Multiple myeloma

Question 1

What is multiple myeloma?

Answer 1

Haematological malignancy characterised by proliferation of antibody-releasing plasma B cells resulting in bone lesions and production of a monoclonal immunoglobulin (paraprotein, usually IgG or IgA)

Question 2

What is a paraprotein?

Answer 2

A monoclonal immunoglobulin.

Question 3

What is the aetiology of multiple myeloma?

Answer 3

Unknown though theories suggest genetics, viral triggers, ionizing radiation, agricultural work and occupational chemical exposures including benzene. Associated with various chromosomal abnormalities, notably in Chr13 and Chr14.

Question 4

What is the pathophysiology of multiple myeloma? Kidneys and anaemia?

Answer 4

• B cells become plasma cells when they reside and mature in the lymph node.
• In MM, B plasma cells undergo immunoglobulin gene rearrangement, hypermutation and class switching of immunoglobulin heavy chains
• Class switching results in myeloma cell adhesion to bone marrow stromal cells (BMSCs) resulting in cytokine secretion from BMSCs, stimulating osteoclast activity and impairing osteoblast formation
• The produced antibodies are deposited in various organs, leading to kidney failure and various other myeloma-associated symptoms.
• Anaemia results from replacement of normal bone marrow by infiltrating tumour cells and inhibition of normal red blood cell production by cytokines

Question 5

What is the epidemiology of multiple myeloma: Age? Ethnicity?

Answer 5

Peak incidence in 70-year-olds. Afro-Caribbean > white people > Asians.

Question 6

What are the signs and symptoms of multiple myeloma? (x7)

Answer 6

• CRAB HIM
• CALCIUM: hypercalcaemia leads to neurological symptoms
• RENAL: polyuria, thirst
• ANAEMIA: tiredness, pallor, signs of heart failure
• BONE: pain, often in back and ribs. Sudden if caused by pathological fracture or vertebral collapse
• HYPERVISCOSITY: bleeding, purpura, headaches, visual disturbances
• INFECTIONS: often recurrent, due to normal Ig production impairment resulting in relative hypogammaglobinaemia
• MOUTH: macroglossia, numbness, pain and numbness

Question 7

What is the pathophysiology of neurological symptoms in multiple myeloma?

Answer 7

Osteolysis results in hypercalcaemia which results in decreased neuronal excitability (outcompeting sodium influx) and subsequent depression and cognitive impairment.

Question 8

What are the blood investigations for multiple myeloma?

Answer 8

Low Hb, normocytic, raised ESR (and CRP), high creatine, high calcium, typically normal alkaline phosphatase (sign of osteoblast activity), sometimes raised LDH (indicates extensive disease)

Question 9

What are the other investigations for multiple myeloma? (x4)

Answer 9

• SERUM/URINE ELECTROPHERESIS: diagnostic; paraprotein spike of IgG or IgA (secreted into serum and urine), free light chains in urine, and relative hypogammaglobulinaemia
• BONE MARROW ASPIRATE and TREPHINE: diagnostic; raised plasma cells (large cells with perinuclear halo, eccentric nuclei and blue cytoplasm) – usually at least 20%. Look at photo
• WHOLE BODY LOW-DOSE CT: to screen for osteolytic lesions with surrounding sclerosis
• BLOOD FILM: rouleaux formation (stacked RBCs) with bluish background (indicating high protein)