Plasma cell neoplasms

Question 1

Immunophenotype of normal and abnormal plasma cells

Answer 1

Normal: CD45+, CD138+, bright CD38, CD19+, CD56-
Abnormal: Absent/dim CD45, weakened CD38, brighter CD138, CD19-/CD56+ or CD19-/CD56+, may have aberrant expression of other antigens e.g. CD20, CD200

Question 2

Risk factors for progression of MGUS to symptomatic myeloma, plasmacytoma or amyloidosis

Answer 2

1. Predominance (>90%) of aberrant plasma cells by flow cytometry.
2. Abnormal serum free light chain ratio
3. Type of paraprotein: IgA paraprotein (~1.5% per year) is higher than IgG or light chain MGUS. IgM paraprotein has highest risk.
4. High paraprotein > 15 - 25g/L

Question 3

Diagnostic criteria for asymptomatic/smouldering myeloma

Answer 3

Paraprotein > 30g/L or urinary M protein > 0.5g/24hrs AND/OR clonal plasma cells in bone marrow 10-60%
No end-organ damage including amyloidosis

Question 4

Diagnostic criteria for MGUS

Answer 4

Paraprotein < 30g/L
Plasma cells <10%
No end organ damage
No lymphoproliferative disorder

Question 5

Diagnostic criteria for symptomatic plasma cell myeloma

Answer 5

Clonal plasma cells in BM ≥ 10% or plasmacytoma
End-organ damage / myeloma-defining events:
- Hypercalcaemia
- Renal impairment (CrCl <40ml/min or Creat >177umol/L)
- Anaemia (<100g/L or >20g/L below LLN
- Bone lesions (osteolytic, seen on imaging)

OR ≥1 biomarker of malignancy if end-organ damage is not present

• Clonal BM plasma cells ≥ 60%
• SFLC ratio ≥100 (involved to uninvolved)
• > 1 focal lesion on MRI

Question 6

Diagnosis of plasma cell leukaemia

Answer 6

Plasma cells > 20% of WBCs or plasma cells > 2 x E+9/L

Immunophenotype: Usually CD56- and CD20+

Question 7

Name two paraneoplastic syndromes associated with myeloma

Answer 7

POEMS syndrome and TEMPI syndrome

Question 8

What is TEMPI syndrome?

Answer 8

Telangiectasia
Elevated erythropoietin and erythrocytosis
Monoclonal gammopathy
Perinephric fluid collections
Intrapulmonary shunting

Question 9

Diagnostic criteria for POEMS syndrome

Answer 9

Mandatory:
Polyneuropathy and monoclonal gammopathy.
Major criteria (1 or more required)
- Castleman disease (plasma cell variant)
- Osteosclerotic bone lesions
- VEGF elevation
Minor criteria (1 or more required)
- Organomegaly
- Endocrinopathy
- Skin changes
- Papilloedema
- Thrombocytosis
- Extravascular volume overload

Question 10

How is light chain deposition disease different from primary amyloidosis (4)

Answer 10

1. No beta-pleated sheets
2. No serum amyloid P protein
3. No staining with Congo red
4. Usually kappa (80%)

Question 11

Name the common coagulopathy found in amyloid disease

Answer 11

Acquired factor X deficiency (factor X binds to the amyloid)

Question 12

t(11;14) in myeloma is associated with:

Answer 12

Associated with:
Plasma cell leukaemia, 
CD20 expression,
Lymphoplasmacytic morphology
Hyposecretory disease
Lambda light chains