Plasma Cell Myeloma and Amyloid

Question 1

what is multiple myeloma?

Answer 1

Cancer of the BM plasma cells, terminally differentiated and Ig secreting B cells

Question 2

What kind of tumours do myeloma plasma cells produce?

Answer 2

Bone expansile / soft tissue tumours

Question 3

What kind of Ig do myeloma plasma cells produce?

Answer 3

MONOCLONAL Ig

either IgA or IgG

Question 4

What is the most important structure produced by myeloma plasma cells?

Answer 4

Excess of monoclonal (K/lambda) serum free light chains

aka BENCE JONES PROTEIN

Question 5

What condition can predispose to MM?

Answer 5

Pre-malignant condition called:

Monoclonal Gammopathy of Uncertain Significance (MGUS)

Question 6

What is median survival for MM?

Answer 6

4-7 years

POOR prognosis

Question 7

Explain pathophysiology of MM

Answer 7

Early in plasma cell, error occurs in genome
This leads to monoclonal accumulation of plasma cells (MGUS)
1% of people every year acquire extra mutations (KRAS, NRAS) which transform MGUS into MM

Question 8

What is the average age for myeloma?

Answer 8

67

Question 9

What are RF for myeloma?

Answer 9

Age
Obesity
Genetic (sporadically familial)
Black

Question 10

What proportion of patients a year go from MGUS too MM?

Answer 10

1%

Question 11

What disease occurs if from MGUS there is excess IgM production?

Answer 11

Lymphoma

Question 12

What bone marrow plasma cell percentage is required for MGUS classification?

Answer 12

<10%

Question 13

What disease sits between MGUS and MM?

Answer 13

Smouldering myeloa

Question 14

What is the progression of MM?

Answer 14

Incurable
Periods of remission-relapse
Becomes refractory to tx
Becomes extramedullary disease, with circulating plasma cells

Question 15

What is the most common primary event that causes MM?

Answer 15

HYPERPLOIDY (additional odd number chromosome)

Question 16

What is another primary event that causes MM?

Answer 16

heavy immunoglobulin chain rearrangement

Question 17

What occurs genetically in each pt with MM’

Answer 17

In each patient there are multiple subclones with genetic lesions
As tumour develops, more lesions accumulate in linear /branching fashion
This creates evolutionary pressure
Selects either indolent or aggressive clones

Question 18

What is the aetiology of MM causing bone destruction?

Answer 18

MM releases cytokines

cytokines stimulate osteoclasts to induce bone resorptiìon

Question 19

What percentage of plasma cells in bone marrow are required for MM dx?

Answer 19

> =10% plasma cells in bone marrow

Question 20

What are the clinical presentations of MM? ACRONYM

Answer 20

CRAB

Calcium elevated
Renal impairment
Anaemia
Bone lesions

Question 21

What diagnosis is a good indicator that pt will develop myeloma in coming months?

Answer 21

MDE (Myeloma Defining Event)

Question 22

What cellular markers is MM positive for?

Answer 22

CD138
CD38
CD56
CD58

Question 23

What cellular markers in MM negative for?

Answer 23

CD19
CD20
Surface IgG

Question 24

What does bone disease present like in MM?

Answer 24

Proximal skeleton affected
Spine, chest wall, pelvic pain 
OsteoLYTIC lesions 
Osteopoenia 
Pathological fractures 
Hypercalcaemia

Question 25

What is the key bone emergency in MM?

Answer 25

Cord compression | Due to spine fracture > soft tissue enters spinal canal or soft tissue mass forms

Question 26

What is tx for cord compression in MM?

Answer 26

Dexamethasone Radiotherapy Neurosurgery

Question 27

How do you image MM bone lesions?

Answer 27

MRI or CT scan (or PET) | NOT plain X ray film. obsolete as low sensitivity

Question 28

What is the key cause of kidney injury in MM'

Answer 28

FLC and Bence Jones Proteins

Question 29

How do light chains cause kidney injury in MM?

Answer 29

High quantity of free light chains produced Proximal tubule can no longer uptake them, as under high stress FLC travel to distal tubule Here they bind to THP This complex obstructs the tubule and eventually destroys the nephron

Question 30

How do you treat kidney disease in MM?

Answer 30

BORTEXOIB

Question 31

What marker of mM do you look for in bone marrow aspirate?

Answer 31

CD138

Question 32

What does AL amyloidosis occur due to?

Answer 32

Misfolded free light chains aggregate into amyloid fibrils in target organs

Question 33

What kind of stain do you use for AL amyloidosis?

Answer 33

CONGO red

Question 34

What are 2 common target organs of AL amyloidosis=?

Answer 34

Kidney - nephrotic syndrome | Heart - heart failure

Question 35

What are the 4 key domains for MM treatment=?

Answer 35

Cytostatic drugs e.g. melphalan, cycophosphamide Steroids Immunomodulators e.g. thalidomide Proeasome inhibitors

Question 36

What are other immunomodulators that are used for M M?

Answer 36

Lenalidomide | Pomalidomide

Question 37

What are examples of protease inhibitors?

Answer 37

Bortezomib