentially spares the biliary tree buy may involve more of the lobule; destructive and nondestructive cholangitis and ductopenia in 25% patients; plasma cell infiltrate; fibrosis in all but the mildest forms of AIH.
   AIH (esp type 2) is associated with a multiple other disorders; most are immunologic in origin.

Question 68

6. which doesn’t cause pancreatitis
7. pagets
8. trauma
9. CBD inspisation
10. Hyperparathyroidism
11. Virus

Answer 68

1. Pagets - F
2. Which doesn’t cause pancreatitis: (TW)
3. Pagets - F
4. trauma - T
5. CBD inspisation - T
6. Hyperparathyroidism - T - Endocrine/metabolic - hyperlipoproteinaemia, hypercalcaemia, uraemia, DKA
7. Virus - T - Infection - bacterial, viral, parasitic (mumps, coxsackie, mycoplasma, ascaris, Clonorchis)

Question 69

8. Man from middle east with schistosomiasis:
9. Periportal fibrosis
10. ureteric fibrosis
11. Cirrhosis

Answer 69

2. ureteric fibrosis - T - S. haematobium most common in Middle East; causes GU disease. Eggs laid in bladder wall incite a granulomatous response with chronic inflammation and subsequent fibrosis. Granulomatous cystitis, bladder wall calcification and bladder calculi (also seminal vesicle and distal ureteric calcifn), distal ureteric strictures (cobra-head pseudoureterocoele in VUJ region), pseudopolyps and ureteritis cystica. Reduced bladder capacity in fibrotic stage. SCC of bladder after 20-30yr latency period.
3. Man from middle east with schistosomiasis: (GC)
4. Periportal fibrosis T- cause ‘pipestem’ fibrosis.
5. ureteric fibrosis - T - S. haematobium most common in Middle East; causes GU disease. Eggs laid in bladder wall incite a granulomatous response with chronic inflammation and subsequent fibrosis. Granulomatous cystitis, bladder wall calcification and bladder calculi (also seminal vesicle and distal ureteric calcifn), distal ureteric strictures (cobra-head pseudoureterocoele in VUJ region), pseudopolyps and ureteritis cystica. Reduced bladder capacity in fibrotic stage. SCC of bladder after 20-30yr latency period.
6. Cirrhosis - T –
7. • Infectious cycle: fresh water snails release cercarial form into water; cercarie are mobile and penetrate human skin or mucosa, enter circulation, pass through lungs and lodge in hepatic branches of portal vein; mature into adults, copulate and migrate to colonic and rectal submucosa where female releases ova that enter colonic lumen, are defecated, and infect other snails; ova may also enter portal circulation and cause periportal fibrosis.
   [Dahnert; Path outlines]

Question 70

9. 6cm calcified cyst in liver –
10. Boy who plays with sheep or dog
11. Ate wild boar with muscle calcifications

Answer 70

1. Boy who plays with sheep or dog - T - (play, or “play”). Echinococcus granulosus (more common) and echonococcus multilocularis. Note that calcification usually requires 5-10y to develop. Calcification occurs in 10-33% and is in the pericyst (unless dead parasite in which calcification occurs in all layers). See below.
2. 6cm calcified cyst in liver – (TW)
3. Boy who plays with sheep or dog - T - (play, or “play”). Echinococcus granulosus (more common) and echonococcus multilocularis. Note that calcification usually requires 5-10y to develop. Calcification occurs in 10-33% and is in the pericyst (unless dead parasite in which calcification occurs in all layers). See below.
4. Ate wild boar with muscle calcifications - F (less true) - humans become T.solium tapeworm carriers by ingesting undercooked pork contain cysticerci in muscle tissue (crunchy steak). Cystercicosis is caused by larval stage of T. solium(ie calcifications) is from eating the turds of infected humans (ie human tapeworm carriers), however auto-inoculation can occur (hence “less true”). Cysticercosis should be viewed as a disease largely transmitted from person-to-person, with infected pigs as perpetuators of infection. See below.

Question 71

10. Regarding necrosis, which is the most correct:
11. Liquefactive necrosis is a characteristic of ischaemic destruction of cardiac muscle
12. Councilman bodies in the liver in toxic or viral hepatitis is an example of apoptosis
13. The dead cell usually shows decreased eosinophilia
14. Caseous necrosis is encountered principally in the centre of an Aschoff nodule
15. Expansion of the nucleus of dead cells with unravelling of the chromatin is called pyknosis

Answer 71

2. Councilman bodies in the liver in toxic or viral hepatitis is an example of apoptosis – T – cell injury in certain viral diseases, eg viral hepatitis, in which apoptotic cells in the liver are known as Councilman bodies
3. Regarding necrosis, which is the most correct: (TW)
4. Liquefactive necrosis is a characteristic of ischaemic destruction of cardiac muscle – F – coagulative necrosis. Implies preservation of basic outline of the coagulated cell for a span of at least some days. MI is an excellent example in which acidophilic, coagulated, anucleated cells may persist for weeks.
5. Councilman bodies in the liver in toxic or viral hepatitis is an example of apoptosis – T – cell injury in certain viral diseases, eg viral hepatitis, in which apoptotic cells in the liver are known as Councilman bodies.
6. The dead cell usually shows decreased eosinophilia – F – increased eosinophilia. Attributable in part to loss of the normal basophilia imparted by the RNA in the cytoplasm and in part to the increased binding of eosin to denatured intracytoplasmic proteins.
7. Caseous necrosis is encountered principally in the centre of an Aschoff nodule – F – Aschoff body (or nodule) is in rheumatic fever (foci of fibrinoid degeneration).
8. Expansion of the nucleus of dead cells with unravelling of the chromatin is called pyknosis – F – pynkosis: nuclear shrinkage and increased basophilia. Karyolysis: basophilia of chromatin may fade. Karyorrhexis: pnknotic or partially pnknotic nucleus undergoes fragmentation.

Question 72

1. Regarding haemochromatosis, which is least correct:
2. Autosomal dominant C282Y mutation is most common
3. Less common in females
4. Accumulation is life long
5. Effects are due to direct toxic effect of iron on cells
6. End stage cirrhosis and hyperbilirubinaemia

Answer 72

1. Autosomal dominant C282Y mutation is most common - F - most common form is an AR disease of adult onset caused by mutations in the HFE gene (located on short arm of chromosome 6). Two common mutations in the HFE gene: C282Y and H63D. Carrier frequency in Causasians of the C282Y mutation is 1 in 70, and homozygotes 1 in 200. Approx 80% of haemochromatosis pts are homozygous for the C282Y mutation.
2. Regarding haemochromatosis, which is least correct: (GC)
3. Autosomal dominant C282Y mutation is most common - F - most common form is an AR disease of adult onset caused by mutations in the HFE gene (located on short arm of chromosome 6). Two common mutations in the HFE gene: C282Y and H63D. Carrier frequency in Causasians of the C282Y mutation is 1 in 70, and homozygotes 1 in 200. Approx 80% of haemochromatosis pts are homozygous for the C282Y mutation.
4. Less common in females - T - males predominate (5-7:1), with slightly earlier clincal presentation, partly because physiologic iron loss retards Fe accumulation in women.
5. Accumulation is life long - T - Fe accumulates over the lifetime of an individual from excessive intestinal absorption.
6. Effects are due to direct toxic effect of iron on cells - T - by the following mechanisms: lipid peroxidation by iron-catalyzed free-radial reactions; stimulation of collagen formation; direct interactions of iron with DNA.
7. End stage cirrhosis and hyperbilirubinaemia - T - iron accumulation - haemosiderin granules in cytoplasm of periportal hepatocytes (stain blue with Prussian blue) - progressive involvement of lobule, bile duct epithelium and Kupffer cell pigmentation - fibrous septa form - micronodular cirrhosis. High bilirubin is due to impaired secretion of conjugated bilirubin into bile.
   [Robbins; eMedicine]

Question 73

4. What does not cause chronic pancreatitis:
5. Alcohol
6. Cholelithiasis.
7. Divisum
8. Hypercalcaemia
9. Hyperinsulinaemia

Answer 73

5. Hyperinsulinaemia
6. What does not cause chronic pancreatitis: (–) (TW)
7. Alcohol
8. Cholelithiasis.
9. Divisum (controversial, see below)
10. Hypercalcaemia
11. Hyperinsulinaemia
    Predisposing factors
    • More commonly middle-aged male alcoholic than gallstone disease
    • Also hypercalcaemia and hyperlipoproteinaemia
    • Structural anomaly - 12% (Pancreas divisum with anomalous duct system or stricture at Ampulla)
    • Maybe familial - Familial hereditary pancreatitis - begins in childhood & predisposes to carcinoma in later years
    • Nonalcoholic tropical pancreatitis
    • Idiopathic - 40% - no recognizable predisposing factors
    UTD: It is estimated that fewer than 5% of patients with pancreas divisum develop pancreatic symptoms. The low frequency of symptoms has created a controversy as to whether PD and its associated small minor papilla orifice are ever a cause of obstructive pancreatitis. There may be a group of patients with PD who are subject to recurrent bouts of seemingly idiopathic pancreatitis.

Question 74

6. Following are true of pancreatic carcinoma (except):
7. Most arise from duct epithelium
8. Most are incurable
9. Insidious
10. Risk factors include smoking diet and exogenous chemical
11. 45% involve the body and the tail
12. May secrete mucin.

Answer 74

Answer: 45% involve the body and tail (false)

ROBBINS
Invasive pancreatic cancers arise from well-defined non-invasive precursor lesions in small ducts referred to as pancreatic intraepithelial neoplasia.

Epidemiology
- disease of older adults with 80% occurring 60-80 years old
- blacks and Ashkenazi Jews
- strongest environmental influence is cigaret smoking (doubles risk)
- other risk factors: DM, obesity, diet rich in fat/proteins, family history, hereditary syndromes (BRCA2, HNPCC, Peutz Jeghers syndrome)

Is insidious (remains silent) until they invade into the adjacent structures.

60% arise in head of gland.
20% diffusely involves the entire gland
15% in body, 5% in tail

The vast majority of carcinomas are ductal adenocarcinoma, that recapitulate to some degree normal ductal epithelium by forming gland and secreting mucin.

The 5-year survival rate is <5%.

Question 75

7. Alpha 1 anti-trypsin deficiency, which is incorrect:
8. Autosomal recessive
9. Von Meyenberg complexes
10. End stage get cirrhosis + cholestasis

Answer 75

Answer: Von Meyenberg complexes (False)

Von Meyenberg complexes - F = multiple bile duct hamartomas; associated with polycystic liver disease.

ROBBINS
Alpha-1 antitrypsin deficiency is an Autosome Recessive disorder of protein folding marked by very low level of circulating a1AT.

a1AT deficiency leads to the development of pulmonary emphysema because the activity of the destructive proteases is not inhibited.
It also causes liver disease as a consequence of hepatocellular accumulation of the protein.

Most common clinically significant mutation is PiZ, homozygous PiZZ genotype.

Most commonly diagnoses inherited hepatitic disorder in infants and children.

Neonatal hepatitis with cholestatic jaundice appears in 10-20% of newborns with the deficiency.
Attacks of hepatitis in adolescence can lead to cirrhosis.
Alternatively, the disease may remain silent until cirrhosis appears in middle-later life.

Question 76

1. What is not associated with clinical aspect of portal HT
2. Ascites
3. Porto systemic shunts
4. Congestive splenomegaly
5. Pancreatitis
6. Hepatic encephalopathy

Answer 76

4. Pancreatitis - F
5. What is not associated with clinical aspect of portal HT (TW)
6. Ascites - T - multifactorial.
7. Porto systemic shunts - T - shunts open with increasing portal venous pressures.
8. Congestive splenomegaly - T - venous congestion in visceral organs. Splenomegaly occurs as a result of increased splenic vein pressure.
9. Pancreatitis - F
10. Hepatic encephalopathy - T - with shunting of blood, substances that are normally removed by liver pass into the general circulation and reach the brain.

Question 77

4. 60 yo male, asymptomatic, with a pancreatic tail mass measuring 6cm, contains multiple small cysts and no solid components: most likely
5. serous tumour
6. mucinous tumour
7. intraductal papillary mucinous tumour
8. adenocarcinoma
9. pseudocyst

Answer 77

Answer: Serous tumour

ROBBINS
Serous cystic neoplasms
- aka serous cystadenomas.
- multi cystic neoplasms. Usually occur in tail.
- cysts of 1-3 mm.
- account for 25% of all cystic neoplasms
- F>M 2:1. 60-70 years old.
- most common genetic abnormality is VHL inactivation.

Mutinous cystic neoplasm
- aka mutinous cystadenoma
- large uni/multilocular cystic pancreatic neoplasm
- usually arise in the tail. Painless, slow growing.
- 95% arise in women.
- 1/3 harbor an associated invasive adenocarcinoma

Intraductal papillary mucinous tumor
- mucin producing neoplasms that involve the large ducts of the pancreas.
- M>F. usually occur in head. 10-20% multifocal.
- can progress to invasive cancer.

Pancreatic ductal adenocarcinoma
- 80% occur in 60-80 years old
- blacks and ashkenazi jews.
- smoking, obesity, DM, family history, hereditary syndromes (BRCA2, HNPCC, Puetz-Jegher)
- 60% arise in head, 20% diffuse, 15% body, 5% tail
- hard, stellate, gray-white poorly differentiated masses.

Pseudocyts
- nmost common and most frequently encountered unilocular cystic lesion. A unilocular cyst in a patient with a clinical hx of pancreatitis is almost always a pseudocyst. Supportive fx: pancreatic inflam, atrophy or calcs; dilatation of / calculi in thin-walled duct.

DAHNERT
- Microcystic = >6 cysts, each <2cm; usually serous cystadenoma
- Macrocystic = >6 cysts, each >2cm; usu mucinous cystic neoplasm or branch-IMPN
- Unilocular: <3cm almost always benign; Ddx pseudocyst, IPMN, unilocular serous cystadenoma, lymphoepithelial (eg. congenital, infectious)

Question 78

5. Cystic Fibrosis:
6. Late onset recognized as ‘chronic’ pancreatitis
7. If significant liver disease, consider alternative diagnosis
8. Mg co factor for Cl channel
9. Does not present with liver diesase

Answer 78

1. Late onset recognized as ‘chronic’ pancreatitis - T - An increased prevalence of CFTR mutations has been observed in pts with idiopathic chronic and acute pancreatitis. With increased CFTR, get other abnormalities. Late presenters / non-classic CF tend to have some functioning CFTR cf classic CF (NEJM, UTD). “Idiopathic” chronic pancreatitis occurs in a subset of patients with pancreas-sufficient CF and is associated with recurrent abdominal pain with life-threatening complications. [Robbins]
2. Cystic Fibrosis: (TW, GC)
3. Late onset recognized as ‘chronic’ pancreatitis - T - An increased prevalence of CFTR mutations has been observed in pts with idiopathic chronic and acute pancreatitis. With increased CFTR, get other abnormalities. Late presenters / non-classic CF tend to have some functioning CFTR cf classic CF (NEJM, UTD). “Idiopathic” chronic pancreatitis occurs in a subset of patients with pancreas-sufficient CF and is associated with recurrent abdominal pain with life-threatening complications. [Robbins]
4. If significant liver disease, consider alternative diagnosis - F - although may remain symptomatic till late in disease process, can lead to fibrosis and cirrhosis (esp. now with improved life expectancy). See ans 4.
5. Mg co factor for Cl channel - T - Regulation of the CFTR channel gating is unusually complex. It requires phosphorylation by protein kinase C and protein kinase A, and binding a hydrolysis of ATP in the presence of Mg2+ by the two nucleotide binding domains.
6. Does not present with liver disease - ?T - liver disease in CF can often be difficult to Dx as patients may remains asymptomatic until late in the disease process. In the liver CFTR is located in the biliary epithelium. Get thick tenacious bile with blockage if the intrahepatic bile ducts. Lead to progressive fibrosis and eventually cirrhosis

Question 79

32 With regards to cirrhosis which is false?
1. Micronodular with alcohol.
2. Macronodular with viral infections.
3. Kupffer cells involved in process.

Answer 79

32 With regards to cirrhosis which is true? (TW) ?(False)

1. Micronodular with alcohol - T - the prototype of micronodular (nodules less than 3mm) cirrhosis is alcoholic cirrhosis, but this pattern may also be observed in cirrhosis of many other causes. Can become macronodular particularly if drinking stops.
2. Macronodular with viral infections - T - macronodular cirrhosis is classically associated with chronic hepatitis (chronic viral hepatitis UTD)
3. Kupffer cells involved in process - F - Kupffer cells are specialised macrophages in liver forming part of reticulendothelial system. The hepatic stellate cell (Ito cell) is the primary source of extracellular matrix in normal and fibrotic liver.
   The morphological classification sustem for cirrhosis (macro- / micronodular) has a number of limitations and has thus largely been abandonded. It is realtively nonspecific with regard to aetiology; morphologic appearance of liver can change as disease progresses; serological markers today are more specific.

Question 80

Which is not true in regards to liver disease?
1. Peliosis seen in HIV.
2. Iron storage in Wilsons.
3. Cholangiocarcinoma is an adenocarcinoma of the bile ducts.

Answer 80

2. Iron storage in Wilsons - F - autosomal recessive defect in cellular copper transport. Decreased transport of copper from liver into bile, leading to copper excess. Normall Cu is used to form ceruloplasmin (major carrier of Cu in the blood) in liver whic his released into serum. Wilsons usually have lower ceruloplasmin levels (see below).

33 Which is not true in regards to liver disease? (TW)
1. Peliosis seen in HIV - T - Bacillary angiomatosis and peliosis hepatis have most often involved HIV-infected individuals, other immunocompromised individuals, such as cancer patient and solid organ transplant recipients have also developed these manifestation.
2. Iron storage in Wilsons - F - autosomal recessive defect in cellular copper transport. Decreased transport of copper from liver into bile, leading to copper excess. Normall Cu is used to form ceruloplasmin (major carrier of Cu in the blood) in liver whic his released into serum. Wilsons usually have lower ceruloplasmin levels (see below).
3. Cholangiocarcinoma is an adenocarcinoma of the bile ducts - T - cholangiocarcinoma is an adenocarcinoma arising from bile ducts (so don’t produce bile like hepatocytes). Gray-white and firm, rarely bile stained.
Ceruloplasmin: originates as an inactive, non-copper containing form called “apoceruloplasmin”. When Cu is added to apoceruloplasmin in liver - produces holoceruloplasmin, which is the functionally active form of ceruloplasmin. Routine measurement of ceruloplasmin measures apoceruloplasmin and holoceruloplasmin.

Question 81

34 Which is true in regards to the Gallbladder?
1. Cystic change in Adenomyomatosis.
2. Stones are seen in 70% of cases Gallbladder CA.
3. Mirrizzis due to CBD stone.

Answer 81

Answer: Stones are seen in 70% of cases Gallbladder CA. ***Note that in Robbins, the figure quoted is 95%. Also, only 1-2% of patients with gallstones develop gallbladder cancer.

Adenomyomatosis
- hyperplastic cholecystoses
- hyperplasia of wall with formation of Rokitansky-Aschoff sinuses (intramural diverticula lined by mucosal epithelium) +/- gallbladder wall thickening.
- cholesterol accumulation is intraluminal, as cholesterol crystals precipitate in the bile trapped in the sinuses.

Mirrizzis
- extrinsic compression of an extra hepatic biliary duct from on or more calculi within the cystic duct or gallbladder.

Lemmel Syndrome
- Obstructive jaundice caused by a periampullary duodenal diverticulum compressing the intrapancreatic CBD with resulting bile duct dilatation

Question 82

35 Which is true regarding Biliary disease?
1. Caroli’s is both intrahepatic and extrahepatic duct dilatation
2. Association of choledochal cyst and HCC
3. Surgical management of biliary cysts
4. Biliary fibrosis in Primary Biliary cirrhosis

Answer 82

3. Surgical management of biliary cysts - T - Because of the risk of malignant degeneration of the cysts, the current standard treatment for Types I, II, and IV biliary cysts is surgical excision.

35 Which is true regarding Biliary disease? (TW)
1. Caroli’s is both intrahepatic and extrahepatic duct dilatation - F - Caroli’s disease is a congenital disorder characterised by multifocal, segmental dilatation of large intrahepatic bile ducts (type V choledochal cysts). However: although the Todani classification of choledochal cysts includes Caroli’s disease as a type V choledochal cyst, the pathogenesis of Caroli’s disease (AR and often assoc with renal disorders) makes these disorders unrelated.
2. Association of choledochal cyst and HCC - F - increased risk of cholangiocarcinoma, esp type IV, and to a lesser extent type V. Type III has a lower rate of cholangiocarcinoma. (GC: also at increased risk for gallbladder carcinoma).
3. Surgical management of biliary cysts - T - Because of the risk of malignant degeneration of the cysts, the current standard treatment for Types I, II, and IV biliary cysts is surgical excision.
4. Biliary fibrosis in Primary Biliary cirrhosis - F - Cause of PBC is unknown and appears related to genetic and environmental factors. It is characterised by a T-lymphocyte mediated attack on small intralobular bile ducts. Loss of intralobular bile ducts causes signs of cholestasis, and eventually results in cirrhosis and liver failure (get portal fibrosis, nodular regeneration, shrinkage of hepatic parenchyma). Primary Sclerosing Cholangitis has “onion skin” fibrosis around affected ducts.

Question 83

38. Hepatic Adenoma features include?
39. No risk of malignant degeneration
40. Subcapsular in location
41. Occurs in cirrhosis
42. Due to profileration of kupffer cells

Answer 83

Answer: Subcapsular location

Hepatocellular Adenoma
- benign neoplasms developing from hepatocytes.
- three large subtypes: HNF1-alpha inactivated, B-catenin activated, inflammatory

HNF-1 Alpha inactivated
- most common in women
- associated with MODY-3
- some association with OCP.
- no risk of malignant transformation

Beta-Catenin activated
- associated with OCP and anabolic steroid use
- found in both men and women
- very high risk of malignant transformation

Inflammatory
- found in both men/women
- most common subtype
- high bleed rate
- associated with NALFD
- small but definite risk of malignant transformation

Question 84

38. Which of the following are false in regards to focal nodular hyperplasia?
39. Presence of a scar
40. Spoke pattern on Doppler
41. Subcapsuar
42. Commonly haemorrhage is associated with the OCP

Answer 84

4. Commonly haemorrhage is associated with the OCP - F - unlike hepatic adenomas, FNH rarely presents with acute onset of hemorrhage, necrosis, or infarction. Hepatic adenomas are strongly associated with OCP which also increases their chance of hemorrhage.
5. Which of the following are false in regards to focal nodular hyperplasia? (TW)
6. Presence of a scar - T - presence of a central stellate scar containing an inappropriately large artery with multiple branches radiating through the fibrous septae to the periphery. The scar-like tissues within FNH are composed of abnormally large portal tracts including large feeding arteries, portal veins, and bile ducts.
7. Spoke pattern on Doppler - T - US is able to identify central scar in only 20% cases. Sensitivity is increased with contrast US.
8. Subcapsular - T - usually a solitary, subcapsular nodular mass.
9. Commonly haemorrhage is associated with the OCP - F - unlike hepatic adenomas, FNH rarely presents with acute onset of hemorrhage, necrosis, or infarction. Hepatic adenomas are strongly associated with OCP which also increases their chance of hemorrhage.

Question 85

1. Regarding Cirrhosis, which aetiology would typically have a micronodular pattern?
2. Alcohol
3. Viral

Answer 85

1. Regarding Cirrhosis (not sure if this is complete question) (TW)
2. Alcohol - micronodular - T - the prototype of micronodular (nodules less than 3mm) cirrhosis is alcoholic cirrhosis, but this pattern may also be observed in cirrhosis of many other causes. Can become macronodular particularly if drinking stops.
3. Viral - macronodular - macronodular cirrhosis is classically associated with chronic hepatitis. Micronodular cirrhosis can be converted into a macronodular pattern by continued regeneration and expansion of existing nodules.

*AJL changed the question to improve the learning opportunity

Question 86

3. Which is likely to produce liver cirrhosis among the cardiac condition
4. Mitral Stenosis
5. Aortic Stenosis
6. Constrictive pericarditis
7. ASD

Answer 86

3. Constrictive pericarditis - T - probably most correct. Constrictive pericarditis is associated with hepatic vein pressures generally higher than those seen in patients with right-sided heart failure, making patients with constrictive pericarditis relatively more likely to develop hepatic necrosis and ultimately cirrhosis.
4. Which is likely to produce liver cirrhosis among the cardiac condition (TW)
5. Mitral Stenosis - less true
6. Aortic Stenosis - F - unless has resulted in LVF with secondary RHF
7. Constrictive pericarditis - T - probably most correct. Constrictive pericarditis is associated with hepatic vein pressures generally higher than those seen in patients with right-sided heart failure, making patients with constrictive pericarditis relatively more likely to develop hepatic necrosis and ultimately cirrhosis.
8. ASD - F
   Cardiac cirrhosis (congestive hepatopathy) includes a spectrum of hepatic derrangemetns that occur in the setting of right-sided heart failure. Any cause of right-sided heart failure can result in hepatic congestion, including constrictive pericarditis, mitral stenosis, tricuspid regurgitation, cor pulmonale, and cardiomyopathy. TR in particular can be associated with severe hepatic congestion (due to transmission of RV pressure directly into hepatic veins). UTD.
   Congested liver has ‘nutmeg’ appearance.
   Not sure which would be correct if ‘tricuspid regurgitation’ was also given as an option.

Question 87

1. What is the commonest cause of liver disease during pregnancy?
2. Intrahepatic cholestasis
3. Viral infections
4. HELLP syndrome
5. Acute fatty liver
6. Pre-eclampsia

Answer 87

Answer: Viral infections

ROBBINS
Viral hepatitis is the most common cause of jaundice in pregnancy. Pregnancy does not specifically alter its course, UNLESS infected with HEV, where there is a 20% mortality associated with pregnancy.

Other hepatic complications attributable to pregnancy make up <0.1% of cases and include: pre-eclampsia, acute fatty liver of pregnancy, intra-hepatic cholestatis of pregnancy.

EDWH: yes viral for jaundice however most commonly is a benign cholestasis.

Question 88

2. Which is true regarding gallstones?
3. 25% of cholesterol stones are radiopaque
4. 50-75% of black pigment stones are radiopaque
5. > 50% are symptomatic
6. Marginal decrease in incidence after age of 40.

Answer 88

Answer: 50-75% of black pigment stones are radiopaque

ROBBINS
Cholelithiasis
>80% cases are silent.
F>M.
Incidence increases as you age.

Black pigment stones
- found in sterile gallbladder bile
- calcium saltes + uncojugated bilirubin, cholesterol, mucin.
- friable, small.
- 50-75% are radiopaque

Brown pigment stnoes
- found in fetched large bile ducts.
- cholesterol, calcium salts (palmitate and stearate).
- laminated, soft and soaplike/greasy.
- radiolucent.

Cholesterol stones
- arise exclusively in gallbladder
- 10-20% are radiopaque

Question 89

3. Which is true regarding cholangiocarcinomas?
4. Local lymph nodes positive in 30%
5. Typically well to moderately differentiated adenocarcinoma
6. Typically green (bile stained)
7. Associated with cirrhosis of any cause

Answer 89

2. Typically well to moderately differentiated adenocarcinoma – T - resemble adenocarcinomas elsewhere in body. Most are moderately differentiated sclerosing adenocarcinomas with clearly defined glandular and tubular structures (Robbins, Pathoutlines)
3. Which is true regarding cholangiocarcinomas? (TW)
4. Local lymph nodes positive in 30% - F - 50% metastatic to perihilar, peripancreatic and para-aortic nodes. 50-75% met to regional lymphnodes, lungs, vertebrae, adrenals, brain, elsewhere. (Pathoutlines)
5. Typically well to moderately differentiated adenocarcinoma – T - resemble adenocarcinomas elsewhere in body. Most are moderately differentiated sclerosing adenocarcinomas with clearly defined glandular and tubular structures (Robbins, Pathoutlines)
6. Typically green (bile stained) - F - arise from bile duct epithelium, don’t produce bile (unlike HCC). Gray-white and firm (but note that may see – albeit rarely – peripheral bile staining)
7. Associated with cirrhosis of any cause - F - No association with cirrhosis
   Added option d

Question 90

19. Fibrolamellar HCC (false)
    a. Female>Male
    b. 20-40 yo
    c. No association with hepatitis B
    d. Hard scirrhous tumour
    e. No cirrhosis

Answer 90

a. Female>Male - False - M=F

19. Fibrolamellar HCC, which is False (JS)
    a. Female>Male - F - M=F
    b. 20-40 yo - T - occurs in young adults 20-40y (Robbins)
    c. No association with hepatitis B - T - no association with HBV or cirrhosis risk factors
    d. Hard scirrhous tumour - T - usually a single hard “scirrhous” tumour with fibrous bands coursing through it
    e. No cirrhosis - T

Question 91

42. Hepatitis D can only cause disease in the presence of…
    a. Hep A
    b. Hep B
    c. Hep C
    d. EBV
    e. Only arise in liver parenchyma

Answer 91

b. Hep B - T - HDV is absolutely dependent on the genetic information provided by HBV for multiplication and causes hepatitis only in the presence of HBV

Question 92

86. Fibrolamellar HCC, which is false:
    a. Normal AFP
    b. 20 – 40 years
    c. Hard tumour
    d. No association with cirrhosis
    e. More common in females

Answer 92

e. More common in females - F - M=F [Robbins]

86. Fibrolamellar HCC, which is false: (GC)
    a. Normal AFP - T - 50% of pts with classic HCC have an elevated serum AFP.
    b. 20 – 40 years - T - occurs in young adults 20-40yo.
    c. Hard tumour - T - usually a single hard “scirrhous” tumour with fibrous bands coursing through it, vaguely resembling FNH. Histo: well-differentiated polygonal cells growing in nests or cords, separated by parallel lamellae of dense collagen bundles.
    d. No association with cirrhosis - T - or any of the other risk factors for HCC.
    e. More common in females - F - M=F [Robbins]