Table 1.

Differential diagnosis of monoclonal gammopathies

Diagnosis	Description
Monoclonal gammopathy of undetermined significance (MGUS)	Serum monoclonal protein < 3.0 g/dL, bone marrow plasma cells < 10% with minimal or no monoclonal urinary protein and no evidence of end organ damage Always precedes symptomatic myeloma, usually progresses at a rate of 1% per year, which is constant
Smoldering multiple myeloma (SMM)	Serum monoclonal protein >= 3.0 g/dL, or bone marrow plasma cells >= 10%, asymptomatic with no evidence of end organ damage This intermediate stage may not be recognized in all patients, progression rate is 10% per year during the first five years after diagnosis
Symptomatic multiple myeloma	Plasma cell proliferation in the presence of end organ damage; typical symptoms/findings include hypercalcemia, renal insufficiency, anemia and bone lesions (CRAB features)
Solitary Plasmacytoma	Presence of a plasmacytoma (homogenous plasma cell collection) in the absence of multiple osteolytic lesions, no evidence of monoclonal plasma cells in bone marrow, or other features of myeloma. Half of the patients will eventually develop myeloma, especially patients with persistent monoclonal protein after treatment
Primary Systemic Amyloidosis	Tissue deposition of light chain derived amyloid fibrils (beta pleated sheets), apple green birefringence on polarizing microscopy May present as cardiomyopathy, nephrotic syndrome, malabsorption, hepatic failure, peripheral neuropathy or other symptoms based on organ involvement Typically, lytic lesions and hypercalcemia not seen, associated with low level of marrow plasmacytosis
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes)	Major criteria: polyneuropathy, presence of monoclonal plasma cells Minor criteria: sclerotic bone lesions, Castleman’s disease, organomegaly (spleen, liver, or lymph nodes), Volume overload (peripheral edema, pleural effusion, ascites), endocrinopathy (adrenal, thyroid, pituitary, gonadal, parathyroid, pancreatic), skin changes (hyperpigmentation, hypertrichosis, hemangiomata, white nails), papilledema Two major criteria plus at least one minor criterion needed for diagnosis
Waldenström's Macroglobulinemia	IgM monoclonal gammopathy >= 10% bone marrow infiltration by lymphoplasmacytic cells, often accompanied by lymphadenopathy and or hepatosplenomegaly Typical immunophenotype (surface IgM+, CD5+/−, CD10-, CD19+, CD20+, CD22+, CD23−)