Primary Systemic Amyloidosis Workup

Updated: Sep 03, 2021
  • Author: Judit H Nyirady, MD, MBA; Chief Editor: Dirk M Elston, MD  more...
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Workup

Approach Considerations

The diagnosis of AL amyloidosis is difficult because no single blood test or imaging test is pathognomonic. The extent and number of organs involved determines the clinical picture, which in most cases is not specific. [5, 27]

Hematologists may play a key role in diagnosing patients with amyloidosis. Diagnostic algorithms are available, and typing of amyloid is important for establishing the diagnosis and guiding the treatment choice.

The clinical course of patients with AL amyloidosis is heterogenous and depends on which organs are involved and to what extent. There are prognostic models used for risk stratification in amyloidosis, which include the Mayo AL amyloidosis 2004 model; the Mayo AL amyloidosis 2012 model; the European model, which is a modification of the Mayo 2004 model; and a more recently validated Boston prognostic model. [28]

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Laboratory Studies

In a review of 132 primary systemic amyloidosis cases, Kyle and Bayrd reported that laboratory studies revealed anemia in less than 50% of the cases. [10] The white cell count was usually within the reference range, and the erythrocyte sedimentation rate was higher than 50 mm/h in one half of the cases. Hepatic function was abnormal, and the serum creatinine level was increased in 50% of patients. Proteinuria was present in more than 90% of the cases.

Conventional urine heat testing and electrophoresis of serum and urine samples may fail to demonstrate small quantities of monoclonal paraprotein or Bence-Jones protein. Immunoelectrophoresis of serum and concentrated urine samples is essential.

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Imaging Studies

Endomyocardial biopsy is the criterion standard for diagnosing cardiac amyloidosis, but it is an invasive procedure and should be avoided if possible. [28]

Echocardiography is valuable in the evaluation of amyloid heart disease. It usually reveals a concentrically thickened left ventricle and often a thickened right ventricle, with a normal-to-small cavity. Cardiovascular magnetic resonance imaging provides high-definition structural imaging and tissue characterization that are often incremental to information obtained on echocardiography. [28, 29]

Doppler studies are useful and may show abnormal relaxation early in the course of the disease. Advanced involvement is characterized by restrictive hemodynamics.

18F-Fluorodeoxyglucose positron-emission tomography has been used in primary systemic amyloidosis evaluation. [30]

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Procedures

Biopsy of a cutaneous lesion, if present, has the advantage of safety and a high diagnostic yield.

Biopsy results in clinically normal skin may be positive in as many as 50% of cases of primary systemic amyloidosis.

Findings from abdominal fat aspiration are positive in almost 80% of patients.

Rectal biopsy reveals positive findings in about 80% of patients.

If specimens from the biopsy sites are negative for amyloid, tissue should be obtained from an organ or area with suspected involvement, such as the kidney, liver, heart, or sural nerve. [31]

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Histologic Findings

The best way to identify amyloid is to stain paraffin-embedded sections with alkaline Congo red and to examine them with polarized light to elicit a green fluorescence. Routine hematoxylin-eosin staining may show a homogenous, faintly eosinophilic mass if enough amyloid is present. See the image below.

Amorphous eosinophilic interstitial amyloid observ Amorphous eosinophilic interstitial amyloid observed on a renal biopsy.

Analysis of a skin biopsy specimen of a papule reveals an amorphous or fissured eosinophilic mass in the papillary dermis with associated thinning or obliteration of the rete ridges. Nodules and plaques may demonstrate diffuse amyloid deposition in the reticular dermis or subcutis. Amyloid depositions are usually not associated with an inflammatory infiltrate.

The appearance of amyloid infiltration of the blood vessel walls, pilosebaceous units, arrector pili muscles, and lamina propria of sweat glands and infiltration around individual fat cells in the subcutis (known as amyloid rings) are characteristic findings. Amyloid may be deposited in the nail bed of dystrophic nails.

The finding of light chain–restricted plasma cells with amyloid may be a manifestation of myeloma or a marginal cell lymphoma. Clinical correlation is required. [32]

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