Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Year 5 Path Haematology > Multiple Myeloma, MGUS, Plasma Cell > Flashcards

Multiple Myeloma, MGUS, Plasma Cell Flashcards

1
Q

What Symptoms does Multiple Myeloma generally present with?

A

CRAB

  • Calcium (high),
  • Renal failure
  • Anaemia,
  • Bone lesions (osteoporosis, osteolytic lesions)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What cells are malignant in Multiple Myeloma?

Where are they usually located?

A

Long-lived Monoclonal plasma cells proliferating in Bone Marrow,

producing monoclonal antibodies (IgG, IgA) or Serum Free Light Chains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the epidemiology of Multiple Myeloma?

What is the prognosis?

A
  • Old (67) (Middle-aged to elderly)
  • incidence increases with age (3% prevalence in patients >50)
  • Men>women
  • Black>Caucasian and asian
  • 30% 10 year survival (Average 5-7 years)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the aetiology of Multiple Myeloma?

A

Unknown, Risk Factors

  • Obesity
  • age
  • genetics (black, familiar myeloma sporadic cases)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the abbreviation MGUS?

A

Monoclonal Gammopathy of Uncertatin significant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the diagnostic criteria for MGUS?

A

Premalignant condition, where

  1. Paraproteins: monoclonal immunoglobulins (IgG or IgA) detectable in serum < 3 g/dL
  2. AND <10% of the BM is monoclonal plasma cells
  3. AND NO no CRAB symtpoms
    ( or no evidence of other B-cell proliferative disorders)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the progression risk for MGUS to Mutliple Myeloma per year?

A

1-2%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are risk factors that increase the risk of progression from MGUS to Multiple Myeloma?

A

Cumulative Risk for the following:

  • Non-IgG M-spike
  • M-spike >15g/L
  • Abnormal Serum free light chain ratio

(M-spike = monoclonal spike on electrophoresis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is smouldering myeloma?
What are the diagnostic criteria?

A

Premalignant condition (between MGUS and MM) with NO CRAB symptoms and

  • Monoclonal serum protein ≥ 30g/L
  • BM plasma cells ≥ 10%
  • Annual risk of progression to MM 10%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the progression rate of SMmouldering myeloma to Multiple Myeola within 2 years?

A

Up to 46% (if 2+ risk factors present)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the defyining Biomarkers of Multiple Myeloma?

Aka biomarkers as diagnostic criteria

A
  • ≥ 60% clonal bone marrow plasma cells (or any if CRAB symprotms present)
  • SFLC level ≥ 100 mg/L with an involved:uninvolved SFLC ratio ≥ 100
  • > 1 focal skeletal lesion on MRI (≥ 5 mm in size)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the defyning clinical features of Multiple Myeloma?

A
  • Any signs of organ damage (CRAB symtpoms)
  • Calcium > 11 mg/dL or > 1 mg/dL above the ULN
  • Renal insufficiency: GFR < 40 mL/min or serum creatinine > 2 mg/dL
  • Anemia: Hb < 10 g/dL or more than 2 g/dL below the LLN
  • Bone lesions: ≥ 1 osteolytic lesions on imaging
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are primary and secondary genetic events in the disease development of MM?

A

Usually
Primary Either

  1. Hyperdiploidy (60% of cases) (additional odd number chromosomes)
  2. IGH rearrangements (immunoglobulin heavy chains) (with chromosome 14)

Secondary:
Number of specifc mutations in TSG (e.g. p53) / pro-oncogenes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does MM lead to Bone lesions?

A

Interaction of Plasma Cell-Osteoclast interaction

  • production of osteoclastogenic factors (e.g. TNF alpha, IL-1, RANK-L) –> osteolytic lesions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does MM cause Anaemia?

A

Due to bone Marrow infliltration by malignant cells and replacement of normal marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What criteria have to be met, to be diagnosed with Myeloma without any CRAB symtpoms?

A

People would develop MM within next 2 months

  • > 60% Plasmacytes in BM or plasmaocytes
  • Involved:uninvolved FLC ratio >100
  • > 1 focal lesion of MRI >5mm
17
Q

What are typicla features of Myeloma Bone disease?

A

Generally 80% of patients present with bone

  • proximal skeleton (common spine, chest, pelvic pain)
  • osteolytic (not osteoblastic lesions)
  • continue
18
Q

How is Myeloma Bone disease diagnosed?

A
  • Whole body CT low dose (Xray now obsolete)
  • FDG PET scan
  • whole body diffusion weighted MRI (sensitive to residual treated disease)
19
Q

What are the characteristics of Myeloma Kidney disease?

A

Due to overproduction and renal deposition of monoclonal immunoglobulins / light chains

  • Serum creatinine >177 umol/l or eGFR <40
  • AKI as reslt of myeloma
20
Q

How does MM cause Renal disease?

A
  • High serum free light chains and Bence Jones Protien (causing cast nephropathy)
  • Also:hypercalcaemia contributing
21
Q

What is the renal effects of high levels of Serum Free light chains?

A

Serum Free light chains can’t be abrobed –> high in Tubule –> SFLC bind to THP? protein presentt in kidney –> form blop

22
Q

What is the management of Myeloma Kidney disease

A

Treat MM to reduce Serum free light chains:
Bortezombid (Proteasome inhibitor) based therapy

+ Acutely: reyhdration (but don’t fluid overload)

23
Q

What investigations are done for the Diagnosis of Multiple Myeloma?

What results would you expect?

A

Immunoglobulin studies

  • Serum proein elecrophoresis (dense, narrow band in “gamma” region)
  • serum FLC levels
  • 24h bence jones protein (urine)

Blood film

  • rouleaux formation

BM aspirate + Biopsy
* IHC for CD138

FISH analysis (to exclude high risk variants)
Flow cytometroy

24
Q

How is MM staged?

A

Revised 2-International Stageing system (ISS/ Durie-Salmon staging)

  • Microglobulin levels and genetic high risk groups taken into consideration
25
Q

What is the Relationship of Amyloidosis and MM?

A

MGUS and Myeloma can both cause Amyloisis (with production of musfolded free light chains)

26
Q

What are the main target organs of Amyloidosis?

A

Can be any organ but most commonly

  • Cardiac (Unexplained heart failure)
  • Renal (Neprhotic syndrome (70%)
  • Anything else (Sensory neuropathy, abnormal LFT, macroglossia etc.)
27
Q

What is MGRS

A

Rare
Monclonal Gammopathy of renal signsificance

Pre-malignionant condittion where the SFLC produced cause some form of renal disease (treated like Myeloma with aim of renal survival)

28
Q

WHat is a key cell surface marker for myeloma?

A

CD138

29
Q

What is the diffference of AL and AA Amyloidosis?

A

AL: due to deposition and increased production of light chains (Myeloma)

AA: reactive due to chronic disease (inflammation, infection, malignancy)

30
Q

What is the role of steroids in MM treatment?

A

Induces apoptosis in Myeloma Cells

Strong synergy (part of almost all other regimes)

31
Q

Who is eligible for Stem cell transplantation in MM

A

Generally Fit patients <65
(auto-SCT when in remission of disease)

32
Q

What is the aim of treatment of MM?

A

Generally disease free, however treatment is not curative usually (not minimal redisual disease) for best outcome

33
Q

What is the first line treatment for Multiple Myeloma?

A

First line – Bortezomib (Protease inhibitor) + / - dexamethasone,

cyclophosphamide (alkylating agent)

lenalidomide (in conjunction with one other treatments and dexamethasone)

34
Q

What additional proteins are most commonly produced in Multiple Myeloma?

A

Usually IgG

Other common:
IgA and Serum Free light chains

35
Q

How would Amyloidosis be diagnosed?

A

AL: amyloidosis: serum free light chains will show abnormal kappa:lambda light chain ratio

Definitively diagnosed by biopsy (with congo-red stain showing apple-green birefringence)

Year 5 Path Haematology (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions