Surgical Pathology Criteria

Monoclonal Gammopathy of Undetermined Significance

Differential Diagnosis

Symptomatic Plasma Cell Myeloma Asymptomatic / Smoldering Myeloma MGUS
Usually but not always >10% clonal plasma cells in bone marrow or plasmacytoma ** ≥10% clonal plasma cells in bone marrow AND/OR <10% clonal plasma cells in bone marrow
M protein in serum or urine or free light chain in urine Serum M-protein >3g/dL Serum M-protein <3g/dL
** Lytic bony lesions or  end-organ damage (hypercalcemia/ anemia/ renal insufficiency etc) No lytic lesions or end-organ damage No lytic lesions or end-organ damage
** Critical points: bone marrow plasma cells or M-protein above threshholds separates asymptomatic myeloma from MGUS and bone or other end organ damage separates symptomatic from asymptomatic myeloma

MGUS Lymphoplasmacytic Lymphoma, Chronic Lymphocytic Leukemia or Other Low Grade B Cell Lymphoma with M-protein
Uniform plasma cell morphology Lymphoid component present
CD20 often negative CD20 usually uniformly positive
Uniformly CD138 positive Scattered CD138 positive cells in plasmacytoid component

MGUS Reactive Plasmacytosis
Light chain restriction by flow cytometry, immunohistochemistry or in situ hybridization No light chain restriction
Aberrant immunophenotype (e.g. CD56+, CD19-) CD19+, CD56-
Myeloma-associated cytogenetic abnormalities by FISH in >50% Normal cytogenetics by FISH

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