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WSC 11-12 Conf 23 Layout Joint Pathology Center Veterinary Pathology Services WEDNESDAY SLIDE CONFERENCE 2011-2012 Conference 23 02 May 2012 CASE I: S788/08 (JPC 3102484). Contributor’s Histopathologic Description: The liver had a regular architecture. There were irregularly Signalment: 1.2-year-old female common squirrel distributed, sublobular foci of coagulation necroses. monkey, Saimiri sciureus, New World monkey. Hepatocytes adjacent to the necrotic areas displayed cytoplasmic vacuoles of variable size interpreted as History: The animal showed severe dyspnea, apathy, fatty degeneration. Furthermore, in some perilesional hypothermia and mucous nasal discharge. In the oral hepatocytes large eosinophilic intranuclear inclusion cavity a mucous exudate and multifocal moderate bodies causing chromatin margination and clumping gingival erosions were observed. The animal’s were observed. The liver also displayed a mild to condition worsened gradually and it died moderate, acute congestion. spontaneously. Contributor’s Morphologic Diagnosis: Liver: Gross Pathology: At necropsy the body was in a multifocal moderate acute coagulation necrosis with moderate nutritional condition. In the oral cavity eosinophilic intranuclear inclusion bodies, and multifocal gingival ulcerations of 1 to 2 mm in multifocal moderate hepatic lipidosis. diameter were observed. The lung showed severe congestion, moderate alveolar edema and multifocal Contributor’s Comment: In the submitted liver hemorrhages of 2 to 4 mm in diameter. The spleen was tissue, the main lesion consists of multifocal moderately enlarged. The liver displayed moderate coagulation necrosis, and eosinophilic intranuclear diffuse lipidosis. On the left shoulder (at the level of inclusion bodies in adjacent hepatocytes. the supraspinatus muscle) a subcutaneous hemorrhage, 2 x 2 cm, was observed. Upon histological examination of other tissues, a severe multifocal ulcerative to necrotizing gingivitis Laboratory Results: with hydropic degeneration of epithelial cells, Radiological findings: mild multifocal radiodense multinucleated giant cells (syncytia), eosinophilic areas in the thoracic cavity. intranuclear inclusion bodies, and a moderate Using an antibody against human Herpes simplex virus necrotizing vasculitis was observed. The cerebellum type 1, a strong positive reaction (Herpes simplex virus showed a moderate subacute multifocal necrotizing infection) was observed in tissue sections of the oral inflammation with eosinophilic intranuclear inclusion mucosa and liver. bodies in neurons. The small intestine displayed a Ultrastructurally, in hepatocytes intranuclear subacute multifocal moderate necrotizing enteritis with herpesviral nucleocapsids were observed. multinucleated cells (syncytia) and intranuclear 1 WSC 2011-2012 Nonhuman primates are primary hosts of a number of alpha- and gammaherpesviruses, whereas some host specific herpesviruses (e.g. Herpesvirus ateles, Herpesvirus saimiri, Rhesus rhadinovirus) were described.2,8,11 In their natural hosts these viruses cause mild or inapparent infections, but they generally are associated with severe infections when interspecies transmission occurs.3,4,10 The ability of herpesviruses to cross interspecies barriers is responsible for a major zoonotic risk of these pathogens.5,8 Hence, the human herpesviruses are transmissible from humans to primates; however, spontaneous infections in monkeys appear to be rare.5,8 In Old World primates, HHV-1 infections remain localized at the mucocutaneous tissues 1-1. Liver, squirrel monkey: At the edges of the scattered foci of necrosis, degenerating and the virus-host relationship is hepatocytes contain a large magenta intranuclear viral inclusion that peripheralizes the comparable to that of humans.6,8 In chromatin. (HE 400X) contrast, New World monkeys and prosimians are more susceptible to eosinophilic inclusion bodies in enterocytes. In the infection and systemic disease.5 In spontaneously spiral ganglion of the ear, numerous eosinophilic infected owl monkeys, (Aotus trivirgatus), tree shrews intranuclear inclusion bodies were observed. The (Tupaia glis), common marmosets (Callithrix jacchus), lymphoid tissues showed a severe lymphocytic black-tufted-ear marmosets (Callithrix penicillata) and depletion. In the nasal cavity a mild subacute diffuse lemurs, a severe disease leading to death occurs in purulent inflammation was present. In the lung, a mild most cases.8 In most mentioned species, erosions and multifocal subacute histiocytic pneumonia, moderate ulcers of the oral mucous membranes and fibrin-rich alveolar edema, severe multifocal mucocutaneous junction of the lips, and focal necrosis hemorrhages and severe congestion were found. and hemorrhage and eosinophilic intranuclear The detection of syncytia and eosinophilic intranuclear inclusion bodies were observed.5,8 The source of the inclusion bodies as well as the ultrastructural herpesvirus infection in nonhuman primates seems to demonstration of herpesviral nucleocapsids indicates a be, in most cases, the close contact with persons systemic herpesviral infection. Using shedding virions.8 Close contact is also necessary for immunohistochemistry an infection with human the transmission of the infection, hence most cases of Herpes virus type 1 (HHV-1; Herpes simplex virus 1) herpesvirus infections in nonhuman primates occur in was confirmed. Based on the ulcerative to necrotizing animals kept by private persons.8 Therefore, the use of lesions, syncytia formation and the detection of appropriate protective measures for humans handling eosinophilic intranuclear inclusion bodies in the mouth nonhuman primates should greatly reduce the risk of of the affected animal, an oral route of infection should infection. be considered. JPC Diagnosis: 1. Liver: Hepatitis, necrotizing, Herpesviruses are a family of large DNA viruses which multifocal and random, mild, with hepatocellular infect humans, mammals, vertebrates and intranuclear viral inclusion bodies. invertebrates.1,9 The virions are 200-250 nm in 2. Liver, hepatocytes: Lipidosis, micro- and diameter, consist of a linear double-stranded DNA macrovesicular, diffuse, moderate. genome of 120-240 kbp packaged in an icosahedral capsid approximately 125 nm in diameter, embedded Conference Comment: Herpes simplex (Herpesvirus in a matrix containing many viral proteins, itself hominis) has two distinct subtypes. Herpes simplex wrapped in a lipid membrane containing several type 1 (HSV-1) causes oral lesions and encephalitis in glycoproteins.2,9 The family Herpesviridae is divided adult humans, and HSV-2 causes genital lesions in in three subfamilies Alpha-, Beta- and adult humans and systemic disease in human infants. Gammaherpesvirinae on the basis of their genomic Both types produce the same fatal disease in New attributes.2,9 World monkeys. 2 WSC 2011-2012 Discussion during the conference was focused on 9. McGeoch DJ, Dolan A, Ralph AC. Toward a developing a plausible differential diagnosis for these comprehensive phylogeny for mammalian and avian lesions in both New and Old World monkeys: herpesviruses. J. Virol. 2000;74(22):10401-1046. Macaqacine herpesvirus (herpesvirus B), which causes 10. Rootman DS, Haruta Y, Hill JM. Reactivation of fatal encephalomyelitis in man, produces similar HSV-1 in primates by transcorneal iontophoresis of lesions as seen in this case of necrotizing hepatitis as adrenergic agents. Invest Ophthalmol. Vis. Sci. 1990;31 well as hemorrhagic necrosis in the lung, brain, and (3):597-600. lymphoid organs. Herpesvirus tamarinus (herpesvirus 11. Schäfer A, Lengenfelder D, Grillhösl C, et al. The T), which is asymptomatically carried by squirrel latency-associated nuclear antigen homolog of monkeys, and herpes simplex both cause identical herpesvirus saimiri inhibits lytic virus replication. J. necrotizing lesions in other New World monkeys such Virol. 2003;77(10):5911-5925. as aotus monkeys, marmosets, and tamarins. Virus isolation or immunohistochemical staining is necessary to differentiate them. Simian varicella virus causes similar necrotizing lesions with herpetic viral inclusions and syncitial cells of vesicular rash and encephalitis, pneumonia, and hepatitis in African green monkeys and other Old World monkeys.7 Contributor: University of Veterinary Medicine, Hannover Department of Pathology Bünteweg 17 D-30559, Hannover Germany http://www.tiho-hannover.de/ http://www.tiho-hannover.de/einricht/patho/index.htm References: 1. Batista FM, Arzul I, Pepin JF, et al. Detection of ostreid herpesvirus 1 DNA by PCR in bivalve molluscs: a critical review. J. Virol. Methods. 2007;139 (1):1-11. 2. Davison AJ, Trus BL, Cheng N, et al. A novel class of herpesvirus with bivalve hosts. J Gen Virol. 2005;86,41-53. 3. Fickenscher H, Fleckenstein B. Herpesvirus saimiri. Philos. Trans. R . Soc. Lond. B Biol. Sci. 2001;356 (1408):545-567. 4. Hall KT, Giles MS, Goodwin DJ, et al. Characterization of the herpesvirus saimiri ORF73 gene product. J. Gen. Virol. 2000;81(Pt 11):2653-2658. 5. Juan-Sallés C, Ramos-Vara JA, Prats N, et al. Spontaneous herpes simplex virus infection in common marmosets (Callithrix jacchus). J. Vet. Diagn. Invest. 1997;9(3):341-345. 6. Kik MJ, Bos JH, Groen J, et al. Herpes simplex infection in a juvenile orangutan (Pongo pygmaeus pygmaeus). J. Zoo. Wildl. Med. 2005;36(1):131-4. 7. Mansfield K, King N. Viral diseases. In: Bennett BT, Abee CR, Henrickson R, eds. Nonhuman Primates in Biomedical Research, Diseases. San Diego, CA: Academic Press; 1998:5-12. 8. Mätz-Rensing K, Jentsch KD,
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