Signalment:
3-year-old male pigtail macaque (
Macaca nemestrina) non-human primateThe monkey received a total dose of 1200cGy total body irradiation on 9/18 and 9/19/2010. Antibiotic
prophylaxis was instituted immediately. Cell infusion was performed on 9/20, during which the monkey had an
anaphylactic episode, and was given Benadryl and recovered. Multiple whole blood transfusions were given
between then and the time of death. Two weeks post-radiation, the monkey started doing poorly and showed signs of
edema, petechiae, and watery diarrhea. Five days later, the monkey became hypothermic and died the next day while
under light sedation with ketamine.
Gross Description:
Multifocal cutaneous petechiae; subcutaneous edema; diarrhea staining in the perianal region;
mild hydrothorax; hydropericardium 10 ml; mild ascites; diffuse collapsed/atelectatic lungs due to hydrothorax;
marked diffuse edema of the stomach and intestinal wall.
Histopathologic Description:
Stomach: Diffusely the mucosa is mildly thickened by a combination of necrosis,
hemorrhage and innumerable small protozoans which surround, separate, and occasionally replace necrotic gastric
glands. Glandular mucosa is multifocally and transmucosally necrotic glandular epithelium is shrunken, with
karyolytic or pyknotic nuclei. Often glands are lined with attenuated epithelium, with dilated lumens which contain
sloughed epithelial cells, cellular debris, and protein. Glands are often separated with a combination of hemorrhage,
edema, and cellular debris. Innumerable 4-6 um pyriform protozoans with flocculent basophilic cytoplasm and a
single round basophilic nucleus are present within the lamina propria, numerous gastric glands, and transmigrate the
muscularis mucosa into the submucosa, where they often fill dilated lymphatics and are present in variable
concentrations throughout the surrounding submucosa (where they are occasionally phagocytosed by macrophages).
The submucosa is markedly expanded by edema, and multifocally, there is marked perivascular hemorrhage. The
walls of affected arterioles are often expanded by brightly eosinophilic protein and cellular debris (necrotizing
vasculitis). Protozoans are also present within the interstitium and lymphatics of the muscularis and serosa, but
rarely associated with significant inflammation.
Morphologic Diagnosis:
Stomach; mucosa, lamina propria: Diffuse, severe edema and hemorrhage with myriads of extracellular/interstitial and intravascular/intralymphatic protozoa. (trichomonad gastritis.)
Jejunum; mucosa, lamina propria: Diffuse, severe edema and hemorrhage with myriads of extracellular/interstitial and intravascular/intralymphatic protozoa.
Bone marrow; sternum, femur, and tibia: Myeloid hypoplasia, severe, radiation-induced.
Lab Results:
Hypoproteinemia, pancytopenia.
Condition:
Trichomonas sp.
Contributor Comment:
Histopathology revealed a severe infection of the stomach and intestines by protozoal
organisms; these organisms originated in the lumen and infiltrated through the mucosa into the submucosa and
muscular layers, and were also present within blood and possibly lymphatic vessels. This caused marked disruption
of the gastric and intestinal walls and was likely the cause of the severe protein loss indicated in the clinical
chemistry finding of hypoproteinemia. Hypoproteinemia causes decreased osmotic pressure and loss of fluid from
vessels, resulting in interstitial edema and accumulation of fluid in the body cavities. The size and morphology of
the protozoal organism is consistent with a trichomonad. Trichomonads are anaerobic flagellated protozoa that are
commensal organisms in many species of mammals and birds and, with some exceptions, are considered
nonpathogenic. In monkeys, trichomonads may be present in the lumen or within crypts of the gastrointestinal tract
but rarely elicit an inflammatory response or other pathologic changes, but have been reported as a cause of gastritis
in SIV-infected macaques(1). It is likely in the present case that the radiation induced hydrochloria and damage to the
gastric and intestinal epithelium, resulting in breaks of the mucosal barrier and allowing entry and colonization of
the protozoa and that the radiation-induced bone marrow immunosuppression rendered the monkey incapable of
eliminating the infection. The protozoan was confirmed to be a trichomonad by electron microscopy.
JPC Diagnosis:
Stomach: Gastritis, necrotizing, multifocal to coalescing, moderate to severe, with marked
submucosal edema, necrotizing vasculitis, and innumerable protozoan trophozoites.
Conference Comment:
Conference participants discussed the histologic changes that are likely attributed to the
ablative dose of radiation received by the macaque including the profound lack of inflammation present in relation
to the protozoal infection. Non-human primates with simian immunodeficiency virus (SIV) can also be similarly
affected, but there is usually accompanying neutrophilic inflammation(1). The mucosal necrosis is also likely due to
the direct effects of radiation providing a route of entry for the normally commensal organism. Radiation injury in
the stomach results in parietal cell death, hypochlorhydria, and the increased pH would lead to breakdown of the
mucosal barrier and is another route of entry for the protozoa, as well as increased survivability of the parasite
within the stomach. The marked submucosal edema is likely due to several factors, including lymphatic obstruction
by the protozoa and decreased oncotic pressure due to hypoproteinemia from maldigestion and malabsorption as
well as loss from diarrhea.
References:
1. Kondova I, Simon MA, Klumpp SA, et al. Trichomonad gastritis in rhesus macaques (
Macaca mulatta) infected
with simian immunodeficiency virus.Â
Vet Pathol. 2005;42(1):19-29.
