Myeloma is a cancer of the plasma cells. These are a type of B lymphocyte that produce antibodies. Cancer in a specific type of plasma cell results in large quantities of a single type of antibody being produced. Myeloma accounts for around 1% of all cancers.

Multiple myeloma is where the myeloma affects multiple areas of the body.

Monoclonal gammopathy of undetermined significance (MGUS) is where there is an excess of a single type of antibody or antibody components without other features of myeloma or cancer. This is often an incidental finding in an otherwise healthy person and as the name suggests the significance is unclear. It may progress to myeloma and patients are often followed up routinely to monitor for progression.

Smouldering myeloma is where there is progression of MGUS with higher levels of antibodies or antibody components. It is premalignant and more likely to progress to myeloma than MGUS. Waldenstrom’s macroglobulinemia is a type of smouldering myeloma where there is excessive IgM specifically.



Plasma cells are B cells (B lymphocytes) of the immune system that have become activated to produce a certain antibody. They are called B cells because they are found in the bone marrow. Myeloma is a cancer of a specific type of plasma cell where there is a genetic mutation causing it to rapidly and uncontrollably multiply.

These plasma cells produce one type of antibody. Antibodies are also called immunoglobulins. They are complex molecules made up of two heavy chains and two light chains arranged in a Y shape. They help the immune system recognise and fight infections by targeting specific proteins on the pathogen. They come in 5 main types: A, G, M, D and E. When you measure the immunoglobulins in a patient with myeloma, one of those types will be significantly abundant. More than 50% of the time this is immunoglobulin type G (IgG). This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein. This means a single type of abnormal protein.

The “Bence Jones protein” that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains.



The cancerous plasma cells invade the bone marrow. This is described as bone marrow infiltration. This causes suppression of the development of other blood cell lines leading to anaemia (low red cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets).


Myeloma Bone Disease

Myeloma bone disease is a result of increased osteoclast activity and suppressed osteoblast activity. Osteoclasts absorb bone and osteoblasts deposit bone. This results in the metabolism of bone becoming imbalanced as more bone is being reabsorbed than constructed. This is caused by cytokines released from the plasma cells and the stromal cells (other bone cells) when they are in contact with the plasma cells.

Common places for myeloma bone disease to happen are the skull, spine, long bones and ribs. The abnormal bone metabolism is patchy, meaning that in some areas the bone becomes very thin whereas others remain relatively normal. These patches of thin bone can be described as osteolytic lesions. These weak points in bone lead to pathological fractures. For example, a vertebral body in the spine may collapse (vertebral fracture) or a long bone such as the femur may break under minimal force.

All the osteoclast activity causes a lot of calcium to be reabsorbed from the bone into the blood. This results in hypercalcaemia (high blood calcium).

People with myeloma can also develop plasmacytomas. These are individual tumours made up of the cancerous plasma cells. They can occur in the bones, replacing normal bone tissue or can occur outside bones in the soft tissue of the body.


Myeloma Renal Disease

Patients with myeloma often develop renal impairment. This is due to a number of factors:

  • High levels of immunoglobulins (antibodies) can block the flow through the tubules
  • Hypercalcaemia impairs renal function
  • Dehydration
  • Medications used to treat the conditions such as bisphosphonates can be harmful to the kidneys



The normal plasma viscosity, or internal friction in the flow of blood, is between 1.3 and 1.7 times that of water. To oversimplify it: blood is 1.3 to 1.7 times thicker than water. Plasma viscosity increases when there are more proteins in the blood. These are proteins like immunoglobulins and fibrinogen, both of which increase with inflammation. In myeloma there are large amounts of immunoglobulins in the blood causing the plasma viscosity to be significantly higher.

Raised plasma viscosity can cause many issues:

  • Easy bruising
  • Easy bleeding
  • Reduced or loss of sight due to vascular disease in the eye
  • Purple discolouration to the extremities (purplish palmar erythema)
  • Heart failure


Four Features to Remember for Exams

You can use the mnemonic CRAB to remember four key features of myeloma:

  • CCalcium (elevated)
  • RRenal failure
  • AAnaemia (normocytic, normochromic) from replacement of bone marrow.
  • BBone lesions/pain


Risk Factors

  • Older age
  • Male
  • Black African ethnicity
  • Family history
  • Obesity


Suspecting Myeloma

This is a simplified version of the 2016 NICE guidelines on suspected myeloma. They suggest considering myeloma in anyone over 60 with persistent bone pain, particularly back pain, or an unexplained fractures. Perform initial investigations:

  • FBC (low white blood cell count in myeloma)
  • Calcium (raised in myeloma)
  • ESR (raised in myeloma)
  • Plasma viscosity (raised in myeloma)

If any of these are positive or myeloma is still suspected do an urgent serum protein electrophoresis and a urine Bence-Jones protein test.


Testing for Myeloma

NICE guidelines from 2016 provide guidance on investigating and managing myeloma. They recommend the following initial investigations when myeloma is suspected. You can remember these with the mnemonic “BLIP”. You cannot exclude myeloma with just one investigation.

  • BBence–Jones protein (request urine electrophoresis)
  • L – Serum‑free Light‑chain assay
  • I – Serum Immunoglobulins
  • P – Serum Protein electrophoresis

Bone marrow biopsy is necessary to confirm the diagnosis of myeloma and get more information on the disease.

Imaging is required to assess for bone lesions. The order of preference to establish this is:

  1. Whole body MRI
  2. Whole body CT
  3. Skeletal survey (xray images of the full skeleton)

Patients only require one investigation but may not tolerate or be suitable for MRI or CT.


Xray Signs

  • Punched out lesions
  • Lytic lesions
  • Raindrop skull” caused by many punched out (lytic) lesions throughout the skull that give the appearance of raindrops splashing on a surface



The aim of treatment is to control disease. It usually takes a relapsing-remitting course and treatment aims to improve quality and quantity of life. Management will be undertaken by the haematology and oncology specialist multidisciplinary team.

First line treatment usually involves a combination of chemotherapy with:

  • Bortezomid
  • Thalidomide
  • Dexamethasone

Stem cell transplantation can be used as part of a clinical trial where patients are suitable.

Patients require venous thromboembolism prophylaxis with aspirin or low molecular weight heparin whilst on certain chemotherapy regimes (e.g. thialidomide) as there is a higher risk of developing a thrombus.


Management Myeloma Bone Disease

  • Myeloma bone disease can be improved using bisphosphonates. These suppress osteoclast activity.
  • Radiotherapy to bone lesions can improve bone pain.
  • Orthopaedic surgery can stabilise bones (e.g. by inserting a prophylactic intramedullary rod) or treat fractures.
  • Cement augmentation involves injecting cement into vertebral fractures or lesions and can improve spine stability and pain



There are a number of complications of myeloma itself and the treatments:

  • Infection
  • Pain
  • Renal failure
  • Anaemia
  • Hypercalcaemia
  • Peripheral neuropathy
  • Spinal cord compression
  • Hyperviscocity


Last updated April 2019
WordPress Theme built by Shufflehound. Copyright 2016-2022 - Zero to Finals - All Rights Reserved