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Case 5 - Discussion

Hematopathology Case




WHO Criteria for Diagnosis of Multiple Myeloma

  • Major criteria (3)

    • Bone marrow plasmacytosis >30%

    • Plasmacytoma on biopsy

    • Monoclonal protein (M-component) in serum or urine

      • Serum IgG >3.5 g/dL, or

      • Serum IgA >2 g/dL, or

      • Urine Bence-Jones protein >1g/24 hours

  • Minor criteria (4)

    • Bone marrow plasmacytosis,10-30%

    • Monoclonal protein present but less than the above concentrations

    • Presence of lytic bone lesions

    • Reduced normal immunoglobulins to <50% of normal

      • IgG <600 mg/dL, or

      • IgA <100 mg/dL, or

      • IgM <50 mg/dL

  • Diagnostic requirements: The diagnosis of multiple myeloma requires a minimum of one major criterion and one minor criterion, or three minor criteria which must include bone marrow plasmacytosis of 10-30 percent and the presence of a monoclonal protein. These criteria must be manifest in a symptomatic patient with progressive disease.



  • Most common lymphoid malignancy in Blacks and the second most common in Whites in US, 15% of all hematology malignancy;

  • Median age at diagnosis: male 68 years and female 70 years, M:F=1.1:1;

  • Clinical presentations: serum monoclonal protein and skeletal destruction with osteolytic lesions, pathological fractures, bone pain, hypercalcemia and anemia;

  • M-component in 99% of cases, of which 55% IgG, 22% IgA, 18% light chain only, 2% IgD and 1% biclonal;

  • Monoclonal light chain (Bence-Jones protein) in the serum of 15% and in the urine of 75% cases;


  • Lytic bone lesions, filled with soft gelatinous, fish-flesh, hemorrhagic tissues.


  • Mature plasma cells: oval, basophilic cytoplasm, perinuclear hof; round eccentric nucleus with "spoke wheel" or "clock-face" chromatin, no nucleolus;

  • Immature plasma cells (plasmablasts): high nuclear/cytoplasm ratio, dispersed chromatin and prominent nucleoli. 10% MM cases exhibit plasmablastic morphology and associate with poorer prognosis.

  • Multinucleated, polylobated and pleomorphic plasma cells, not seen in reactive plasma cells;

  • Mott/Morula cells: multiple pale blue-white, grape-like accumulation of cytoplasmic Ig; Russell bodies: cherry-red refractive round bodies; Flame cells: vermilion staining glycogen-rich IgA; Crystalline rods.


  • Non-secretory myeloma: 1%

  • Indolent myeloma: meet MM criteria, but less symptoms, including no more than 3 lytic bone lesions and intermeidate M protein levels (IgG<7g/dL, IgA<5g/dL). No treatment necessary, typically follow-up;

  • Smoldering myeloma: high M-component, meet minimal criteria for MM, but no symptoms;

  • Plasma cell leukemia: peripheral blood plasma cells >2x10^9/Liter or >20% of WBC;  more common with light-chain only, IgD or IgE than in IgG or IgA.


  • cIg+ but sIg-; 85% IgH and IgL expression, 15% IgL only

  • CD38+, CD138+, CD56 often +, CD58+

  • CD19-, CD20- (normal plasma cell CD19+ and CD56-/CD58-).


  • Most common gains: 3, 5, 7, 9, 11, 15 and 19;

  • Most common losses: monosomy or partial deletion of 13 (13q14);

  • Most common translocation: t(11; 14) (q13; q32), IgH/CCND1 fusion.


  • WHO Pathology & Genetics. Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon 2001