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Review
. 2022 Jul;50(5):638-659.
doi: 10.1177/01926233221084634. Epub 2022 Apr 1.

Common and Not-So-Common Pathologic Findings of the Gastrointestinal Tract of Rhesus and Cynomolgus Macaques

Amanda L Johnson  1 , Rebekah I Keesler  2 , Anne D Lewis  1 , J Rachel Reader  3 , Steven T Laing  4
Affiliations
Review

Common and Not-So-Common Pathologic Findings of the Gastrointestinal Tract of Rhesus and Cynomolgus Macaques

Amanda L Johnson et al. Toxicol Pathol. 2022 Jul.

Abstract

Rhesus and cynomolgus macaques are the most frequently used nonhuman primate (NHP) species for biomedical research and toxicology studies of novel therapeutics. In recent years, there has been a shortage of laboratory macaques due to a variety of competing factors. This was most recently exacerbated by the surge in NHP research required to address the severe acute respiratory syndrome (SARS)-coronavirus 2 pandemic. Continued support of these important studies has required the use of more varied cohorts of macaques, including animals with different origins, increased exposure to naturally occurring pathogens, and a wider age range. Diarrhea and diseases of the gastrointestinal tract are the most frequently occurring spontaneous findings in macaques of all origins and ages. The purpose of this review is to alert pathologists and scientists involved in NHP research to these findings and their impact on animal health and study endpoints, which may otherwise confound the interpretation of data generated using macaques.

Keywords: diagnostic pathology; diarrhea; digestive system; macaque; primate pathology.

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Conflict of interest statement

Declaration of Conflicting Interests

The author(s) declared no real, perceived or potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Multiple long spiral bacteria, consistent with H. heilmannii, are present within the gastric pits and minimally dilated gastric glands. There is no inflammatory response associated with these bacteria. Cynomolgus macaque, stomach. Hematoxylin and eosin (H&E).
Figure 2.
Figure 2.
Sarcina occur as groups of cocci arranged in cubes. Rhesus macaque, stomach. Hematoxylin and eosin (H&E).
Figure 3.
Figure 3.
The gastric lumen contains a large mat of elongate rod-shaped organisms. Historically, these organisms have been referred to as megabacteria; however, they are likely Ascomycetous yeasts. Cynomolgus macaque, stomach. Hematoxylin and eosin (H&E).
Figure 4.
Figure 4.
The gastric pits contain numerous pear-shaped trichomonads. Similar organisms may also be seen in the colon of normal macaques. Rhesus macaque, stomach. Hematoxylin and eosin (H&E).
Figure 5.
Figure 5.
The gastrointestinal segments are highlighted by the following colors: the esophagus is dark yellow, stomach is pink, duodenum is lilac, jejunum is periwinkle, ileum is mint green, cecum is yellow-green, ascending colon is blue, transverse colon is purple, descending colon is bright green, and rectum is yellow. Rhesus macaque, gastrointestinal tract.
Figure 6.
Figure 6.
Scattered syncytial cells are present within the lymphoid follicles of the normal cecal GALT. Cynomolgus macaque, cecum. Hematoxylin and eosin (H&E).
Figure 7.
Figure 7.
The lacteals of the small intestine are often notably dilated. Macrophages containing apoptotic debris (arrow) are also commonly seen at the villous tips. Rhesus macaque, jejunum. Hematoxylin and eosin (H&E).
Figure 8.
Figure 8.
Macrophages with abundant pale eosinophilic to gray cytoplasm (muciphages; arrow) are present in clusters in the basal lamina propria. Rhesus macaque, colon. Hematoxylin and eosin (H&E).
Figure 9.
Figure 9.
A dense mat of bacteria colonize the apical enterocytes of the normal colon. This finding is sometimes referred to as the blue brush border. These bacteria have been genetically identified as Helicobacter macacae in rhesus macaques and are regularly seen in normal cynomolgus macaques. Cynomolgus macaque, colon. Hematoxylin and eosin (H&E).
Figure 10.
Figure 10.
Balantidium coli are large (20 to 150 micron) ciliated protozoa with a prominent bean-shaped macronucleus. Rhesus macaque, cecum. Hematoxylin and eosin (H&E).
Figure 11.
Figure 11.
Necrohemorrhagic and ulcerative colitis with pseudomembrane formation. Rhesus macaque, colon, Shigella flexneri.
Figure 12.
Figure 12.
The mucosa is ulcerated and necrotic with infiltration of high numbers of neutrophils, hemorrhage, fibrin deposition and formation of a superficial pseudo- or diphtheritic membrane. Rhesus macaque, colon, Shigella flexneri. Hematoxylin and eosin (H&E).
Figure 13.
Figure 13.
A. Proliferative typhlocolitis, with cecocolic valve hyperemia. Rhesus macaque, colon, Campylobacter coli. B. Hemorrhagic colitis (and enteritis, not shown) may be noted in C. jejuni infections, but this presentation may be colony specific (for example this is seen infrequently at the CNPRC, but has not been noted at the ONPRC). Rhesus macaque, colon, Campylobacter jejuni.
Figure 14.
Figure 14.
The mucosa is hyperplastic with infiltration of neutrophils, lymphocytes, and plasma cells. Additionally, there is tufting of the superficial epithelial cells, reduced numbers of Goblet cells, and multifocal crypt abscesses. Rhesus macaque, colon, Campylobacter coli. Hematoxylin and eosin (H&E).
Figure 15.
Figure 15.
Thickened and edematous colonic mucosa, with multifocal well demarcated ulcers frequently covered by a tan diphtheritic membrane. Rhesus macaque, colon, Yersinia pseudotuberculosis.
Figure 16.
Figure 16.
There is necrosis of the superficial mucosa characterized by abundant cellular debris and large colonies of bacterial coccobacilli. The lamina propria is infiltrated by high numbers of neutrophils and fewer macrophages. Rhesus macaque, colon, Yersinia pseudotuberculosis. Hematoxylin and eosin (H&E).
Figure 17.
Figure 17.
The gastric mucosa is variably thickened with multifocal raised nodules throughout the erythematous body and to a lesser extent the pylorus. Rhesus macaque, stomach, Helicobacter pylori.
Figure 18.
Figure 18.
The pyloric mucosa is hyperplastic with prominent gut-associated lymphoid hyperplasia. The lamina propria is infiltrated by lymphocytes, plasma cells, and very few eosinophils. Rhesus macaque, stomach, Helicobacter pylori. Hematoxylin and eosin (H&E).
Figure 19.
Figure 19.
The small intestinal mucosa is mildly thickened and diffusely erythematous. Rhesus macaque, jejunum, Attaching and Effacing Escherichia coli.
Figure 20.
Figure 20.
Bacterial rods line the apical aspect of villous enterocytes. Rhesus macaque, jejunum, Attaching and Effacing Escherichia coli. Hematoxylin and eosin (H&E).
Figure 21.
Figure 21.
The small intestinal mucosa is thick and edematous with elevated yellow-white folds. Rhesus macaque, jejunum, Mycobacterium avium.
Figure 22.
Figure 22.
Villi are expanded and distorted by high numbers of foamy macrophages. Macrophages contain abundant intracytoplasmic acid-fast bacilli (not shown). Rhesus macaque, jejunum, Mycobacterium avium enteritis. Hematoxylin and eosin (H&E).
Figure 23.
Figure 23.
There are numerous 2–5 micron diameter spherical trophozoites lining the apical enterocytes. Rhesus macaque, ileum, Cryptosporidia. Hematoxylin and eosin (H&E).
Figure 24.
Figure 24.
Within the ascending colon, there are numerous slender nematodes whose narrower anterior ends are embedded in the superficial mucosa. Rhesus macaque, colon, Trichuris trichiuria.
Figure 25.
Figure 25.
Visible from the serosal surface, are multifocal to coalescing raised reddish-brown submucosal abscesses or granulomas. Pigtailed macaque, colon, Oesophagostomum spp.
Figure 26.
Figure 26.
The small intestinal mucosa is expanded by multifocal red, raised proliferative masses. Rhesus macaque, jejunum, cytomegalovirus.
Figure 27.
Figure 27.
The lamina propria is predominantly infiltrated by high numbers of neutrophils, with low numbers of cytomegalic cells that contain large basophilic intranuclear inclusion body surrounded by a clear halo (Cowdry Type A) characteristic of cytomegalovirus. Rhesus macaque, jejunum, cytomegalovirus. Hematoxylin and eosin (H&E).
Figure 28.
Figure 28.
Multiple enterocytes contain large basophilic intranuclear inclusion bodies, characteristic of adenovirus. Cynomolgus macaque, colon. Hematoxylin and eosin (H&E).
Figure 29.
Figure 29.
The mucosa is markedly hyperplastic with decreased numbers of goblet cells and attenuated (but non-ulcerated) superficial enterocytes. The lamina propria is expanded by a lymphocytic and plasmacytic infiltrate and there is a focal dilated gland containing cellular debris. Rhesus macaque, colon, idiopathic chronic diarrhea. Hematoxylin and eosin (H&E).
Figure 30.
Figure 30.
Multiple linear circumferential ulcers with associated mild fibrous constrictions are present in the cecum and ascending colon. Rhesus macaque, ileocecolic junction, cicatrizing ulcerative colitis.
Figure 31.
Figure 31.
Abundant soft tan material fills the intestinal lumen (mucus). The muscular tunics are markedly hypertrophic. Rhesus macaque, small intestine, malabsorptive enteropathy with goblet cell hyperplasia.
Figure 32.
Figure 32.
There is marked goblet cell hyperplasia and loss of villous structures (large intestinal metaplasia). Rhesus macaque, jejunum, malabsorptive enteropathy with goblet cell hyperplasia. Hematoxylin and eosin (H&E).
Figure 33.
Figure 33.
The small intestinal mucosa is diffusely thickened by crowded mucosal folds. Rhesus macaque, jejunum, amyloidosis.
Figure 34.
Figure 34.
Normal villous appearance is distorted and the lamina propria is expanded by variable amounts of homogenous eosinophilic extracellular amyloid. Rhesus macaque, jejunum, amyloidosis.
Figure 35.
Figure 35.
Saccular protrusions are evident between the bands of taenia coli. Rhesus macaque, colon, diverticulosis.
Figure 36.
Figure 36.
The diverticulum is composed of a normal, to slightly inflamed mucosal layer surrounded by markedly attenuated submucosal and muscular layers. Rhesus macaque, colon, diverticulosis. Hematoxylin and Eosin (H&E).
Figure 37.
Figure 37.
An intussusception of the descending colon at the level of the pelvic canal shown here was associated with rectal prolapse of a portion of the intussuscepted colon. Rhesus macaque, pelvic canal, intussusception.
Figure 38.
Figure 38.
The presence of an adenocarcinoma has created a stricture in the colon and subsequent dilation of the proximal intestinal tract. Rhesus macaque, colon, adenocarcinoma.
Figure 39.
Figure 39.
Transmural invasion of a mucinous intestinal adenocarcinoma imparts a ‘bubbled’ appearance to the serosal surface. Rhesus macaque, colon, adenocarcinoma.
Figure 40.
Figure 40.
Lakes of pale basophilic mucin, partially lined by neoplastic columnar to attenuated epithelial cells distend the submucosa. Rhesus macaque, ileocecocolic junction, mucinous adenocarcinoma. Hematoxylin and eosin (H&E).
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