CAPONE


Capone is a nine year old American bulldog who's brought to you for evaluation. He's been having difficulty walking:  for the past week he's seemed a little clumsy and has been a lot more lethargic than normal.  Capone's owner brought him in because there was a short episode that looked like a seizure, and since that time Capone's had a pronounced head tilt to the right and walks with great reluctance. This is clearly a neurological problem, as the history of seizure and post-seizure disorientation show. It could be due to a number of causes. An MRI and CAT scan show that this dog has a tumor of the normally protective astrocytes in the brain.


Part of Capone's brain has undergone liquefactive necrosis. Liquefactive necrosis is a mode of cell death that is characterized by a well-circumscribed and visible (grossly or in the microscope) region of dull, opaque, gray-white-yellow material. This is the remains of tissue that has been liquified by digestion with lytic enzymes, especially proteoytic enzymes released from leukocytes.

Bacterially-caused liquefactive necrosis is created by the enzymes of neutrophils that have attacked the bacteria: in essence it's the bodies of neutrophils and their targets that have been liquified. If this material is sequestered into a discrete region by connective tissue, it's termed an "abscess."

 

Here's an example of liquefactive necrosis forming a large brain abscess. The gross specimen is encapsulated and filled with that "dull, opaque, gray-white-yellow material," which as you can imagine does no good to normal brain function. The low-magnification microscopic view is a similar (but smaller) lesion. There is nothing in the well-defined space in the right image except "soup" of lysed cells and cellular debris. It's eosinophilic because it has a good deal of protein in it.

A closer view of the interface between the liquified area and the surrounding inflammatory region in the abscess shows large numbers of neutrophils, and macrophages, as well as a great deal of cellular debris.

This type of liquefactive necrosis can occur in response to bacterial invasion in almost any location, not just the brain. We'll see another example of it in a different case. But in Capone's case the causative agent wasn't bacteria: it was a rapidly growing tumor, and not necessarily a malignant one.

As Capone's tumor grew, it displaced normal tissue, developing a rim of necrosis around the leading edge. The brain is a particularly bad place to have a tumor. In addition to direct disruption of the neuropil, a growing neoplasm has very little room for free expansion, and raises intracranial fluid pressures. As the tumor enlarges, somethings got to give: that something is whatever part of the brain that's nearby. In Capone's brain it was the part dedicated to motor control. He has ataxia and lethargy as a result.

Growth of the tumor caused increased intracranial pressure, disruption of normal brain activity, and readily apparent gross physical signs such as ataxia, head tilt, and seizures. Furthermore, necrosis occurs on the perimeter of the tumor from the pressure exerted by the mass. This perimeter of necrosis forms a sort of capsule around the tumor and can infiltrate into the surrounding neuropil, much like an infection in the muscle planes can result in an abscess or a cellulitis.


This is a another example of liquefaction in the brain, a case of polioencephalomalacia.

This condition is usually caused by ischemia or infarction. In response to this situation, the brain undergoes its characteristic form of liquefactive necrosis. Liquefaction of the cortex of the brain has begun in this image (left). The central region is beginning to break down. The cells are starting to undergo autolysis. This type of liquefactive necrosis differs from the previous one mainly in what causes it: this isn't due to bacterial invasion. Ischemia is one cause: trauma to the brain tissue is also likely to trigger it.

Liquefaction is the "default" form of necrosis in the central nervous system. At right, the breakdown of tissue has elicted the collection of macrophages, who've come in to clean up the debris left by lysis. This is seen at higher magnification at left. The macrophages are the large, eosinophilic cells. Neurons in the area of liquefaction undergo karyolysis and die (right, arrows) and are removed as well.

 

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