Table 2.

Diagnostic criteria for plasma cell disorders

Disorder	Disease definition	References
Monoclonal gammopathy of undetermined significance (MGUS)	All three criteria must be met:	6
	Serum monoclonal protein <3 g/100 ml
	Clonal bone marrow plasma cells <10% and
	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
Smoldering multiple myeloma (also referred to as asymptomatic multiple myeloma)	Both criteria must be met:	6
	Serum monoclonal protein (IgG or IgA) ≥3 g/100 ml and/or clonal bone marrow plasma cells ≥10% and
	Absence of end-organ damage such as lytic bone lesions, anemia, hypercalcemia or renal failure that can be attributed to a plasma cell proliferative disorder
Multiple myeloma	All three criteria must be met except as noted:	6,7
	Clonal bone marrow plasma cells ≥ 10%
	Presence of serum and/or urinary monoclonal protein (except in patients with true non-secretory multiple myeloma) and
	Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically
	Hypercalcemia: serum calcium ≥ 11.5 mg/100 ml or
	Renal insufficiency: serum creatinine >1.73 mmol/l)
	Anemia: normochromic, normocytic with a hemoglobin value of >2 g/100 ml below the lower limit of normal or a hemoglobin value <10 g/100 ml
	Bone lesions: lytic lesions, severe osteopenia or pathologic fractures
Waldenström’s macroglobulinemia	Both criteria must be met:	8–12
	IgM monoclonal gammopathy (regardless of the size of the M protein) and ≥ 10% bone marrow lymphoplasmacytic infiltration (usually intertrabecular) by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation and a typical immunophenotype (e.g. surface IgM+, CD5+/−, CD10−, CD19+, CD20+, CD23−) that satisfactorily excludes other lymphoproliferative disorders, including chronic lymphocytic leukemia and mantle cell lymphoma.
	Note: IgM MGUS is defined as
	Serum IgM monoclonal protein <3 g/100 ml, and bone marrow lymphoplasmacytic infiltration <10% and
	No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy or hepatosplenomegaly
	Smoldering Waldenström’s macroglobulinemia (also referred to as indolent or asymptomatic Waldenström’s macroglobulinemia) is defined as:
	Serum IgM monoclonal protein ≥ 3 g/100 ml and/or bone marrow lymphoplasmacytic infiltration ≥ 10%, and
	No evidence of end-organ damage such as anemia, constitutional symptoms, hyperviscosity, lymphadenopathy or hepatosplenomegaly that can be attributed to a lymphoplasma cell proliferative disorder
Solitary plasmacytoma	All four criteria must be met:	13,14
	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)
	Absence of end-organ damage such as CRAB lesions that can be attributed to a lymphoplasma cell proliferative disorder
Systemic AL amyloidosis	All four criteria must be met:	15
	Presence of an amyloid-related systemic syndrome (such as renal, liver, heart, gastrointestinal tract or peripheral nerve involvement)
	Positive amyloid staining by Congo red in any tissue (e.g. fat aspirate, bone marrow or organ biopsy)
	Evidence that amyloid is light chain-related established by direct examination of the amyloid (immunohistochemical staining, direct sequencing, and so on) and
	Evidence of a monoclonal plasma cell proliferative disorder (serum or urine M protein, abnormal free light chain ratio or clonal plasma cells in the bone marrow).
	Note: Approximately 2–3% of patients with AL amyloidosis will not meet the requirement for evidence of a monoclonal plasma cell disorder listed above; the diagnosis of AL amyloidosis must be made with caution in these patients
POEMS syndrome	All three criteria must be met:	16
	Presence of a monoclonal plasma cell disorder
	Peripheral neuropathy and
	At least one of the following seven features: osteosclerotic bone lesions, Castleman’s disease, organomegaly, endocrinopathy (excluding diabetes mellitus or hypothyroidism), edema, typical skin changes and papilledema.
	Note: Not every patient meeting the above criteria will have POEMS syndrome; the features should have a temporal relationship with each other and no other attributable cause. The absence of osteosclerotic lesions should make the diagnosis suspect. Elevations in plasma or serum levels of vascular endothelial growth factor and thrombocytosis are common features of the syndrome and are helpful when the diagnosis is difficult.

Abbreviations: AL, amyloid light chain; MRI, magnetic resonance imaging.

Modified and reproduced with permission from Rajkumar et al.^{15 ©}Mayo Clinic Proceedings PDEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes).