Light Chain Disease

(Bence Jones Myeloma)

Discussion

Definition:

Light Chain Disease (LCD) is a variant of multiple myeloma in which the malignant population of marrow cells produces free monoclonal light chains but no associated heavy chain or complete immunoglobulin. The monoclonal light chains are small enough to be freely filtered by the kidneys and become Bence-Jones protein. LCD comprises about 18% of multiple myeloma patients.

Clinical Features:

  1. More malignant course as compared to classic myeloma.
  2. Extremely rapid doubling time.
  3. Tendency for more osteolytic lesions.
  4. Increased hypercalcemia.
  5. Higher incidence of renal failure (including azotemia at presentation) as compared to other patients with Multiple Myeloma.
  6. Higher incidence of amyloidosis and plasma cell leukemia in the terminal stages of the disease. Renal failure is the principle cause of death in these patients.

 

Pathogenesis:

Structural gene loss involving the deletion of the J-H segment of the heavy chain locus (situated on Chromosome 14) is the most probable cause leading to isolated production of light chains in the disease.

 

Pathophysiology:

Light chains can cause a rapid decline of renal function and early onset of clinical deterioration in LCD. Renal damage caused by the freely filtered light chains affects every segment of the nephron.

  1. In the glomerulus, they can cause a non-fibrillary glomerulopathy involving deposition of light chains as well as a fibrillary glomerulopathy characterized by amyloidosis.
  2. In the proximal tubules, reabsorption leads to formation of toxic metabolites and an acquired Fanconi syndrome.
  3. The distal tubules suffer what has been termed "cast nephropathy" as a result of epithelial damage due to cast formation in the lumina (Ref Fig 4 a&b). Proteinaceous casts are prominent in the distal convoluted tubules and collecting ducts. Some of the casts are surrounded by multi-nucleated giant cells derived from fusion of infiltrating macrophages.

 

Laboratory Features:

The laboratory features of LCD show distinction from classical myeloma.

  1. The serum total protein is normal to low.
  2. Hypogammaglobulinemia is common.
  3. 100% of the patients show evidence of Bence-Jones proteins in the urine.
  4. Many patients do not have a serum M (monoclonal) component on electrophoresis as most light chains are quickly filtered by the kidneys. Urine electrophoresis (Ref Fig 1b) becomes an important test in such cases.

Using Immuno Fixation Electrophoresis (Ref Fig. 2a & 2b), the ratio of kappa to lambda chains in the disease population is about 2:1. This distinction is important because lambda LCD has a three times worse prognosis than kappa LCD.

Bone marrow aspirates in patients with suspected myeloma show an increased number of abnormal plasma cells with a morphologic appearance outside the range of a reactive process. In many instances, the neoplastic cells appear as mature plasma cells, but all ranges of immaturity may be encountered including undifferentiated cells resembling lymphoid precursors (Ref. Fig. 3). The minimum percentage of plasma cells in the marrow smear necessary to make a diagnosis is generally placed at 10%.

 

Additional Information:

Internet:

 

References:

  1. Acute Leukemia Group B Cooperative Study Correlation of Abnormal Immunoglobulins with Clinical Features of Myeloma. Arch Int Med; 1975,135:46.
  2. Brunning and McKenna: Plasma Cell Dyscrasias and Related Disorders Tumors of the Bone Marrow AFIP 3rd series, 1993.
  3. Cotran, Kumar, and Robbins (editors): Robbins Pathologic Basis of Disease (5th ed), WB Saunders; 1995,662-5.
  4. Picken MM and Shan S: Immunoglobulin Light Chains and The Kidney : An Overview . Ultrastrutural Pathology; 1994,18:105-12.
  5. Schustik C et al: Kappa and Lambda Light Chain Disease:Survival Rates and Clinical Manifestations Blood; 1976,48:41.

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