Oncology / Haematology 3

Question 1

A 32yo male presents to your clinic for review. He has a history of Hereditary Spherocytosis and recently underwent a splenectomy.
Since the operation, he’s noticed a major improvement in his energy levels.
If a blood film was taken from the patient, what new histological finding would be observed, which would have been absent prior to splenectomy?

Answer 1

Howell-Jolly bodies

Howell-Jolly bodies are present in Hereditary Spherocytosis post-splenectomy

Question 2

What are Howell-Jolly bodies?

Are these present post-splenectomy?

Answer 2

The remnants of the red blood cell nucleus which are normally removed by the spleen.
Post-splenectomy, these Howell-Jolly bodies persist and can be observed on histology.

Question 3

Which is the most common Hereditary Haemolytic anaemia in people of Northern European descent?

Answer 3

Hereditary spherocytosis

Question 4

How is Hereditary spherocytosis inherited?

Answer 4

Autosomal dominant defect of red blood cell cytoskeleton

Question 5

What change in RBC morphology is seen in Hereditary Spherocytosis compared to a normal RBC?

Answer 5

Normal biconcave disc shape is replaced by a sphere-shaped red blood cell
* Red blood cell survival is reduced as it is destroyed by the spleen.

Question 6

How might someone with Hereditary Spherocytosis present?

Answer 6

• Failure to thrive
• (Neonatal) Jaundice, gall stones
• Splenomegaly
• Aplastic crisis precipitated by parvovirus infection
• Degree of haemolysis variable
• MCHC elevated

Question 7

How should Hereditary Spherocytosis be diagnosed?

Answer 7

British Journal of Haematology guidelines state:
‘Patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration (MCHC), increase in reticulocytes) do not require any additional tests.

If the diagnosis is equivocal, the BJH recommend the cryohaemolysis test and EMA binding.

For atypical presentations, electrophoresis analysis of erythrocyte membranes is the method of choice.

Question 8

What is the management of an Acute Haemolytic crisis in a patient with Hereditary Spherocytosis?

Answer 8

• Treatment is generally supportive

- Transfusion if necessary

Question 9

What is the longer term treatment for someone with Hereditary Spherocytosis?

Answer 9

• Folate replacement

- Splenectomy

Question 10

What is seen on a blood film of a patient with Hereditary Spherocytosis?

Answer 10

Spherocytes (round, lack of central pallor)

Question 11

Which gender does Hereditary Spherocytosis affect and why?

Answer 11

• Affects both genders

- Autosomal dominant inheritance

Question 12

Who does G6PD affect and why?

Answer 12

• Males

- X-linked recessive pattern of inheritance

Question 13

Which ethnicity does G6PD tend to affect?

Answer 13

People of African & Mediterranean descent

Question 14

Give a typical history of a patient with G6PD.

Answer 14

• Neonatal jaundice
• Infection / drugs precipitate haemolysis
• Gallstones

Question 15

What is seen on a blood film of a patient with G6PD ?

Answer 15

Heinz Bodies

Question 16

What is the diagnostic test used to identify a patient with G6PD?

Answer 16

Measure enzyme activity of G6PD.

Question 17

People of which ethnicity are usually affected by Hereditary Spherocytosis?

Answer 17

Northern European descent

Question 18

Give a typical history of a patient presenting with Hereditary Spherocytosis.

Answer 18

• Neonatal jaundice
• Chronic symptoms, although haemolytic crises may be precipitated by infection
• Gall stones
• Splenomegaly is common

Question 19

What is the diagnostic test for a patient with suspected Hereditary Spherocytosis?

Answer 19

EMA binding test.

Question 20

A 68yo man presents with lymphadenopathy. On examination you note splenomegaly. Investigations reveal:
Hb: 125g/dl
Calcium: 2.34 mmol/l
Creatinine: 101 mol/l
Further investigations reveal an IgM paraprotein of 40g/l and skeletal survey shows no bone lesions.
What’s the most likely diagnosis?

Answer 20

Waldenstrom’s macroglobulinaemia

In this case, the patient most likely has a type of lymphoma (lymphopasmacytic lymphoma) producing excess IgM.

Question 21

How does Waldenstrom’s macroglobulinaemia usually present?

Answer 21

• Bone marrow infiltration
• Splenomegaly
• Sometimes lymphadenopathy
• In contrast to myeloma, it does not cause lytic bone lesions or hypercalcaemia.

Question 22

What level of Monoclonoal paraprotein band is required for a diagnosis of MGUS (Monoclonal gammopathy of unknown significance)?

Answer 22

Patients must have a monoclonal paraprotein band less than 30g/l.

Question 23

Who is usually affected by Waldenstrom’s macroglobulinaemia?

Answer 23

• Usually seen in older men (an uncommon condition)

Question 24

What is Waldenstrom’s macroglobulinaemia?

Answer 24

A lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein.

Question 25

What are the features of Waldenstrom's macroglobulinaemia?

Answer 25

- Monoclonal IgM paraproteinaemia - Systemic upset: weight loss, lethargy - Hyperviscosity syndrome eg. visual disturbance: the pentameric configuration of IgM increases serum viscosity. - Hepatosplenomegaly - Lymphadenopathy - Cryoglobulinaemia eg. Raynaud's

Question 26

A 28yo gentleman was diagnosed with Hodgkin's Lymphoma after presenting to his GP with painless lymphadenopathy. Following a staging PET scan, nodes involving both sides of the diaphragm were found. Which stage of the Ann-Arbor classification does his presentation fall under?

Answer 26

Stage III Stage III of the Ann-Arbor clinical staging of lymphomas involve nodes on both sides of the diaphragm.

Question 27

Hodgkin's Lymphoma Ann Arbor Stage 1

Answer 27

Involves a single regional lymph node.

Question 28

Hodgkin's Lymphoma Ann Arbor Stage 2

Answer 28

Involves 2 or more lymph nodes on one side of the diaphragm.

Question 29

Hodgkin's Lymphoma Ann Arbor Stage 3

Answer 29

Involves lymph nodes on both sides of the diaphragm.

Question 30

Hodgkin's Lymphoma Ann Arbor Stage 4

Answer 30

Distant spread involving one or more extra lymphatic lymph nodes

Question 31

Each stage of the Ann-Arbor classification for staging Hodgkin's Lymphoma can be divided into 'A' or 'B' subtypes. Explain the difference between these.

Answer 31

A: No systemic symptoms other than pruritus. B: - Weight loss > 10% in the last 6 months - Fever > 38oC - Night sweats * * Type B has a poor prognosis

Question 32

What is the genetic change associated with Burkitt's Lymphoma?

Answer 32

C-myc gene translocation

Question 33

What is Burkitt's Lymphoma?

Answer 33

A high-grade B-cell neoplasm

Question 34

What are the two major forms of Burkitt's lymphoma?

Answer 34

1. Endemic (African) form: typically involves the maxilla or mandible 2. Sporadic form: Abdominal (ileo-caecal) tumours are the most common form. More common in patients with HIV.

Question 35

Burkitt's lymphoma is associated with the c-myc gene translation. How is this expressed in numbers?

Answer 35

t(8:14)

Question 36

Which virus is strongly implicated in the development of the African form of Burkitt's lymphoma (and, to a lesser extent, the sporadic form)?

Answer 36

Epstein-Barr Virus

Question 37

What would you find on microscopy of a patient with Burkitt's lymphoma?

Answer 37

'Starry sky' appearance: | Lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells.

Question 38

Explain the management of a patient with Burkitt's Lymphoma.

Answer 38

- Chemotherapy BUT this may cause Tumour Lysis Syndrome. - Rasburicase (a recombinant version of urate oxidase, and enzyme which catalyses the conversion of uric acid to allantoin) is often given before the chemotherapy to reduce the risk of this occurring.

Question 39

Give 5 complications of Tumour Lysis Syndrome/

Answer 39

- Hyperkalaemia - Hyperphosphataemia - Hypocalcaemia - Hyperuricaemia - Acute renal failure

Question 40

Which of the following is a good prognostic factor in Chronic Lymphocytic Leukaemia? - Female sex - Lymphocyte doubling time <12 months - CD38 expression positive - Age > 70 years - Raised LDH

Answer 40

Female sex

Question 41

List 8 poor prognostic factors in Chronic Lymphocytic Leukaemia.

Answer 41

- Male sex - Age > 70 years - Lymphocyte count > 50 - Prolymphocytes comprising more than 10% of blood lymphocytes - Lymphocyte doubling time <12 months - Raised LDH - CD38 expression positive - TP53 mutation

Question 42

Which chromosomal change in CLL is associated with a good prognosis?

Answer 42

- Deletion of the long arm of Chr 13 (del 13q) - Most common abnormality - Seen in around 50% of patients.

Question 43

Which chromosomal change in CLL is associated with a poor prognosis?

Answer 43

- Deletion of part of the short arm of chromosome 17 (del 17p) - Seen in around 5-10% of patients - Associated with a poor prognosis