Multiple Myeloma

Question 1

Definition

Answer 1

Neoplastic monoclonal proliferation of a plasma cell - excess secretion of one type of immunoglobulin’s:
Excess IgG - 55%
Excess IgA - 20%

Question 2

Epidemiology

Answer 2

65 + (MC 65-69)
Afro Caribbean’s > Whites

Question 3

Risk Factors

Answer 3

Increasing age
Family history
Radiation exposure

Question 4

Pathophysiology

Answer 4

Cancer of differentiates B lymphocytes (plasma cells) = malignant plasma cell accumulate in the bone marrow -> BM failure
Other antibodies low = IMMUNOPARESIS = more susceptible to infections
“BENCE JONES PROTEINS” - may be found in the urine = light chain subunit of the antibody

Question 5

How does Multiple Myeloma cause hypercalcaemia

Answer 5

Neoplastic cells release cytokines (IL-1) causing activation of osteoclasts via RANK receptor. This leads to bone resorption, resulting in bone pain and lytic lesions on imaging.
Also release DKK-1 = inhibit OPG which usually inhibits osteoclasts

Question 6

How does Multiple Myeloma cause renal insufficiency

Answer 6

Deposition of Bence jones proteins, nephrocalcinosis (calcium deposition in renal parenchyma)

Question 7

How does Multiple Myeloma cause Anaemia

Answer 7

bone marrow infiltration by plasma cells = reduced haematopoiesis + pancytopenia

Question 8

How does multiple myeloma cause bone lesions

Answer 8

Osteoclast activation

Question 9

Signs

Answer 9

Signs due to amyloidosis:
- Macroglossia
- Carpel Tunnel Syndrome: Tinels and Phalens sign positive
- Peripheral neuropathy
Pallor

Question 10

Symptoms

Answer 10

Hypercalcaemia : bones, stones, abdo groans, thrones and psychiatric moans
Fatigue (anaemia)
Bleeding and bruising (thrombocytopaenia)
Recurrent infections (Reduction in normal immunoglobulins)

Question 11

OLD CRAB

Answer 11

Old = Over 75
C = Hypercalcaemia
R = Renal Insufficiency
A = Anaemia
B = Bone Lesions (OSTEOLYTIC LESIONS)

Question 12

Diagnosis

Answer 12

FBC + Blood film = normocytic normochromic + high ESR
- ROULEAUX FORMATION = aggregation of RBC together
Urine Dipstick = BENCE JONES PROTEINS
U + E = renal failure XR KUB (kidney stones)
Serum electrophoresis = Ig “M spike” paraprotein, hypergammaglobulinaemia for that specific Ig
XR = skull = PEPPER POT SKULL, OSTEOLYTIC LESIONS -> PUNCHEDOUT HOLES
Bone profile = hypercalcaemia + high ALP
GOLD STANDARD = Bone Marrow Aspiration > 10% monoclonal plasma cells in the bone marrow

Question 13

Monoclonal gammopathy of uncertain significance (MGUS)

Answer 13

A precursor for myeloma
<10% BM plasma cells
No little paraprotein spike
ASYMPTOMATIC

Question 14

Treatment

Answer 14

Incurable + follows a relapsing remitting course
- Good performance < 70 years: Cyclophosphamide, thalidomide + dexamethasone (CTD) followed by stem cell transplant
- Poor performance >70 years:
Vincristine, Adriamycin, Dexamethasone (VAD) followed by stem cell transplant
- Bisphosphonates = ZOLENDRONATE or CLODRONATE