Light-Chain Deposition Disease 

  • Author: Yasodah Jayamohan, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Dec 2, 2011
 

Background

Light-chain deposition disease (LCDD) is the deposition of monoclonal, amorphous, noncongophilic light chains in multiple organs that do not exhibit a fibrillar structure when examined ultrastructurally.[1, 2, 3]

In 1976, Randall et al recognized LCDD as an infiltration of light chains involving multiple organs.[4] Renal involvement is a constant feature which include renal insufficiency, proteinuria, and nephrotic syndrome. Extrarenal involvement is primarily noted at autopsy and is usually confined to the perivascular regions of the affected organs. Approximately 50-60% of patients with LCDD have associated lymphoproliferative disorder, most commonly multiple myeloma. The remaining cases develop LCDD in the setting of progression of monoclonal gammopathy of unknown significance (MGUS) or with no evidence of neoplastic plasma cell proliferation.

Approximately 85% of cases are associated with kappa light-chain deposition.[5, 6] A monoclonal protein of the same light-chain type is usually demonstrated in serum or urine, but approximately 25% of patients have no demonstrable light chain in serum or urine by immunoelectrophoresis or immunofixation. Even in the absence of a monoclonal light chain in serum or urine, immunofluorescence usually demonstrates a monoclonal population of plasma cells in the bone marrow of these patients.

The renal lesion is usually a nodular mesangial lesion that is often indistinguishable from diabetic lesions by light microscopy. Immunofluorescence and electron microscopy are essential in making the diagnosis, and the findings on renal biopsy are often the first evidence of LCDD.[7, 8, 9, 10, 11]

The frequency of LCDD is unknown. Treatment with high-dose chemotherapy with or without autologous stem cell transplantation may result in disease stabilization and/or improvement in end-organ damage.[1, 9, 12, 13, 14]

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center and Kidneys and Urinary System Center. Also, see eMedicine's patient education article Myeloma.

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Pathophysiology

LCDD is characterized by deposition of monoclonal, amorphous light chains. Sites of light-chain deposition include the kidney, liver, heart, small intestine, spleen, skin, nervous system, and bone marrow.[4, 13, 15, 16, 17] The histologic appearance can mimic immunoglobulin-related amyloidosis (AL-amyloidosis), causing considerable diagnostic challenge.[18] However, unlike AL amyloidosis, LCDD deposits lack the beta-pleated configuration, with no affinity for Congo red stain. Immunofluorescence of the bone marrow usually demonstrates a monoclonal population of plasma cells, and the characteristic "apple green" birefringence of amyloid is not observed under polarization.

AL-amyloidosis consists predominantly of lambda light chains, whereas kappa light chains dominate LCDD lesions. Electron microscopy is helpful in distinguishing between both these lesions. Amyloid deposits are characteristically fibrillar, whereas the LCDD deposits are ultrastructurally granular.[5, 7, 8, 9, 10, 11, 19, 20, 21]

A study by Keeling et al revealed that altered expression of matrix metalloproteinases (MMPs), a group of enzymes with diverse proteolytic activities, occurs in LCDD and, to a greater degree, in amyloidosis.[22]

Renal involvement in the form of proteinuria or renal insufficiency is the most common manifestation. The renal lesion is usually a nodular glomerulosclerosis that mimics the Kimmelstiel-Wilson disease of diabetic nephropathy by light microscopy. Sites of deposit in the kidney can vary and include the glomeruli, tubular basement membrane, and Bowman capsule. Cases of LCDD have been reported to occur in patients with renal allografts, either de novo or in patients with a previous history of LCDD.[23]

Approximately 25% of patients with LCDD have cardiac and liver involvement. The cardiac manifestations include cardiomyopathy, congestive heart failure, and arrhythmias. The deposits in the liver are usually confined to the sinusoids and basement membrane of biliary ducts without associated parenchymal lesions. These patients are usually asymptomatic, with mild to moderate liver function abnormalities. Hepatomegaly may or may not be present. However, hepatic failure and portal hypertension may supervene in a small number of cases.

Although pulmonary LCDD is rare, Bhargava et al reported 5 new cases that included both the nodular and diffuse forms parallel to AL-amyloidosis.[24] Colombat et al also reported a new form of LCDD that presented as a severe cystic lung disorder requiring lung transplantation.[25] This entity was derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor.

Occasionally, peripheral nerves are affected, resulting in polyneuropathy, However, a case of LCDD restricted to the brain was reported by Popovic et al wherein the periventricular foci of intracerebral vessels were overloaded with amorphous, eosinophilic material that stained for lambda light chains.[16]

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Epidemiology

Frequency

United States

The frequency of LCDD is unknown. In a renal biopsy study by Mallick et al of 260 patients with idiopathic proteinuria, 5 had LCDD.[26] A renal biopsy study by Pirani et al reported 47 patients with plasma cell dyscrasia, in whom 24 had cast nephropathy and 10 had LCDD.[27] The disease is found in approximately 5% of patients with multiple myeloma at autopsy.

Mortality/Morbidity

Most of the morbidity that is associated with LCDD is related to renal failure manifesting as nephrotic syndrome and its clinical sequelae. Liver dysfunction can also occur, with progression to hepatic failure. Other symptoms of LCDD relate to congestive heart failure, peripheral neuropathy, and skin lesions secondary to the deposition of light chains.[15] LCDD may occasionally complicate Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia, and nodal marginal zone lymphoma.

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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 Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

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.

Specialty Editor Board

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 Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences

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

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.

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, 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 College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous coauthor Dr Jaya Juturi to the development and writing of this article.

References

  1. Weichman K, Dember LM, Prokaeva T, et al. Clinical and molecular characteristics of patients with non-amyloid light chain deposition disorders, and outcome following treatment with high-dose melphalan and autologous stem cell transplantation. Bone Marrow Transplant. Sep 2006;38(5):339-43. [Medline].

  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].

  8. Brockhurst I, Harris KP, Chapman CS. Diagnosis and monitoring a case of light-chain deposition disease in the kidney using a new, sensitive immunoassay. Nephrol Dial Transplant. Jun 2005;20(6):1251-3. [Medline]. [Full Text].

  9. Heilman RL, Velosa JA, Holley KE, Offord KP, Kyle RA. Long-term follow-up and response to chemotherapy in patients with light-chain deposition disease. Am J Kidney Dis. Jul 1992;20(1):34-41. [Medline].

  10. Confalonieri R, Barbiano di Belgiojoso G, et al. Light chain nephropathy: histological and clinical aspects in 15 cases. Nephrol Dial Transplant. 1988;3(2):150-6. [Medline].

  11. Hill GS, Morel-Maroger L, Méry JP, Brouet JC, Mignon F. Renal lesions in multiple myeloma: their relationship to associated protein abnormalities. Am J Kidney Dis. Jan 1983;2(4):423-38. [Medline].

  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].

  13. Royer B, Arnulf B, Martinez F, et al. High dose chemotherapy in light chain or light and heavy chain deposition disease. Kidney Int. Feb 2004;65(2):642-8. [Medline].

  14. Firkin F, Hill PA, Dwyer K, Gock H. Reversal of dialysis-dependent renal failure in light-chain deposition disease by autologous peripheral blood stem cell transplantation. Am J Kidney Dis. Sep 2004;44(3):551-5. [Medline].

  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].

  16. Popovic M, Tavcar R, Glavac D, Volavsek M, Pirtosek Z, Vizjak A. Light chain deposition disease restricted to the brain: The first case report. Hum Pathol. Jan 2007;38(1):179-84. [Medline].

  17. Ronco P, Plaisier E, Aucouturier P. Monoclonal immunoglobulin light and heavy chain deposition diseases: molecular models of common renal diseases. Contrib Nephrol. 2011;169:221-31. [Medline].

  18. 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].

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

  20. 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].

  21. 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].

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

  23. Uppin MS, Prayaga AK, Srinivas BH, Rapur R, Desai M, Dakshina Murthy KV. Light chain immunofluorescence in various nephropathies. Indian J Pathol Microbiol. Jan-Mar 2011;54(1):55-8. [Medline].

  24. 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].

  25. 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].

  26. 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].

  27. 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].

  28. 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].

  29. 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].

  30. 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].

  31. 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].

  32. Gharwan H, Truica CI. Bortezomib-based chemotherapy for light chain deposition disease presenting as acute renal failure. Med Oncol. Apr 9 2011;[Medline].

  33. 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].

  34. 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].

  35. 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].

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

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

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

  39. 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].

  40. 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].

  41. 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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