The diagnosis of multiple myeloma (MM) requires a combination of clinical manifestations, bone marrow smear, serum M protein, and X-ray (or CT or MRI) examination of bones to determine the diagnosis, and MM is divided into different types according to the type of increased abnormal immunoglobulins.
I. Clinical and laboratory features of multiple myeloma
Clinical/laboratory features
Anemia
Bone damage (osteolytic lesions, pathological fractures or severe osteoporosis)
Renal failure (blood creatinine) Hypercalcemia
Monoclonal protein seen in serum protein electrophoresis
Monoclonal protein in serum immunofixation electrophoresis
Monoclonal protein in serum or urine immunofixation electrophoresis
Serum free light chain analysis
Type of protein
Light chain only
Clonal bone marrow plasma cells increased ≥
1. Typing of multiple myeloma.
It can be divided into the following eight types: IgG type, IgA type, IgD type, IgM type, IgE type, light chain type, biclonal type, and nonsecretory type. According to the light chain type, there are κ and λ types.
(a) IgG type: The heavy chain is γ chain, and the light chain is κ chain or λ chain, which is the most common subtype, accounting for about 50% of MM, with typical clinical manifestations of MM.
(2) IgA type: the heavy chain is α chain and the light chain is κ chain or λ chain, accounting for about 15-20% of MM. Myeloma cells are flame-like, and IgA easily aggregates into multimers and causes hyperviscosity, hypercalcemia and hypercholesterolemia.
The M component of serum protein electrophoresis is often in the α2 region rather than the γ region.
(iii) Light chain type: monoclonal κ chain or λ chain, heavy chain is absent, about 15-20%, serum protein electrophoresis does not appear M component, immunoelectrophoresis and light chain quantification: a large number of monoclonal light chain in blood and urine (urine is positive for this-peripheral protein), tumor cells are often poorly differentiated, rapid proliferation, bone destruction is common, and renal function is more impaired.
(iv) IgD type: heavy chain is δ chain, light chain is κ chain or λ chain. Foreign: 1~2% Domestic: 8~10%. The age of onset is relatively young, extramedullary infiltration is common, and osteosclerotic lesions are relatively common.
(E) IgM type: heavy chain is μ chain, light chain is κ chain or λ chain, rare, accounting for only about 1%, the molecular weight is large (molecular weight 950,000) and easy to form pentamers to increase blood viscosity, so prone to high viscosity syndrome is its characteristics.
(F) IgE type: heavy chain is ε chain, light chain is κ chain or λ chain, rare. The serum monoclonal IgE can be as high as 45-60g/L, the light chain is mostly λ chain, osteolytic lesions are rare, the peripheral blood plasma cells increase, may present signs of plasma cell leukemia.
(vii) biclonal or polyclonal type: rare, accounting for less than 1%, often monoclonal IgM + monoclonal IgG / monoclonal IgM + monoclonal IgA, light chains mostly belong to the same type, occasionally two biclonal light chain type although there are case reports, but is rare, polyclonal (tri-clonal or tetra-clonal) type rare.
(H) non-secretory type: about 1% of patients have the typical clinical manifestations of MM, no M component in the serum, no monoclonal light chain in the urine (urine this – week protein negative), immunofluorescence method is further divided into non-forming and non-secretory type
II. Diagnosis of multiple myeloma
(a) The Chronic Leukemia-Myeloma Task Force recommends the diagnosis of multiple myeloma.
Recommendations of the Chronic Leukemia-Myeloma Task Force on the Diagnosis of Multiple Myeloma (1972)
If M protein is present in the blood or urine, one or more of the following conditions must be met.
Bone marrow abnormal plasma cells > 5% (non-reactive plasma cells)
Abnormal plasma cells confirmed by tissue biopsy
Abnormal plasma cells in peripheral blood > 500
Osteolytic bone damage without other explanations
In the absence of M protein in blood or urine, there must be radiological evidence of osteolytic bone damage or definite neoplasia with one or more of the following conditions.
Bone marrow abnormal plasma cells >20% (non-reactive plasma cells, from both bone marrow puncture sites)
Tissue biopsy confirmed the presence of abnormal plasma cells
(ii) Kyle et al. diagnostic criteria for MM
Table 3 Kyle et al. diagnostic criteria for MM
Main criteria
1. Plasmacytoma confirmed by tissue biopsy
2. Plasma cells >30% in the bone marrow
3. Monoclonal immunoglobulin IgG>35g/L or IgA>20g/L or light chain ≥1g/24h in urine (except amyloidosis)
Secondary criteria
1. 10-30% plasma cells in the bone marrow
2. monoclonal immunoglobulin levels below the above levels
3. osteolytic lesions
Normal immunoglobulin IgM176.8μ
Anemia
Hemoglobin <100g/L or more than 20g/L below normal
Bone destruction
Osteolytic damage or osteoporosis with compression fracture
Other
Symptomatic hyperviscosity, amyloidosis, recurrent bacterial infections (≥2 times/year)
III. Diagnostic criteria
Main criteria.
①Tissue biopsy proves the presence of plasmacytoma or bone marrow smear examination: plasma cells > 30%, often accompanied by morphological changes.
② monoclonal immunoglobulin (M protein): IgG>35g/L, IgA>20g/L, IgM>15g/L, IgD>2g/L, IgE>2g/L, monoclonal K or λ light chain in urine>1g/24 hours, and exclude amyloidosis.
Secondary criteria.
①Bone marrow examination: 10%-30% plasma cells.
② Presence of monoclonal immunoglobulin or its fragments, but below the above criteria.
③ X-ray examination with osteolytic damage and/or extensive osteoporosis.
④Decreased amount of normal immunoglobulins.