FOREIGN BODY GRANULOMA


You are a staff veterinarian at a contract laboratory that does work for the pharmaceutical industry, responsible for the welfare of 25,000 rats, 40,000 mice, and 3,000 rabbits involved in several studies for various drugs, procedures, and toxicants.

A study technician comes to you because he is concerned about the rats kept on a study involving a minor surgical procedure. The technician handles and observes the rats every day and is worried that the rats' surgical wounds are becoming infected.

The rats are all females, weighing about 400 grams each. They are fed rodent food on an ad libitum basis and have water available from Lixit taps 24 hours a day. They're housed individually in drawer-type plastic-bottomed cages with pine shavings for bedding. They'll be in the study for one year and all had a device implanted in their abdomens, 21 days before.

The incision sites are all quite inflamed and swollen and there's an exudative discharge from several of them. It also appears that the rats have been scratching at themselves. You decide to remove the sutures on one of the rats and find that the wound has more or less healed but there is inflammatory exudate throughout the site.

Three weeks is a long time: you ask the technician when the protocol required that the sutures be removed, but on examination the study notebook indicates that there is no removal date: the sutures were to be dissolvable, to minimize disturbance of the rats. You look at the suture you removed...and you're pretty sure that it's silk! A quick check of the other rats turns up the same thing silk suture was used in all of them: someone didn't read the protocol carefully!


DIAGNOSIS

In this case, the diagnosis is a foreign body granuloma caused by the presence of nondissolvable sutures in the wounds. Silk is nondissolvable, and potentially a source of irritation if left in place. Silk is a foreign protein and the body responds to, predictably, by launching an immune response. Signs in this case are fairly typical: the site of a granuloma is hard and nodular, because it's are made up of packed cells (unlike seromas or abscesses, which are cellular but contain large percentages of fluid). Furthermore, there's leakage of serum from the site, as well as dehiscence of some of the surgical wounds. The ongoing inflammation has rendered the tissue friable and delicate.

In cases where an insult to the immune system cannot be handled by complement and attack by neutrophils, macrophages are summoned to join the fray. Macrophages attempt to resolve the problem by phagocytosis. If the individual macrophage cannot handle the problem, many macrophages join to form a syncytium—a giant cell—to engulf the foreign invader. In this case, the silk suture is far too large to be engulfed, so the macrophages pile up against it and against themselves, resulting in a nonresolving granuloma. The present macrophages continue to send cytokinetic signals that attract ever more macrophages, prolonging the inflammatory response, delaying wound healing and taxing the animal's immune system.

Treatment for these granulomas is based on removal of the foreign body to eliminate the irritation, stop the in-migration of inflammatory cells, and concurrent treatment with NSAIDs or steroids such as prednisone to suppress the inflammation. Inflammation is part of healing, and you don't want to suppress it too much, but in this case it's got out of hand and has to be brought back under control.


HISTOPATHOLOGY

 

The low-power image above at left clearly shows three retained sutures and the respose they've elicited. Two of them are surrounded by a large encapsulation of inflammatory and scar tissue, enlarged at right to show the extent of the reaction. There's quite bit of fibrosis in the immediate vicinity as well as some neutrophils and many macrophages.

The suture on the right in the low-magnification image is eliciting a powerful reaction. It's shown here in detail. The the "cap" of basophilic cells on one side contains neutrophils, macrophages, and a giant cell is visible in this area. The surrounding connective tissue is starting to proliferate in an attempt to wall off the offending stimulus.

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