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Path Y > Haematology - Plasma cell myeloma and Monoclonal Gammopathy of Uncertain Significance > Flashcards

Haematology - Plasma cell myeloma and Monoclonal Gammopathy of Uncertain Significance Flashcards

1
Q

What immunoglobin is produced by myeloma cells?

A

One single type (eith IgG or IgA) which is known as paraprotein or M spike

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2
Q

What are Bence Jones proteins?

A

Urine monoclonal free light chains

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3
Q

What is -Lymphoplasmacytic lymphoma?

A

A type of non-Hodgkin lymphoma with IgM paraprotein that causes visual disturbances

aka Waldenstrom’s macroglobunlinaemia

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4
Q

What is the name of the premalignant condition that always precedes myeloma?

A

Monoclonal gammaopathy of uncertain significance (MGUS)

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5
Q

What are the two most significant risk factors for myeloma?

A

Obesity
Black > causasians/ asians

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6
Q

What are the diagnostic criteria for MGUS?

A

Serum Monoclonal-protein (often IgG)<30g/L
BM clonal plasma cells <10%
Asymptomatic

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7
Q

What is smouldering myeloma?

A

Serum M-protein (often IgG) >30g/L
BM clonal plasma cells >10%
Asymptomatic

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8
Q

What % of plasma cells is there in symptomatic multiple myeloma?

A

>10%

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9
Q

What is the most notable interaction of myeloma cells with the bone marrow micro-environment?

A

Produce RANK ligand which stimulates osteoclasts to cause bone resorptions

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10
Q

What is the incidence of IgM myeloma?

A

Very rare (<1% of myelomas)

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11
Q

What does CRAB stand for in myeloma diagnosis?

A

Calcium (hypercalcaemia, >2.75)

Renal (creatinine >177/ eGFR <40)

Anaemia

Bone disease (see lytic lesions)

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12
Q

What is the most common and 2nd most common cytogenetic abnormality in myeloma?

A
  1. Hyperdiploid karyotype
  2. IgH gene rearrangement
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13
Q

What are the 3 2014 Myeloma Defining Events

A

BM plasma cells >60%
involved:uninvolved FLC ratio >100
>1 focal lesion on MRI

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14
Q

Which part of the skeleton is affected by myeloma?

A

Proximal skeleton (spine, skull, knees)

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15
Q

Where are myeloma patients most likely to feel pain?

A

Back, chest wall, pelvis

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16
Q

What % of myeloma patients present with bone disease?

A

80%

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17
Q

What scan is necessary to detect bone lesions in myeloma? What is gold standard

A

Whole body CT is first line (X ray is obsolete for this use)
PET scan can also be used
Gold-standard = whole body diffusion-weighted MRI as this shows active vs treated disease

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18
Q

What are the 2 most likely emergency presentations of myeloma?

A

Cord compression

Hypercalcaemia

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19
Q

What 5 investigations to diagnose myeloma?

A

Serum protein electrophoresis (dense bands of IgG or IgA monoclonal proteins)
blood film - rouleaux stacks
bence jones proteins in urine
high ESR
more than 10% plasma cells in BM biopsy

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20
Q

What is the best way to treat cord compression in myeloma?

A

Dexamethosone
Radiotherapy

21
Q

What risk does myeloma present to the kidney?

A

Cast nephropathy - FLCs and Bence Jones proteinuria cause proximal tubule cell injury

22
Q

How should myeloma kidney disease be treated in an emergency?

A

Bortezomib-based therapy (proteasome inhibitor) is the cornerstone of myeloma kidney disease treatment - once the patients can become independent from dialysis their outcomes improve dramatically

23
Q

How does myeloma affect immunity?

A

Serum levels of normal Igs reduced

BM micro-environment interference also impairs myeloid, T and NK cells

24
Q

What is tested for in BM biopsy in suspected myeloma?

A

Immunohistochemistry for CD138 - specific for myeloma cells in BM

25
What test can detect cytogenetic abnormalities of prognostic significance in myeloma?
FISH
26
How does AL amyloidosis link to myeloma?
Misfolded free light chains aggregate into amyloid in target organs
27
How does amyloidosis affect the kidney?
Nephrotic syndrome
28
Give 5 features of the clinical presentation of AL amyloidodis?
Nephrotic syndrome Unexplained heart failure Sensory neuropathy Abnormal liver function tests Macroglossia
29
What is MGRS?
Monoclonal gammaopathy of Renal significance
30
How is MGRS defined?
1. One or more kidney lesions caused by mechanisms related to the produced monoclonal immunoglobulin (Ig) 2. The underlying B cell clone does not cause tumor complications or meet current hematological criteria for immediate specific therapy
31
How do proteasome inhibitors work in multiple myeloma
Proteasomes are involved in removing misfolded proteins If you inhibit this, you get accumulation of misfolded proteins in myeloma cell leading to their death
32
Which monoclonal antibody is used in myeloma treatment?
Anti-CD38 (daratumumab)
33
What are the 3 risk factors for MGUS progression?
1. Non-IgG M spike 2. Monoclonal spike \>15g/L 3. Abnormal serum free light chain ratio
34
What is the cause of de novo angiogenesis in myeloma?
CD34 expression on myeloma cells promotes angiogenesis
35
What type of nephropathy does myeloma cause?
Cast nephropathy
36
What are the first investigations to be done in suspected myeloma?
Serum protein electrophoresis Serum free light chains
37
What condition can produce MGUS/ myelomas part of its progression?
B cell leukaemia
38
Recall 5 options for myeloma therapy
1. Alkylating agents - melphalan 2. Steroids (eg dex + pred) 3. Immunomodulatory drugs -Thalidomide 4. Proteosome inhibitors (bortezomib) 5. Anti-CD38 monoclonal antibody (daratumumab) cause apoptosis through complement cascade
39
6 features of myeloma
monoclonal plasma proteins (IgG, IgA) paraprotein - bence jones osteolytic lesions anaemia infections kidney failure
40
MM is a cancer of what cells specifically
transformed plasma cells (terminally differentiate B cells)
41
median survival of MM
4-7 years debilitating and incurable
42
outline the 4 steps of progression of myeloma
1. MGUS 2. Smoudlering myeolma 3. MM 4. B cell leukaemia
43
which step of myeloma has CRAB symptoms
MM does not in MGUS or smouldering
44
median age diagnosis of myeloma
old - 60-70
45
what staging system in MM
durie salmon
46
2 genes implicated in MM
p16 methylation - 40% N-RAS, K-RAS - 30%
47
plasma and myeloma cells have what highly developed organelle
secretory apparatus - large endoplasmic reticulum & (golgi)
48
list 5 myeloma markers seen in MM
CD 38 CD138 CD56/58 monotypic cytoplasmic Ig light chain restriction (kappa or lambda +ve)
49
list 3 markers NOT seen in MM (negative)
CD 19 CD 20 Surface Ig

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