Familial Amyloidosis Support Meeting
2011-10-29, Finkel
Supply, Wood
Biopsies are required to make a diagnosis of amyloidosis, including FAP.
Pathologists work in laboratories, looking at tissue samples. They usually do not work directly with patients.
Pathologists stain tissue samples routinely using blue and pink dyes (hematoxylin and eosin). They are usually looking for cancers and other conditions that are much more common than amyloid. Amyloid, including FAP, can be diagnosed only with a special stain – i.e. a Congo red stain. With more advanced disease, when deposits are larger, amyloid can be suspected on a routine stain as homogeneous deposits devoid of cells and nuclei. Since other pathologies can look similar, a Congo red stain is needed to confirm the suspicion of amyloid. Congo red stains proteins that have undergone a conformational change and acquired a beta pleated sheet structure. This structure is different from the usual alpha helix structure typically seen in most “healthy” proteins. All types of amyloid, including familial, stain red with Congo red stain. However, even the red color is not entirely specific and examination of sections under polarized light is required, when amyloid will show apple green birefringence, which is specific to amyloid. While other, less specific, stains may be at times used to detect amyloid, Congo red stain with apple green birefringence is considered the gold standard, i.e. the most specific stain. The term apple green comes from the color of amyloid deposits under polarized light, which look like green apples.
Thus, in order to diagnose amyloid there is a need either to have your doctor suspect amyloid and specifically request a Congo stain, or for a pathologist to detect amyloid that is not suspected clinically.
Dr. Picken recommends that the Congo red stain be used for all native heart and peripheral nerve biopsies and many kidney biopsies. Gastrointestinal biopsies are, nowadays, frequently done for various symptoms, but detection of amyloid in this location is more challenging and increased suspicion is needed to perform a Congo red stain. This is true, in particular, in the early stages of amyloidosis when deposits are small, and not suspicious, on routine stains.
Amyloid can be very unevenly distributed within an organ; therefore, lack of detection in a biopsy sample does not guarantee that the patient is free of the disease.
A small surgical fat biopsy is better than a syringe-extracted (“needle aspiration”) biopsy. Surgical biopsy allows examination of multiple slices, and consequently a more thorough examination.
Examination of Congo red with polarized light requires a strong light to facilitate detection of small deposits.
There are other technical pitfalls. Most pathologists seldom use Congo red stain and are not experienced with this stain.
There are also other conditions that mimic the amyloid pathology
Detecting amyloid in the first-affected person in a family (the “index patient”) is particularly challenging since there is frequently no known family history of amyloidosis and screening for amyloid is not done due to the rarity of the disease.
Q: I had a fat biopsy that was negative for amyloid. Is that conclusive? A: No. Negative diagnosis is never conclusive. Technical challenges and variability of amyloid distribution in fat may lead to false negative results. A second biopsy, yielding a larger piece of fat, may be needed to reach a more definitive result. Also, a second opinion, requesting evaluation of the biopsy by a pathologist experienced in the diagnosis of amyloid, may be advisable.
Q: How do you determine if you have the mutant gene, but it is not active (not producing bad TTR)? A: This issue will be discussed during the later sessions.
Q: I asked my MD to have the pathologist do a Congo red staion under polarized light. The results came back negative, although Dr. Benson found amyloid in a slide. How can I educate our pathology group? A: Get a second opinion (to double-check the pathologist’s result). The issue of educating providers & MDs is tricky – another session may be organized to address this.