Haematological Malignancies

Question 1

Where do multiple myelomas originate?

Answer 1

MM is a disease of proliferative B plasma cells, but the initial event probably occurs earlier

Question 2

What is M-protein (in the context of multiple myeloma?)

Answer 2

The large amounts of clonal protein secreted by B plasma cells in MM. Also known as Bence-Jones protein

Question 3

Describe the pathophysiology of multiple myeloma

Answer 3

• B plasma cell proliferation
• M-protein hypersecretion
  
  • Amyloidosis, hyperviscosity, renal failure
  • Suppression of other Igs - immunosuppression
• Bone marrow infiltration
  
  • Anaemia, bone pain, hypercalcaemia

Question 4

Myelomas are described by three major groups. What are they and how are they distinguished?

Answer 4

• Monoclonal gammopathy of uncertain significance
  
  • Serum M-protein < 30 g/L
  • Marrow clonal plasma cells > 10%
• Smouldering myeloma
  
  • Serum M-protein > 30 g/L but no CRAB
  • Marrow clonal plasma cells > 10%
• Symptomatic multiple myeloma
  
  • Serum M-protein > 30 g/L with CRAB
  • Marrow clonal plasma cells > 10%

Question 5

What are the signs of end-organ damage in multiple myeloma?

Answer 5

• C - hypercalcaemia
• R - renal failure
• A - anaemia
• B - lytic bone lesions

Question 6

What are the some red flags that may indicate multiple myeloma?

Answer 6

• Pathological fractures/bone pain
• Unexplained anaemia (with rouleaux)
• High total protein but low albumin
• Unexplained hypercalcaemia/renal failure

Question 7

What investigations are warranted in suspected multiple myeloma?

Answer 7

• FBE (exclude anaemia)
• U&E (renal function)
• Ca (hypercalcaemia?)
• Protein electrophoresis
• BM aspirate/trephine - flow cytometry, FISH
• Bone scan

Question 8

How is symptomatic multiple myeloma managed?

Answer 8

• Steroids (high dose)
• Management of underlying disease
  
  • Local radiotherapy
  • Systemic chemotherapy
• Management of complications
  
  • Bisphosphonates (hypercalacemia)
  • Transfusions (anaemia)

Question 9

What are the two main types of lymphoma? One of them is distinguished histologically by …?

Answer 9

• Hodgkin’s lymphoma - Reed-Sternberg binucleate cells
• Non-Hodgkin’s lymphoma

Question 10

What is the most aggressive non-Hodgkin’s lymphoma? The least? The most common/curable?

Answer 10

• Most aggressive - Burkitt
• Least aggressive - follicular
• Most common/curable - diffuse large B cell

Question 11

What red flags on presentation should prompt consideration of lymphoma?

Answer 11

• Lymphadenopathy (especially firm, rubbery, non-tender)
• Cough/dyspnoea with mediastinal mass
• Abdominal swelling
• PUO/night sweats

Question 12

How is lymphoma staged?

Answer 12

• Ann Arbor classifcation
  
  1. Single region
  2. Two regions but one side of diaphragm
  3. Both sides of diaphragm
  4. Extralymphatic involvement
• A or B denotes absence or presence of constitutional symptoms

Question 13

What features might form the acute presentation of a patient with a leukaemia?

Answer 13

• A - anaemic symptoms
• N - neutropaenia (fever, rigors, infections)
• T - thrombocytopaenia
• B-symptoms (fever, sweats, weight loss)

Question 14

How is CML diagnosed? What are the management principles?

Answer 14

• Philadelphia chromosome (BCR-ABL)
• Tyrosine kinase inhibitors

Question 15

How is CLL diagnosed? What are the management principles and prognosis?

Answer 15

• Flow cytometry
• Chemotherapy based on symptoms. Cytogenetics may offer prgnostic significance

Question 16

How is AML diagnosed? What are the management principles and prognosis?

Answer 16

• Cytogenetics (also indicates prognosis)
• Chemotherapy (according to symptoms and prognosis), with consideration of BMT

Question 17

How is APML diagnosed? What are the management principles and prognosis?

Answer 17

• Deranged coagulation studies, cytogenetics (PML-RARA)
• Good prognosis
• Correct coagulopathy, ATRA therapy