** 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
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
Clinical
Present in approximately 3% of general population over age 50
10% of population over age 80
1-1.5% annual risk of progression to plasma cell or B cell neoplasm
Risk increases with % plasma cells, size of M component, serum free light chain ratio
IgG and IgA MGUS may progress to plasma cell myeloma or primary amyloidosis
IgM MGUS may progress to non-Hodgkin B cell lymphoma, especially lymphoplasmacytic lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma, or primary amyloidosis
May also be associated with non-neoplastic conditions including
Infection
Autoimmune disease
Dermatologic disorders
Grading / Staging / Report
Grading is not applicable
Staging is not applicable
The pathology report should contain the following information:
Diagnosis in the World Health Organization (WHO) classification
Equivalent diagnosis in other classifications used by relevant clinicians
Results of supplementary studies if performed
Relationship to other specimens from the same patient
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW . WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, International Agency for Research on Cancer, Lyon, 2008
Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
Blade J, M. Dimopoulos, L. Rosinol, S. V. Rajkumar, and R. A. Kyle. Smoldering (Asymptomatic) Multiple Myeloma: Current Diagnostic Criteria, New Predictors of Outcome, and Follow-Up Recommendations J. Clin. Oncol., February 1, 2010; 28(4): 690 - 697.
Martin W, Abraham R, Shanafelt T, Clark RJ, Bone N, Geyer SM, Katzmann JA, Bradwell A, Kay NE, Witzig TE. Serum-free light chain-a new biomarker for patients with B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. Transl Res. 2007 Apr;149(4):231-5.
Perez-Persona E et al, New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering mutliple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 2007 Oct 1;110(7):2586-92.
Raja KR, Kovarova L, Hajek R.Review of phenotypic markers used in flow cytometric analysis of MGUS and MM, and applicability of flow cytometry in other plasma cell disorders. Br J Haematol. 2010 Mar 1. [Epub ahead of print]
Van Camp B, Durie BG, Spier C, De Waele M, Van Riet I, Vela E, Frutiger Y, Richter L, Grogan TM. Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56. Blood. 1990 Jul 15;76(2):377-82.