Epidemiology

Etiology

Pathophysiology

• Neoplastic proliferation of plasma cells
  • Bone marrow infiltration by malignant plasma cells → suppression of hematopoiesis → leukopenia, thrombocytopenia, anemia
  • Cell proliferation → pro-osteoclastogenic factors (e.g., TNF-α, IL-1, RANK-L) → osteolytic lesions → hypercalcemia
• Overproduction of monoclonal immunoglobulin and/or light chains → dysproteinemia (a state of pathologically increased synthesis of immunoglobulins and/or their subunits) → kidney damage (e.g., myeloma cast nephropathy) and/or paraprotein tissue deposition (may cause amyloidosis)
  • Nonfunctioning antibodies → functional antibody deficiency
  • ↑ Serum viscosity → hyperviscosity syndrome

Clinical features

• Often asymptomatic
• Bone pain, especially back pain (most common symptom)
• Symptoms of hypercalcemia, e.g. constipation
• Foamy urine (caused by Bence Jones proteins in urine)

Diagnostics

• Calcium > 11 mg/dL or > 1 mg/dL above the ULN
• Renal insufficiency: GFR < 40 mL/min or serum creatinine > 2 mg/dL
• Anemia: Hb < 10 g/dL or more than 2 g/dL below the LLN
  • Normocytic anemia
  • Rouleaux formation
• Bone lesions: ≥ 1 osteolytic lesions on imaging

Bone marrow biopsy

• Cytology: clusters of plasma cells
  • Mildly organized monoclonal cells
  • Perinuclear lucent zone
    • Active Golgi apparatus
  • Clockface nuclei: Chromatin in the periphery of the nucleus resembles a cartwheel or clock face arrangement.
  • Intracytoplasmic crystalline inclusion bodies containing IgG

Treatment

Complications

• Myeloma cast nephropathy (i.e., myeloma kidney): most common cause of renal injury and renal failure in patients with multiple myeloma
  • Clinical features: oliguria, peripheral edema, dyspnea
  • Pathophysiology: excessive production and filtration of light chains into the urine → precipitation of light chains in renal tubules → tubular obstruction
  • Diagnosis: markedly positive urine sulfosalicylic acid test and/or urine protein electrophoresis
    • On light microscopy, numerous large, glassy eosinophilic casts are seen.
  • May progress to end-stage renal disease (ESRD)
• AL amyloidosis: Light chains can accumulate as amyloids and may lead to restrictive cardiomyopathy, renal insufficiency, macroglossia, and malabsorption syndromes.
• Infections
• Secondary plasma cell leukemia