By ProPath Staff

 

The patient is a 57-year-old female who originally presented to her primary care physician with a history of moderate fatigue and edema. A subsequent evaluation by a cardiologist revealed a left ventricular dysfunction and an infiltrative amyloid cardiomyopathy was suspected. Continued evaluation by an oncologist revealed monoclonal free Kappa light chains in a 24-hour urine sample. With this high level of suspicion for amyloidosis, a bone marrow evaluation was obtained. The bone marrow demonstrated a normal cellularity with a mild (8%) increase in plasma cells, which were Kappa light chain restricted.

 

Immunohistochemistry confirmed that these were amyloid deposits.

Amyloid A IP Stain

The amyloids are a heterogeneous group of disorders characterized by the extracellular deposition of protein in an abnormal fibrillar form. Amyloidosis may be hereditary or acquired, and the deposits may be focal, localized, or systemic in distribution. Amyloidosis is not a single disease but a term for diseases that share a common feature: the extracellular deposition of pathologic insoluble fibrillar proteins in organs and tissues.

 

Many different precursor proteins have been found which undergo partial proteolytic cleavage and fibril formation. It is not known at this time why amyloid is deposited in certain individuals and not in others with apparently identical precursor protein supply, nor are the factors governing anatomic distribution, the rate of onset and progression, and the clinical effects of amyloid understood.

Amyloid P 3200 IP Stain

Clinical Amyloidosis Syndromes

  1. Reactive Amyloidosis (AA). The AA protein which forms AA amyloid fibrils is derived from the circulating acute phase reactant, serum amyloid (SSA). Any pathologic process resulting in a sustained, acute phase response may, therefore, be complicated by AA amyloidosis. The most common causes in the Western world are idiopathic inflammatory rheumatic diseases.

H & E Stain

  1. Systemic Amyloidosis associated with immunocyte dyscrasia, AL Amyloidosis. AL amyloid fibrils are derived from the internal region of monoclonal, immunoglobulin light chains. AL amyloidosis can complicate most clonal B cell dyscrasias, including up to 15% of patients with multiple myeloma, and a much smaller proportion of those with lymphomas and other benign monoclonal gammopathies. AL amyloid may involve almost any organ. The heart is histologically involved in most cases, with symptomatic restrictive cardiomyopathy the presenting feature in up to 1/3 of cases.
  2. Hereditary Systemic Amyloidosis. This form is an extremely rare form and is due to autosomal dominant inheritance of variant amyloidogenic proteins. The most common cause of hereditary amyloidosis is variant transthyretin (TTR), usually resulting in the clinical syndrome of familial amyloidotic polyneuropathy.
  3. This case is characterized by monoclonal proteinuria, mildly increased marrow plasma cells which demonstrated a Kappa light chain restriction and an immunohistochemical staining pattern consistent with AL amyloidosis. The treatment of amyloidosis is directed both toward the affected organ and to the specific type of disease. The past few years have seen several advances in our understanding of amyloidosis and in our ability to provide treatment options.

 

References:

  1. British Journal of Haematology. Falk, R. H., Comenzo, R.L., and Skinner, M. 1997, 99, 245 – 256.
  2. “The Systemic Amyloidoses”. New England Journal of Medicine. 1997; 337: 898 – 909.
  3.  Murphy, C.L., et al. American Journal of Clinical Pathology, 2001; 116: 135 – 142.