Snapshot A 65-year-old man presents to his primary care physician with generalized fatigue and lower back bone pain. He reports an unexpected 20-pound weight loss over the course of 3 months. Physical examination is notable for conjunctival pallor and tenderness upon palpation of the lower spine. Laboratory studies are notable for a normocytic, normochromic anemia, hypercalcemia, and renal insufficiency. Urine electrophoresis is notable for Bence Jones proteins. Introduction Overview neoplastic proliferation of plasma cells within the bone marrow leads to the production of monoclonal immunoglobulin (Ig) mostly IgG (52%) and IgA (21%) results in skeletal destruction Epidemiology Demographics older adults median age is 66 years of age Risk factors monoclonal gammopathy of undetermined significance (MGUS) ETIOLOGY Pathophysiology clonal malignant plasma cell proliferation Associated conditions Fanconi syndrome renal tubular acidosis type 2 ↑ susceptibility to infection primary amyloidosis Presentation Symptoms fatigue secondary to anemia bone pain especially in the back and chest radiculopathy especially in the thoracic or lumbosacral area it's the most common neurological complication of multiple myeloma secondary to paravertebral plasmacytoma bone collapse peripheral neuropathy rare and usually secondary to amyloidosis sequelae associated with hypercalcemia e.g., constipation, abdominal pain, muscle pain, and frequent urination edema secondary to effects of amyloidosis on kidneys Imaging Radiography indication can be used as an initial imaging study when evaluating bone pain it is the least sensitive method for detecting skeletal lesions findings lytic bone lesions Whole body low-dose CT scan indication used in most cases to have a baseline assessment of how much the bone is involved MRI whole body (or spine and pelvis) indication when CT scan does not demonstrate bone lesions but there is a high suspicion of multiple myeloma most sensitive in evaluating bone involvement when there is concern for cord compression PET scan indication suspected extramedullary disease most sensitive in evaluating extramedullary involvement Studies Serum labs normocytic, normochromic anemia secondary to bone marrow replacement renal damage hemodilution with large M protein elevated serum creatinine secondary to light chain cast nephropathy (myeloma kidney) Bence Jones protein on urine electrophoresis hypercalcemia hypercalcemia from osteolytic bone lesions protein electrophoresis of the serum (SPEP) monoclonal immunoglobulin spike (M protein) peripheral blood smear rouleaux formation of red blood cells "stack of coins" appearance Invasive studies bone marrow aspiration ≥ 10% clonal plasma cells multiple plasma cells with a "clock-face" chromatin pattern renal biopsy amyloid desposits will show apple-green birefringence under polarized light with Congo red stain Imaging punched-out lytic bone lesions on radiograph Differential MGUS differentiating factors < 10% clonal plasma cells absence of lytic lesions serum M protein is low Waldenstrom macroglobulinemia differentiating factors IgM gammopathy absence of hypercalcemia, renal involvement, anemia, and bone lytic lesions Treatment Medical chemotherapy indication treatment of choice optimal treatment has not been established yet Complications May lead to ↑ susceptibility to infection anemia primary amyloidosis (AL) cast nephropathy due to excess light chain production peripheral neuropathy