Pathology EMQ template

Pathology EMQ template.

Name: Yu Zhi Zhang

Theme: Causes of jaundice and abdominal pain

OPTION LIST

A	Autoimmune pancreatitis	I	Caroli’s disease
B	Autoimmune hepatitis (AIH)	J	Amoebic liver abscess
C	Hepatocellular carcinoma	K	Sickle cell disease (SCD)
D	Biliary colic	L	Hepatitis A infection
E	Acute cholangitis	M	Cholangiocarcinoma
F	Alcoholic hepatitis	N	Mirizzi’s syndrome
G	Primary Sclerosing Cholangitis (PSC)	O	Zieve’s syndrome
H	Pancreatic head adenocarcinoma	P	Acute calculous cholecystitis

For each scenario below, choose the most appropriate answer from the list above. Each option may be used once, more than once or not at all.

1. A 30 year-old Nigerian man presented with 6 week history of abdominal pain and jaundice. He also presented with fever and malaise. On further questioning he’s had a recent travel to Thailand, and drinks 3 cans of beer per week. The rest of examination was unremarkable.

Investigations: Hb 13g/dL, WCC 9.8×10⁹/L (Neutrophil: 60%), CRP 30mg/L, bilirubin 80 µmol/L, ALT 1450U/L, AST 960U/L, ALP 110U/L, ƔGT 55. Ultrasound scan shows normal size liver with smooth edge, without heteroechoic lesions.

2. A 55 year-old Caucasian man presented with 3 year history of intermittent upper abdominal pain and intermittent jaundice, without fever. He also complained about losing some appetite and “a bit of weight”. On further questioning he recalled having 15 year history of ulcerative colitis. He was worried he might have cancer, as his cousin had been recently diagnosed with “a cancer of the bile duct” which invaded into a major blood vessel.

Investigations: Hb 11.9g/dL, WCC 6.8×10⁹/L (Neutrophil: 56%), CRP 65mg/L, bilirubin 45 µmol/L, ALT 70U/L, AST 56U/L, ALP 296U/L, ƔGT 65, pANCA positive, CEA 21ng/mL, CA19-9 101ng/mL, AFP 90ng/mL. IgG₄ screen was negative. ERCP showed multifocal intra- and extra-hepatic biliary strictures. CT scan was unremarkable.

3. A 28 year-old woman with BMI of 23, presented to Accident & Emergency with 4 day history of acute onset right upper quadrant pain. The pain was colicky in nature and was aggravated by eating. On examination you noticed mild jaundice and a Lanz incision scar, but otherwise unremarkable. There was no fever and BP was 115/75. On further questioning she’s had 7 similar episodes in the last 2 years, but decided not to seek medical help as she managed to fight off the pain with painkillers.

Investigations: Hb 12.5g/dL, WCC 7.8×10⁹/L (Neutrophil: 57%), CRP 2mg/L, bilirubin 38 µmol/L, ALT 75U/L, AST 65U/L, ALP 310U/L, ƔGT 35. Ultrasound scan showed an enlarged gallbladder with rugged wall containing a large gallstone. ERCP showed dilated common hepatic duct and both intrahepatic ducts. The cystic duct was not visible.

4. A 45 year-old interior designer, on a background of Grave’s disease and type I diabetes, presented to gastroenterology clinic with a 6 week history of abdominal pain and jaundice. She’s been generally unwell and running low grade fever during this period. On examination the liver was tender on palpation, and you noticed jaundice. There was no hepatosplenomegaly and other signs of chronic liver disease. On further questioning she had made frequent business trips to New York in the past 6 months. She drinks wine on social occasions.

Investigations: Hb 11g/dL, WCC 14.7×10⁹/L (Neutrophil: 75%), CRP 110mg/L, bilirubin 60 µmol/L, ALT 550U/L, AST 260U/L, ALP 60U/L, ƔGT 42. A non-invasive liver screen was performed and she was negative for pANCA, anti-HAV and anti-mitochondrial antibodies (AMA), positive for anti-nuclear antibodies (ANA) and anti-smooth muscle antibody (Anti-Sm). In addition, there was elevated IgG with normal IgM titre. Liver biopsy was performed and showed extensive neutrophil infiltration without cirrhosis. Ultrasound scan was normal.

5. A 57 year-old ex-smoker (40 pack years) presented with a 6 week history of abdominal pain and gradual onset of jaundice. The pain was dull and constant, and he had noticed significant weight loss (10kg in past 3 months). He attributed the latter as a result of feeling full easily when eating. On examination the inferior edge of liver was non-palpable, and Troisier’s sign was negative.

Investigations: Hb 13.5g/dL, WCC 7.5×10⁹/L (Neutrophil: 55%), CRP 6mg/L, bilirubin 115 µmol/L, ALT 43U/L, AST 26U/L, ALP 160U/L, ƔGT 22, Anti-HBV and anti-HCV were negative, CEA 40ng/mL, CA19-9 620ng/mL, AFP 1ng/mL. Autoantibody screen was negative. Ultrasound scan showed prominent dilatation of common bile duct (CBD), and normal liver parenchyma. Perihilar and intrahepatic ductal infrastructure were normal.

ANSWERS

1. L

2. G

3. N

4. B

5. H

Explanations to answers:

1. The answer is L. The presence of fever suggests an infective or autoimmune cause. However, the reasonably short history of symptoms renders the latter unlikely. His alcohol consumption was within the normal limit, thus alcoholic hepatitis (which unlike decompensating cirrhosis, could present with a short history) would not be the top differentials. His haemoglobin level was normal (considering SCD could predispose veno-occlusive crisis), therefore we are left with Hepatitis A infection and amoebic liver abscess. HAV infection typically presents with high ALT (usually >1000U/L) and ALT/AST ratio, whilst a normal WCC and white cell differential and CRP, add further weight to a diagnosis of HAV infection. In this case the diagnosis would be confirmed with a positive anti-HAV IgM antibody. Amoebic abscess does not commonly cause (<25%) jaundice, and would show up on ultrasound as hyperechoic/heteroechoic lesion.

2. The answer is G. A long history of intermittent upper abdominal pain and intermittent jaundice exclude most acute causes (D, E). The differentials therefore divide into 2 categories: autoimmune conditions (A, B, G), and malignancies (H, M). Anorexia and weight loss, especially when not prominent, could be non-specific presentations here. The negative IgG₄ screen, alongside the absence of any features outlined in HISORt criteria, excludes autoimmune pancreatitis (It could cause biliary strictures in a similar fashion as PSC). Although AIH overlaps with PSC as well as ulcerative colitis, the presence of pANCA antibody (present in up to 85% patients with PSC) and absence of AIH-specific antibodies (e.g. anti-LKM1) suggest PSC is the more likely diagnosis. This was confirmed by the ERCP findings. The fact the patient was worried about cholangiocarcinoma, was largely irrelevant. Cholangiocarcinoma is indeed associated with long-term PSC, however, diagnosis is unlikely (I would personally struggle to differentiate between a long-term PSC patient with or without early stage cholangiocarcinoma). There is evidence that PSC causes elevated CEA and CA19-9, although to a lesser extent than cholangiocarcinoma. Ideally the patient would then be put on regular follow-up/imaging, to pick up early cholangiocarcinoma.

3. The answer is N. The major differentials are other (and more common) causes of acute onset upper right quadrant pain (D, E, I). The nature of pain and the presence of jaundice suggest an obstructive picture of the biliary tree. The absence of fever, a normal blood pressure, and normal WCC/CRP, renders acute cholangitis unlikely (Despite being a possible complication in advanced Mirizzi’s syndrome, especially with fistula formation). Ultrasound scan findings are consistent with acute calculous cholecystitis, however, it does not explain the isolated elevation in ALP, as well as the ERCP findings. The jaundice was caused by the gallstone stuck at the neck of gallbladder, which compressed the common bile duct, leading to CHD and IHD ectasia (The patient in this case presented with Stage 1B disease, as there is no fistula formation). Caroli’s disease is a congenital condition presenting as intrahepatic ductal ectasia with signs of obstruction. Although many patients presented after 18 years of age, it is a very rare condition (1 in 1000000).

4. The answer is B. PMH of Grave’s and Type 1 diabetes suggests the likelihood of an autoimmune condition. History and clinical examination findings are consistent with a recent onset of hepatic disease. The presence of fever and markers of inflammation suggest there could also be an infectious cause (J, L). However, the travel destination was not an endemic area of Hepatitis A infection. An elevated WCC with left shift, alongside normal IgM titre and the absence of anti-HAV (diagnostic), makes HAV infection unlikely. The presence of autoantibodies left us with 2 differentials (B, G). There is crossover in terms of autoantibody profile between AIH and PSC, nonetheless, the absence of pANCA (associated with PSC) and liver histology were consistent with an inflammatory picture observed in AIH.

5. The answer is H. Gradual onset jaundice, early satiety and significant weight loss raised suspicion of a possible GI malignancy. Troisier’s sign is not a sensitive marker of GI malignancy, therefore its absence does not rule out the latter. Blood results showed signs of biliary obstruction without hepatic insult. Together with a negative AFP and normal ultrasound scan, HCC is unlikely. Since the autoantibody screen was negative, it is safe to exclude autoimmune causes (A, B, G). Pancreatic head carcinoma and cholangiocarcinoma can clinically present indistinguishably. Both could show elevated CEA and CA19-9. Since most cholangiocarcinoma associate with perihilar (50%) and intrahepatic ducts (20-25%), it is therefore a less likely diagnosis in this case. Endoscopic ultrasound with FNA biopsy is required for confirmation.

Reference

Harrison’s Principles of Internal Medicine, 18^th edition

Oxford Handbook of Gastroenterology and Hepatology, 2^nd edition