Multiple Myeloma: Etiology, Pathophysiology

Multiple myeloma is also called plasma cell dyscrasia. A kind of cancer known as multiple myeloma develops in plasma cells, a subset of white blood cells. In order to fight infections, healthy plasma cells produce proteins known as antibodies. Antibodies seek for and destroy pathogens. Cancerous plasma cells accumulate in the bone marrow of patients with multiple myeloma. The soft substance found inside bones, called bone marrow, is where blood cells are created. The cancer cells push out healthy blood cells in the bone marrow. Instead of producing beneficial antibodies, cancer cells produce malfunctioning proteins. Multiple myeloma complications result from this.

Etiology of Multiple Myeloma 

• The most important risk factor for almost all blood cancers is radiation exposure.
• The woodworkers and farm workers are under regular exposure to petrochemicals hence they are at risk of developing multiple myeloma due to petrochemical exposure.
• Deletion of chromosome 17p.
• Hyperploidy at 13q14.

Also Read: Peripheral Arterial Disease

Pathophysiology of Multiple Myeloma 

• There is the development of myeloma cells. These are actually the overproduction of defective light chain antibodies which further progresses into the production of defective antibodies.
• Bony lytic lesions are developed and PET- CT can be done to diagnose the multiple myeloma at early stages.
• In myeloma there is an activation of osteoclasts which leads to Bony destruction. 
• There is the production of a cytokine called MIP- 1A or macrophage inflammatory protein which is responsible for bone lytic lesions. 
• Bone pain is the common presentation of multiple myeloma and it mainly presents in vertebrae. 
• The bone destruction leads to hypercalcemia.
•  Amyloidosis will develop and it is of AA variety which can occlude the kidney vessels and hence can damage the kidney.
• The patient will be prone to many infections due to defective antibody production.
• Pyelonephritis will develop which contributes to scarring of the kidney. 
• The patient may use NSAID daily due to Bone pain and this decreases the prostaglandins in the kidneys hence the filtration in the kidney is hampered. 

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Clinical Manifestations of Multiple Myeloma

• It can be remembered with pneumonic called CRAB

C- hypercalcemia it is due to lytic lesions and there are chances of systolic arrest in the heart.

R- Renal failure hypercalcemia is the leading cause of renal failure.

A-Anemia

B-Bleeding and Bony lytic lesions.

• Normocytic Normochromic Anemia- The plasma cells colonize the bone marrow and the normal blasts don’t have the space and nourishment for development thus anemia occurs.
• Bleeding- The plasma cells colonize in bone marrow and the megakaryoblasts don’t have this space for division which will lead to thrombocytopenia. Sometimes the defective antibodies again coat the platelets and cause the accelerated clearance of platelets.
• Bone pain or low backache
• The features to be ruled out in the work of the patient are osteoporosis, disc prolapse, and metastasis to the spine because of carcinoma prostate.
• There are many cases where a fracture of the vertebra will occur and there is a risk of paraplegia due to compressive myelopathy.
• The patient might present with lethargy or fatigue due to anemia.
• Due to a defect in the kidney the features of uremia will develop. The urea won’t get excreted via urine and hence it will begin to get excreted via sweat. This forms crystalline deposits on the layer resulting in a bad smell after the evaporation of sweat uremic frost.
• Uremia- It can cause brain damage and hence asterixis and metabolic encephalopathy will occur.
• Hyperviscosity syndrome can present as dizziness and Vertigo.
• Carpal tunnel syndrome can develop due to amyloidosis.

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Investigations

• Hematological analysis
• CBC is the first Test of choice.
• ESR will show 100 mm of fall during the first hour and the peripheral smear will show the rouleaux formation.
• At the aggressive stage of multiple myeloma, plasma cell leukemia will be seen.
• The albumin: globulin ratio will be high.
• PET- CT scan is done to detect the Bony lytic lesions.
• There will be a reduced anion gap
• The best screening test for the diagnosis of multiple myeloma is serum protein electrophoresis. The electrophoresis will see the M spike.
• The serum light chain assay will show the elevation and urine beta 2 microglobulin levels will be high.
• An amyloid fat pad biopsy is done to diagnose the amyloidosis.
• The Investigation of choice for the confirmation of diagnosis is bone marrow biopsy with CRAB features and serum protein electrophoresis.
• The X-ray of the skull can show raindrop lesions in some patients.

Also Read: Bronchiectasis : Causes, Pathophysiology

Treatment of Multiple Myeloma

• Drugs used for the induction phase are:
  • Steroids- dexamethasone
  • Immunomodulators- thalidomide and lenalidomide
  • Proteasome inhibitor- bortezomib
• Autologous bone marrow transplantation can be done if the patients are eligible for transplantation.
• In the process of bone marrow transplantation all the cancerous cells are killed in the induction phase using drugs and GMCSF injection is given which leads to the proliferation of normal cells in the bone marrow.

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