Multiple myeloma diagnostic criteria: Difference between revisions

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{{Multiple myeloma}}
{{Multiple myeloma}}
{{CMG}} {{AE}} {{SSK}}
{{CMG}} {{AE}} {{HMHJ}}; {{SSK}}; {{shyam}}
 
==Overview==
==Overview==
The International Myeloma Working Group (IMWG) proposed updated criteria for the diagnosis of multiple myeloma in November 2014. The diagnosis requires >10% clonal [[plasma cell]] proliferation in the [[bone marrow]], or biopsy-proven [[plasmacytosis]] at an extramedullary site plus one of more of the [[multiple myeloma]]-defining CRAB features ([[hypercalcemia]], [[renal failure]], [[anaemia]], and [[bone]] lesions) or one or more of the newly added biomarkers of malignancy (clonal bone marrow [[plasma cell]] percentage ≥60%, involved:uninvolved serum free light chain ratio ≥100, and >1 focal lesions on MRI studies).<ref name="lancet">Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548</ref>
The diagnosis of monoclonal gammopathy of undetermined significance requires the presence of clonal plasma cells < 10% and serum monoclonal protein <3g/dl but the absence of end-organ damage. The diagnosis of smoldering multiple myeloma requires the presence of clonal plasma cells 10%-60% and serum monoclonal protein >3g/dl but the absence of end-organ damage. The diagnosis of active multiple myeloma requires the presence of end-organ damage. In November 2014, the International Myeloma Working Group (IMWG) updated the criteria for the diagnosis of multiple myeloma to include novel validated biomarkers to better encompass the extent of disease. Prior to 2014, the original diagnostic criteria for end-organ damage included CRAB features ([[hypercalcemia]], [[renal failure]], [[anemia]], and [[bone]] lesions) without consideration of the plasma cell burden or free light chain ratio. The 2014 update also clarified the underlying laboratory and radiographic findings of CRAB features, as well as the histological and monoclonal protein requirements for the disease diagnosis.<ref name="lancet">Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548</ref>
 
==Diagnostic Criteria==


= Table 1 =
===Revised Criteria for the Diagnosis of Multiple Myeloma===
International Myeloma Working Group Diagnostic Criteria for Multiple Myeloma and Related Plasma Cell Disorders
The [[diagnosis]] of [[multiple myeloma]] requires the following:<ref name="lancet">Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548</ref><ref name="pmid18971951">{{cite journal |vauthors=Kyle RA, Rajkumar SV |title=Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma |journal=Leukemia |volume=23 |issue=1 |pages=3–9 |date=January 2009 |pmid=18971951 |pmc=2627786 |doi=10.1038/leu.2008.291 |url=}}</ref><ref name="pmid12780789">{{cite journal |vauthors= |title=Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group |journal=Br. J. Haematol. |volume=121 |issue=5 |pages=749–57 |date=June 2003 |pmid=12780789 |doi= |url=}}</ref><ref name="pmid16212152">{{cite journal |vauthors=Rajkumar SV, Kyle RA |title=Multiple myeloma: diagnosis and treatment |journal=Mayo Clin. Proc. |volume=80 |issue=10 |pages=1371–82 |date=October 2005 |pmid=16212152 |doi=10.4065/80.10.1371 |url=}}</ref>
<ref name="pmid26763514">{{cite journal |vauthors=Rajkumar SV, Kumar S |title=Multiple Myeloma: Diagnosis and Treatment |journal=Mayo Clin. Proc. |volume=91 |issue=1 |pages=101–19 |date=January 2016 |pmid=26763514 |pmc=5223450 |doi=10.1016/j.mayocp.2015.11.007 |url=}}</ref><ref name="pmid24130968">{{cite journal |vauthors=Eslick R, Talaulikar D |title=Multiple myeloma: from diagnosis to treatment |journal=Aust Fam Physician |volume=42 |issue=10 |pages=684–8 |date=October 2013 |pmid=24130968 |doi= |url=}}</ref>
*≥10% clonal [[plasma cells]] in [[bone marrow]]
{| class="wikitable"
'''OR'''
! rowspan="1" colspan="1" |Disorder
*[[biopsy]]-proven bony or [[Plasmacytoma|extramedullary plasmacytoma]],
! rowspan="1" colspan="1" |Disease Definition
'''With''' one or more of the [[Multiple myeloma|myeloma]]-defining events:
|-
*CRAB features:
| rowspan="1" colspan="1" |Non-IgM monoclonal gammopathy of undetermined significance (MGUS)
**'''[[Hypercalcemia]]''': [[Calcium|serum calcium]] >0·25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2·75 mmol/L (>11 mg/dL)
| rowspan="1" colspan="1" |All 3 criteria must be met:
**'''[[Renal insufficiency]]''': [[creatinine]] clearance <40 mL per min or [[serum creatinine]] >177 μmol/L (>2 mg/dL)
* Serum monoclonal protein (non-IgM type) <3gm/dL
**'''[[Anemia]]''': [[hemoglobin]] value of >2 g/dL below the lower limit of normal, or a [[hemoglobin]] value <10 g/dL
* Clonal bone marrow plasma cells <10%<sup>*</sup>
**'''[[Bone]] [[lesion]]''': one or more osteolytic [[lesions]] on [[Skeleton|skeletal]] [[radiography]], [[CT-scans|CT]], or [[PET scan|PET-CT]]
* Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to the plasma cell proliferative disorder
*Biomarkers of malignancy:
|-
**'''[[Bone marrow]] [[plasma cell]] burden''': Clonal [[bone marrow]] [[plasma cell]] percentage ≥60%
| rowspan="1" colspan="1" |Smoldering multiple myeloma
**'''[[Light chain|Free light chain]] ratio''': Involved-to-uninvolved free [[light chain]] ratio ≥100
| rowspan="1" colspan="1" |Both criteria must be met:
**'''[[MRI]]''': >1 focal [[Bone|bony]] [[lesion]] of 5mm or greater on [[MRI]] studies
* Serum monoclonal protein (IgG or IgA) ≥3gm/dL, or urinary monoclonal protein ≥500 mg per 24h and/or clonal bone marrow plasma cells 10–60%
{|  
* Absence of myeloma defining events or amyloidosis
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Revised Criteria for the Diagnosis of Multiple Myeloma
|-
| rowspan="1" colspan="1" |Multiple Myeloma
| rowspan="1" colspan="1" |Both criteria must be met:
* Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma
* Any one or more of the following myeloma defining events:
** ○ Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
*** ▪ Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)
*** ▪ Renal insufficiency: creatinine clearance <40 mL per minute or serum creatinine >177 μmol/L (>2 mg/dL)
*** ▪ Anemia: hemoglobin value of >2 g/dL below the lower limit of normal, or a hemoglobin value <10 g/dL
*** ▪ Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT)
** ○ Clonal bone marrow plasma cell percentage ≥60%)
** ○ Involved: uninvolved serum free light chain (FLC) ratio ≥100 (involved free light chain level must be ≥100 mg/L))
** ○ >1 focal lesions on magnetic resonance imaging (MRI) studies (at least 5mm in size)
|-
| rowspan="1" colspan="1" |IgM Monoclonal gammopathy of undetermined significance (IgM MGUS)
| rowspan="1" colspan="1" |All 3 criteria must be met:
* Serum IgM monoclonal protein <3gm/dL
* Bone marrow lymphoplasmacytic infiltration <10%
* No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder.
|-
| rowspan="1" colspan="1" |Light Chain MGUS
| rowspan="1" colspan="1" |All criteria must be met:
* Abnormal FLC ratio (<0.26 or >1.65)
* Increased level of the appropriate involved light chain (increased kappa FLC in patients with ratio > 1.65 and increased lambda FLC in patients with ratio < 0.26)
* No immunoglobulin heavy chain expression on immunofixation
* Absence of end-organ damage that can be attributed to the plasma cell proliferative disorder
* Clonal bone marrow plasma cells <10%
* Urinary monoclonal protein <500 mg/24h
|-
| rowspan="1" colspan="1" |Solitary Plasmacytoma
| rowspan="1" colspan="1" |All 4 criteria must be met
* Biopsy proven solitary lesion of bone or soft tissue with evidence of clonal plasma cells
* Normal bone marrow with no evidence of clonal plasma cells
* Normal skeletal survey and MRI (or CT) of spine and pelvis (except for the primary solitary lesion)
* Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, or bone lesions (CRAB) that can be attributed to a lympho-plasma cell proliferative disorder
|-
|-
| rowspan="1" colspan="1" |Solitary Plasmacytoma with minimal marrow involvement<sup>**</sup>
| align="left" style="background:#F5F5F5;" + |
| rowspan="1" colspan="1" |All 4 criteria must be met
*≥10% clonal [[plasma cells]] in [[bone marrow]]
* Biopsy proven solitary lesion of bone or soft tissue with evidence of clonal plasma cells
'''OR'''
* Clonal bone marrow plasma cells <10%
*Biopsy-proven bony or [[Plasmacytoma|extramedullary plasmacytoma]] with one or more of the following:
* Normal skeletal survey and MRI (or CT) of spine and pelvis (except for the primary solitary lesion)
**'''[[Hypercalcemia]]''': [[Calcium|serum calcium]] >0·25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2·75 mmol/L (>11 mg/dL)
* Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, or bone lesions (CRAB) that can be attributed to a lympho-plasma cell proliferative disorder
**'''[[Renal insufficiency]]''': [[creatinine]] clearance <40 mL per min or [[serum creatinine]] >177 μmol/L (>2 mg/dL)
**'''[[Anemia]]''': [[hemoglobin]] value of >2 g/dL below the lower limit of normal, or a [[hemoglobin]] value <10 g/dL
**'''[[Bone]] [[lesion]]''': one or more osteolytic [[lesions]] on [[Skeleton|skeletal]] [[radiography]], [[CT-scans|CT]], or [[PET scan|PET-CT]]
**'''[[Bone marrow]] [[plasma cell]] burden''': Clonal [[bone marrow]] [[plasma cell]] percentage ≥60%
**'''[[Light chain|Free light chain]] ratio''': Involved-to-uninvolved free [[light chain]] ratio ≥100
**'''[[MRI]]''': >1 focal [[Bone|bony]] [[lesion]] of 5mm or greater on [[MRI]] studies
|}
|}
From ''Lancet Oncol''.<sup>1</sup>
<sup>*</sup>A bone marrow can be deferred in patients with low risk MGUS (IgG type, M protein <15 gm/L, normal free light chain ratio) in whom there are no clinical features concerning for myeloma
<sup>**</sup>Solitary plasmacytoma with 10% or more clonal plasma cells is considered as multiple myeloma
==Diagnostic Criteria==
In November 2014, the International Myeloma Working Group (IMWG) updated the criteria for the diagnosis of multiple myeloma to include novel validated biomarkers that are associated with the development of CRAB features ([[hypercalcaemia]], [[renal failure]], [[anaemia]], and [[bone]] lesions). The update also clarified the underlying laboratory and radiographic findings of CRAB features, as well as the histological and monoclonal protein requirements for the disease diagnosis.<ref name="lancet">Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548</ref>


===Criteria for the Diagnosis of Monoclonal Gammopathy of Undetermined Significance (MGUS)===
===Criteria for the Diagnosis of Monoclonal Gammopathy of Undetermined Significance (MGUS)===
'''All three criteria must be met:'''
All three criteria must be met:<ref name="lancet">Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548</ref><ref name="pmid18971951">{{cite journal |vauthors=Kyle RA, Rajkumar SV |title=Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma |journal=Leukemia |volume=23 |issue=1 |pages=3–9 |date=January 2009 |pmid=18971951 |pmc=2627786 |doi=10.1038/leu.2008.291 |url=}}</ref><ref name="pmid12780789">{{cite journal |vauthors= |title=Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group |journal=Br. J. Haematol. |volume=121 |issue=5 |pages=749–57 |date=June 2003 |pmid=12780789 |doi= |url=}}</ref>
* Presence of serum monoclonal protein (IgG or IgA) <3 g/dL
* Presence of serum monoclonal [[protein]] ([[IgG]] or [[IgA]]) <3 g/dL
* Presence of bone marrow clonal plasma cells <10%
* Presence of [[bone marrow]] clonal [[plasma cells]] <10%
* Absence of multiple myeloma-defining events or amyloidosis
* Absence of [[multiple myeloma]]-defining events or [[amyloidosis]]


===Criteria for the Diagnosis of Smoldering Multiple Myeloma===
Both criteria must be met:<ref name="lancet">Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548</ref><ref name="pmid18971951">{{cite journal |vauthors=Kyle RA, Rajkumar SV |title=Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma |journal=Leukemia |volume=23 |issue=1 |pages=3–9 |date=January 2009 |pmid=18971951 |pmc=2627786 |doi=10.1038/leu.2008.291 |url=}}</ref>
* Serum monoclonal [[protein]] ([[IgG]] or [[IgA]]) ≥3 g/dL or [[urinary]] monoclonal [[protein]] ≥500 mg per 24 h and/or clonal [[bone marrow]] [[plasma cells]] 10–60%
* Absence of [[multiple myeloma]]-defining events or [[amyloidosis]]


===Criteria for the Diagnosis of Smoldering Multiple Myeloma<ref name="lancet">Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548</ref>
=== Criteria for the Diagnosis of Solitary Plasmacytoma ===
Both criteria must be met:
All four [[criteria]] must be met:<ref name="pmid18971951">{{cite journal |vauthors=Kyle RA, Rajkumar SV |title=Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma |journal=Leukemia |volume=23 |issue=1 |pages=3–9 |date=January 2009 |pmid=18971951 |pmc=2627786 |doi=10.1038/leu.2008.291 |url=}}</ref>
* Serum monoclonal protein (IgG or IgA) ≥3 g/dL or urinary monoclonal protein ≥500 mg per 24 h and/or clonal bone marrow plasma cells 10–60%
* [[Biopsy]]-proven [[solitary]] [[lesion]] of [[bone]] or [[soft tissue]] with evidence of clonal [[plasma cells]]
* Absence of multiple myeloma-defining events or amyloidosis
* Normal [[bone marrow]] with no evidence of clonal [[plasma cells]]
* Normal [[skeletal survey]] and [[MRI]] of [[spine]] and [[pelvis]] (except for the primary [[solitary]] [[lesion]])
* No evidence of [[End organ damage|end-organ damage]] such as CRAB [[lesions]] that can be attributed to a lymphoplasma cell proliferative [[disorder]]
==References==
{{Reflist|2}}


===Revised Criteria for the Diagnosis of Multiple Myeloma<ref name="lancet">Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548</ref>
[[Category:Medicine]]
*Both criteria must be met:
'''≥10% clonal expansion of bone marrow plasma cells '''or''' biopsy-proven bony or extramedullary plasmacytoma and one or more of the following features:'''
 
* Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder:
::* '''Hypercalcemia''': serum calcium >0·25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2·75 mmol/L (>11 mg/dL)
::* '''Renal insufficiency''': creatinine clearance <40 mL per min or serum creatinine >177 μmol/L (>2 mg/dL)
::* '''Anemia''': hemoglobin value of >2 g/dL below the lower limit of normal, or a hemoglobin value <10 g/dL
::* '''Bone lesion''': one or more osteolytic lesions on skeletal radiography, CT, or PET-CT
* Any one or more of the following biomarkers of malignancy:
::* Clonal bone marrow plasma cell percentage ≥60%
::* Involved:uninvolved serum free light chain ratio ≥100
::* >1 focal lesions on MRI studies
}}
 
 
}}
 
==References==
{{Reflist|1}}
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]; Serge Korjian M.D.; Shyam Patel [3]

Overview

The diagnosis of monoclonal gammopathy of undetermined significance requires the presence of clonal plasma cells < 10% and serum monoclonal protein <3g/dl but the absence of end-organ damage. The diagnosis of smoldering multiple myeloma requires the presence of clonal plasma cells 10%-60% and serum monoclonal protein >3g/dl but the absence of end-organ damage. The diagnosis of active multiple myeloma requires the presence of end-organ damage. In November 2014, the International Myeloma Working Group (IMWG) updated the criteria for the diagnosis of multiple myeloma to include novel validated biomarkers to better encompass the extent of disease. Prior to 2014, the original diagnostic criteria for end-organ damage included CRAB features (hypercalcemia, renal failure, anemia, and bone lesions) without consideration of the plasma cell burden or free light chain ratio. The 2014 update also clarified the underlying laboratory and radiographic findings of CRAB features, as well as the histological and monoclonal protein requirements for the disease diagnosis.[1]

Diagnostic Criteria

Revised Criteria for the Diagnosis of Multiple Myeloma

The diagnosis of multiple myeloma requires the following:[1][2][3][4]

OR

With one or more of the myeloma-defining events:

Revised Criteria for the Diagnosis of Multiple Myeloma

OR

Criteria for the Diagnosis of Monoclonal Gammopathy of Undetermined Significance (MGUS)

All three criteria must be met:[1][2][3]

Criteria for the Diagnosis of Smoldering Multiple Myeloma

Both criteria must be met:[1][2]

Criteria for the Diagnosis of Solitary Plasmacytoma

All four criteria must be met:[2]

References

  1. ↑ 1.0 1.1 1.2 1.3 Rajkumar, S. Vincent, Meletios A. Dimopoulos, Antonio Palumbo, Joan Blade, Giampaolo Merlini, María-Victoria Mateos, Shaji Kumar et al. "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma." The Lancet Oncology 15, no. 12 (2014): e538-e548
  2. ↑ 2.0 2.1 2.2 2.3 Kyle RA, Rajkumar SV (January 2009). "Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma". Leukemia. 23 (1): 3–9. doi:10.1038/leu.2008.291. PMC 2627786. PMID 18971951.
  3. ↑ 3.0 3.1 "Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group". Br. J. Haematol. 121 (5): 749–57. June 2003. PMID 12780789.
  4. ↑ Rajkumar SV, Kyle RA (October 2005). "Multiple myeloma: diagnosis and treatment". Mayo Clin. Proc. 80 (10): 1371–82. doi:10.4065/80.10.1371. PMID 16212152.
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