Diagnosis and differential diagnosis of multiple myeloma

  The common symptoms of multiple myeloma (MM) include malaise, bone pain, and recurrent infections. 70% of patients have anemia at diagnosis. 1/4 of patients have hypercalcemia. Routine X-rays show skeletal abnormalities in nearly 80% of patients. 82% of patients are positive for serum protein electrophoresis and 93% are positive for immunofixation electrophoresis for M protein.  Nearly 20% of patients with MM lack heavy chain expression and are considered to have light chain MM, which often has M protein in the urine but not a high M component in the blood. Therefore, serum protein electrophoresis and immunofixation electrophoresis of blood and urine are performed in all patients with suspected MM.  The 1% of patients with no M component in both blood and urine immunofixation electrophoresis are considered to have nonsecretory myeloma. In such patients, serum free light chain (FLC) quantification, i.e., the detection of serum free light chain κ and λ, is useful for diagnosis and evaluation of outcome. λ ratio (reference range 0.26-1.65) is used to differentiate between polyclonal elevations due to abnormal renal function and monoclonal elevations due to clonal disorders of plasma cells. κ/λ ratios less than 0.26 represent the presence of monoclonal λ light chains, while ratios greater than 1.65 represent monoclonal κ light chains.  The diagnosis of MM requires a bone marrow aspiration (or biopsy for plasmacytoma) of 10-15% plasma cells, blood and/or urine M protein (no M protein in unsecreted myeloma), and end-organ damage secondary to MM (hypercalcemia, renal insufficiency, anemia, bone destruction).  Differential diagnosis: 1, reactive plasmacytosis: primary disease such as chronic inflammation, typhoid fever, SLE, cirrhosis, metastatic carcinoma; plasma cells ≤ 30% and no morphological abnormalities; immunophenotype CD38+CD56-, (MM is CD38+CD56+); M protein (-); IgH gene clone rearrangement negative.  2, primary macroglobulinemia: increased blood IgM monoclonal, while other immunoglobulins are normal or mildly depressed; X-ray is less likely to see osteoporosis, no osteolytic changes; plasma cell-like lymphocytes are seen in the bone marrow; immunophenotype CD19 + CD20 + CD22 + (MM is CD19-CD20-CD22 -).  3.Metastatic cancer: primary tumor; elevated serum alkaline phosphatase; osteogenic manifestations; bone penetration into a pile of specific cancer cells.  4, monoclonal gammopathy of undetermined significance (MGUS): M protein <30g/l; bone marrow clonal plasma cells.