Cardiac Amyloidosis: Key Histological Features

Cardiac amyloidosis is a condition characterized by the deposition of abnormal proteins, known as amyloid fibrils, in the heart tissue. These protein deposits disrupt the heart’s normal structure and function, leading to serious health complications. The disease progresses as these misfolded proteins accumulate, causing the heart muscle to become stiff and thickened.

Understanding Cardiac Amyloidosis

Cardiac amyloidosis originates from proteins that misfold and aggregate into insoluble fibrils that the body cannot easily clear. Over time, these fibrils build up in the extracellular space within the heart muscle, disrupting the normal cardiac cells and architecture. This infiltration leads to a progressive stiffening and thickening of the heart walls, a condition known as restrictive cardiomyopathy.

The stiffened heart muscle struggles to relax and fill with blood properly, leading to symptoms of heart failure. Furthermore, the amyloid deposits can interfere with the heart’s electrical conduction system, which can cause arrhythmias or irregular heartbeats. While several different proteins can form these damaging deposits, the fundamental disease process is this progressive accumulation.

The buildup of these deposits impairs the heart’s ability to pump blood effectively. This can cause a range of symptoms, including shortness of breath, fatigue, and swelling in the legs and abdomen. The severity of the disease correlates with the extent of amyloid deposition in the heart, and early diagnosis is important for management.

The Role of Histology in Diagnosis

Histology, the microscopic study of biological tissues, is a foundational method for the definitive diagnosis of cardiac amyloidosis. It allows physicians to directly visualize the amyloid protein deposits within the heart muscle, confirming their presence. While non-invasive imaging techniques have advanced, the gold standard for diagnosis involves obtaining a tissue sample for histological analysis. A diagnosis requires histological evidence of amyloid deposits from the heart or another affected organ.

To perform this analysis, a small piece of heart tissue is acquired through a procedure called an endomyocardial biopsy. During this procedure, a catheter is guided to the heart to obtain a few small samples of the heart muscle. These tissue samples are then preserved, sliced into thin sections, and mounted on glass slides for examination.

The primary purpose of this histological examination is to identify the characteristic amyloid deposits. Pathologists use specific staining techniques to make these deposits visible. This direct visualization moves from suspicion based on clinical signs or imaging to a confirmed diagnosis based on the physical presence of the amyloid fibrils.

Key Microscopic Features of Cardiac Amyloid

Under a standard hematoxylin and eosin (H&E) stain, amyloid deposits appear as a glassy, pink material accumulating between the heart muscle cells (cardiomyocytes). This substance can vary in distribution, from small, scattered deposits to large sheets that replace normal heart tissue. These deposits are found in the interstitium, the tissue that supports the cardiomyocytes, and around small blood vessels.

The most definitive feature for identifying amyloid in tissue is its reaction to a special stain called Congo red. When stained with Congo red and viewed under normal light, the amyloid deposits take on a salmon-pink or orange-red color. The diagnostic sign, however, appears when the stained slide is viewed with a polarizing microscope.

Under this specific light, the Congo red-stained amyloid exhibits a unique “apple-green” birefringence. This optical characteristic is caused by the highly organized structure of the amyloid fibrils interacting with polarized light. This apple-green birefringence with Congo red is the most widely accepted and specific feature for histological diagnosis.

In some cases, electron microscopy may be used for a more detailed view. This technique can visualize the ultrastructure of the deposits, revealing their composition of non-branching fibrils that are 7.5 to 10 nanometers in diameter. This fibrillar nature is the fundamental characteristic of all amyloid deposits, regardless of the precursor protein.

Differentiating Amyloid Types Through Histology

Identifying the presence of amyloid is only the first step; determining the specific type of protein forming the deposits is necessary for appropriate treatment. The two most common types to affect the heart are immunoglobulin light chains (AL amyloidosis) or transthyretin (ATTR amyloidosis). Histological techniques are instrumental in this differentiation, primarily through immunohistochemistry (IHC).

Immunohistochemistry works by using antibodies specifically designed to recognize and bind to a particular protein. In cardiac amyloidosis, tissue sections are treated with antibodies that target either the light chain proteins or the transthyretin protein. If the deposits are the AL type, the anti-light chain antibodies will bind, and a chemical reaction makes this visible. Similarly, if it is ATTR amyloidosis, the anti-transthyretin antibodies will bind.

Some subtle morphological clues in standard stained sections may suggest one type over another. For instance, AL amyloid deposits are sometimes described as having a more pericellular and reticular pattern, whereas ATTR deposits may appear more patchy or nodular. However, there is significant overlap in these patterns, making IHC necessary for an accurate classification.

For cases where immunohistochemistry is inconclusive, a more advanced technique called mass spectrometry can be performed on the tissue sample. This method can precisely identify the protein composition of the amyloid deposits by analyzing their mass-to-charge ratio. This provides a definitive typing of the amyloid, which is foundational for guiding modern, targeted therapies.