Oncology / Haematology 3 Flashcards
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?
Howell-Jolly bodies
Howell-Jolly bodies are present in Hereditary Spherocytosis post-splenectomy
What are Howell-Jolly bodies?
Are these present post-splenectomy?
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.
Which is the most common Hereditary Haemolytic anaemia in people of Northern European descent?
Hereditary spherocytosis
How is Hereditary spherocytosis inherited?
Autosomal dominant defect of red blood cell cytoskeleton
What change in RBC morphology is seen in Hereditary Spherocytosis compared to a normal RBC?
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.
How might someone with Hereditary Spherocytosis present?
- Failure to thrive
- (Neonatal) Jaundice, gall stones
- Splenomegaly
- Aplastic crisis precipitated by parvovirus infection
- Degree of haemolysis variable
- MCHC elevated
How should Hereditary Spherocytosis be diagnosed?
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.
What is the management of an Acute Haemolytic crisis in a patient with Hereditary Spherocytosis?
- Treatment is generally supportive
- Transfusion if necessary
What is the longer term treatment for someone with Hereditary Spherocytosis?
- Folate replacement
- Splenectomy
What is seen on a blood film of a patient with Hereditary Spherocytosis?
Spherocytes (round, lack of central pallor)
Which gender does Hereditary Spherocytosis affect and why?
- Affects both genders
- Autosomal dominant inheritance
Who does G6PD affect and why?
- Males
- X-linked recessive pattern of inheritance
Which ethnicity does G6PD tend to affect?
People of African & Mediterranean descent
Give a typical history of a patient with G6PD.
- Neonatal jaundice
- Infection / drugs precipitate haemolysis
- Gallstones
What is seen on a blood film of a patient with G6PD ?
Heinz Bodies
What is the diagnostic test used to identify a patient with G6PD?
Measure enzyme activity of G6PD.
People of which ethnicity are usually affected by Hereditary Spherocytosis?
Northern European descent
Give a typical history of a patient presenting with Hereditary Spherocytosis.
- Neonatal jaundice
- Chronic symptoms, although haemolytic crises may be precipitated by infection
- Gall stones
- Splenomegaly is common
What is the diagnostic test for a patient with suspected Hereditary Spherocytosis?
EMA binding test.
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?
Waldenstrom’s macroglobulinaemia
In this case, the patient most likely has a type of lymphoma (lymphopasmacytic lymphoma) producing excess IgM.
How does Waldenstrom’s macroglobulinaemia usually present?
- Bone marrow infiltration
- Splenomegaly
- Sometimes lymphadenopathy
- In contrast to myeloma, it does not cause lytic bone lesions or hypercalcaemia.
What level of Monoclonoal paraprotein band is required for a diagnosis of MGUS (Monoclonal gammopathy of unknown significance)?
Patients must have a monoclonal paraprotein band less than 30g/l.
Who is usually affected by Waldenstrom’s macroglobulinaemia?
- Usually seen in older men (an uncommon condition)
What is Waldenstrom’s macroglobulinaemia?
A lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein.
What are the features of Waldenstrom’s macroglobulinaemia?
- 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
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?
Stage III
Stage III of the Ann-Arbor clinical staging of lymphomas involve nodes on both sides of the diaphragm.
Hodgkin’s Lymphoma
Ann Arbor
Stage 1
Involves a single regional lymph node.
Hodgkin’s Lymphoma
Ann Arbor
Stage 2
Involves 2 or more lymph nodes on one side of the diaphragm.
Hodgkin’s Lymphoma
Ann Arbor
Stage 3
Involves lymph nodes on both sides of the diaphragm.
Hodgkin’s Lymphoma
Ann Arbor
Stage 4
Distant spread involving one or more extra lymphatic lymph nodes
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.
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
What is the genetic change associated with Burkitt’s Lymphoma?
C-myc gene translocation
What is Burkitt’s Lymphoma?
A high-grade B-cell neoplasm
What are the two major forms of Burkitt’s lymphoma?
- Endemic (African) form: typically involves the maxilla or mandible
- Sporadic form: Abdominal (ileo-caecal) tumours are the most common form. More common in patients with HIV.
Burkitt’s lymphoma is associated with the c-myc gene translation. How is this expressed in numbers?
t(8:14)
Which virus is strongly implicated in the development of the African form of Burkitt’s lymphoma (and, to a lesser extent, the sporadic form)?
Epstein-Barr Virus
What would you find on microscopy of a patient with Burkitt’s lymphoma?
‘Starry sky’ appearance:
Lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells.
Explain the management of a patient with Burkitt’s Lymphoma.
- 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.
Give 5 complications of Tumour Lysis Syndrome/
- Hyperkalaemia
- Hyperphosphataemia
- Hypocalcaemia
- Hyperuricaemia
- Acute renal failure
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
Female sex
List 8 poor prognostic factors in Chronic Lymphocytic Leukaemia.
- 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
Which chromosomal change in CLL is associated with a good prognosis?
- Deletion of the long arm of Chr 13 (del 13q)
- Most common abnormality
- Seen in around 50% of patients.
Which chromosomal change in CLL is associated with a poor prognosis?
- Deletion of part of the short arm of chromosome 17 (del 17p)
- Seen in around 5-10% of patients
- Associated with a poor prognosis
