Myeloma pathology

Question 1

What are plasma cells?

Answer 1

Plasma cells are derived from terminally differentiated B cells

Question 2

Tests and suspected findings for pt with multiple myeloma:
1 renal function
2 FBC
3 CXR
4 spinal X-Ray
5 serum protein electrophoresis
6 bone marrow biopsy: kappa, lambda, CD138, H&E

Answer 2

1 reduced

2 anaemia of chronic disease (normochromic, normocytic)
AND
fever BUT impaired neutrophil production

3 pneumonitis: RML pneumonia

4 fracture of vertebral body: T6 crush #

5 spike in gamma globulin region compared to smooth distribution of protein bands (normal)
- Gamma spike: M protein produced by myeloma cells

6 kappa»lambda, CD138 +, abnormal plasma cells

Question 3

What does ESR measure?

Answer 3

chronic, non specific inflammation

Question 4

Complications of myeloma (3)

Answer 4

1 bones: pathological fractures (e.g. spine)
2 renal dysfunction: due to blockage
3 hypercalcaemia: due to widespread tumour induced bone destruction
- effect of hypercalcaemia (bones, stones, moans (GI) and groans (psychic))

Question 5

Clinical features of multiple myeloma? (5)

Answer 5

1 anaemia
2 bone pain
3 renal impairment
4 polyuria/polydipsia/
weakness/constipation/confusion
5 recurrent bacterial infections

Question 6

Pathophysiology of multiple myeloma?

Answer 6

Monoclonal plasma cells proliferate in bone marrow, resulting in:
1 overabundance of monoclonal paraprotein (M protein)
2 destruction of bone
3 displacement of other haemopoietic cell lines

Question 7

End organ damage as diagnostic criteria for MM

Answer 7

hyperCalcaemia
Renal insufficiency
Anaemia
Bone lytic lesions

Question 8

Treatment of MM

Answer 8

1 supportive: hypercalcaemia, dialysis, pain management, infection treatment, IV immunoglobulin etc.

2 anti-myeloma therapy
- steroids, conventional chemotherapy, immunomodulatory drugs, stem cell transplant

Question 9

Labaratory features of multiple myeloma? (12)

Answer 9

1 FBC: normocytic, normochromic anaemia + other cytopenias (advanced disease)
2 raised ESR
3 raised EUC: renal damage
4 raised calcium: bone resorption
5 LFT: raised total protein and globulin
6 LDH: raised
7 protein electrophoresis: M protein
8 immuno-
electrophoresis: paraprotein (IgG 60%)
9 immunoglobulins: immunoparesis
10 serum free light chains: kappa/lambda ratio
11 bone marrow biopsy: aspirate (plasmablastic), trephine (plasma cells and definitive architecture), flow cytometry and cytogenetics (prognosis)
12 imaging: lytic lesions: conventional radiography of spine, skull and pelvis etc., MRI to evaluate symptoms, CT/MRI procedures of choice in cord compression

Question 10

Etiology of multiple myeloma? (3 factors)

Answer 10

1 environmental agents
- no single, well defined environmental agent
- benze, pesticides, radiation exposure

2 genetic factors
- karyotypic abnormalities, chromosomal translocations/deletions, epigenetic dysregulation, silencing of tumour suppressor genes

3 bone marrow microenvironment
- significant role in proliferation, survival and resistance in MM
- mediated through cytokines and growth factors

Question 11

What is multiple myeloma?

Answer 11

Clonal proliferation of plasma cells characterized by a monoclonal protein in the blood or urine and associated organ dysfunction

Causes diffuse, systemic sclerotic lesions

Question 12

Effects of hypercalcaemia (4)

Answer 12

1 Bones: pain, arthritis, osteoporosis, fractures
2 Stones: kidney stones, diabetes insipidus, dehydration
3 Moans: nausea, vomiting, constipation, pancreatitis, peptic ulcers
4 Groans: impaired concentration, confusion, muscle weakness, fatigue, corneal calcification