Case 18 - Discussion

Uploaded: 2007-08-27, Updated: 2007-08-27

MICROSCOPIC EXAM:

 

PERIPHERAL BLOOD        

 

     

BONE MARROW CORE BIOPSY AND CLOT SECTION:

  

     

BONE MARROW ASPIRATE SMEAR AND TOUCH IMPRINTS:

 

     

DIFFERENTIAL:

      

FLOW CYTOMETRY INTERPRETATION

 

 

CYTOGENETICS (UNMC, Cytogenetics)

   

IMMUNOHISTOCHEMISTRY STAINS

   

DIAGNOSIS

 

 

PLASMA CELL MYELOMA

     

    WHO criteria for the 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.

Clinical Futures
 
  • Most common lymphoid malignancy in Blacks and the second most common in Whites in US, 15% of all hematology malignancy;
  • M-component in 80% of cases, of which 50% IgG, 20% IgA, 2% IgD and 1% biclonal;
  • Monoclonal light chain (Bence-Jones protein) in the serum of 15% and in the urine of 75% cases;
Gross Findings
 
  • Lytic bone lesions, filled with soft gelatinous, fish-flesh, hemorrhagic tissues.
Microscopic Findings
 
  • 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 cels;
  • 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.
Subtypes
 
  • Non-secretory myeloma: 1%

  • Indolent myeloma: meet MM criteria, but less symptoms. No treatment, typically follow-up;
  • Smoldering myeloma: high M-component, meet minimal criteria for MM, but no symptoms;

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

Differential Diagnosis
 

Monoclonal gammopathy of undetermined significance (MGUS)

  • M-component present, but less than myeloma levels;

  • Marrow plasmacytosis <10%;

  • No lytic bone lesions;

  • No myeloma-related symptoms.

Reactive plasma cell granuloma: polyclonal by kappa and lambda expressions.

Immunohistochemistry Staining
 
  • cIg+ but sIg-; 85% IgH and IgL expression, 15% IgL only; CD38+, CD79a+, CD56+, CD58+, CD138+;

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

Election Microscopy
   
Cytogenetics
 
  • 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.
Treatment and Prognosis
   
Reference
 
  • WHO Pathology & Genetics. Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon 2001
  • http://path.upmc.edu/cases/case515.html