Myeloma, Amyloid and MGUS

Question 1

What are the clinical features of multiple myeloma

Answer 1

Calcium high
Renal failure
Anaemia
Bone lesions

Monoclonal proteins

Question 2

What does MM develop from?

Answer 2

MM begins from a pre-malignant condition “Monoclonal Gammopathy of Undetermined Significance (MGUS)

Question 3

What is smouldering myeloma

Answer 3

An intermitant phase between MGUS and MM

Higher chance of developing MM than MGUS

Question 4

Investigations of MM

Answer 4

o Electrophoresis (dense band of monoclonal proteins, often IgG or IgA)
o Rouleaux stacks on blood film
o Bence-Jones proteins in urine Lymphoplasmacytic lymphoma = Waldenstrom’s macroglobulinemia
o ESR high
o >10% plasma cells in BM

Question 5

Describe B cell development

Answer 5

o Antigen contact - either: (1) virgin B cell to create low-affinity plasma cells(IgM or IgD); or (2) migration to germinal centre
o Germinal centre: affinity maturation mediated through somatic hypermutation and antigen selection
o Class switching and recombination occurs - Ig isotype development
o Plasmablast leaves germinal centre to migrate to bone marrow to become a long-lived plasma cell

Question 6

Bone marrow aspirates of myeloma

Answer 6

Very large Golgi and ER: types of multiple myeloma (immature = poorer prognosis):

o Mature plasmocytic myeloma cells = clumped chromatin, abundant cytoplasm, rare nucleoli
o Immature plasmoblastic myeloma cells = prominent nucleoli, reticular chromatin, less abundant cytoplasm

Question 7

Key histopathological myeloma markers

Answer 7

	CD38
	CD138
	CD56/58
	Monotypic cytoplasmic Ig
	Light Chain restriction (Kappa or Lambda positive)

Question 8

Treatment of myeloma

Answer 8

o (1) “Classical” cytostatic drugs = melphalan (alkylating agents)
o (2) Proteasome inhibitors
o (3) “IMIDs” / Immunomodulatory Drugs = thalidomide, lenalidomide, pomalidomide
o (4) MoAbs / Monoclonal Antibodies = daratumumab

Question 9

Mutations of MGUS and MM

Answer 9

o MGUS:
 t(14q32) = 50%
 del (Chr13) = 50%

o MM:
 N-RAS, K-RAS = 30%
 p16 methylation = 40%
More than half of patients have hyper-diploids karyotype