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

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

2. Lungs (8%)

Note : Haematogenous spread NOT common even with vascular invasion

Question 4

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

(*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

3. Metastatic Kaposi Sarcoma

Kaposi sarcoma
MIcroscopic examination discloses only dilated perhaps irregular and angulated blood vessels lined by endothelial cells with an interspersed infiltrate of lymphocytes, plasma cells, and macrophages (sometimes containing hemosiderin), lesions difficult to distinguish from granulation tissue. Over time, lesions in the classic disease spread proximally and usually convert into larger, violaceous, raised plaques that reveal dermal, dilated, jagged vascular channels lined by somewhat plump spindle cells accompanied by perivascular aggregates of similar spindled cells. Scattered between the vascular channels are red cells, hemosiderin-laden macrophages, lymphocytes, and plasma cells. Pink hyaline globules of uncertain nature may be found in the spindled cells and macrophages. Occasional mitotic figures may be present.
Angiosarcoma
Angiosarcomas are malignant endothelial neoplasms (Fig. 12-35) with structure varying from highly differentiated tumors that resemble hemangiomas ( hemangiosarcoma) to those whose anaplasia makes them difficult to distinguish from malignant epithelial neoplasms, such as carcinoma or melanoma. They occur in both sexes and more often older adults anywhere in the body but most often in the skin, soft tissue, breast, and liver.
Hepatic angiosarcomas are rare but of interest because they are associated with distinct carcinogens, including arsenic (exposure to arsenical pesticides), Thorotrast (a radioactive contrast medium formerly widely used in radiology), and polyvinyl chloride (PVC) (widely used in plastics). The increased frequency of angiosarcomas among workers in the PVC industry is one of the truly well-documented instances of chemical carcinogenesis in humans. With all three agents, there is a long latent period of many years between exposure and the development of tumors.
Angiosarcomas may also arise in the setting of lymphedema, most typically approximately 10 years after radical mastectomy for breast cancer. In such cases, the tumor presumably arises from dilated lymphatic vessels ( lymphangiosarcomas). Clinically the edematous arm may undergo acute swelling followed by the appearance of subcutaneous nodules, hemorrhage, and skin ulceration. The nodules are frequently multiple, but they later become confluent, forming a large mass. Angiosarcomas may also be induced by radiation in the absence of lymphedema, although both factors may be present in some cases after treatment for breast cancer or other neoplasm. Some have been associated with foreign material introduced into the body either iatrogenically or accidentally.
MORPHOLOGY.
Grossly, cutaneous angiosarcoma may begin as deceptively small, sharply demarcated, asymptomatic, often multiple red nodules, but eventually most angiosarcomas become large, fleshy masses of pale gray-white soft tissue. The margins blend imperceptibly with surrounding structures. Central softening and areas of necrosis and hemorrhage are frequent.
Microscopically, all degrees of differentiation of these tumors may be found, from those that are largely vascular with plump, anaplastic but recognizable endothelial cells producing vascular channels to tumors that are quite undifferentiated produce no definite blood vessels, and are markedly atypical. The more malignant variant tends to have a solid spindle cell appearance.
Clinical Features.
Clinically, angiosarcomas have all the usual features of a malignancy, with local invasion and distal metastatic spread. The majority of patients have a poor outcome with few surviving 5 years.
Glomus Tumor (Glomangioma)
A glomus tumor is a biologically benign but often exquisitely painful tumor that arises from the modified smooth muscle cells of the glomus body, a specialized arteriovenous anastomosis that is involved in thermoregulation. Glomus tumors may be located anywhere in the skin (or soft tissue and sometimes in the gastrointestinal tract) but are most commonly found in the distal portion of the digits, especially under the fingernails. Excision is curative.
MORPHOLOGY.
Grossly the lesions are usually small (<1 cm in diameter), slightly elevated, rounded, red-blue, and firm nodules, which may appear as minute foci of fresh hemorrhage under the nail. Histologically; two components are present; branching vascular channels separated by a connective tissue stroma that contains the second element– aggregates, nests, and masses of the specialized glomus cells that typically are arranged around vessels. Individual cells are usually small, regular in size, and round or cuboidal, with scant cytoplasm and features similar to smooth muscle cells on electron microscopy. Glomangiomas constitute a distinct subgroup that resemble cavernous hemangiomas.

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

4. Haematuria (only one not seen in text anywhere)
5. 19.APRIL02 Which of the following is the LEAST likely to be a clinical manifestation of primary hemochromatosis;
6. Arthritis (50%)
7. Loss of libido (due to hypogonadism)
8. Cardiac arrhythmias (15%)
9. Haematuria (only one not seen in text anywhere)
10. Polyuria /polydipsia (diabetes due to pancreatic involvement)

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

**LJS - HBsAg presence for > 6 mo defines chronic state. This can be with or without HBeAg or HBV DNA, which if presence indicates infectivity. Robbins says chronic asymptomatic carrier state is rare outside of endemic areas. ?chronic hepatitis by definition since HBsAg > 6 mo

• LW: agrees with above: –> Option 5.
• diagnosis of chronic HBV infection is based upon the persistence of HBsAg for more than six months (definition)
• In the setting of chronic HBV infection, HBeAg-negative patients who have normal serum ALT and low (<2000 international units/mL) or undetectable HBV DNA are considered to be in an inactive carrier state.
• HBsAG alone doesnt indicate replication, can be asymptomatic, and without liver damage.

*AJL - (agree with above) For those who misread it (like me) the question is saying they were told HBsAg and they weren’t told any other tests. Therefore the only thing that can be determined is chronic carrier state (by definition >6 months).
If the staff member had become immune, they would have developed anti-HBs. The antigen (HBsAg) would have disappeared.
They will always have anti-HBc as this indicates current or previous infection.
As outlined above, HBeAg and HNV DNA indicate infectivity/replication.
https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf

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

1. Severe right-sided heart failure, Budd Chiari Syndrome and constrictive pericarditis

• The most frequent abnormality of circulation to affect the liver is congestive heart failure, which leads to reduced outflow of blood from the liver.
• Other causes of hepatic congestion include constrictive pericarditis, obstruction of the inferior vena cava and hepatic veins (Budd-Chiari syndrome) and occlusion of the small hepatic veins (veno-occlusive disease).

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

2. 20% chance based on epidemiology

• First-degree relatives have a 570- to 1000-fold increased chance of developing this disease

LW: not inherited in any recessive/dominant pattern.
Prevalence: 19-151 cases per million people
Incidence: 3.9-15 cases per million people each year
Assuming on average prevalance of 100/1000000, multiply by 1000 fold increased risk = 0.1% incidence.
Thus if correct option is “an increased risk” then this would be correct, 20% chance compared to overall incidence would be wrong, as is 50% (as no true auto dominant / recessive inheritance, but does have increased risk compared to general population.
No documentation to state if the 100fold increase “doubles” if father also has it, but one would presume it would, however I think that option is trying to distract and imply an autosomal inheritance pattern which is incorrect.
Furthermore the prescribed text book of robbins doesnt mention any form of inheritence facts… typical.

• A striking feature of the disease is the presence of serum autoantibodies, especially antimitochondrial antibodies in more than 90% of patients.
• However, 5% to 10% of patients with granulomatous destruction of bile ducts do not exhibit antimitochondrial antibodies.
• patients may develop extrahepatic autoimmune associations including Sjogren syndrome, scleroderma, thyroiditis, rheumatoid arthritis, Raynaud phenomenon, membranous glomerulonephritis, and celiac disease.
• Granulomatous destruction of the bile ducts (the florid duct lesion), accompanied by a dense portal tract infiltrate of lymphocytes, macrophages, plasma cells, and occasional eosinophils
• obstruction to intrahepatic bile flow leads to progressive hepatic damage. Portal tracts upstream from damaged bile ducts exhibit bile ductular proliferation, inflammation, and necrosis of the adjacent periportal hepatic parenchyma. The parenchyma develops generalized cholestasis. In years to decades, relentless portal tract scarring and bridging fibrosis lead to cirrhosis (over a 2-3 decade time frame)
• In most cases, the end-stage picture is indistinguishable from secondary biliary cirrhosis or the cirrhosis that follows chronic active hepatitis

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

4. Amyloid

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

7. RCC

Greater-than-normal levels of CEA may indicate: 
•	Colon cancer 
•	Breast cancer 
•	Lung cancer 
•	Pancreatic cancer 
•	Thyroid cancer 
•	Genitourinary carcinomas 
•	Inflammatory gastrointestinal diseases (for example, ulcerative colitis, diverticulitis, cholecystitis, pancreatitis) 
•	Cirrhosis 
•	Other liver disease 
•	Peptic ulcer 
•	Heavy smoking 
•	Pulmonary infections

Question 17

17. Sep03.19 Definition of chronic cholecystitis
18. > twice the normal wall thickness
19. presence of Rockitansky Aschoff sinuses. (may be prominent)

Answer 17

17. Sep03.19 Definition of chronic cholecystitis
18. > twice the normal wall thickness
19. presence of Rockitansky Aschoff sinuses. (may be prominent)

*LW:
StatDx definition: Chronic inflammation of gallbladder (GB) causing wall thickening and fibrosis, following single or recurrent episodes of cystic duct obstruction
Per below notes; technically both options are present in chronic cholecystits, so unsure of exact defintion.

Most common pathology of gallbladder
95% associated with gallstone disease
Intermittent obstruction of cystic duct causes chronic low-grade inflammatory infiltration of wall, which can lead to fibrosis and contraction
Gross Path: thickened fibrotic GB wall.
Micro Path:
- Chronic inflammatory cells, lymphocytes predominate
- Rokitansky-Aschoff sinuses are characteristic (seen in 90%)
- Focal or diffuse subepithelial and subserosal fibrosis
- May be associated with Helicobacter pylori
- Often associated with acute cholecystitis

The morphologic changes in chronic cholecystitis are extremely variable and sometimes minimal.
• The serosa is usually smooth and glistening, but often it is dulled by subserosal fibrosis.
• Dense fibrous adhesions may remain as sequelae of preexistent acute inflammation.
• the wall is variably thickened, rarely to more than thrice normal.
• wall has an opaque gray-white appearance and may be less flexible than normal.
• In the uncomplicated case, the lumen contains fairly clear, green-yellow, mucoid bile and usually stones. The mucosa itself is generally preserved.
• On histologic examination, the degree of inflammatory reaction is variable. In more developed cases, there is marked subepithelial and subserosal fibrosis, accompanied by mononuclear cell infiltration
• Inflammatory proliferation of the mucosa and fusion of the mucosal folds may give rise to buried crypts of epithelium within the gallbladder wall
• Outpouchings of the mucosal epithelium through the wall (Rokitansky-Aschoff sinuses) may be prominent
• Superimposition of acute inflammatory changes implies acute exacerbation of a previously chronically injured gallbladder.
• In rare instances, extensive dystrophic calcification within the gallbladder wall may yield a porcelain gallbladder, notable for a markedly increased incidence of associated cancer
• In xanthogranulomatous cholecystitis the gallbladder is shrunken and nodular and exhibits histiocytes packed with lipids admixed with an exuberant fibrous tissue response. Gallstones are usually present. This rare condition can be confused macroscopically with a malignant neoplasm
• Finally, an atrophic, chronically obstructed gallbladder may contain only clear secretions, a condition known as hydrops of the gallbladder

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

*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

DEFINITION
• Chronic, progressive, and often fatal cholestatic liver disease, characterised by non-suppurative granulomatous destruction of intrahepatic bile ducts, portal inflammation and scarring, and eventual development of late cirrhosis and liver failure

• Primary feature = non-suppurative granulomatous destruction of medium sized intrahepatic bile ducts
INCIDENCE/EPIDEMIOLOGY
• Middle aged women
• M:F = 1:6
• Onset 20-80 years, peak 40-50 years
ASSOCIATIONS
• Sicca complex
• scleroderma
• thyroiditis
• RA
• Raynaud’s
• membranous GN
• coeliac disease
AETIOLOGY/PATHOGENESIS
• Probably autoimmune
• 90% have anti-mitochondrial antibodies (AMA)
• Abnormal expression of MHC class I & II antigens on biliary epithelium & accumulation of T-cells in and around BDs
• Low complement from activation and formation of immune complexes
• Polyclonal hypergammaglobulinaemia
• Initiating events unclear, and mechanism of granuloma formation unknown
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

5. females 80%
6. 16.03.56 Choledochal cysts
7. If jaundiced implies secondary stricture
8. Primary abnormality is stricture with secondary dilatation proximal (congenital dilatations of the common bile duct)
9. presents 10-20’s (<10 years, only 20% in adulthood)
10. pain always means pancreatitis
11. females 80%

Question 21

22. Sep03.89 Epidemiology and incidence of hepatoma

Answer 21

Hepatoma
• USA 2-4/100000, Mediterranean 20, Korea, China 150/100000
• Blacks:whites 4:1
• M:F 2-8:1
• The global distribution of HCC is strongly linked to the prevalence of HBV infection
• Maternal transmission HBV- 200x increased risk of HCC, cirrhosis only present in 50% HCC pts
• Western world cirrhosis 90-95%
• HCV and alcohol

Question 22

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

Answer 22

Cholelithiasis Cx's 
•	70-80% asymptomatic throughout life 
•	asymptomatic->symptomatic 1-3% per year 
•	biliary colic 
•	cholecystitis 
•	Empyema, perforation, fistulas, cholangitis, obstructive cholestasis, pancreatitis. 
•	Gallstone ileus 
•	Increased risk of cancer.

Question 23

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

Answer 23

1. primary liver cancer

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

3. HCC - T - Arises in the setting of cirrhosis; may be pale pink-yellow or bile-stained (dpt on capacity of tumour cells to secrete bile).
   *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.
4. PATH2004 52yo male with ulcerative colitis and cirrhosis. A 7cm green tumour in the liver exists. What is the most likely diagnosis: (GC)
5. Cavernous haemangioma - F - soft red-blue mass composed of large cavernous vascular spaces, no bile pigment.
6. Cholangiocarcinoma - F - 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).
7. HCC - T - Arises in the setting of cirrhosis; may be pale pink-yellow or bile-stained (dpt on capacity of tumour cells to secrete bile).
8. Nodular regenerative hyperplasia - F - 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.
9. Hepatic adenoma - F - 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

4. smoking - T - Occasionally, levels of CEA are elevated in healthy smokers.
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

4. Haemochromatosis - F - causes pancreatic fibrosis and may be a cause of chronic pancreatitis.

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:

1. >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

13. Patient sent with liver ultrasound, mother has primary biliary cirrhosis, which is true:
14. Patient has 50% chance of having it
15. 20% chance based on epidemiology
16. 50% risk if the dad has it as well
17. Has same risk as general population

Answer 44

13. Patient sent with liver ultrasound, mother has primary biliary cirrhosis, which is true: (TW)
14. Patient has 50% chance of having it - F - in general, data indicate that 1-6% of PBC cases have at least one family member presenting with the disease. This is much higher in twin studies (63% corcordance rate among MZ twins) (Liver Immunology, E.Gershwin / Journal clinical gastroenterology 2007). UTD: prevalence of PBC in familes with 1 affected member is estimated to be 1000x greater than general population, however is not inherited in any simple recessive or dominant pattern. A hepatology paper from 2005 said a first-degree relative had increased risk (OR 10.736).
15. 20% chance based on epidemiology - F - see option 1.
16. 50% risk if the dad has it as well - F - see option 1.
17. Has same risk as general population - F - ?previously true
    Added option 4. based on a previous question

Not sure about this question as none seem correct based on current data - the previous ?CME or question was Qu13 at the top of the document.

Question 45

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 45

*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 46

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 46

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 47

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

Answer 47

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 48

17. Myelofibrosis, patient with hepatosplenomegaly:

1. Typical finding

Answer 48

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 49

18. Epidemiology and incidence of hepatoma:

1. Hep B

Answer 49

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 50

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

Answer 50

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 51

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 51

*LW: Favoured answer is 2 - atypical for HCC.

Robbins states in countries with high rates of HBV (such as African countries), HBV carier state begins in infancy, conferring 200 fold increased risk for HCC, and cirrhosis may be absent in upto half of these patients, with cancer appearing between 20-40yrs old. HCC also likes venous invasion, with portal vein favoured.
In similar countries, high exposure to aflotixin, which is synergistic with HBV.
Thus:
1. HCC in early stages of Hep B: possible but i think technically incorrect as “early” stages of HBV would be wrong, as likely had since infancy.

2. Atypical for HCC: probably most correct, as atypical appearance for Western HCC, but probably typical for African / Eastern HCC.
3. In absence of alfatoxin exposure, HCC would be unlikely: false as HCC still likely given endemic HBV.
4. Cholangiocarcinoma should be considered: False
5. Leishmaniasis should be considered: false.

(Previous answers)
3. In absence of aflatoxin exposure HCC would be unlikely - T - Although when considering answer 2., given history of non-cirrhotic liver, aflatoxin (mycotoxin produced by many species of Aspergillus) would be a consideration, especially when considering that HBV + aflatoxin effect is synergistic increasing the risk of HCC 60x.

21. 32 yo African negro with 5cm mass invading IVC, non cirrhotic liver, Which is the most likely? (TW) ** do you think 2. or 3. correct **
22. HCC in early stages of Hep B - F - 60-90% occur in cirrhotic livers (8 months to 14yr latent period from onset of cirrhosis). Majority of HCCs occur in patients with chronic liver disease or cirrhosis.
23. Atypical for HCC - ?F - In sub-Saharan Africa, mean age of HCC is decreasing with a mean age of 33yo at presentation. Otherwise generally older age and chronic liver disease (60-70yo, Asia and Western Europe).
24. In absence of aflatoxin exposure HCC would be unlikely - T - Although when considering answer 2., given history of non-cirrhotic liver, aflatoxin (mycotoxin produced by many species of Aspergillus) would be a consideration, especially when considering that HBV + aflatoxin effect is synergistic increasing the risk of HCC 60x.
25. Cholangiocarcinoma should be considered - F - typical age 50-70yo (unless have PSC / choledochal cysts, who present nearly 2 decades earlier).
26. Leishmaniasis should be considered - F - protozoan parasite transmitted by female sandflys. Endemic in scattered foci on every continent except Australia and Antarctica. Massive splenomegaly (Kalar-azar).
    Aflatoxin: mutations of the p53 tumor suppressor gene have been demonstrated in patients with HCC who have chronically been exposed to aflatoxin.

Question 52

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 52

2. Lungs, peritoneum and lymph nodes - T - lymph nodes mets (50% at presentation), the peritoneal cavity, or distant organs (10-20% involvement) (Radiographics 2008)
   * LW still thinks this is the best option of those listed, however, would depend on the location of the cholangiocarcinoma, per my long and over detailed explanation below (apologies)

*LW:
Annoyingly Robbins quotes:
Haematogenous mets to lungs, bones (vertebrae), adrenals, brain or elsewhere, present at autopsy 50%. Node mets to regional nodes also found in half of cases.

UTD states the following:
Metastatic disease:
●Intrahepatic cholangiocarcinomas most commonly metastasize to other intrahepatic locations, to the peritoneum, and subsequently to lungs and pleura.
–> For all intrahepatic cholangiocarcinomas, spread to the celiac, periaortic, and/or pericaval lymph nodes is considered distant metastatic disease. The usual metastatic pattern is to intrahepatic sites (which is classified in the tumor [T] stage category as multiple tumors), to the peritoneum, and subsequently, to the bone, lungs, and pleura.

●For perihilar cholangiocarcinomas, the liver is a common site of metastases, but spread to extraabdominal sites (eg, peritoneum, lung, brain, and bone) is uncommon.

• -> Perihilar cholangiocarcinomas are characterized by intrahepatic ductal extension, as well as spread along perineural and periductal lymphatic channels. Hilar and pericholedochal nodes in the hepatoduodenal ligament are most often involved. Hilar, cystic duct, choledochal, portal, hepatic arterial, and posterior pancreaticoduodenal lymph nodes are classified as regional nodes [2]. Lymph node metastases distal to the hepatoduodenal ligament are classified as distant metastases.
• –> liver is a common site of metastases, and spread to extraabdominal sites (eg, peritoneum, lung, brain, and bone) is uncommon. In addition to these spreading routes, the left peripheral type or hilar type of cholangiocarcinoma tends to spread along the left gastric nodes through the lesser curvature.

●For distal cholangiocarcinomas, distant metastases occur late in the course of the disease and are most often found in the liver, lungs, and peritoneum.
—> regional nodes for distal cholangiocarcinomas are the same as for exocrine cancers of the pancreatic head (along the common bile duct, common hepatic artery, portal vein, posterior and anterior pancreaticoduodenal nodes, and nodes along the right lateral wall of the superior mesenteric artery) [1]. Distal cholangiocarcinomas can spread locally to involve the pancreas, duodenum, stomach, colon, or omentum. Distant metastases occur late in the course of the disease and are most often found in the liver, lungs, and peritoneum.

So all options kinda correct:

1. Haematogenous to bone (vert bodies commonly) lungs and brain: True
2. Lungs, peritoneum and lymph nodes: peritoneum not speificially mentioned by Robbins but other resources do, and this option involves nodes.
3. Haematogenous to lungs, liver and adrenal: Robbins doesnt mention liver mets, so least likely option.

Question 53

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 53

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 54

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 54

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 55

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 55

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 56

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

Answer 56

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 57

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 57

1. Giant haemangioma causes low platelets and bleeding tendency - T - Kasabach-Merritt syndrome: consumptive coagulopathy in children that has been described in association with giant hemangiomas. Pts have severe thrombocytopenia, hypofibrinogenemia, elevated fibrin degredation production, and fragmentation of RBCs.
2. Capillary and cavernous haemangioms, which is true: (–)
3. Giant haemangioma causes low platelets and bleeding tendency - T - Kasabach-Merritt syndrome: consumptive coagulopathy in children that has been described in association with giant hemangiomas. Pts have severe thrombocytopenia, hypofibrinogenemia, elevated fibrin degredation production, and fragmentation of RBCs.
4. Cavernous better circumscribed than capillary
5. Capillary not a recognized entity in liver - F - hemangioma is the most common primary hetaptic tumor. Capillary are the most common. Cavernous are more clinically relevant due to associated symptoms and potential complications.
   Small (typically <2cm) hemangiomas that show complete and immediate filling with contrast during initial arterial phase have been referred to as capillary hemangiomas, but this distinction is without andy clinical indication. MRI of the liver, G.Schneider.

Question 58

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 58

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 59

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

Answer 59

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 60

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 60

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 61

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 61

*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 62

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

Answer 62

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 63

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 63

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 64

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 64

**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 65

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 65

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 66

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 66

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 67

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

Answer 67

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 68

5. Rheumatoid arthritis and auto-immune hepatitis

1. non-dilated ducts and acute hepatitis

Answer 68

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 69

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

Answer 69

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 70

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

Answer 70

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 71

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

Answer 71

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 72

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 72

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 73

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 73

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 74

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

Answer 74

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 75

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 75

5. 45% involve the body and the tail – F – see option 1.
6. Following are true of pancreatic carcinoma (except): (TW)
7. Most arise from duct epithelium – T – ductal carcinoma accounts for 85-90% of pancreatic tumors (60-70% in the head, 5-10% in the body, 10-15% in the tail).
8. Most are incurable - T - due to late presentation of disease only 15-20% of patients are candidates for pancreatectomy.
9. Insidious – T - late presentation. Tumors in pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhoea, weight loss, and jaundice.
10. Risk factors include smoking diet and exogenous chemical - T – RR for developing pancreatic cancer among smokers at least 1.5. Diet is inconclusive (“Western” dietary pattern: high intake fat and/or meat, has been linked to pancreatic cancer in many, but not all studies). Protective effect from fresh fruits and vegetables (retrospective, but not prospective studies). Extended regular use of aspirin may increase risk.
11. 45% involve the body and the tail – F – see option 1.
12. May secrete mucin – T – mucinous cysadenocarcinoma

Question 76

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

Answer 76

2. Von Meyenberg complexes - F = multiple bile duct hamartomas; associated with polycystic liver disease.
3. Alpha-1 antitrypsin deficiency, which is incorrect: (GC)
4. Autosomal recessive - T Co-dominant
5. Von Meyenberg complexes - F = multiple bile duct hamartomas; associated with polycystic liver disease.
6. End stage get cirrhosis + cholestasis - T
   • Rare AR disease, causing low serum levels of alpha-1-antitrypsin, and leading to emphysema (80%) and liver disease.
   • AAT is a protease inhibitor (Pi), which inhibits neutrophilic elastase released at sites of inflammation; also inhibits trypsin.
   • Although there are 75 AAT forms, PiMM (normal phenotype) is present in 90% of population.
   • PiZZ: 1 per 7,000; have 10-15% of normal AAT levels, are at high risk for clinical disease; accumulate AAT variant Z in endoplasmic reticulum and have slowdown in degradation pathway, but only 10% get clinical disease.
   • PiZZ hepatic syndromes range from neonatal hepatitis (10%), biliary atresia (intra- or extrahepatic), fibrosis, childhood cirrhosis; 2% develop HCC, not always assocd with cirrhosis.
   [Path outlines]

Question 77

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 77

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 78

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 78

1. serous tumour - ?T - more common in females (4:1) >60yo.; 70% in head/neck; may be microcystic; amorphous calcification in 40%; central stellate scar in 15%. This option could be true, since “multiple small cysts” implies microcystic, but statistically less common in males and in pancreatic tail. ** opinions **
2. 60 yo male, asymptomatic, with a pancreatic tail mass measuring 6cm, contains multiple small cysts and no solid components: most likely: (GC)
3. serous tumour - ?T - more common in females (4:1) >60yo.; 70% in head/neck; may be microcystic; amorphous calcification in 40%; central stellate scar in 15%. This option could be true, since “multiple small cysts” implies microcystic, but statistically less common in males and in pancreatic tail. ** opinions **
4. 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.
5. intraductal papillary mucinous tumour - F - more common in older men, and in head/neck of pancreas (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 be macrocystic or unilocular, not typically microcystic.
6. adenocarcinoma F - more common in males (2:1) >60yo. but usually solid, scirrhous (hypovascular). A post obstructive pseudocyst may be seen in a minority.
7. pseudocyst - F - 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.

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)
[Dahnert; Cystic pancreatic lesions RG 2005

Question 79

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 79

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 80

32 With regards to cirrhosis which is false?

1. Micronodular with alcohol.
2. Macronodular with viral infections.
3. Kupffer cells involved in process.

Answer 80

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 81

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 81

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 82

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 82

2. Stones are seen in 70% of cases Gallbladder CA - T - gallstones are present in 70-90% of patients with GBC. Hx of gallstones appears to be one of the strongest risk factors, however overall incidence of GBC with cholelithiasis os only 0.5-3%.

34 Which is true in regards to the Gallbladder? (TW)

1. Cystic change in Adenomyomatosis - F - mucosal outpouching of epithelium-lined cystic spaces into or all the way through a thickened muscular layer as tubules / crypts / saccules. Intramural diverticula resemble cystic spaces within the wall.
2. Stones are seen in 70% of cases Gallbladder CA - T - gallstones are present in 70-90% of patients with GBC. Hx of gallstones appears to be one of the strongest risk factors, however overall incidence of GBC with cholelithiasis os only 0.5-3%.
3. Mirrizzis due to CBD stone - F - Mirizzi syndrome refers to common hepatic duct obstruction caused by an extrinsic compression from an impacted stone in the cystic duct.

Adenomyomatosis; GB abnormality characterized by overgrowth of mucosa, thickening of the muscle wall, and intramural diverticula (mucosal outpouching of epithelium-lined cystic spaces into (46%) or all the way thorugh (30%) a thickened muscular layer as tubules / crypts / saccules). Eventually form cystic structures that are visible on gross inspection as pools of bile in the GB wall (Rokitansky-Aschoff sinuses). Despite the name, does not involve any adenomatous change in gallbladder epithelium and is not a premalignant condition.

Mirizzi syndrome. Impacted stone in distal cystic duct which is obstructing the common hepatic duct by extrinsic compression.

Question 83

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 83

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 84

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 84

2. Subcapsular in location - T - right lobe of liver in subcapsular location (75%). Dahnert.
3. Hepatic Adenoma, features include? (TW)
4. No risk of malignant degeneration - F - Beta catenin subtype has malignant potential. (*AJL)
5. Subcapsular in location - T - right lobe of liver in subcapsular location (75%). Dahnert.
6. Occurs in cirrhosis - F - associated with OCP, steroids, pregnancy, diabetes, glycogen storage disease, Fanconi anemia (Dahnert)
7. Due to profileration of kupffer cells - F - They are atypical hepatocytes with low numbers of kupffer cells (hence can use sulfur colloid to distinguish from FNH.) (*AJL)

HAs are more numerous, larger, and more likely to bleed with OCP use. 25-41% bleeding risk in symptomatic patients, however actual incidence is uncertain (as many are asymptomatic).
Adenoma cells resemble normal hepatocytes, are typically larger than normal hepatocytes and contain glycogen and lipid. Kupffer cells may be present, but only in small numbers, and have little or no function, as reflected by absent of diminished uptake of Tc-99m sulfur colloid.
Bile ductules are notably (largely) absent which is a key histologic feature that helps distinguish HA’s from FNH.
Arterially enhance on CECT due to supply by hepatic artery, and are hypoattenuating on delayed-phase images.
Changed option 1. from “May spontaneously haemorrhage”, otherwise 2 correct answers.

Question 85

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 85

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 86

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

Answer 86

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 87

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

Answer 87

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 88

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 88

2. Viral infections – acute viral hepatits is the most common cause of jaundice in pregnancy (aaFP)
   * LW agrees.
3. What is the commonest cause of liver disease during pregnancy? (TW)
4. Intrahepatic cholestasis – 0.1% to 15.6% or pregnancies (UpToDate)
5. Viral infections – acute viral hepatits is the most common cause of jaundice in pregnancy (aaFP)
6. HELLP syndrome – 10-20% patients with severe preeclampsia / eclapmsia. About 1:1000 pregnancies overall.
7. Acute fatty liver – 1 in 10000. Deficiency in 3-hydroxyacyl-CoA dehydrogenase) leads to an accumulation of medium & long chain fatty acids. AR inheritance.
8. Pre-eclampsia – 3-14% of all pregnancies, typically during 3rd TM (preg induced / aggravated HTN, proteinuria, peripheral oedema + wt gain). 25% severe, 75% mild.
   Unique and small subgroup of pregnant patients (0.1%) develop hepatic complications directly attributable to pregnancy. *LW - Pre eclampsia, acute fatty liver of pregnancy, intra hepatic cholestasis of pregnancy.

Question 89

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 89

• RY - Both brown and black pigment stones. BROWN stones are radiolucent. 50-75% of BLACK stones are radio-opaque. 10-20% cholesterol stones radiopaque. Big Robbins 9th ed pg 877.
  2. 50-75% of black pigment stones are radiopaque – T.

2. Which is true regarding gallstones? (TW)
3. 25% of cholesterol stones are radiopaque – radiolucent 80-90%
4. 50-75% of black pigment stones are radiopaque – T.
5. > 50% are symptomatic - >80% are silent
6. Marginal decrease in incidence after age of 40 – prevalence of gallstones increases throughout life.
   Added options c,d

*AJL - I changed the answer to black rather than brown.

Question 90

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 90

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 91

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 91

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 92

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 92

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 93

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 93

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]