Pathology of Plasma Cell Lesions and Amyloid Flashcards
What are the red flags for back pain?
Pain at night Pain at rest Trauma Constitutional symptoms Incontinence Radicular pain IVDU Other neurological symptoms Localised tenderness
What do rouleaux on the blood film indicated?
Happen when plasma protein level high
Presence of disease
For what diseases is beta 2 microglobulin measured?
Multiple myeloma
Lymphoma
What is Congo Red stain used for?
Amyloid
What are plasma cell neoplasms?
Proliferation of clone of plasma cells
Often produce
- Monoclonal Ig = paraprotein/M protein
- Free light chains
Which plasma cell neoplasm often affects the axial skeleton?
Multiple myeloma
What happens in monoclonal gammopathy of undetermined significance (MGUS)?
Bone marrow based clonal proliferation of plasma cells
Make up <10% of total cells
Low levels of M protein
What happens in solitary plasmacytoma of bone, or extraosseus plasmacytoma?
Single clonal proliferation of plasma cells within bone/soft tissue
May produce M protein
What happens in multiple myeloma?
Multifocal, bone marrow based, monoclonal proliferation of plasma cells
More than 10% of plasma cells
High levels of M protein
What happens in symptomatic multiple myeloma?
Organ/tissue impairment = CRAB
- C = hyper-calcaemia
- R = renal insufficiency
- A = anaemia
- B = bone lesions
Is MGUS considered neoplastic?
No
What can MGUS evolve into?
Plasma cell myeloma
Other lymphoproliferative disorders
Amyloidosis
What is the cell of origin in multiple myeloma?
Post-germinal centre B cell
What is the median age of diagnosis of multiple myeloma?
70 yrs
Other than CRAB, what other things can occur in symptomatic multiple myeloma?
Increased susceptibility to infection
Hyper-viscosity
Amyloidosis
How does hyper-calcaemia present?
Neurological manifestations Polyuria Constipation Nephrocalcinosis Renal calculi
How do bone lesions occur in multiple myeloma?
Neoplastic cells produce factors > activate osteoclasts and inhibit osteoblasts > bone erosion
How do bone lesions present?
Pain
Pathological fractures
Hyper-calcaemia
Why do patients with multiple myeloma get anaemia?
Neoplastic proliferation in bone marrow > pancytopaenia
How do bisphosphonates work?
Bind to Ca > ingested by osteoclasts > cause apoptosis > overall decrease in bone resorption
Why are bisphosphonates used in the symptom management of multiple myeloma?
Decrease hyper-calcaemia and bone resorption
What are the circulating monoclonal immunoglobulins in multiple myeloma?
IgG in 50%
IgA in 20%
Light chains in 20%
What causes hyper-viscosity syndrome in symptomatic multiple myeloma?
Increased blood viscosity
- ESR
- Rouleaux
What causes increased susceptibility to infection in symptomatic multiple myeloma?
Abnormal Ig > impaired humoral immunity
What causes renal insufficiency in symptomatic multiple myeloma?
Hyper-calcaemia Hyper-viscosity syndrome Increased susceptibility to infection Light chains filtered by kidney Light chains deposit in tissues, including kidney, as amyloid
What are light chains when detected in the urine in plasma cell lesions called?
Bence-Jones proteins
What is amyloid?
Pathological extracellular protein
Fibrillary ultrastructural appearance
Due to mis-folding of normal/abnormal proteins
Can’t be removed
What is primary amyloidosis?
Associated with plasma cell/lymphoplasmacytic lesion
Usually light chains - usually lambda
Usually deposits in multiple organs
What sort of light chains can be excreted, and what cannot?
Lambda can’t be excreted
Kappa excreted in urine = Bence-Jones proteins
What is secondary amyloidosis?
Associated with systemic chronic inflammatory conditions/tumours
Derived from serum amyloid associated protein (SAA) = acute phase reactant
Usually deposits in multiple organs
What are some systemic chronic inflammatory conditions and tumours with which secondary amyloidosis is associated?
IBD TB Rheumatoid arthritis Hodgkin's lymphoma Renal cell carcinoma
What is the amyloid in Alzheimer’s disease?
Amyloid beta protein (ABP)
Derived from amyloid precursor protein (APP)
Forms senile plaques
In which conditions does CNS amyloid deposit in vessel walls?
Alzheimer’s disease
cerebral amyloid angiopathy
What are the complications of amyloidosis?
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
