Pathology of Plasma Cell Lesions and Amyloid

Question 1

What are the red flags for back pain?

Answer 1

Pain at night
Pain at rest
Trauma
Constitutional symptoms
Incontinence
Radicular pain
IVDU
Other neurological symptoms
Localised tenderness

Question 2

What do rouleaux on the blood film indicated?

Answer 2

Happen when plasma protein level high

Presence of disease

Question 3

For what diseases is beta 2 microglobulin measured?

Answer 3

Multiple myeloma

Lymphoma

Question 4

What is Congo Red stain used for?

Answer 4

Amyloid

Question 5

What are plasma cell neoplasms?

Answer 5

Proliferation of clone of plasma cells
Often produce
- Monoclonal Ig = paraprotein/M protein
- Free light chains

Question 6

Which plasma cell neoplasm often affects the axial skeleton?

Answer 6

Multiple myeloma

Question 7

What happens in monoclonal gammopathy of undetermined significance (MGUS)?

Answer 7

Bone marrow based clonal proliferation of plasma cells
Make up <10% of total cells
Low levels of M protein

Question 8

What happens in solitary plasmacytoma of bone, or extraosseus plasmacytoma?

Answer 8

Single clonal proliferation of plasma cells within bone/soft tissue
May produce M protein

Question 9

What happens in multiple myeloma?

Answer 9

Multifocal, bone marrow based, monoclonal proliferation of plasma cells
More than 10% of plasma cells
High levels of M protein

Question 10

What happens in symptomatic multiple myeloma?

Answer 10

Organ/tissue impairment = CRAB

• C = hyper-calcaemia
• R = renal insufficiency
• A = anaemia
• B = bone lesions

Question 11

Is MGUS considered neoplastic?

Answer 11

No

Question 12

What can MGUS evolve into?

Answer 12

Plasma cell myeloma
Other lymphoproliferative disorders
Amyloidosis

Question 13

What is the cell of origin in multiple myeloma?

Answer 13

Post-germinal centre B cell

Question 14

What is the median age of diagnosis of multiple myeloma?

Answer 14

70 yrs

Question 15

Other than CRAB, what other things can occur in symptomatic multiple myeloma?

Answer 15

Increased susceptibility to infection
Hyper-viscosity
Amyloidosis

Question 16

How does hyper-calcaemia present?

Answer 16

Neurological manifestations
Polyuria
Constipation
Nephrocalcinosis
Renal calculi

Question 17

How do bone lesions occur in multiple myeloma?

Answer 17

Neoplastic cells produce factors > activate osteoclasts and inhibit osteoblasts > bone erosion

Question 18

How do bone lesions present?

Answer 18

Pain
Pathological fractures
Hyper-calcaemia

Question 19

Why do patients with multiple myeloma get anaemia?

Answer 19

Neoplastic proliferation in bone marrow > pancytopaenia

Question 20

How do bisphosphonates work?

Answer 20

Bind to Ca > ingested by osteoclasts > cause apoptosis > overall decrease in bone resorption

Question 21

Why are bisphosphonates used in the symptom management of multiple myeloma?

Answer 21

Decrease hyper-calcaemia and bone resorption

Question 22

What are the circulating monoclonal immunoglobulins in multiple myeloma?

Answer 22

IgG in 50%
IgA in 20%
Light chains in 20%

Question 23

What causes hyper-viscosity syndrome in symptomatic multiple myeloma?

Answer 23

Increased blood viscosity

• ESR
• Rouleaux

Question 24

What causes increased susceptibility to infection in symptomatic multiple myeloma?

Answer 24

Abnormal Ig > impaired humoral immunity

Question 25

What causes renal insufficiency in symptomatic multiple myeloma?

Answer 25

``` Hyper-calcaemia Hyper-viscosity syndrome Increased susceptibility to infection Light chains filtered by kidney Light chains deposit in tissues, including kidney, as amyloid ```

Question 26

What are light chains when detected in the urine in plasma cell lesions called?

Answer 26

Bence-Jones proteins

Question 27

What is amyloid?

Answer 27

Pathological extracellular protein Fibrillary ultrastructural appearance Due to mis-folding of normal/abnormal proteins Can't be removed

Question 28

What is primary amyloidosis?

Answer 28

Associated with plasma cell/lymphoplasmacytic lesion Usually light chains - usually lambda Usually deposits in multiple organs

Question 29

What sort of light chains can be excreted, and what cannot?

Answer 29

Lambda can't be excreted | Kappa excreted in urine = Bence-Jones proteins

Question 30

What is secondary amyloidosis?

Answer 30

Associated with systemic chronic inflammatory conditions/tumours Derived from serum amyloid associated protein (SAA) = acute phase reactant Usually deposits in multiple organs

Question 31

What are some systemic chronic inflammatory conditions and tumours with which secondary amyloidosis is associated?

Answer 31

``` IBD TB Rheumatoid arthritis Hodgkin's lymphoma Renal cell carcinoma ```

Question 32

What is the amyloid in Alzheimer's disease?

Answer 32

Amyloid beta protein (ABP) Derived from amyloid precursor protein (APP) Forms senile plaques

Question 33

In which conditions does CNS amyloid deposit in vessel walls?

Answer 33

Alzheimer's disease | cerebral amyloid angiopathy

Question 34

What are the complications of amyloidosis?

Answer 34

``` Organ failure - function deteriorates with progressive amyloid deposition Vessels become - Brittle - Prone to rupture Cardiac amyloid - Restrictive cardiomyopathy - Cardiac failure - Arrhythmias Renal amyloid - Proteinuria - Nephrotic syndrome - Chronic renal failure ```