Multiple Myeloma (MM)
Diagnosis & Staging

Updated: February 2012

Diagnosis

Required tests:

• Serum and urine protein studies

  • serum protein electrophoresis

  • serum protein immunofixation and quantitative immunoglobulin

  • urine protein 24 hour quantitation and electrophoresis

  • serum free light chain levels: should be considered where there is a high suspicion of myeloma but the serum protein electrophoresis is negative.

• Serum calcium, uric acid, creatinine, albumin, LDH
• beta-2-microglobulin for staging at diagnosis only (not used for monitoring)
• CBC
• Skeletal radiographic survey (skull, spine, humeri, pelvis, femora, ribs)
• MRI should be considered for patients with high clinical suspicion for cord compression or to exclude soft tissue lesions in a painful area.  CT may be considered but intravenous contrast studies are relatively contra-indicated because they may cause renal injury.
• PET scan for patients with a solitary plasmacytoma.
• Bone marrow aspiration and biopsy, with:
  • FISH probe for chromosome 13q deletion
  • FISH probe for translocation t(4;14)
  • FISH probe for chromosome 17p deletion
• Hepatitis B_surface Ag, hepatitis B_core Ab, hepatitis C Ab

Note: Bone scanning is seldom useful in myeloma.

The diagnostic criteria of myeloma have recently been modified (B J Hematology 2003;121:749). All three of the following must be present for a diagnosis of symptomatic multiple myeloma:

1. Monoclonal paraprotein in serum and/or urine
2. Bone marrow plasmacytosis or biopsy proven plasmacytoma
3. Related organ or tissue impairment (note mnemonic CRAB)

The following additional finding can be helpful supportive evidence for the diagnosis of myeloma if present:

• depression of the levels of the uninvolved immunoglobulins

Remember that 2-5% of myeloma patients have no abnormal protein detectable in urine or serum, so-called non-secretory myeloma. Some of these patients may have detectable abnormalities in the serum free light chain levels which can be helpful for diagnosis and monitoring. For patients who truly have non-secretory myeloma should be accepted as symptomatic myeloma only if criteria 2 and 3 above are present.

Staging

Durie and Salmon Staging System

(Durie, Cancer, 1975;36:842-54).

Stage	Findings
1	Hgb > 100 g/L Calcium < 2.88 mmol/L Bones = no more than 1 lytic lesion
	M-protein: IgG < 50 g/L IgA < 30 g/L
	Total urinary light chain < 4 g/24 h
2	Between 1 and 3
3	Any one of these:
	Hgb < 85 g/L Calcium > 2.88 mmol/L Bones = multiple lytic lesions
	M-protein: IgG > 70 g/L IgA > 50 g/L
	Total urinary light chain > 12 g/24 h
	A = creatinine ≤ 180 mmol/L
	B = creatinine > 180 mmol/L

International Staging System (ISS)

The International Staging System (ISS) for myeloma is currently becoming more widely adopted. It depends only on the serum albumin and beta-2-microglobulin (B2M) and is actually more of a prognostic score than a staging system (Greipp, J Clin Oncol, 2005;23:3412)

Stage	Findings
I	Serum B2M < 3.5 mg/L and serum albumin ≥ 35 g/L
II	Neither stage I or II
III	Serum B2M ≥ 5.5 mg/L