AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

November 2019

I-V07 (NP)

 

Signalment (JPC# 1856170): 2.5-year-old female grey kangaroo (Macropus fuliginosus)

 

HISTORY: Two cutaneous masses, one on the right distal tibia and one on the left forelimb digit, were excised.

 

HISTOPATHOLOGIC DESCRIPTION: Haired skin: There is a focally extensive area of marked follicular epithelial and to a lesser extent epidermal hyperplasia characterized by a thickened stratum spinosum (acanthosis) that markedly compresses the interfollicular superficial dermis. Keratinocytes within the stratum spinosum frequently exhibit ballooning degeneration with pale, swollen cytoplasm and often contain a single, 15 - 20 µm, amphophilic to basophilic, irregularly shaped, intracytoplasmic viral inclusion body (molluscum body) that is surrounded by a clear halo and peripherally displaces the nucleus. There is moderate epidermal and follicular orthokeratotic and parakeratotic hyperkeratosis; the stratum corneum also contains remnant molluscum bodies. There are multifocal erosions overlain by a serocellular crust composed of viable and degenerate neutrophils, fibrin, erythrocytes, and high numbers of expelled molluscum bodies. The subjacent dermis is infiltrated by dense, nodular aggregates of moderate numbers of lymphocytes, plasma cells, macrophages, and fewer viable and degenerate neutrophils.

 

MORPHOLOGIC DIAGNOSIS: Haired skin: Hyperplasia, epidermal and follicular, marked, with parakeratotic and orthokeratotic hyperkeratosis, lymphoplasmacytic and histiocytic dermatitis, and numerous intracytoplasmic viral inclusion bodies (molluscum bodies), grey kangaroo (Macropus fuliginosus), marsupial

 

ETIOLOGY: Molluscum contagiosum virus

 

ETIOLOGIC DIAGNOSIS: Molluscipoxviral dermatitis

 

CONDITION: Molluscum contagiosum

 

GENERAL DISCUSSION:

·      Mildly contagious, self‑limiting, cutaneous infection primarily of humans caused by a molluscipoxvirus (linear double stranded DNA)

·      Transmission via direct skin-to-skin contact and through infected fomites

·      May be anthropozoonosis (infectious disease in which the etiologic agent is carried by humans and transferred to other animals)

·      Immunocompromised animals are more susceptible

·      Clinical, histological, and ultrastructural similarity of lesions have been reported in birds, (chickens, sparrows, and pigeons) chimpanzees, horses, donkeys, South American sea lions, macropod marsupials

·      World-wide distribution

 

PATHOGENESIS:

·      Transmitted through direct contact with skin lesions and fomites, or through sexual contact in humans

·      Presence of a DNA sequence encoding a conserved domain of epidermal growth factor may explain the proliferative nature of the lesions; a similar sequence has been described in some orthopoxviruses

·      Molluscum contagiosum viral protein binds to FADD using a death effector domain-mediated interaction that results in interference with apoptotic signaling pathways and protects cells from Fas- and TNFR-induced apoptosis

 

TYPICAL GROSS FINDINGS:

·      Multiple, 1 ‑ 8 mm, circular, smooth or roughened surface, gray to white papules

·      Umbilicated with a central pore; often a caseous plug or waxy exudate

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·      Well-demarcated foci of epidermal hyperplasia and hypertrophy forming pear or flask shaped lobules in the superficial dermis

·      Markedly hypertrophic or swollen, brightly eosinophilic, dyskeratotic individual centrally enlarged keratinocytes

·      Contain pathognomonic large intracytoplasmic viral inclusion bodies ‘molluscum bodies’ that peripheralize the nuclei

 

ULTRASTRUCTURE:

·      Electron dense, intranuclear particles that spare the nucleolus in keratinocytes of the stratum spinosum immediately superficial to the basal cells

·      Intracytoplasmic, large clusters of oval to brick-shaped pox virions within keratinocytes

·      Individual mature virions measure 300 x 200 x 100 nm and contain a biconcave nucleoid and two lateral bodies

·      As keratinocytes move toward the surface, molluscum body enlarges

·      In the dermis subjacent to epithelial lesions, fibroblasts have bizarre nuclei, and virus or inflammatory cells are absent

 

ADDITIONAL DIAGNOSTIC TESTS:

·      Cytology: Sebum-like material expressed from the lesions and stained with Wright’s stain may contain keratinocytes with large, basophilic cytoplasmic inclusion bodies

 

DIFFERENTIAL DIAGNOSIS:

·      Viral Papillomas: Swollen, degenerate keratinocytes in viral papillomas may contain condensed eosinophilic cytoplasmic aggregates of keratin due to the cytopathic effects of the virus; these differ from the characteristic molluscum bodies with molluscipoxvirus which are larger and more prominent

 

COMPARATIVE PATHOLOGY:

·      Chimpanzees: Multifocal to coalescing, circular, gray to white papules with smooth or roughened surface and depressed centers on the palms and soles of feet, face, eyelids, and inguinal area

·      Horses and donkeys: Numerous multifocal to coalescing cauliflower like nodules or plaques; commonly affects glabrous skin; usually non pruritic and non painful

·      Clinically similar to two other orthopoxviral infections that bear resemblance to molluscum contagiosum, but differ in having generalized and larger lesions:

·      Uasin Gishu (UGDV): can be grown in culture unlike molluscum contagiosum

·      Equine viral papular dermatitis (horsepox virus)

 

Animal poxviruses in subfamily Chordopoxvirinae5

Orthopoxvirus

·      Cowpox virus

·      Vaccinia virus (buffalopox virus, rabbitpox virus)

·      Horsepox virus

·      Camelpox virus

·      Ectromelia virus (mousepox virus) (I-V06)

·      Monkeypox virus

Unassigned member of the genus:

·      Uasin Gishu disease virus

Parapoxvirus

·      Orf virus (contagious pustular dermatitis virus, contagious ecthyma virus) (I-V11, D-V22)

·      Pseudocowpox virus (milker's nodule virus)

·      Bovine papular stomatitis virus (D-V21)

·      Parapox virus of red deer

Unassigned members in the genus:

·      Auzduk disease virus (camel contagious ecthyma virus)\

·      chamois contagious ecthyma virus

·      sealpox virus

Avipoxvirus

·      Fowlpox virus (I-V05)

·      Pigeonpox virus

Capripoxvirus

·      Sheeppox virus (P-V24)

·      Goatpox virus

·      Lumpy skin disease virus

Leporipoxvirus

·      Myxoma virus (I-V10)

·      Rabbit fibroma virus (Shope fibroma virus, I-V09A)

Suipoxvirus

·      Swinepox virus

Molluscipoxvirus

·      Molluscum contagiosum virus

Yatapoxvirus

·      Tanapox virus

·      Yaba monkey tumor virus (I-V08)

 

REFERENCES:

1.    Abee CR, Mansfiled K, Tardif S, Morris T. Nonhuman primates in biomedical research. Volume 2: Diseases. 2nd ed. San Diego, CA: Elsevier; 2012:7.

2.    Fox R, Thiemann A, Everest D, Steinbach F, Dastjerdi A, Finnegan C. Molluscum contagiosum in two donkeys.Vet Rec. 2012;170:649-651.

3.    Hargis AM, Myers S. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016:1068,1119.e5.

4.    Lowenstine, LJ, McManamon, R, Terio, KA. Apes. In: Terio, KA, McAloose, D, St. Leger, J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press Elsevier; 2018:383.

5.    MacLachlan NJ, Dubovi EJ. Fenner’s Veterinary Virology, 4th ed. London, UK: Elsevier; 2011: 161.

6.    Maudlin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: 616,621-22.

7.    Scott DW, Miller WH. Equine Dermatology. 2nd ed. St Louis: Elsevier Saunders; 2011: 253-255.

8.    Vermi W, et al. Spontaneous regression of highly immunogenic molluscum contagiosum virus (MCV)-induced skin lesions is associated with plasmacytoid dendritic cells and IFN-DC infiltration. J Invest Dermatol. 2011:131(2); 426-434.


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