AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

December 2019

I-V16

 

Signalment (JPC# 2593663): An adult male cynomolgus monkey (Macaca fascicularis)

 

HISTORY: This monkey developed generalized, acute, multifocal to coalescing, erythematous and vesicular skin lesions and died.

MICROSCOPIC DESCRIPTION: Mucocutaneous junction, lip: Affecting approximately 70% of the hyperplastic oral mucosal epithelium and 10% of the epidermis are multifocal to coalescing intact and ruptured vesicles within the stratum spinosum. Vesicles contain enlarged, pale, degenerate and necrotic sloughed individualized and small clusters of epithelial cells that often form syncytial cells with up to 10 nuclei that contain multifocal eosinophilic intranuclear viral inclusion bodies that measure up to 15um and are surrounded by a clear halo with peripheralized chromatin. Vesicles also contain low numbers of neutrophils, pale flocculent eosinophilic material, and occasional scant hemorrhage. Keratinocytes overlying intact vesicles are often shrunken and hypereosinophilic with pyknotic nuclei (necrotic). Keratinocytes within the epithelium surrounding vesicles are often discohesive, exhibit variable intracellular edema (hydropic degeneration), and often form similar syncytial cells with previously described intranuclear viral inclusions. Sebaceous gland epithelium also contains intranuclear viral inclusion bodies. There is hyperplasia of the mucosal epithelium and (to a lesser degree) the epidermis characterized by acanthosis and prominent rete ridges; there is also multifocal spongiosis. Multifocally within both the superficial subepithelial connective tissue and dermis are areas of hemorrhage admixed with few neutrophils and few moderately ectatic lymphatics (edema). Multifocally separating, surrounding, and occasionally replacing labial salivary glands are moderate numbers of plasma cells, fewer Mott cells, occasional lymphocytes, macrophages, and rare neutrophils.

 

MORPHOLOGIC DIAGNOSIS: Mucocutaneous junction: Cheilitis, vesicular, multifocal, moderate, with viral syncytia and intraepithelial (epidermal, mucosal, and sebocytic) eosinophilic intranuclear viral inclusion bodies, cynomolgus monkey (Macaca fascicularis), primate.

 

ETIOLOGIC DIAGNOSIS: Herpesviral cheilitis

 

CAUSE: Simian varicella virus (Cercopithecine herpesvirus 9)

 

ETIOLOGY SYNONYMS: Delta herpes, Liverpool vervet virus, patas herpesvirus, medical lake macaque virus

 

CONDITION: Simian varicella

 

GENERAL:

·      Simian varicella virus (SVV) is an alphaherpesvirus sharing similar antigenic properties with the human varicella-zoster (chickenpox/shingles) virus

·      SVV affects the cutaneous, digestive, respiratory, and lymphoid organs

·      SVV occurs naturally in a variety of Old World nonhuman primates, especially macaques

·      Acute, fatal, highly contagious, systemic disease of African green monkeys (Ceropithecus aethiops), pig-tailed macaques (Macaca nemestrina), Japanese macaques (Macaca fuscata), cynomolgus monkey (Macaca fascicularis), and patas monkeys (Erythrocebus patas)

 

PATHOGENESIS:

·      Simian varicella pathogenesis closely parallels fatal human varicella zoster virus; rapid spread via respiratory route with possible transmission through direct contact with skin lesions

·      Virus attaches to the host cell via surface heparin sulphates, engages mannose 6-phosphate receptor

·      Transient viremia by day 3; virus transported in B and T cells

·      Vesicular dermatitis by day 10 which is often hemorrhagic; lesions progress from papule to vesicle to crust

·      By 8 days the virus has disseminated to the liver, lungs, spleen, adrenal glands, kidneys, lymph nodes, and trigeminal ganglion, and causes necrotizing lesions in the liver, lungs, and throughout the gastrointestinal tract

·      Dissemination is more likely in immunosuppressed animals

·      Latency established within neural ganglia; competing hypotheses suggest hematogenous versus transaxonal transport to ganglia

·      SVV infection is lifelong and reactivation may occur

 

CLINICAL SIGNS:

·      Diffuse inguinal rash spreads centripetally and progresses to vesiculoulcerative dermatitis

·      Vesicular eruption extends to trunk, face, extremities +/- mucocutaneous junctions and oral mucosa, but spares the palms and soles

·      Lesions are pruritic with evidence of self-excoriation

·      Disseminated form - hemorrhagic vesicular exanthema with fever, pneumonia, and hepatitis

·      Animals may experience spontaneous resolution or a high fatality rate

 

TYPICAL GROSS FINDINGS:

·      Lungs- edema, hemorrhage, necrosis, and emphysema

·      Gastrointestinal tract - diffuse ulcerative, hemorrhagic and necrotic disease

·      Skin, oral mucosa, esophagus - generalized hemorrhagic epidermal rash with vesicle formation

·      Liver, spleen, lymph nodes, endocrine organs, and bone marrow - necrosis

 

TYPICAL MICROSCOPIC FINDINGS:

·      Cutaneous lesions - multiple vesicles within epidermis that contain acantholytic epithelial cells, debris, erythrocytes, and rare syncytial cells; hyperplasia of basal cell layer; eosinophilic Cowdry-type A intranuclear inclusions in acantholytic cells and cells adjacent to vesicle; necrotizing vasculitis in dermis with inclusions in endothelial cells

·      Lungs - hemorrhage and necrosis of alveolar walls and vasculature; ulcerated bronchiolar epithelium; vascular endothelial hyperplasia; intranuclear inclusions in endothelial cells, vascular smooth muscle, and bronchial epithelium; diffuse neutrophilic and histiocytic infiltrate

·      Other systemic lesions - multifocal to diffuse necrosis and hemorrhage of liver, spleen, lymph nodes, adrenal cortex and bone marrow with intranuclear inclusions in cells bordering foci of necrosis

 

ULTRASTRUCTURE:

·      Enveloped, 150 nm diameter virions with a 100 nm icosahedral nucleocapsid

·      Capsid surrounded by "tegument" enclosed by a lipoprotein envelope

·      Envelope covered by small glycoprotein peplomers (heparan sulfate proteoglycan)

·      Viral capsids form in the nucleus and bud through the nuclear membrane to acquire the cell derived envelope

 

ADDITIONAL DIAGNOSTIC TESTS:

·      Electron microscopy

·      Viral culture

 

DIFFERENTIAL DIAGNOSIS:

·      Macacine herpesvirus 1 (B virus)- commonly causes latent infection in young macaques via trigeminal and lumbosacral ganglia; vesicles and ulcers may occur on dorsal surface of tongue, on the lip, and less extensively the skin

·      Morbillivirus infection (measles) – rash is not vesicular

·      Monkey pox – syncytial cells, large eosinophilic intracytoplasmic inclusion bodies, generalized cutaneous rash and pocks

 

COMPARATIVE PATHOLOGY:

·      Chimpanzee, gorilla, and orangutan varicella virus causes a mild self-limiting vesicular dermatitis

 

REFERENCES:

1.    Bailey C, Mansfield K. Emerging and reemerging infectious diseases of nonhuman primates in the laboratory setting. Vet Pathol. 2010;47:462-481.

2.    MacLachlan NJ, Dubovi EJ. Herpesvirales. In: Fenner’s Veterinary Virology. 4th ed. San Diego, CA: Elsevier, Inc.; 2011:188.

3.    Matz-Rensing K, Lowenstine LJ. New World and Old World Monkeys. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:350.

4.    Ouwendijk WJD, Verjans GMGM. Pathogenesis of varicelloviruses in primates. J Pathol. 2015;235:298-311.

5.    Wachtman L, Mansfield K. Viral diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardiff S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases Vol 2. San Diego, CA: Elsevier Inc.; 2012:17-18.


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