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Multiple Myeloma Differential Diagnoses

  • Author: Dhaval Shah, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Feb 05, 2016
 
 

Diagnostic ConsiderationsActive multiple myelomaIndolent and smoldering multiple myelomaOther problems to be considered

The most widely accepted schema for the diagnosis of multiple myeloma (MM) uses particular combinations of laboratory, imaging, and procedure findings as diagnostic criteria. (See Workup.) The findings are as follows:

  • I = Plasmacytoma on tissue biopsy
  • II = Bone marrow with greater than 30% plasma cells
  • III = Monoclonal globulin spike on serum protein electrophoresis, with an immunoglobulin (Ig) G peak of greater than 3.5 g/dL or an IgA peak of greater than 2 g/dL, or urine protein electrophoresis (in the presence of amyloidosis) result of greater than 1 g/24 h
  • a = Bone marrow with 10-30% plasma cells
  • b = Monoclonal globulin spike present but less than category III
  • c = Lytic bone lesions
  • d = Residual IgM level less than 50 mg/dL, IgA level less than 100 mg/dL, or IgG level less than 600 mg/dL

The following combinations of findings are used to make the diagnosis of MM:

  • I plus b, c, or d
  • II plus b, c, or d
  • III plus a, c, or d
  • a plus b plus c
  • a plus b plus d

Criteria for the diagnosis of active (symptomatic) MM are as follows[2] :

  • Clonal bone marrow plasma cells ≥10% or
  • Biopsy-proven bony or extramedullary plasmacytoma and
  • One or more myeloma-defining events

Myeloma-defining events include the following[2] :

  • Serum calcium level >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)
  • Renal insufficiency (creatinine >2 mg/dL [>177 μmol/L] or creatinine clearance <40 mL/min)
  • Anemia (hemoglobin <10 g/dL or hemoglobin >2 g/dL below the lower limit of normal)
  • One or more osteolytic bone lesions on skeletal radiography, CT, or PET-CT
  • Clonal bone marrow plasma cells ≥60%
  • Abnormal serum free light chain (FLC) ratio ≥100 (involved kappa) or <0.01 (involved lambda)
  • One or more focal >5 mm lesions on MRI scans

Active disease may also be indicated by repeated infections, amyloidosis, or hyperviscosity.

Indolent MM is a subset of MM with the following features:

  • Bone disease absent (or very limited)
  • Performance status greater than 70%
  • Hemoglobin level greater than 10 g/dL
  • Serum calcium level within the reference range
  • Creatinine level <2 mg/dL
  • No infections
  • Low M protein levels (ie, <7 g/dL for IgG, <5 g/dL for IgA)

Smoldering (asymptomatic) MM is similar to indolent MM. Diagnostic criteria for smoldering MM are as follows[2] :

  • Serum monoclonal protein: IgG or IgA ≥3 g/dL, or
  •  Bence-Jones protein ≥500 mg/24 h and/or
  • Clonal bone marrow plasma cells 10%–60% and
  • Absence of myeloma-defining events or amyloidosis

The NCCN recommends that a patient whose bone survey is negative should be assessed for bone disease with whole-body MRI or PET/CT.[2]

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare syndrome consisting of polyneuropathy, organomegaly, endocrinopathy, M protein deviations, and skin changes.

Amyloidosis is often secondary to MM, but it may develop without MM. Patients with amyloidosis typically lack sufficient numbers of plasma cells in the bone marrow or sufficiently high levels of M protein to meet the diagnostic criteria for MM.

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Dhaval Shah, MD Regional Cancer Care Associates, Virtua Fox Chase Cancer Program

Dhaval Shah, MD is a member of the following medical societies: American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Howard A Chansky, MD Associate Professor, Department of Orthopedics and Sports Medicine, University of Washington Medical Center

Howard A Chansky, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society

Disclosure: Nothing to disclose.

Sara J Grethlein, MD Senior Attending Physician, Cancer Treatment Center, Bassett Healthcare Network

Sara J Grethlein, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Koyamangalath Krishnan, MD, FRCP, FACP Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Seema S Rizvi, MD Associate Medical Director, Lutheran Care Center

Seema S Rizvi, MD is a member of the following medical societies: American Academy of Family Physicians and American Medical Association

Disclosure: Nothing to disclose.

Miguel A Schmitz, MD Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic

Miguel A Schmitz, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, and North American Spine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Lilian M Thomas, MD Fellow, Department of Hematology/Oncology, State University of New York Upstate Medical University

Lilian M Thomas, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

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Amyloidosis infiltrating the tongue in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
Radiograph of the skull demonstrating a typical lytic lesion in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
Bone marrow aspirate demonstrating plasma cells of multiple myeloma. Note the blue cytoplasm, eccentric nucleus, and perinuclear pale zone (or halo). All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
Bone marrow biopsy demonstrating sheets of malignant plasma cells in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
 
 
 
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