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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 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==
==Diagnostic Criteria==
In November 2014, the International Myeloma Working Group (IMWG) updated the criteria for the diagnosis of multiple myeloma (MM) 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>


===Revised Criteria for the Diagnosis of Multiple Myeloma<SMALL><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></SMALL>===
===Revised Criteria for the Diagnosis of Multiple Myeloma===
{{cquote|
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>
'''≥10% clonal expansion of bone marrow plasma cells '''or''' biopsy-proven bony or extramedullary plasmacytoma and one or more of the following features:'''
*≥10% clonal [[plasma cells]] in [[bone marrow]]
'''OR'''
*[[biopsy]]-proven bony or [[Plasmacytoma|extramedullary plasmacytoma]],
'''With''' one or more of the [[Multiple myeloma|myeloma]]-defining events:
*CRAB features:
**'''[[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)
**'''[[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]]
*Biomarkers of malignancy:
**'''[[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
{|
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Revised Criteria for the Diagnosis of Multiple Myeloma
|-
| align="left" style="background:#F5F5F5;" + |
*≥10% clonal [[plasma cells]] in [[bone marrow]]
'''OR'''
*Biopsy-proven bony or [[Plasmacytoma|extramedullary plasmacytoma]] with one or more of the following:
**'''[[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)
**'''[[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
|}


* Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder:
===Criteria for the Diagnosis of Monoclonal Gammopathy of Undetermined Significance (MGUS)===
::* '''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)
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>
::* '''Renal insufficiency''': creatinine clearance <40 mL per min or serum creatinine > 177 μmol/L (>2 mg/dL)
* Presence of serum monoclonal [[protein]] ([[IgG]] or [[IgA]]) <3 g/dL
::* '''Anemia''': hemoglobin value of >20 g/L below the lower limit of normal, or a hemoglobin value <100 g/L
* Presence of [[bone marrow]] clonal [[plasma cells]] <10%
::* '''Bone lesion''': one or more osteolytic lesions on skeletal radiography, CT, or PET-CT
* Absence of [[multiple myeloma]]-defining events or [[amyloidosis]]
* 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
}}


===Criteria for the Diagnosis of Smouldering Multiple Myeloma<SMALL><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></SMALL>===
===Criteria for the Diagnosis of Smoldering Multiple Myeloma===
{{cquote|
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>
'''Both criteria must be met:'''
* 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%
* Serum monoclonal protein (IgG or IgA) ≥30 g/L 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]]
* Absence of myeloma-defining events or amyloidosis
}}


=== Criteria for the Diagnosis of Solitary Plasmacytoma ===
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>
* [[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]] 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==
==References==
{{Reflist|1}}
{{Reflist|2}}
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Latest revision as of 22:46, 29 July 2020

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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.