Multiple Myeloma

Nabil Ebraheim
4 min readFeb 12, 2018

Multiple myeloma is a cancer and malignant proliferation of the plasma cells. Plasma cells are a type of blood cell that produces antibodies. Antibodies are an important part of the immune system and fight infection. Multiple myeloma cells produce a single protein — Monoclonal protein; M protein.

Multiple myeloma occurs more often in males and twice as often in African-Americans. This condition typically occurs in patients older than 40 years of age and is the most common primary malignant bone tumor.

The monoclonal proteins are immunoglobulins (Igs), and are composed of heavy chains and light chains. Both heavy chains and light chains are produced in multiple myeloma. The heavy chains are IgG (about 52%) followed by IgA (21%). The light chains are the kappa and lambda chains. The Bence Jones protein is a monoclonal globulin protein or immunoglobulin light chain found in the urine. The plasma cells secrete osteoclast activating factors such as interleukin 6, macrophages, and inflammatory factors in addition to RANKL. Osteoclasts are recruited, activated, and multiply. The osteoclasts then absorb the bone; however, the osteoblast bone formation is suppressed by the tumor necrosis factor (why there is a cold bone scan in multiple myeloma). In about 30% of cases, the bone scan is negative. A skeletal survey should be acquired.

The useful mnemonic tool to help remember the most common features of multiple myeloma is: CRAP — hyperCalcemia, Renal Failure, Anemia, and Back Pain. These clinical features will be insidious in presentation. Bone pain, especially back pain with possible fractures, weakness, and fatigue, cord compression, infections, and fever are all common symptoms. Multiple myeloma can occur in any bone; although, it occurs more in the hematopoietic bone marrow. In terms of lab work, sedimentation rates may be elevated and the physician may find renal insufficiency, hypercalcemia, and anemia.

Electrophoresis will find a spike in the serum, the urine, or in both. Serum Protein ElectroPhoresis (SPEP) will detect the monoclonal elevation of the immunoglobulin and identify the protein types that are present. Urine Protein ElectroPhoresis (UPEP) will detect Bence-Jones Proteinuria and light chains (about 95% sensitivity).

What are the tumor markers that indicate a bad prognosis?

1. Increased serum beta2-microglobulin level

2. Decreased serum albumin

How do you establish the diagnosis?

The physician will need to find one major and one minor criteria or three minor criteria. The major criteria’s are: Plasmacytoma tissue diagnosis on biopsy, more than 30% plasma cells in the bone marrow, and SPEP with great value for IgG or IgA and/or UPEP (Bence-Jones Proteinuria). The minor criteria are as follows: 10–30% plasma cells in the bone marrow; monoclonal protein in the serum or the urine (SPEP/UPEP) — these values are usually lower than in the major criteria; multiple “punched-out” lytic bone lesions; end-organ damage (renal insufficiency, hypercalcemia,anemia); lower than normal IgG levels.

Imaging will usually have a “punched out” lytic lesions throughout the skeleton. Radiolucent lesions or destructive lesions with no sclerosis (skull lesions and vertebral fractures). Osteopenia is common as well as a negative bone scan. Minimal osteoblastic activity with multiple myeloma due to the tumoral necrosis factor. A skeletal survey can be used. Sometimes a magnetic resonance imaging (MRI) or positron emission tomography (PET) scan may be used. Bone scans are generally not done in cases of multiple myeloma (bone scans will be cold).


· Sheets of plasma cells

· Eccentric nucleus (clock faced)

· Signet-ring appearance

· Perinuclear clearing

· Abundant eosinophilic cytoplasm

· Immunohistochemical stains are for CD38+


Treatment is usually comprised of high-dose chemotherapy. Radiation treatment for progressive lesions, structurally important lesions, or radiation is used to decrease pain. Bone marrow transplants can be performed and are usually done in younger patients. Biphosphonate is also used to decrease bone pain, calcium, and the number of lesions. Surgical stabilization is used for prophylactic fixation or prevention of pathological fractures. It can also be used for the treatment of fractures. The median survival rate is about three years; however this rate worsens with renal failure.

In plasmacytomas, there is a tumor located in a single skeletal site and occurs in about 5% of patients with plasma cell tumors. There will be negative serum and urine electrophoresis, negative bone marrow biopsy and aspirate. Plasmacytomas is very sensitive to radiation and progresses to multiple myeloma in about 50% of the cases. Ostosclerotic Myeloma occurs in about 3% of the cases. A mnemonic tool POEMS in order to remember the signs and symptoms of Osteosclerotic Myeloma — Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Spike, and Skin Changes.



Nabil Ebraheim

Dr. Ebraheim is an orthopedic surgeon in Toledo, Ohio, who is very interested in education; he is trying to make a difference in people's lives.