Multiple Myeloma Clinical Presentation

Updated: Sep 13, 2023
  • Author: Dhaval Shah, MD; Chief Editor: Emmanuel C Besa, MD  more...
  • Print


Presenting signs and symptoms of multiple myeloma (MM) include bone pain, pathologic fractures, weakness, anemia, infection (often pneumococcal), hypercalcemia, spinal cord compression, and renal failure. In approximately 30% of cases, MM is discovered through routine blood screening when patients are being evaluated for unrelated problems. Typically, a large gap between the total protein and the albumin levels observed on an automated chemistry panel suggests a problem (ie, protein minus albumin equals globulin).

In one third of patients, MM is diagnosed after a pathologic fracture occurs; such fractures commonly involve the axial skeleton. Two thirds of patients complain of bone pain, commonly with lower back pain. This bone pain is frequently located in the back, long bones, skull, and/or pelvis.

Patients may also complain of nonspecific constitutional symptoms related to hyperviscosity and hypercalcemia.

Bone pain

Bone pain is the most common presenting symptom in MM. Most case series report that 70% of patients have bone pain at presentation. The lumbar spine is one of the most common sites of pain.

Pathologic fractures and bone lesions

Pathologic fractures are very common in MM; 93% of patients have more than one site of bony involvement. A severe bony event is a common presenting issue.

Spinal cord compression

The symptoms that should alert physicians to consider spinal cord compression are back pain, weakness, numbness, or dysesthesias in the extremities. Because spinal cord compressions in MM occur at multiple levels, comprehensive evaluation of the spine is warranted. Patients who are ambulatory at the start of therapy have the best likelihood of preserving function and avoiding paralysis.


Occasionally, a patient may come to medical attention for bleeding resulting from thrombocytopenia. Rarely, monoclonal protein may absorb clotting factors and lead to bleeding.


Confusion, somnolence, bone pain, constipation, nausea, and thirst are the presenting symptoms of hypercalcemia. This complication may be present in as many as 30% of patients with MM at presentation. In most solid malignancies, hypercalcemia carries an ominous prognosis, but in MM, its occurrence does not adversely affect survival.


Abnormal humoral immunity and leukopenia may lead to infection. Pneumococcal organisms are commonly involved, but shingles (ie, herpes zoster) and Haemophilus infections are also more common in patients with MM.


Hyperviscosity may be associated with a number of symptoms, including generalized malaise, infection, fever, paresthesia, sluggish mentation, and sensory loss. Patients may report headaches and somnolence, and they may bruise easily and have hazy vision. Patients with MM typically experience these symptoms when their serum viscosity is greater than 4 times that of normal serum.

Epistaxis may be a presenting symptom of MM with a high tumor volume. Occasionally, patients may have such a high volume of monoclonal protein that their blood viscosity increases, resulting in complications such as stroke, myocardial ischemia, or infarction.

Neurologic symptoms

Carpal tunnel syndrome is a common complication of myeloma. Meningitis (especially that resulting from pneumococcal or meningococcal infection) is more common in patients with MM. Some peripheral neuropathies have been attributed to MM. Long-term neurologic function is directly related to the rapidity of the diagnosis and the institution of appropriate therapy for MM.


Anemia, which may be quite severe, is the most common cause of weakness in patients with MM.


Physical Examination

On head, ears, eyes, nose, and throat (HEENT) examination, the eyes may show exudative macular detachment, retinal hemorrhage, or cotton-wool spots. Pallor from anemia may be present. Ecchymoses or purpura from thrombocytopenia may be evident.

Bony tenderness is not uncommon in MM, resulting from focal lytic destructive bone lesions or pathologic fracture. Pain without tenderness is typical. Pathologic fractures may be observed. In general, painful lesions that involve at least 50% of the cortical diameter of a long bone or lesions that involve the femoral neck or calcar femorale are at high (50%) risk for a pathologic fracture. The risk of fracture is lower in upper-extremity lesions than in lower-extremity lesions. Even a small cortical defect can decrease torsional strength by as much as 60% (stress riser effect).

Neurologic findings may include a sensory level change (ie, loss of sensation below a dermatome corresponding to a spinal cord compression), neuropathy, myopathy, a Tinel sign, or a Phalen sign due to carpel tunnel compression secondary to amyloid deposition.

Extramedullary plasmacytomas, which consist of soft-tissue masses of plasma cells, are not uncommon. Plasmacytomas have been described in almost every site in the body. Although the aerodigestive tract is the most common location, reports also describe orbital, ear canal, cutaneous, gastric, rectal, prostatic, and retroperitoneal lesions.

On evaluation of the abdomen, hepatosplenomegaly may be discovered. Cardiovascular system examination may reveal cardiomegaly secondary to immunoglobulin deposition.

Amyloidosis may develop in some patients with MM. The characteristic physical examination findings that suggest amyloidosis include the following:

  • Shoulder pad sign
  • Macroglossia
  • Typical skin lesions
  • Post-proctoscopic peripalpebral purpura 

The shoulder pad sign is defined by bilateral swelling of the shoulder joints secondary to amyloid deposition. Physicians describe the swelling as hard and rubbery. Amyloidosis may also be associated with carpal tunnel syndrome and subcutaneous nodules.

Macroglossia may occur secondary to amyloid deposition in the tongue and is a common finding in patients with amyloidosis (see the image below).

Amyloidosis infiltrating the tongue in multiple my Amyloidosis infiltrating the tongue in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.

Skin lesions that have been described as waxy papules or nodules may occur on the torso, ears, or lips.

Post-proctoscopic peripalpebral purpura strongly suggests amyloidosis. The term originated in the time when rectal biopsy was the initial procedure of choice for diagnosing amyloidosis, and the hemodynamic effect of the procedure—comparable to a prolonged Valsalva maneuver—would lead to burst capillaries in patients with amyloid infiltration of the vessels around the eyes, Patients also may develop these raccoonlike dark circles around their eyes as a result of coughing, vomiting, or forced expiration during spirometric testing).



Renal failure and insufficiency are seen in 25% of patients with MM, [24]  and may reflect any of the following:

  • Myeloma kidney syndrome with multiple etiologies
  • Amyloidosis with light chains
  • Nephrocalcinosis due to hypercalcemia

Anemia, neutropenia, or thrombocytopenia is due to bone marrow infiltration of plasma cells. Thrombosis and Raynaud phenomenon due to cryoglobulinemia may be present.

Bone disease may result in the following:

  • Severe bone pain, pathologic fracture due to lytic lesions: Lytic disease or fracture may be observed on plain radiographs.
  • Increased bone resorption leading to hypercalcemia
  • Spinal cord compression: This is one of the most severe adverse effects of MM. Reports indicate that as many as 20% of patients develop spinal cord compression at some point during the course of their disease. Symptoms typically include back pain, weakness or paralysis in the legs, numbness, or dysesthesias in the lower extremities. However, depending on the level of involvement, patients may present with upper-extremity symptoms.

Radiculopathy and/or cord compression may occur because of skeletal destruction and nerve compression.

Bacterial infection may develop; it is the leading cause of death in patients with myeloma. The highest risk is in the first 2-3 months of chemotherapy.

Purpura, retinal hemorrhage, papilledema, coronary ischemia, seizures, and confusion may occur as a result of hyperviscosity syndrome.

Hypercalcemia may cause polyuria and polydipsia, muscle cramps, constipation, and a change in the patient’s mental status.