41 Lymphoma and myeloma

Question 1

Describe the process of B cell differentiation:

Answer 1

Pro-B gains surface immunoglobulins to become naive B cell in bone marrow.
Then antigens are presented to it in a secondary lymphoid organ.
Last stage is NF-κB pathway.

Question 2

Name the proteins found during electrophoresis of blood serum: (5).

Answer 2

Serum albumin.
Alpha-1 globulins.
Alpha-2 globulins.
Beta globulins.
Gamma globulins.

Question 3

When is immunofixation performed and what does it detect/identify.

Answer 3

When an M spike is seen on protein electrophoresis.

Monoclonal immunoglobulins.

Question 4

What is myeloma?

Answer 4

Malignant disorder of clonal plasma cells.

Question 5

What is the epidemiology of myeloma?

Answer 5

70 years.
Higher in Afro-Carribeans.
Preceeded by asymptomatic MGUS.

Question 6

What is MGUS?

Answer 6

Monoclonal gammopathy of uncertain significance.

Question 7

What are the diagnostic criteria for a diagnosis of multiple myeloma?

Answer 7

Clonal bone marrow plasma cells or plasmacytoma and at least one CRAB/MDE feature.

Question 8

What are the CRAB features of multiple myeloma?

Answer 8

HyperCalcaemia.
Renal insufficiency.
Anaemia.
Bone lesions.

Question 9

What are MDE’s (myeloma defining events)? (3).

Answer 9

> 60% clonal plasma cells on bone marrow biopsy.
SFLC ratio >100mg/L.
Bone marrow lesion >5mm.

Question 10

Why does renal insufficiency occur in multiple myeloma?

Answer 10

Light chains clog the kidney.

Question 11

What is the treatment for AKI in myeloma?

Answer 11

Steroids.

Question 12

How is myeloma intensively treated? (3)

Answer 12

VCD.
GCSF.
Mephalan.

Question 13

What are the diagnostic criteria for MGUS?

Answer 13

Serum M-protein under 30g/L
Under 10% clonal plasma cells in BM
Absence of CRAB features

Question 14

What are the risks of progression from MGUS? (1,3)

Answer 14

1% per year, majority to myeloma.

Others to: Waldenstrom’s macroglobulinaemia, primary AL amyloidosis, lymphoproliferative disorders.

Question 15

What are the higher risk features for MGUS progressing? (3).

Answer 15

High M-protein level.
IgA/IgM rather than IgG production.
Abnormal SFLC ratio.

Question 16

What is the pathology behind amyloidosis?

Answer 16

Light chain fragments misfold and self aggregate into β-pleated fibrils.

Question 17

What does amyloidosis cause? (4).

Answer 17

Nephrotic-range proteinuria (mainly albumin).
Cardiac/liver problems.
Peripheral neuropathy.
End-stage renal failure.

Question 18

What type of lymphoma is follicular lymphoma?

Answer 18

Non-hodgkin.

Question 19

What is the genetic change in follicular lymphoma?

Effect?

Answer 19

Translocation t(14:18).
Brings bcl-2 under influence of immunoglobulin heavy chain gene. Over expression inhibits apoptosis.

Question 20

What features of follicular lymphoma are bad for prognosis? (5).

Answer 20

> 60y/o.
Ann Arbor stage III or IV.
LDH above normal limit.
Hb less than 120g/L
Mor than 4 nodal sites.

Question 21

What is Hodgkin lymphoma characterised by?

Answer 21

Presence of Hodgkin-Reed Sternberg cells within cellular infiltrate of non malignant inflammatory cells.

Question 22

How do Hodgkin-Reed Sternberg cells evade apoptosis? (3).

Answer 22

Activation of NF-κB.
Incorporation of EBV.
Incorporation of latent membrane proteins (LMP1/2).

Question 23

Which chemotherapy is commonly used for Hodgkin lymphoma?

Long term complications? (3).

Answer 23

ABVD.

Pulmonary toxicity, CVD, 2o malignancies.

Question 24

What is M-protein?

Answer 24

Monoclonal immunoglobulin synthesised by plasma cells in myeloma.

Question 25

What are the common causes of lymphadenopathy? (3)

Answer 25

Infections.
Autoimmune disease (SLE, serum sickness).
Neoplasias (lymphoma, leukaemia).