Interactive Case Studies

Question 1

• A 5-year-old boy of Indian ethnic origin presented with lymphadenopathy and a mediastinal mass on chest radiology
• WBC 180 × 109/l, Hb 93 g/l and platelet count 43 × 109/l
  
  • High (very high, so not infection) WCC a high WCC is bad prognostically
  • Low Hb
  • Low platelets
• What is the most likely diagnosis?
• What is the mediastinal mass?

Answer 1

• ALL
  
  • •The very high WBC (180 × 10⁹/l) in a child means a diagnosis of leukaemia is almost certain
  • The low Hb (93 g/l) and platelet count (43 × 10⁹/l) are the result of bone marrow infiltration
• The mediastinal mass is the thymus, which is infiltrated by T lymphoblasts

Question 2

What would be the best technique to confirm the diagnosis?

• 1 Immunophenotyping
• 2 Cytochemistry

Answer 2

Immunophenotyping

Question 3

What should be the follow-up in this child?

Answer 3

• The high WBC lessens the chance of cure but nevertheless there is a realistic chance of cure in this child
• He requires combination chemotherapy and CNS-directed therapy

Question 4

• 48-year-old male – railway engineer
• 2-week history bleeding gums → attended dentist – severe bleeding
• 1 episode of haematuria and minor bruising
• Attended Accident and Emergency department
  
  • Left subconjunctival haemorrhage Small bruises over abdomen
  • No enlarged lymph nodes No hepatosplenomegaly

Answer 4

Blood count, film and coagulation screen

Question 5

• Normal Renal function
• Minor liver derangement (longstanding)
  
  • Alanine transaminase 97 iu/l (0‒37) HIGH
  • Alkaline phosphatase 72 iu/l (30‒130) Normal
  • Bilirubin 24 μmol/l (0‒17) HIGH
• FBC:
  
  • WBC 7.5 × 109/l (4.0‒11) Normal
  • Hb 109 g/l (130‒170) LOW
  • MCV 83 fl (80-96) Normal/LOW
  • Platelets 21 × 109/l (120‒400) LOW
• Coagulation screen:
  
  • PT 13.4s (9.5-13.5) Normal
  • APTT 21.5s (24-32) LOW
  • Fibrinogen 0.97g/L (1.8-3.6) LOW

How would you explain a short APTT and a low fibrinogen? What other tests do you need?

Answer 5

Raises suspicion of a DIC (activated coagulation factors in circulation making APTT short) → do a D-dimer test to check…

Question 6

Answer 6

• Granules strongly suggest myeloid
• Proof

–Cytochemistry

–Immunophenotyping

–But note that neither test is actually necessary

Question 7

Answer 7

Acute promyelocytic leukaemia

Question 8

Answer 8

Cytogenetic analysis etc

• This can be confirmed using cytogenetic analysis/FISH/molecular genetic analysis – n.b. you already know this is myeloid (Auer rods) so immunophenotyping is not too useful – now you want to determine APML from AML
• This will show the t (15;17) forming the PML-RARA fusion gene

Question 9

What would the cytogenetic test show? How would you manage this patient? What would the prognosis be with tx?

Answer 9

Question 10

• A 68-year-old retired secretary
• Gradual onset of fatigue, lethargy and exertional dyspnoea
• Non-smoker, not much alcohol, good diet
• On examination:
  
  • Pallor (conjunctival and nail bed)
  • Mild ankle oedema
• FBC:
  
  • WBC 4.7 × 109/l (3.7–9.5) Normal
  • Hb 76 g/l (115–150) LOW
  • MCV 110 fl (82–98) HIGH
  • Neutrophils 1.4 × 109/l (NR 1.7–6.1) LOW
  • Platelet count 182 × 109/l (NR 145–350) Normal

Answer 10

Blood film

Question 11

• Serum vitamin B12 — normal
• Red cell folate — normal
• Liver function tests — normal
• Thyroid function tests — normal
• Ferritin — 875 μg/l (normal range 20–200)
  
  • N.B. this is probably not dangerous

•What do you suspect and what would you do next?

Answer 11

She has a dimorphic blood film

Suspect sideroblastic syndrome, BM aspirate

Question 12

• Bone marrow aspirate
• 12% blast cells (normal < 5%)
• 45% of erythroblasts were ring sideroblasts

Answer 12

myelodysplastic syndrome (MDS) (MDS with excess of blasts)

Question 13

What would the management be? What is the prognosis of this?

Answer 13

Question 14

The ferritin was 875 μg/l (NR 20–200) Why?

Does it matter?

1 Yes

2 No

3 Probably not

Answer 14

Probably not - predicted survival not many years so ferritin won’t rise to a point where it would be significant

Question 15

• A 72-year-old Indian woman
• Vegetarian, teetotal, non-smoker
• SOBOE, fatigue
• Painful gums and tongue, unable to eat spicy food
• On examination: pallor only
• Test results:
  
  • WBC and platelets normal
  • Hb 52 g/L
  • MCV 122 fl

What is the most important test?

Answer 15

• Hypersegmented neutrophils (so, measure vitamin B12 and folate)
• Tear drop poikilocytosis
• Oval macrocytes

Question 16

Answer 16

BM aspirate

Question 17

Do you think the patient has a myelodysplastic syndrome?

1 Yes

2 No

Answer 17

No

• Parietal cell antibodies: positive
• Intrinsic factor antibodies: positive
• The patient turned out to be a vegan
• You should now know the correct diagnosis and be able to explain how you would treat the patient

Question 18

• 70yo woman referred to vascular surgeon due to gangrenous toes
• Non-diabetic, 50-pack-year history
• SOBOE and morning cough
• On examination:
  
  • Reduced femoral and distal pulses on side of affected toes
  • Not breathless at rest, no cyanosis
  • Plethora, conjunctival suffusion
  • Spleen not felt

What simple test would you do first?

Answer 18

FBC, blood gas

Question 19

Answer 19

Polycythaemia vera

Question 20

Answer 20

Molecular analysis for JAK2 mutation

Question 21

Answer 21

Venesection plus hydroxycarbamide

Question 22

Answer 22

This would be unsuitable alone as it will not reduce the platelet count