eMedicine Specialties > Hematology > Plasma Cell Disorders

Light-Chain Deposition Disease: Differential Diagnoses & Workup

Author: Yasodah Jayamohan, MD, Transfusion Medicine Fellow, Hoxworth Blood Center, University of Cincinnati Medical Center
Coauthor(s): Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center; Suzanne R Fanning, DO, Fellow, Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, 2004-2007 Director, Hematology, Greenville Memorial Health System, Greenville, SC Medical Oncologist/Hematologist/Transplant Physician, Cancer Centers of the Carolinas; Mohamad A Hussein, MD, Clinical Director, Malignant Hematology, Moffitt Cancer Center
Contributor Information and Disclosures

Updated: Jun 4, 2008

Differential Diagnoses

Amyloidosis, AA (Inflammatory)
IgA Nephropathy
Amyloidosis, Familial Renal
Light Chain-Associated Renal Disorders
Amyloidosis, Immunoglobulin-Related
Multiple Myeloma
Diabetic Nephropathy
Nephrotic Syndrome

Workup

Laboratory Studies

The laboratory workup for LCDD includes the following:

  • Routine serum chemistries to evaluate hepatic and renal function
  • Complete blood cell (CBC) count to assess for anemia
  • Serum and urine electrophoresis with immunofixation to evaluate for a monoclonal protein
  • Repeated studies of serum and urine protein with immunoelectrophoresis or immunofixation, if necessary, to demonstrate the presence of a small amount of monoclonal protein
    • In a minority of patients, a monoclonal protein may never be found in either serum or urine.
  • Sensitive nephelometric immunoassays (NIAs) are now available for the detection of serum free light chains. These methods are also useful to detect response to therapy and to monitor disease activity as well as early relapse.
    • Kaplan et al have a developed a method to isolate and biochemically characterize plasma monoclonal free light chains in amyloidosis and multiple myeloma.27 It is possible that this procedure may be applied to reveal distinguishing chemical features of free light chains in serum, which in turn may predict the pathologic form of disease and yield information that could aid clinicians to better understand the mechanism(s) involved in the deposition of light chains in tissues.

Imaging Studies

  • Echocardiogram in cases of cardiac involvement

Procedures

  • Biopsy of the specific organ suspected of involvement, with immunohistochemical staining for kappa and lambda chains
  • Rectal biopsy or subcutaneous fat aspiration to exclude amyloidosis
  • Bone marrow aspiration/biopsy to rule out multiple myeloma

Histologic Findings

The electron microscopic changes characteristic of LCDD to demonstrate finely granular, electron-dense deposits in the mesangial nodules and along the endothelial aspect of the glomerular basement membrane.28 In cases of tubular involvement, the deposits are noted along the outer aspect of the membrane.

More on Light-Chain Deposition Disease

Overview: Light-Chain Deposition Disease
Differential Diagnoses & Workup: Light-Chain Deposition Disease
Treatment & Medication: Light-Chain Deposition Disease
Follow-up: Light-Chain Deposition Disease
References
Further Reading
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References

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  2. Ronco P, Plaisier E, Mougenot B, Aucouturier P. Immunoglobulin light (heavy)-chain deposition disease: from molecular medicine to pathophysiology-driven therapy. Clin J Am Soc Nephrol. Nov 2006;1(6):1342-50. [Medline]. [Full Text].

  3. Buxbaum JN, Chuba JV, Hellman GC, Solomon A, Gallo GR. Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. Ann Intern Med. Mar 15 1990;112(6):455-64. [Medline].

  4. Randall RE, Williamson WC Jr, Mullinax F, Tung MY, Still WJ. Manifestations of systemic light chain deposition. Am J Med. Feb 1976;60(2):293-9. [Medline].

  5. Tubbs RR, Gephardt GN, McMahon JT, et al. Light chain nephropathy. Am J Med. Aug 1981;71(2):263-9. [Medline].

  6. Seymour AE, Thompson AJ, Smith PS, Woodroffe AJ, Clarkson AR. Kappa light chain glomerulosclerosis in multiple myeloma. Am J Pathol. Dec 1980;101(3):557-80. [Medline]. [Full Text].

  7. Alpers CE, Tu WH, Hopper J Jr, Biava CG. Single light chain subclass (kappa chain) immunoglobulin deposition in glomerulonephritis. Hum Pathol. Mar 1985;16(3):294-304. [Medline].

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  12. Lorenz EC, Gertz MA, Fervenza FC, et al. Long-term outcome of autologous stem cell transplantation in light chain deposition disease. Nephrol Dial Transplant. Jun 2008;23(6):2052-7. [Medline].

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  15. Rongioletti F, Patterson JW, Rebora A. The histological and pathogenetic spectrum of cutaneous disease in monoclonal gammopathies. J Cutan Pathol. Mar 10 2008;epub ahead of print. [Medline].

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  17. Ganeval D, Noël LH, Preud'homme JL, Droz D, Grünfeld JP. Light-chain deposition disease: its relation with AL-type amyloidosis. Kidney Int. Jul 1984;26(1):1-9. [Medline].

  18. Bradley JR, Thiru S, Evans DB. Light chains and the kidney. J Clin Pathol. Jan 1987;40(1):53-60. [Medline]. [Full Text].

  19. Gallo GR, Feiner HD, Katz LA, et al. Nodular glomerulopathy associated with nonamyloidotic kappa light chain deposits and excess immunoglobulin light chain synthesis. Am J Pathol. Jun 1980;99(3):621-44. [Medline].

  20. Noel LH, Droz D, Ganeval D, Grunfeld JP. Renal granular monoclonal light chain deposits: morphological aspects in 11 cases. Clin Nephrol. May 1984;21(5):263-9. [Medline].

  21. Keeling J, Herrera GA. Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. Kidney Int. Oct 2005;68(4):1590-603. [Medline].

  22. Bhargava P, Rushin JM, Rusnock EJ, et al. Pulmonary light chain deposition disease: report of five cases and review of the literature. Am J Surg Pathol. Feb 2007;31(2):267-76. [Medline].

  23. Colombat M, Mal H, Copie-Bergman C, et al. Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor. Blood. May 15 2008;epub ahead of print. [Medline].

  24. Mallick NP, Dosa S, Acheson EJ, Delamore IW, et al. Detection, significance and treatment of paraprotein in patients presenting with 'idiopathic' proteinuria without myeloma. Q J Med. Apr 1978;47(186):145-75. [Medline].

  25. Pirani CL, Silva F, D'Agati V, Chander P, Striker LM. Renal lesions in plasma cell dyscrasias: ultrastructural observations. Am J Kidney Dis. Sep 1987;10(3):208-21. [Medline].

  26. Gipstein RM, Cohen AH, Adams DA, Adams T, Grabie MT. Kappa light chain nephropathy without evidence of myeloma cells. Response to chemotherapy with cessation of maintenance hemodialysis. Am J Nephrol. 1982;2(5):276-81. [Medline].

  27. Kaplan B, Ramirez-Alvarado M, Dispenzieri A, et al. Isolation and biochemical characterization of plasma monoclonal free light chains in amyloidosis and multiple myeloma: a pilot study of intact and truncated forms of light chains and their charge properties. Clin Chem Lab Med. 2008;46(3):335-41. [Medline]. [Full Text].

  28. Knobler H, Kopolovic J, Kleinman Y, et al. Multiple myeloma presenting as dense deposit disease. Light chain nephropathy. Nephron. 1983;34(1):58-63. [Medline].

  29. San-Miguel J, Harousseau JL, Joshua D, Anderson KC. Individualizing treatment of patients with myeloma in the era of novel agents. J Clin Oncol. Jun 1 2008;26(16):2761-6. [Medline].

  30. Leung N, Lager DJ, Gertz MA, et al. Long-term outcome of renal transplantation in light-chain deposition disease. Am J Kidney Dis. Jan 2004;43(1):147-53. [Medline].

  31. Kuypers DR, Lerut E, Claes K, Evenepoel P, Vanrenterghem Y. Recurrence of light chain deposit disease after renal allograft transplantation: potential role of rituximab?. Transpl Int. Apr 2007;20(4):381-5. [Medline].

  32. Pozzi C, D'Amico M, Fogazzi GB, et al. Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors. Am J Kidney Dis. Dec 2003;42(6):1154-63. [Medline].

  33. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457-81.

  34. Kyle RA. Multiple myeloma and the dysproteinemias. In: Stein JH, ed. Internal Medicine. 3rd ed. Boston, Mass: Little Brown & Co; 1990:1146-52.

  35. Kyle RA, Garton JP. Laboratory monitoring of myeloma proteins. Semin Oncol. Sep 1986;13(3):310-7. [Medline].

  36. Sikkink LA, Ramirez-Alvarado M. Biochemical and aggregation analysis of Bence Jones proteins from different light chain diseases. Amyloid. Mar 2008;15(1):29-39. [Medline]. [Full Text].

  37. Tanenbaum ND, Howell DN, Middleton JP, Spurney RF. Lambda light chain deposition disease in a renal allograft. Transplant Proc. Dec 2005;37(10):4289-92. [Medline].

  38. Velosa JA, Holley KE. Pathology and immunopathology of renal diseases. In: Duarte CG, ed. Renal Function Tests: Clinical Laboratory Procedures and Diagnosis. Boston, Mass: Little Brown & Co; 1980:347-85.

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Keywords

LCDD, light chain deposition disease, light-chain disease, light chain disease, free light chains, FLC, renal disease, renal insufficiency, proteinuria, nephrotic syndrome, multiple myeloma, lymphoproliferative disease, lymphoproliferative disorder, end-stage renal disease, ESRD, monoclonal gammopathies, gammopathies, monoclonal gammopathy of unknown significance, MGUS, Bence Jones protein, BJP, immunoglobulin-related amyloidosis, AL-amyloidosis

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Contributor Information and Disclosures

Author

Yasodah Jayamohan, MD, Transfusion Medicine Fellow, Hoxworth Blood Center, University of Cincinnati Medical Center
Yasodah Jayamohan, MD is a member of the following medical societies: American Society for Clinical Pathology, American Society of Cytopathology, College of American Pathologists, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Coauthor(s)

Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Suzanne R Fanning, DO, Fellow, Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, 2004-2007 Director, Hematology, Greenville Memorial Health System, Greenville, SC Medical Oncologist/Hematologist/Transplant Physician, Cancer Centers of the Carolinas
Suzanne R Fanning, DO is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, and American Society of Hematology
Disclosure: Millenium Pharmaceuticals Consulting fee Review panel membership; Celgene Pharmaceuticals Consulting fee Review panel membership

Mohamad A Hussein, MD, Clinical Director, Malignant Hematology, Moffitt Cancer Center
Mohamad A Hussein, MD is a member of the following medical societies: American Association of Blood Banks, American College of Physicians, American Medical Association, and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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