The Basic Workup and Approach
General Overview
For all patients suspected of amyloidosis, a full monoclonal gammopathy screen must be conducted (SFLC, SPEP and UPEP) and organ screening.
If the monoclonal gammopathy screen is negative, a biopsy may not be required if ATTR amyloidosis is suspected. However, if a monoclonal gammopathy is detected, the patient should undergo a biopsy to distinguish between AL and ATTR amyloidosis.
All biopsies required immunohistochemistry with kappa, lambda, AA and TTR staining.
Bone scintigraphy should be conducted in all patients suspected of cardiac involvement.
The presence of amyloid can now be identified using either;
- Cardiac amyloid bone scintigraphy (for cardiac ATTR)
- OR
- Biopsy (for all other amyloidoses)
All cases still require;
- Monoclonal gammopathy tests (to screen for AL)
- AND
- Organ staging
Some cases may require further amyloid typing testing with;
- Mass spectrometry for protein typing
- Genetic testing for amyloidogenic mutations
The most common and critical pitfalls to be aware of are that;
- Immunohistochemical amyloid typing stains only have a positive predictive value of ≈ 60%
- AND THAT
- Cardiac amyloid bone scintigraphy has a high positive predictive rate for cardiac ATTR amyloidosis but can be positive in cardiac AL and does not exclude non-ATTR cardiac amyloidosis
One of the primary purposes of the State based AAN anatomical pathology services is to assist with the typing of amyloidosis. Referrals for this purpose are welcomed and strongly encouraged. Performing the basic workup expedites the diagnostic process.
Organ Staging
Organ staging is an essential component of the basic workup for amyloidosis as this:
- Identifies the most sensitive sites for diagnostic biopsy
- Differentiates between localised and systemic amyloidosis
- Organ tropism patterns can assist with typing
Basic organ screening can be performed using a combination of clinical assessment and simple blood and urine tests
- Investigations such as cardiac magnetic resonance imaging and nerve conduction studies are not routinely required to screen for organ involvement
Table: Basic Screening for Amyloidosis
| ORGAN |
ASSESSMENT MODALITY | ASSESSING FOR |
| Heart | Clinical | Heart Failure
Arrhythmia |
| Blood test | Elevated NT-ProBNP, troponin | |
| +/- TTE
(in clinically suspected cardiac amyloidosis) |
Thickened intraventricular septum and left ventricular wall
Reduced global longitudinal strain with apical sparing (“Cherry on top”/ Bullseye” pattern of GLS) |
|
| Kidney | Urinalysis | Proteinuria by: Random urine protein creatinine and albumin creatinine ratio or 24 hour urine protein |
| Blood test | Creatinine, eGFR | |
| Liver | Clinical | Hepatomegaly |
| Blood test | Liver dysfunction (obstructive pattern) | |
| Gastrointestinal tract (GIT) | Clinical | Upper and lower GIT symptoms:
Weight loss, early satiety, peptic ulceration, diarrhoea, alternating bowel habit, per rectal bleeding, colic |
| Peripheral nervous system | Clinical | Sensory +/- motor peripheral neuropathy
Autonomic nerve dysfunction: Gastric-emptying disorder, pseudo-obstruction, voiding dysfunction abnormal sweating, postural hypotension, sexual dysfunction |
| Tenosynovium | Clinical | Carpel tunnel syndrome
Hand tendon contractures Symptoms of spinal canal stenosis (due to ligamentum flavum deposition) Biceps tendon rupture |
Key: eGFR = estimated glomerular filtration rate, GIT = gastrointestinal tract, GLS = global longitudinal strain, NT-ProBNP= N-terminal pro brain natriuretic peptide, TTE = transthoracic
