eMedicine Specialties > Hematology > Plasma Cell Disorders

Light-Chain Deposition Disease

Author: Yasodah Jayamohan, MD, Transfusion Medicine Fellow, Hoxworth Blood Center, University of Cincinnati Medical Center
Coauthor(s): Ronald A Sacher, MB, BCh, MD, FRCPC, Director of the Hoxworth Blood Center, Professor, Departments of Internal Medicine and Pathology, University of Cincinnati Medical Center; Suzanne R Fanning, DO, Medical Oncologist, Cancer Centers of the Carolinas; Mohamad A Hussein, MD, Clinical Director, Malignant Hematology, Moffitt Cancer Center
Contributor Information and Disclosures

Updated: Jun 4, 2008

Introduction

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.

Related eMedicine topics:
Light Chain-Associated Renal Disorders
Multiple Myeloma [in the Radiology section]
Renal Failure, Chronic and Dialysis Complications

Related Medscape topics:
Resource Center Cancer: Biologic Therapies
Resource Center Diabetic Microvascular Complications
Specialty Site Hematology-Oncology
Specialty Site Nephrology
CME Highlights From the American Society of Hematology 49th Annual Meeting and Exposition: Multiple Myeloma Update
CME/CE Multiple Myeloma: Determining Prognosis and Choosing Therapy (Slides With Transcript)
CME/CE Multiple Myeloma: Optimizing Care Across the Disease Spectrum

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 The histologic appearance can mimic immunoglobulin-related amyloidosis (AL-amyloidosis), causing considerable diagnostic challenge.17 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.5,7,8,9,10,11,18,19,20

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.21

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. 

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.22 Colombat et al also reported a new form of LCDD that presented as a severe cystic lung disorder requiring lung transplantation.23 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

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.24  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.25 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 Waldenström's macroglobulinemia, chronic lymphocytic leukemia, and nodal marginal zone lymphoma.

Related Medscape topics:
Specialty Site Cardiology
Specialty Site Dermatology
Specialty Site Gastroenterology
Specialty Site Hematology-Oncology
Specialty Site Nephrology
Specialty Site Neurology & Neurosurgery

Clinical

History

  • Patients are found to have LCDD when they are evaluated for proteinuria or nephrotic syndrome by renal biopsy.
  • The chief symptoms and signs are related to associated organ involvement and may manifest as renal failure, congestive heart failure, and/or liver failure.
  • Most patients present with advanced disease due to a delay in the diagnosis.

Physical

Patients may present with end organ damage, which chiefly manifests as hypertension, peripheral edema, neuropathy, or congestive heart failure.26 Approximately 50% of patients with LCDD present with nephrotic syndrome. However, in a quarter of patients, the proteinuria is less than 1 g per day as a result of tubulointestitial involvement.

Causes

Specific etiology is unknown.

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
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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].

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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].

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  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].

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  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].

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  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].

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Further Reading

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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 Pathologists, 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, Director of the Hoxworth Blood Center, Professor, Departments of Internal Medicine and Pathology, University of Cincinnati Medical 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, Medical Oncologist, Cancer Centers of the Carolinas
Suzanne R Fanning, DO is a member of the following medical societies: American College of Physicians, American Medical Association, and American Society of Hematology
Disclosure: Nothing to disclose.

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
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: Nothing to disclose.

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, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: 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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