Multiple myeloma overview

Multiple myeloma Microchapters
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Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Multiple Myeloma from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria
Staging
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X Ray
Echocardiograph and Ultrasound
CT
MRI
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Multiple myeloma is a type of cancer of plasma cells which are immune system cells in bone marrow that produce antibodies. Its prognosis, despite therapy, is generally poor, and treatment may involve chemotherapy and stem cell transplant. It is part of the broad group of diseases called hematological malignancies.

Pathophysiology

Multiple myeloma arises from post-germinal center B lymphocytes, that are normally involved in production of human immunoglobulins. Development of multiple myeloma is the result of multiple genetic translocation between the immunoglobulin heavy chain gene and oncogenes which leads to dysregulated multiplication of plasma cells. On microscopic histopathological analysis, abundant eosinophilic cytoplasm, eccentrically placed nucleus, and russell bodies bodies are characteristic findings of multiple myeloma.

Causes

There are no established causes for multiple myeloma.

Differentiating Multiple Myeloma from other Diseases

Multiple myeloma must be differentiated from monoclonal gammopathy of undetermined significance(MGUS), isolated plasmacytoma of the bone, and extramedullary plasmacytoma.

Epidemiology and Demographics

In 2012, the incidence of multiple myeloma was approximately 6.3 per 100,000 cases with a mortality rate of 3.3 per 100,000 cases in the United States. The prevalence of multiple myeloma was estimated to be 89,658 cases in 2012 in the United States. Multiple myeloma is the second most common blood cancer after non-Hodgkin's lymphoma & 14th most common cancer overall in United States. Male are more commonly affected with multiple myeloma than female. The male to female ratio is approximately 2 to 1. Multiple myeloma usually affects individuals of the African American and Native Pacific Islanders race. Asian individuals are less likely to develop multiple myeloma. The incidence of multiple myeloma increases with age; the median age at diagnosis is between 65 to 70 years years.

Risk Factors

The exact etiology behind multiple myeloma is not known but a number of risk factors are implicated, most commonly carcinogenic chemicals.

Natural History, Complications and Prognosis

A number of organ systems are commonly involved, the most common symptoms being bone pain usually involving the spine and the ribs. These frequently lead to pathological fractures and resultant hypercalcemia. Also common are infections such as pneumonias and pyelonephritis. Renal failure from hypercalcemia and Bence Jones protein filtration, anemia from suppressed bone marrow production and neurological symptoms from brain metastasis are also prominent.

According to a report published by National Cancer Institute there is a 43.25 chance of 5 year survival.

Complications associated with multiple myeloma include renal failure, hematologic complications, infections, bony and neurological complications.

Diagnosis

Staging

International Staging System for multiple myeloma, based on β2-microglobulin (β2M) levels and serum albumin levels, was published by International myeloma working group in 2003 and is the most widely used staging system. It is used for both guiding treatment as well as predicting prognosis.

Laboratory Findings

The most frequently advised tests are complete blood count (CBC), erythrocyte sedimentation rate (ESR), Basic metabolic panel, electrophoresis, immunohistochemistry and imaging procedures like X ray, CT scans and MRI's.

History and Symptoms

The sign and symptomatology associated with multiple myeloma is most commonly associated with following 4 systems: Calcium (elevated), kidneys (renal failure), blood (anemias) and cells and bones (fractures and pains).

Some of the most common symptoms include weakness, bone pains, back pain, numbness and paresthesia, bleeding and recurrent infections.

Most common signs include pallor, pain without tenderness, altered sensations on neurological examination etc.

Physical Examination

Multiple myeloma affects not only the bone marrow, but also spreads to other organ systems. This therefore, requires a detailed assessment of various organ systems. A number of times, any of these physical findings may warrant a further evaluation, and thus leads to an incidental diagnosis of multiple myeloma. Pallor, purpura, signs of cord compression, hepatosplenomegaly, bony pain without tenderness and carpal tunnel syndrome are some of the most common physical findings, in a patient presenting with multiple myeloma.

X Ray

Simple radiography is the current gold standard for the initial diagnosis and evaluation of relapses of multiple myeloma. Well defined punched out bony lesions and hair on end appearance are two characteristic findings. The long bones and the spine must always be evaluated. The evaluation of other bones merit consideration based on the symptoms of the patient.

CT

Computed Tomography scan is not the best modality for the diagnosis of multiple myeloma. Contrast CT scans lead to renal failure in multiple myeloma more frequently than otherwise. Hence, other modalities are preferred over CT scan. However, occasionally a CT scan is performed to measure the size of soft tissue plasmacytomas among patients with multiple myeloma.

MRI

The workup of suspected multiple myeloma includes a skeletal survey.Magnetic resonance imaging (MRI) is more sensitive than simple X-ray in the detection of lytic lesions, and may supersede skeletal survey, especially when vertebral disease is suspected.

Other Imaging Findings

Positron emitted tomography (PET) scan has been shown to be highly sensitive and specific, when combined with MRI it can achieve 100% diagnostic efficacy. The use of PET scan has led to earlier diagnosis of multiple myeloma, more accurate therapy assessment, and better prediction of patient outcome. However, these have not been employed as a standard of care by the International Myeloma Working Group.

Treatment

Medical Therapy

The treatment of multiple myeloma is based on differentiating suitability for transplantation or not. Those who are candidates for transplantation are treated with a combination of dexamethasone and one of the following lenalidomide/bortezomib. Alkylating agents are usually avoided in such candidates. Several other agents are also used these include thalidomide, prednisone, melphalan etc.

Surgery

Surgery is not a main treatment for multiple myeloma. Emergency surgery may be needed to help support weight-bearing bones in the spine or legs to prevent bones from breaking.

References

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