A Primer of Primate Pathology: Lesions and Nonlesions

Abstract

Nonhuman primates are important laboratory animals for biomedical, pharmacology, and toxicology research. To effectively use primates as models, their gross and histologic anatomy, physiology and natural history, as well as common health problems and the source from which the primate is obtained, must be known and understood by pathologists involved in study design and/or interpretation. The first very important lesson in the "primer" is: there is no such thing as a generic monkey. Brand names (ie, species and subspecies) are important. Several taxonomic groups of primates are used in research including: prosimians, such as galagos and lemurs; New World monkeys, particularily marmosets; Old World monkeys, especially macaques and baboons; and the chimpanzee, an African ape. Differences between taxa are exemplified by the glucocorticoid resistance of New World monkeys compared to Old World monkeys, which results in the requirement for Vitamin D3 and their high circulating levels of steroids such as cortisone and progesterone. Differences in ovarian histology between Old and New World monkeys probably relate to steroid receptor biology as well. There are also variations in disease manifestations, even among closely related primate species such as rhesus and cynomolgus macaques (cynos). For example type D retrovirus infection is accompanied by lymphomas in cynos, but not rhesus. The second important lesson in this "primer" is: "not test article related" does not always mean "normal." Lymphoid nodules in bone marrow or salivary gland, a common background finding in macaques, often signal the presence of type D retrovirus. Other histologic changes and normal anatomic variations may be confusing to individuals not routinely examining primate tissues. The objective of this paper is to familiarize pathologists with the use of primates in research as well as lesions and nonlesions (normal anatomy or physiology) of primates that may influence study design and confound interpretation.

Digestive System

“…11 Acute necrotizing ulcerative gingivitis affects the interdental papilla which occurs in primate colonies is strongly suggestive of endemic type D retrovirus infection. 11 WBN/Kob rats made severely diabetic with a single dose of alloxan were shown to develop an increase in inflammation in the oral cavity associated with mucosal hyperplasia distributed in the hard palate, central part of tongue and gingiva. The cause was uncertain although alloxan can reduce saliva flow or there may have been an increase in oral commensal microorganisms.…”

“…288 Monkeys may also show a variety of spiral organisms in the gastric mucosa, some of which have associated lymphocytic gastritis with intestinalization of mucosa or atrophy. 11 Gastritis, more prominent in the antrum than in the fundus, is one of the most commonly observed pathologies in laboratory cynomolgus monkeys. 129 It can be also often found in association with the presence of Helicobacter organisms.…”

“…In non-human primate colonies, gastrointestinal disease remains one of the important health problems such that many indoor-housed monkeys commonly have histological evidence of intestinal inflammation, notably micro-abscesses and erosions rather than overt ulcers. 11,129,503 Although the majority of potentially pathogenic organisms affect the primate colon, a number of bacteria, protozoa and metazoan, occur in the small intestine. 504 A useful aid for identification of metazoa in histological sections remains the publication of Chitwood and Lichtenfels.…”

Respiratory Tract

“…152 Even when eliminated by ivemectin the lesions of chronic bronchiolitis, bronchiectasis and pigmentation may persist as an incidental finding. 153 As the mite can produce significant destructive pulmonary pathology and render animals susceptible to secondary pulmonary bacterial infections, it can disrupt or confound the interpretation of toxicity studies performed in primates. The lesions are located most frequently in cranial lobes and are characterized by the presence of bullae distending the pleural surface, parenchymal cysts, nodules and scar tissue.…”

On the apparent rarity of epithelial cancers in captive chimpanzees

“…Earlier surveys reporting on disease profiles and causes of death in captive chimpanzees from US facilities noted the rarity of these cancers [23][24][25][26][27]. A more recent thorough analysis [25] listed all neoplasms documented at two long-standing major US facilities from their inception many decades ago, through mid-2008.…”