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.

• 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;

• 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 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.

• 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.

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.

• 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-).

• 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
• http://path.upmc.edu/cases/case515.html