Amyloid is an abnormal protein that folds into the wrong shape and accumulates in body tissues as dense, insoluble deposits. In healthy cells, proteins fold correctly and perform their normal functions. In some diseases, certain proteins misfold and clump together into a distinctive structure — one that the body cannot easily break down or clear away. Over time, these deposits can build up in organs such as the heart, kidneys, liver, and nerves, interfering with normal function. The group of diseases caused by amyloid accumulation is collectively known as amyloidosis.
What does amyloid look like under the microscope?
Under the microscope, amyloid appears as pale pink, structureless (amorphous) deposits within the tissue. These deposits are identified using a special stain called Congo red. When Congo red is applied to the tissue, amyloid deposits turn a distinctive red or orange color. Under polarized light — a special lighting technique used in microscopy — Congo red-stained amyloid shows a characteristic apple-green glow, a property called birefringence. This apple-green appearance under polarized light is one of the most reliable ways to confirm that deposits are truly amyloid. In some cases, immunohistochemistry (IHC) is also performed to identify the specific protein that makes up the amyloid.
What conditions are associated with amyloid?
Different types of protein can misfold and form amyloid, and the type of protein involved determines the associated disease. The most clinically important types include:
- AL amyloidosis (light chain amyloidosis) — the most common systemic form. Caused by abnormal plasma cells producing excess light chain proteins that deposit in organs. Often associated with multiple myeloma or a related plasma cell disorder. Can affect the heart, kidneys, liver, and peripheral nerves.
- AA amyloidosis (secondary amyloidosis) — caused by a protein called serum amyloid A, which rises in response to prolonged chronic inflammation or chronic infection. Associated with conditions such as rheumatoid arthritis and inflammatory bowel disease. Most commonly affects the kidneys and liver.
- ATTR amyloidosis (transthyretin amyloidosis) — caused by the transthyretin protein, which is produced by the liver. Can be hereditary (due to a gene mutation) or age-related (also called wild-type ATTR), where the protein misfolds spontaneously with aging. Most commonly affects the heart and peripheral nerves. Targeted treatments are now available for ATTR amyloidosis.
- Localized amyloidosis — deposits confined to a single organ or site, without systemic involvement. Examples include amyloid in the larynx (see laryngeal amyloidosis), skin, or bladder. Often less serious than systemic forms and may not require treatment beyond local management.
Amyloid can also be found as a secondary feature in certain tumors. Medullary thyroid carcinoma, for example, characteristically contains amyloid deposits made from calcitonin — a hormone produced by the tumor cells. Identifying amyloid in the thyroid in this setting helps confirm the diagnosis.
What does finding amyloid in my report mean?
The significance of amyloid in a pathology report depends entirely on what type of amyloid is present, where it is found, and how much has accumulated. Finding a small amount of localized amyloid in a single organ is very different from discovering widespread systemic amyloidosis affecting the heart and kidneys.
If amyloid has been identified in your tissue sample, your doctor will arrange further testing to determine the type of amyloid and whether it is localized or systemic. This may include blood tests, urine tests, additional biopsies, or imaging. Identifying the correct type of amyloidosis is essential because treatment differs significantly by type — for example, AL amyloidosis is treated by targeting the abnormal plasma cells, while ATTR amyloidosis can now be treated with drugs that stabilize the transthyretin protein.
Questions to ask your doctor
- What type of amyloid was found in my sample, and is it localized or systemic?
- What further tests are needed to determine the cause and extent of the amyloid deposits?
- Does this finding affect any of my organs, and what treatment options are available?
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