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Mu Heavy Chain Disease Workup

  • Author: Ajeet Gajra, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Sep 10, 2015

Laboratory Studies

Laboratory studies should include the following:

  • Complete blood cell count with differential
  • Renal function studies (eg, BUN and creatinine)
  • Liver function studies (eg, total protein, albumin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase)
  • Calcium levels
  • Beta-2 microglobulin values

Imaging Studies

No definitive guidelines are available regarding the extent of imaging studies that should be performed when diagnosing patients suggested to have mu heavy chain diseaes (mu-HCD). Performing a chest radiograph is reasonable, and a skeletal survey is considered essential given the fact that 40% of patients present with osteolytic lesions.

Obtaining CT scans of the thorax and abdomen is appropriate because hepatosplenomegaly and lymphadenopathy are common. CT scan findings help to objectively quantify disease and are useful for assessing response to therapy.


Other Tests


Serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP) and immunofixation are essential tests. As a rule, the neoplastic cells do not produce large amounts of immunoglobulin, which may make detecting the abnormal immunoglobulin produced in a patient with HCD difficult. Performing a combination of electrophoretic, immunoelectrophoretic, and immunofixation techniques can help establish the diagnosis. In a minority of cases, the proteins can initially be identified as a discrete homogenous band of mobility on SPEP or UPEP findings.

When developed with specific antiheavy and antilight sera, the immunoelectrophoretic pattern reveals a heavy chain–specific arc that does not react with either antikappa or antilambda antisera.

IgM M-proteins sometimes do not react with certain antilight sera. This is more common with immunoelectrophoresis than with immunofixation techniques. In these cases, separating the monoclonal proteins from the serum, treating them with reducing agents to cleave disulfide bonds, and subjecting them to gel electrophoresis to determine the size of the immunoglobulin heavy chain polypeptide may be necessary.

More commonly, the proteins are present in smaller amounts and give a heterogenous pattern on electrophoresis findings. A monoclonal spike was detected in 8 of 19 patients, and 3 of 28 patients had a biclonal gammopathy Again, immunoelectrophoresis or immunofixation findings showing the development of patterns with a panel of antiheavy/antilight antibodies can strongly suggest the diagnosis. In specialized laboratories, more detailed structural analysis can be performed on the isolated, reduced, and alkylated heavy chain monomer to confirm the presence or absence of immunoglobulin light chains.

Urinary excretion of the mu fragment has been noted in only 2 patients; this presumably is because the polymers of the carboxy-terminal mu fragment are too large to be filtered by intact renal glomeruli. Monoclonal light chains have been found in the urine in two thirds of cases. Thus, Bence Jones proteinuria is a common occurrence in patients with this disorder. Nonetheless, renal complications are infrequent. Immunoglobulin light chains capable of producing amyloid are found in approximately 12% of cases, an incidence that is similar to that observed in patients with multiple myeloma.

Immunoglobulin gene rearrangement may be used to differentiate a B-cell lymphoproliferative process from a monoclonal or reactive proliferation of lymphocytes. This technique not only provides a specific marker for B cells, but it also is a true marker for monoclonality.[9]

Maisnar et al presented a case study in which they used immunofixation electrophoresis, capillary zone electrophoresis with immunotyping, and high resolution two-dimensional electrophoresis to detect and characterize monoclonal mu-heavy chains in a patient with multiple malignancies.[10] The investigators were able to determine the molecular weight of the mu-heavy chains and found their patient's abnormally high serum protein concentration, 38 g/L, appears to be the highest reported in the literature.[10]




Almost all patients should undergo bone marrow aspiration and biopsy. Certain histologic features, as outlined below, may aid in making the diagnosis of mu-HCD.

When mu-HCD is not considered, based on the patient's presentation (as is commonly the case), biopsy of the appropriate involved area (eg, lymph node mass) is required to establish the diagnosis of a lymphoproliferative disorder.


Histologic Findings

Marrow involvement is characterized by infiltration with lymphocytes and plasma cells. Cells that often are described as lymphocytic plasmacytes or plasmacytoid lymphocytes are prominent. Although the marrow of almost all patients contains the multivacuolated plasma cells described in the index case, the vacuoles are not universally apparent. The identification of these vacuoles sometimes offers a clue to the diagnosis, which requires confirmation by appropriate electrophoretic and immunoelectrophoretic studies.



Given the rarity of mu-HCD, a clinical staging system has not been developed. Accompanying lymphoproliferative disorders such as CLL, non-Hodgkin lymphoma, and multiple myeloma should be appropriately staged.

Contributor Information and Disclosures

Ajeet Gajra, MD Associate Professor of Medicine, Director of Hematology/Oncology Fellowship Program, State University of New York Upstate Medical University; Consulting Staff, Department of Internal Medicine, Division of Hematology and Oncology, Veterans Affairs Medical Center

Ajeet Gajra, MD is a member of the following medical societies: American Association for Cancer Research, American Medical Association, American Society of Hematology

Disclosure: Nothing to disclose.


Sara J Grethlein, MD Associate Dean for Undergraduate Medical Education, Indiana University School of Medicine

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

Disclosure: Nothing to disclose.

Neerja Vajpayee, MD Associate Professor, Department of Pathology, State University of New York Upstate Medical University

Neerja Vajpayee, MD is a member of the following medical societies: American Society of Hematology, College of American Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

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.

Additional Contributors

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

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