Amyloid

Amyloid is a type of abnormal protein that can accumulate in tissues and organs. Unlike normal proteins, amyloid proteins fold into an unusual shape, forming clumps or fibrils that can interfere with the normal function of tissues and organs.

What is the significance of finding amyloid in a tissue sample?

The presence of amyloid in a tissue sample indicates amyloid deposition, which means that amyloid proteins have accumulated in that specific tissue. This finding is significant because amyloid deposition can be associated with various medical conditions, some of which can affect the function of important organs such as the heart, kidneys, and liver. The term “amyloidosis” refers to the group of diseases caused by amyloid deposition in different tissues and organs.

What does amyloid look like under the microscope?

Under the microscope, amyloid appears as amorphous (shapeless) deposits within tissues. These deposits are often pale pink when stained with a routine dye called hematoxylin and eosin (H&E). However, amyloid is best identified using a special stain called Congo red, which makes amyloid deposits appear red or orange. Under polarized light, Congo red-stained amyloid exhibits an apple-green birefringence, a unique property that helps pathologists confirm its presence.

What special tests do pathologists perform to confirm that something is amyloid?

To confirm that the deposits seen under the microscope are indeed amyloid, pathologists perform several special tests:

1. Congo red staining: This special dye binds to amyloid and, when viewed under polarized light, shows the characteristic apple-green birefringence.
2. Immunohistochemistry (IHC): This technique uses antibodies that specifically bind to amyloid proteins. The antibodies are tagged with a marker that can be seen under the microscope, helping pathologists identify the type of amyloid.
3. Electron microscopy: In some cases, electron microscopy can be used to see the fine fibrillar (thread-like) structure of amyloid at a very high magnification.

What types of proteins can be found in amyloid?

There are several different types of proteins that can form amyloid. The type of protein involved often determines the associated medical condition. Some of the most common amyloid proteins include:

1. Light chains (AL amyloid): Produced by abnormal plasma cells, these proteins are associated with primary amyloidosis.
2. Serum amyloid A (AA amyloid): Associated with chronic inflammatory diseases and infections, leading to secondary amyloidosis.
3. Transthyretin (ATTR amyloid): This protein can misfold and deposit in tissues due to genetic mutations (hereditary amyloidosis) or age-related changes (senile systemic amyloidosis).
4. Amyloid beta (Aβ): This protein is found in the brains of individuals with Alzheimer’s disease and contributes to the formation of plaques.
5. Beta-2 microglobulin (Aβ2M): Can accumulate in patients on long-term dialysis, leading to dialysis-related amyloidosis.

Medical conditions associated with amyloid deposition

Amyloid deposition can be associated with a variety of medical conditions. Some of the most common include:

1. Primary amyloidosis (AL amyloidosis): This condition occurs when abnormal plasma cells in the bone marrow produce excess light chains, which form amyloid deposits.
2. Secondary amyloidosis (AA amyloidosis): This type is often associated with chronic inflammatory conditions, such as rheumatoid arthritis or chronic infections, where a protein called serum amyloid A accumulates in tissues.
3. Hereditary amyloidosis: Genetic mutations can lead to the production of abnormal proteins that form amyloid deposits. Examples include familial Mediterranean fever and transthyretin amyloidosis.
4. Age-related amyloidosis: Also known as senile systemic amyloidosis, this condition typically affects elderly individuals and is often associated with transthyretin protein.
5. Organ-specific amyloidosis: Amyloid deposits can be found in specific organs, such as the brain in Alzheimer’s disease, where amyloid-beta protein accumulates, or the heart in cardiac amyloidosis.

Tumours associated with amyloid deposition

Certain types of tumors can be associated with amyloid deposition. These include:

1. Multiple myeloma: A cancer of plasma cells in the bone marrow that can lead to the production of abnormal light chains, resulting in AL amyloidosis.
2. Medullary thyroid carcinoma: A type of thyroid cancer that can produce calcitonin, which can deposit as amyloid in the thyroid gland.
3. Hodgkin and non-Hodgkin lymphomas: These cancers of the immune system can sometimes be associated with secondary amyloidosis.
4. Renal cell carcinoma: A type of kidney cancer that can be associated with amyloid deposits in the kidneys.

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