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Multiple Myeloma and Immunosecretory Disorders: An Update

Shaheen, Saad P. MD*; Talwalkar, Sameer S. MD; Medeiros, L. Jeffrey MD

Advances in Anatomic Pathology: July 2008 - Volume 15 - Issue 4 - p 196-210
doi: 10.1097/PAP.0b013e31817cfcd6
Review Articles

The immunosecretory disorders are a diverse group of diseases associated with proliferation of an abnormal clone of immunoglobulin (Ig)-synthesizing, terminally differentiated B cells. These disorders include multiple myeloma (MM) and its variants, plasmacytoma, Waldenstrom macroglobulinemia, monoclonal gammopathy of undetermined significance, and monoclonal Ig deposition diseases, the latter including primary amyloidosis and nonamyloidotic types. These disorders are histologically composed of plasma cells, or plasmacytoid cells which produce Ig that is synthesized and usually secreted and can be deposited in some diseases. The Ig can be complete or can be composed of either heavy or light chains and is termed M-(monoclonal) protein. In MM, this proliferation overwhelms the normal cellular counterparts that synthesize and secrete appropriate levels of Ig. Immunosecretory disorders have been classified in multiple schemes, mostly morphologic, to such a degree that the classification of these entities has become a challenge to pathologists. The World Health Organization classification in 2001 was helpful because it provided specific clinicopathologic criteria for diagnosis. However, terms such as “progressive” disease were not well defined. In 2003, the International Myeloma Group defined MM as a disease with related organ and tissue injury, serving to better explain progressive in terms of deterioration of organ (renal, bone, and bone marrow) function over time. Therefore, modern classification of immunosecretory diseases is based on integration of clinical, morphologic, laboratory, radiographic, and biologic (including molecular) parameters, which we review here.

*Department of Pathology, Veterans Affair Medical Center, Louisville, KY

Department of Hematopathology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX

Reprints: L. Jeffrey Medeiros, MD, Department of Hematopathology, Box 72, UT M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030 (e-mail:

All figures can be viewed online in color at

© 2008 Lippincott Williams & Wilkins, Inc.