Multiple Myeloma

Pathophysiology

1) infiltration of bone marrow by malignant plasma cells that secrete a partial or whole immunoglobulin called the M component or paraprotein 2) five subtypes – IgG, IgA, IgD, IgE, and light chain 3) clinical course follows a biphasic pattern – initially chronic and then an accelerated late phase

Signs and Symptoms

1) recurrent infections (pneumonia, Toxoplasma, and Pneumocystis 2) pathologic fractures 3) bleeding episodes 4) lymphadenopathy/organomegaly 5) neurologic deficits 6) chronic renal failure 7) usually presents with bone pain in ribs or vertebrae

Characteristic Test Findings

Laboratory – 1) monoclonal spike on protein electrophoresis 2) Bence Jones proteins in urine (kappa or gamma immunoglobulin light chains) 3) anemia 4) hypercalcemia 5) hyperuricemia 6) increased sed rate Radiology – 7) “punched out” lytic bone lesions (especially in skin and flat bones) or diffuse demineralization

Histology/Gross Pathology

1) Dutcher bodies (intranuclear inclusions of immunoglobulin protein droplets) in plasma cells 2) Russell bodies (cytoplasmic inclusions of immunoglobulin protein droplets) in plasma cells 3) plasmablasts and variants – flame cells, binucleated plasma cells 4) plasma cells > 30% of bone marrow 5) renal tubular casts of light-chain protein fragments 6) RBC rosette formation

Associated Conditions

1) large exposure to ionizing radiation 2) amyloid deposition 3) increased incidence in chronic infection (osteomyelitis) and inflammatory conditions (lupus) 4) nephrocalcinosis 5) hyperviscosity syndrome 6) translocation of chromosomes 11 and 13 7) superimposed AML or myelodysplastic syndrome

Biochemistry

1) translocation of proto-oncogene bcl-1 on chromosome 11 places it next to immunoglobulin heavy-chain gene on chromosome 14 2) development may require a “two-hit” process 3) myeloma cells secrete cytokines that recruit osteoclasts only and thus cause purely lytic bone lesions

Inheritance/Epidemiology

1) 7,500 cases per year in USA 2) blacks to whites, 2:1 3) mean age at diagnosis, 65 years 4) most common variant is IgG myeloma with mean survival of 3-4 years with treatment (other variants more aggressive with shorter survival times)

Treatment

1) radiation to isolated bone lesions 2) alkylating agent (melphalan, cyclophosphamide) and prednisone given as pulse doses 3) stem cell transplant and bone marrow transplant have shown great promise 4) thalidomide in refractory cases

Tips for USMLE

1) if M component is mentioned, think multiple myeloma 2) if a 67 year old black male has had three cases of pneumonia in the past 16 months and now has renal insufficiency and a radiograph of his skull shows punched out lesions, think multiple myeloma