Multiple Myeloma

Question 1

What is multiple myeloma?

Answer 1

It’s a tumor disease of hemopoiesis system with infiltration of the bone marrow by genetically modified plasma cells capable of producing monoclonal Ig or fragments thereof

Or
a B-cell neoplasm with monoclonal expansion of plasma cells
There is increase in immunoglobulin and its corresponding light chain.that is IgG or A(M spike); the light chain(k(kappa or lambda))

Question 2

Etiology of MM

Answer 2

• ionizing radiation
• carcinogens like chemicals

Risk factors
Age from 60yrs,male , black patients, heredity

Question 3

Pathogenesis of MM

Answer 3

Violation of the development of plasma cells will lead to accumulation of malignant plasma cells in bones, brain and pIg synthesis
This leads to destruction of bone tissue, hematological disorders like anemia, thrombocytopenia,violation of immunity, Renal failure and peripheral neuropathy and compression of spinal cord

Triad osterman

• infiltration of bone and brain by plasma cells
• monoclonal secretion
• osteolysis

Question 4

Classification of MM

Answer 4

Clinical anatomical classification 
Based on X-ray data of skeleton, morphological analysis of punctuates and trepanates of bones
-diffuse local in 60% of cases
-diffuse form24%
-multiple focal 15%
-sclerorising form 1%

By immunodeficiency variants
Myeloma G-55 to 65%
                   A-20 to 25%
Myeloma D- 2 to 5%
Myeloma E
Myeloma M about 0,5%
Non-secreting myeloma in 1-4% cases
Myeloma Bens Jones (light chain disease) - 12 to 20%

By International Staging System
Stage 1- B2 microglobulin <3,5mg/l, albumin > or equal 35g/l- median survival 62 months (5 yrs 2 months)
Stage 2-median survival 44 months(3 years 8 months), B2 microglobulin 3,5-5,5mg/l
Stage 3-B2 microglobulin>5,5mg/l, regardless of albumin level-median survival 29 months

Question 5

Clinical picture of MM

Answer 5

-pain in the lumbar, thoracic spine seen as osteochondrosis
-bone pain in back,skull,sternum,vertebrae and ribs . Bones are soft if you touch them
-spontaneous bone fracture (pathological fracture)
-weakness
-fatigue , lethargy
Extramedullary growth
Prolonged bleeding
Neuropathy- carpal tunnel syndrome due to amyloidosis deposits in tissues
Confusion
Loss of bowel and bladder control due to spinal cord compression
Shortness of breath, headache,fatigue
Hyper viscosity syndrome- shortness of breath,headache,fatigue,visual disturbance coz of m protein presence

Question 6

CRAB syndrome

Answer 6

Evidence of end organ damage 
Calcium elevation more than 10,5mg/dl
Renal insufficiency 
Anemia(normocytic , normo chromic)
Bone lesion

Question 7

Stages of development of MM

Answer 7

Divided into stages

1. Monoclonal gammopathy of the obscure genesis(MGNG)
2. Smoldering myeloma
3. MM (symptomatic)

1.MGNG-is assymptomatic clonal proliferation of plasma cells, antecedent malignant tumor. It is characterised by presence of paraprotein in the serum in an amount <30g/l, the content in the bone marrow is less than 10% of plasma cells, the absence of anemia, hypercslcemks, osteolytic foci and renal failure.
MGNG is present in about 3% of people aged 50 and over

Question 8

Diagnosis of MM

Answer 8

On physical examination
Pale skin, nephrotic syndrome seen by edema, xanthomas,retinal bleeding and eye bleeding , the patient leans forward, increase jugular vein pressure which causes cardiac tamponade, extradural mass, carpal tunnel syndrome, pericardial friction rub, brown pigment in nails, fast and deep breathing

Lab instrumental
CBC-normochromic anemia, thrombocytopenia, leukopenia,increased ESR, presence of plasma cells in peripheral blood is rare and only found in terminal stages of the disease
Biochemical- increased creatinine,urea,hypercalcemia,hyperproteinemia
Urine analysis-proteinuria, Bens Jones protein presence ,kidney and liver function tests

• Immunofixation and electrophoresis of blood serum and urine in which M gradient is detected.
• X-ray- to see location and severity of bone lesion
• Puncture biopsy of bone brain- presence of 10% or more plasma cells
• Bone scintigraphy

Question 9

Criteria for diagnosis of MM

Answer 9

Both of the criteria’s must be found
1. Plasma cells> 10% of bone marrow 
2. Any of these myeloma defining events
a. Evidence of end organ damage CRAB
b.Any of these bio markers for cancer
Plasma cells>60%
Serum light chains>100mg/do
>1 focal lesions of MRI

Question 10

Treatment of MM

Answer 10

When to start- end organ damage and M component more than 5g/dl

• High dose chemotherapy
• stem cell transplant for younger patients
• palliative care for the elderly using alkylating agents such as melohalan,plus steroids such as prednisolone
• plasmocytoma radiation

Immunoglobulins, antibiotics,erythrocytes transfusion,erythropoietins, bisphosphonates

Question 11

Complications of MM

Answer 11

• renal tubular acidosis because of B Jones proteins which damage tubules , the kidney cannot produce an acidic normally concentrated urine
• Proteinuria without hypertension
• MM to ALL
• Renal failure
• Leukoerythroblastosis presence of immature WBCs and RBCs in the peripheral blood

Question 12

Prognosis of MM

Answer 12

The median survival is about 3 years but some patients have higher life expectancy