Multiple Myeloma: Plasma Cell Neoplasm

• Multiple myeloma is a plasma cell neoplasm with multifocal involvement of the skeleton
• Solitary myeloma (plasmacytoma) is an infrequent multiple myeloma variant
• Solitary myeloma manifests as a single mass in bone or soft tissue

Origin of Multiple Myeloma

• Multiple myeloma is caused by malignant plasma cell proliferation in the bone marrow

Epidemiology

• Multiple myeloma accounts for 1% of all cancer deaths in Western countries
• It is more common in men and people of African descent
• The peak age for multiple myeloma diagnosis is 65 to 70 years

Common Sites

• The most common sites for multiple myeloma, in descending order of frequency, are the vertebral column, ribs, skull, and pelvis
• "Plasma cell leukemia" occurs when the disease spreads from bone to involve the blood
• Systemic organ involvement can include the spleen, liver, kidneys, lungs, lymph nodes, and other soft tissues

Molecular Pathogenesis

• Ig genes in myeloma cells exhibit somatic hypermutation
• The proliferation and survival of myeloma cells depend on cytokines, notably IL-6

Pathogenesis

• Neoplastic plasma cells produce excess light or heavy chains along with immunoglobulins termed "M protein"
• Free light chains are excreted in the urine as "Bence-Jones proteins"
• High levels of M proteins lead to red cells sticking together in peripheral blood smears, known as "rouleaux formation"
• Factors produced by neoplastic plasma cells mediate bone destruction

Clinical Manifestations and Complications

• Clinical features of multiple myeloma stem from the effects of plasma cell proliferation in the bones
• The production of excessive abnormal Igs and the suppression of normal humoral immunity also contribute to the clinical features
• The effects of abnormal plasma cell proliferation include bone destruction, chronic pain and pathological fractures
• Hypercalcemia results in neurologic manifestations, and contributes to renal dysfunction
• Decreased production of normal Igs leads to recurrent bacterial infections due to abnormal plasma cell proliferation in the bone

Complications

• Renal failure is the most important risk factor, Bence Jones proteinuria, where excreted light chains are toxic to renal tubular epithelial cells
• Amyloidosis of the AL type exacerbates renal dysfunction and deposits in other tissues

Diagnosis

• Diagnosis of multiple myeloma involves radiographic and laboratory investigations, along with bone marrow aspiration and biopsy
• Radiographic investigations include X-rays and MRI
• Laboratory investigations include serum or urine electrophoresis and Immunofixation-characterization of Igs

Immunoelectrophoresis

• Monoclonal Igs are “M protein" and present as abnormal protein spikes in serum or urine
• IgG is the most common monoclonal Ig, seen in about 55% of patients
• IgA occurrs in about 25% of cases

X-ray features of lesions in skull

• Punched-out defects (osteolytic), 1 to 4 cm in diameter and Gross- soft, gelatinous, red tumor masses

Histology

• Histology shows relatively normal-appearing plasma cells
• Plasma cell variants include bizarre multinucleated cells, flame cells (fiery red cytoplasm), and Mott cells (multiple grapelike cytoplasmic droplets)
• Plasma cells may contain Russell bodies (globular inclusions in cytoplasm) and Dutcher bodies (globular inclusions in nucleus)

Prognosis and Cause of Death

• The prognosis for multiple myeloma is generally poor
• The median survival is between 4 to 6 years
• The primary causes of death are infections and renal failure

Multiple myeloma is a plasma cell neoplasm with multifocal involvement of the skeleton. Solitary myeloma manifests as a single mass in bone or soft tissue. It accounts for 1% of all cancer deaths in Western countries and is more common in men.