JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 2424206): A golden lion tamarin (Leontopithecus rosalia)
HISTORY: This animal was found on the floor of a large indoor jungle exhibit in a depressed state. It did not respond to supportive therapy and died 30 minutes later. Its mate had died a few days earlier.
HISTOPATHOLOGIC DESCRIPTION: Liver: Affecting up 30% of the hepatic parenchyma, there are multifocal, random areas of hepatocellular necrosis characterized by loss of hepatic cord architecture and individualization of hepatocytes surrounded by small amounts of necrotic debris, as well as individual shrunken, hypereosinophilic hepatocytes that exhibit karyorrhexis, karyolysis or pyknosis. Hepatocytes adjacent to areas of necrosis are often degenerate, characterized by pale, swollen microvacuolated cytoplasm. Multiple random foci of hepatocytes contain a single, discrete, round cytoplasmic vacuole that often displaces the nucleus (macrovesicular vacuolar degeneration, lipid type). Frequently within the cytoplasm of degenerate hepatocytes, and occasionally within Kupffer cells or free in sinusoids, there are round 5-8 um diameter acidophilic bodies. Within affected areas there are few mitotic figures. Multifocally within portal areas, there are low numbers of lymphocytes, fewer neutrophils and rare plasma cells. Diffusely hepatocytes are mildly swollen, multifocally compressing sinusoids and containing abundant brown to black granular to globular pigment (hemosiderin, normal in this species).
MORPHOLOGIC DIAGNOSIS: Liver: Hepatocellular degeneration and necrosis, acute, random, multifocal, moderate, with acidophilic bodies, golden lion tamarin (Leontopithecus rosalia), non-human primate.
ETIOLOGIC DIAGNOSIS: Arenaviral hepatitis
CAUSE: Lymphocytic choriomeningitis virus (arenavirus)
CONDITION: Callitrichid hepatitis (CH)
- Rapidly progressive, fatal, viral hepatitis of captive marmosets and tamarins, including the endangered golden lion tamarin
- Lymphocytic choriomeningitis virus (LCMV) is a pleomorphic, enveloped, ssRNA arenavirus of the Arenaviridae family and measures 85-105 nm in diameter
- Sporadic outbreaks in zoos and animal parks; 13 reported outbreaks in the United States, Great Britain, and Brazil between 1981 and 1993
- Endemic in mice worldwide (Mus musculus), with long-term asymptomatic infection, persistent viremia and urine shedding; zoonotic
- Moderate iron storage in normal captive tamarins is routinely observed as pigment in hepatic tissue and may be related to captive diet
- In mice, vertical and horizontal transmission
- Non-human primates become infected through ingestion of infected mice
- Virus introduced to animal colonies by either wild mice or the intentional feeding of neonatal laboratory mice (“pinkies”)
- Zoonotic, may cause subclinical disease in humans or meningitis in severe cases
TYPICAL CLINICAL FINDINGS:
- Acute onset; rapid course; usually death within 24-48 hours
- Signs include dyspnea, anorexia, weakness, and lethargy, often followed by prostration and death; or sudden death without clinical signs
- In animals with a longer clinical course: jaundice and coagulopathies with elevations of aspartate aminotransferase (AST), serum bilirubin, and alkaline phosphatase; +/- coagulopathy
TYPICAL GROSS FINDINGS:
- Hepatosplenomegaly, pleural and pericardial effusions, jaundice, and subcutaneous and intramuscular hemorrhage
- Yellow-tan, mottled liver
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Multifocal hepatic necrosis with a lymphocytic and neutrophilic infiltrate
- Round acidophilic bodies, representing apoptotic hepatocytes, are prominent and present in hepatic sinusoids or within Kupffer cells (similar to Councilman bodies in Yellow Fever virus)
- Necrosis in abdominal lymph nodes, adrenal cortex, spleen and gastrointestinal tract
- Lymphocytic meningitis and cerebral perivasculitis
- Pleomorphic, 85-105 nm enveloped virions within hepatocellular intracytoplasmic vesicles
Hepatocellular necrosis in nonhuman primates:
- Dubin-Johnson-like syndrome in golden lion tamarins: Histologically similar, with centrilobular and midzonal non-iron pigment deposition; no acidophilic bodies; dark brown-black liver grossly
- Yellow fever (flavivirus): Similar histologically with midzonal hepatocellular necrosis and Councilman bodies; primarily a disease of wild non-human primates
- Herpesvirus saimiri type 1 and human herpesvirus type 1: Necrosis of the skin, oral mucosa and parenchymal organs; multifocal, random acute hepatocellular necrosis and numerous intranuclear inclusion bodies
- Francisella tularensis: Multifocal hepatocellular caseous necrosis; multiple small white foci scattered throughout the liver and spleen grossly, fibrinous peritonitis and marked mesenteric lymphadenopathy
- Mice: Signs range from asymptomatic (more common) to acute fatal choriomeningoencephalitis (less common); will kill adults but not neonates when inoculated intracerebrally; target cell is the dendritic cell and causes immune exhaustion in adult mice
- Hamsters: Primary source of human infections; clinical disease rare; choriomeningoencephalitis, vasculitis, glomerulonephritis, lymphocytic infiltrates of visceral organs
- Pygmy marmosets: Intense lymphocytic portal hepatitis with extension into portal vessels; lymphocytic gastritis/pancreatitis; interstitial pneumonia
- Guinea pigs, rats, rabbits, dogs, and swine can be infected experimentally
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits. 4th ed. Ames, IA: John Wiley & Sons, Inc.; 2016:23-25, 178, 220.
- Brady AG, Carville AL. Digestive System Diseases of Nonhuman Primates. In: Abee, ed. Nonhuman Primates in Biomedical Research: Diseases. Volume 2. San Diego, CA: Elsevier Inc; 2012:612.
- Montali RJ, Scanga CA, Pernikoff D, et al. A common-source outbreak of callitrichid hepatitis in captive tamarins and marmosets. J Infect Dis. 1993;167:946-950.
- Montali RJ, Connolly BM, Armstrong DL, Scanga CA, Holmes KV. Pathology and immunology of callitrichid hepatitis, an emerging disease of captive new world primates caused by lymphocytic choriomeningitis virus. Am J Path 1995; 148(5):144-149.
- Schulman FY, Montali RJ, Bush M, et al. Dubin-Johnson-like syndrome in Golden lion tamarins (Leontopithecus rosalia rosalia). Vet Pathol. 1993; 30:491-498.
- Wachtman L, Mansfield K. Viral Diseases of Nonhuman Primates. In: Abee, ed. Nonhuman Primates in Biomedical Research: Diseases. Volume 2. San Diego, CA: Elsevier Inc; 2012:54-56.