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Multiple myeloma

Multiple Myeloma


Multiple myeloma is a hematologic malignancy which consists of a clonal proliferation of plasma cells.  The skeletal manifestations are frequent and varied in number and appearance. 

Clinical Manifestations


Multiple myeloma can presents either through the manifestations of a systemic disease or the findings associated with a bone lesion.


The systemic symptoms are akin to those of other hematologic malignancies.  Anemia, fatigue, and symptoms of renal failure (present up to 50%) and subsequent electrolyte imbalance (hypercalcemia) are the primary systemic disease manifestations.  Diagnosis is confirmed by the presence of monoclonal immunoglobulin fractions in the serum or urine (present in 90-95%).


Skeletal lesion often present with pain associated with impending pathologic fracture.

Red flags

 Multiple myeloma presents in the same manner and age group as metastatic carcinoma.  Consider metastases in the differential diagnosis in all cases where myeloma is suspected.  Hypercalcemia can be fatal.  Recognition of the associated medical conditions can avoid perioperative mortality.


Multiple myeloma occurs typically between the ages of 20 and 80 with the average age affected being 60.  Males are more often affected than females and African Americans are more often affected than Caucasians.  Multiple myeloma is the most common primary malignant lesion of bone and is the second most common hematologic malignancy in the United States second only to non-hodkin’s lymphoma.  The overall incidence is 6/100,000 per year with mortaility of 4/100,000 per year according to the NCI.

Pathology and pathophysiology

 The gross tumor is a gelatinous brown tumor.  Microscopically, there are sheets of plasma cells with the characteristic wagon wheel or clockface chromatin distribution.  Immunohistochemical markers are variably positive and include CD56, CD20 and CD33.  Kappa and Lambda light chain immunostains will often be positive.

Differential diagnosis


All hematologic malignancies have similar presenting systemic symptoms associated with the myelosuppression outside of the clonal lineage.  As such all hematalogic malignancies are shared in the differential diagnosis with multiple myeloma.


Given the age group and the tendency for multiplicity, metastatic carcinomas also share many characteristics with myeloma lesions.


From a purely radiographic standpoint in a solitary lesion, myelomas must be distinguished from other infiltrative lesions.  Osteomyelitis, Ewing’s sarcoma, eosiniphilic granulomatosis and metastatic carcinoma all have a permeative lytic appearance on plain radiograph.


 The cause of the disease is a clonal proliferation of plasma cells. 

Radiographic and laboratory findings

 The laboratory findings are of special significance in this disease.  The diagnosis can often be made by minimally invasive means i.e. peripheral blood or urine studies.  The findings are surmised below:


Elevated BUN/Cr

Elevated CRP

Serum Protein Electrophoresis (SPEP) – IgG, IgA, Bence Jones light chains

Urine Protein Electrophoresis (UPEP) - IgG, IgA, Bence Jones light chains

Peripheral smear – can show rouleaux formation


The radiographic appearance of multiple myeloma is that of a purely lytic lesion more often affecting the axial skeleton.  The skull, ribs, vertebra and pelvis are often affected.  The femur, tibia, radius and humerus are also affected.  The classic radiograph for this condition is the lateral skull x-ray demonstrating multiple well defined purely lytic lesions.  This gives the appearance that they have been “punched out”.


Three dimensional imaging adds little to the diagnosis, but confirms the purely lyitc lesion with no matrix production.  Of note, a small proportion of myeloma lesions can be sclerotic (typically in asian populations or as part of POEMS syndrome).


Bone scan typically shows decreased uptake, but can be positive, thus limiting the utility in ruling out unidentified sites of disease or predicting biology.

Risk factors and prevention

There is no effective prevention for multiple myeloma.

Treatment options

Treatments are directed towards the systemic disease as well as the symptomatic skeletal lesions.  Often the chemotherapies are augemented by autogenous bone marrow transplant in candidate patients.  This method improves response rate, event free survival and overall survival.


Treatment of symptomatic skeletal lesions are either treated expectantly (relying on chemotherapy response) and functional bracing or with prophylactic fixation if indicated.  Myeloma lesions are often also responsive to radiotherapy as an adjunct to fixation or as a stand-alone treatment (spine lesions).



 Survival rates are 60-85% at 1 year with continued mortality at a similar pace until 5 years where the survival rate is between 15 and 25%.


Function of skeletal disease treatment is similar to that of fixation for impendin pathologic fracture for metastatic carcinoma.

Holistic medicine

 All sarcoma patients should have access to multidisciplinary care including nutrition, physical therapy and mental health support.



POEMS syndrome is a syndrome typically seen in younger males with the following characteristics:

       Polyneuropathy (in 30-50 %)

       Organomegaly (liver and spleen)

       Endocrine (gynecomastia, amenorrhea)

       Monoclonal Gammopathy

       Skin hyperpigmentation and hirsutism

Key terms

 Myeloma, monoclonal, gammaopathy, metastasis, plasmacytoma, solitary plasmacytoma, punched-out, lucent, permeative, infiltrative, small round blue cell

Skills and competencies

 Students should be able to recognize a purely lytic lesion on plain radiographs and be able to recognize the classic lesions on the lateral skull x-ray.  Students should be able to identify a plasma cell on H&E light microscopy. 


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