JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
December 2021
D-V27

 

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 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 often within sinusoids that exhibit karyorrhexis, karyolysis, or pyknosis (single cell death, acidophilic bodies).  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). Rarely hepatocytes contain intracytoplasmic 3-5µm eosinophilic inclusions. Occasionally within Kupffer cells there are phagocytized, round, 5-8 um diameter acidophilic bodies (apoptotic hepatocytes, 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 contain 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 and intracytoplasmic inclusions, golden lion tamarin (Leontopithecus rosalia), non-human primate.

 

ETIOLOGIC DIAGNOSIS:  Arenaviral hepatitis

 

CAUSE:  Lymphocytic choriomeningitis virus (arenavirus)

 

CONDITION:  Callitrichid hepatitis (CH)

 

GENERAL DISCUSSION:

• 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
• Endemic in mice worldwide (Mus musculus, N-V18), with long-term asymptomatic infection, persistent viremia, and urine shedding
• Zoonotic, may cause subclinical disease in humans or meningitis in severe cases
• Moderate iron storage in normal captive tamarins is routinely observed as pigment in hepatic tissue and may be related to captive diet

 

PATHOGENESIS:

• 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”)
• 1-2 week incubation period

 

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)
• Rare intracytoplasmic 3-5µm eosinophilic inclusions
• Necrosis in abdominal lymph nodes, adrenal cortex, spleen, and gastrointestinal tract
• Lymphocytic meningitis and cerebral perivasculitis

 

ULTRASTRUCTURAL FINDINGS:

• Pleomorphic, 85-105 nm, enveloped virions within hepatocellular intracytoplasmic vesicles

 

DIFFERENTIAL DIAGNOSIS:

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, D-V23): Similar histologically with midzonal hepatocellular necrosis and Councilman bodies; primarily a disease of wild non-human primates
• Herpesvirus saimiri type 1 (D-V14) 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; grossly, multiple small, white foci scattered throughout the liver and spleen, fibrinous peritonitis, and marked mesenteric lymphadenopathy

 

COMPARATIVE PATHOLOGY:

LCMV in other species:

• Mice (N-V18): 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

 

Other selected Arenaviruses:

• Snakes: Boid inclusion body disease (D-V30)
• Humans: several causative agents of viral hemorrhagic fevers, including:
  • Lassa virus: cause of viral hemorrhagic fever in West Africa (must be differentiated from Ebola); studied in guinea pigs (Bell, Vet Pathol. 2017)
  • Machupo virus: causative agent of Bolivian hemorrhagic fever; studied in guinea pigs (Bell, Vet Pathol. 2016)

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents & Rabbits. 4th ed. Ames, IA: John Wiley & Sons, Inc.; 2016:23-25, 178, 220.
2. Bell TM, Bunton TE, Shaia CI, et al. Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs. Vet Pathol. 2016;53(1):190-199.
3. Bell TM, Shaia CI, Bearss JJ, et al. Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus [published correction appears in Vet Pathol. 2018;55(2):355]. Vet Pathol. 2017;54(3):549-562.
4. 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.
5. 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.
6. 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.
7. 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.

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