Role of the clinical immunology laboratory in disease monitoring

Table 2 Common clinical associations of paraproteins[70]

Disorder	Diagnostic features
Monoclonal gammopathy of undetermined significance	All three criteria must be met:
	Serum monoclonal protein < 30 g/L
	Clonal bone marrow plasma cells < 10%
	Absence of end-organ damage ("CRAB"), e.g., hypercalcemia, renal insufficiency, anaemia and bone lesions due to the plasma cell disorder
Smouldering myeloma	Both criteria must be met:
	Serum monoclonal protein (IgG or IgA) > 30 g/L and/or clonal bone marrow plasma cells > 10%
	Absence of "CRAB", as defined above
Multiple myeloma	All three criteria must be met:
	Clonal bone marrow plasma cells > 10%
	Presence of serum and/or urinary monoclonal protein (except in patients with true non-secretory multiple myeloma)
	Evidence of "CRAB", as defined above
Waldenström’s macroglobulinaemia	Both criteria must be met:
	IgM monoclonal gammopathy and
	10% bone marrow infiltration (usually intertrabecular) by lymphoplasmacytic cells (morphology/immunophenotype)1
IgM monoclonal gammopathy of undetermined significance	All three criteria must be met:
	Serum IgM monoclonal protein < 30 g/L
	Bone marrow lymphoplasmacytic infiltration < 10%
	No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy or hepatosplenomegaly
Smoldering Waldenström’s macroglobulinemia	Both criteria must be met:
	Serum IgM monoclonal protein > 30 g/L and/or bone marrow lymphoplasmacytic infiltration > 10%
	No evidence of end-organ damage such as anemia, constitutional symptoms, hyperviscosity, lymphadenopathy or hepatosplenomegaly due to a lymphoplasma cell proliferative disorder

¹Note that other clonal B-cell disorders may be associated with paraproteins and may require careful clinical, morphological and immunophenotypic assessment for diagnosis (e.g., chronic lymphocytic leukaemia, mantle cell lymphoma, etc.). IgM: Immunoglobulin M; IgG: Immunoglobulin G; CRAB: Hypercalcemia, renal insufficiency, anaemia and bone lesions.