JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

November 2022

I-V08 (NP)

 

Signalment (JPC# 1777264): Male baboon (Papio sp.)

 

HISTORY:  A traumatized 4 cm diameter dermal and subcutaneous mass was removed from the right pectoral region. The mass was well vascularized and encapsulated.

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin: Markedly expanding the dermis and subcutis and elevating the hyperplastic and focally ulcerated epidermis is an unencapsulated, infiltrative, poorly demarcated, densely cellular proliferation of atypical mesenchymal cells arranged in sheets on a preexisting moderate fibrovascular stroma. Atypical mesenchymal cells have distinct cell borders and an abundant amount of eosinophilic, granular to finely vacuolated cytoplasm that expands the cells up to 50µm and often contains one to multiple round, 3-6µm diameter eosinophilic viral inclusions. Nuclei are round to irregularly oval with finely stippled chromatin and 1-2 prominent magenta nucleoli. Mitotic figures are rare. Infiltrating the proliferating cell population, separating and surrounding adnexa and vessels, and tracking fascial planes of fibroadipose tissue are variably sized aggregates of lymphocytes, macrophages, eosinophils, and fewer epithelioid macrophages. Fascial planes of fibroadipose tissue are variably necrotic and edematous with few admixed previously described inflammatory cells. Within the superficial dermis and underlying the ulcer, there a band of eosinophilic cellular and karyorrhectic debris (lytic necrosis) and moderate numbers of viable and degenerate neutrophils admixed with increased small caliber blood vessels lined by hypertrophic endothelium arranged perpendicularly to plump fibroblasts (granulation tissue), fibrin, and edema. The adjacent epithelium is moderately hyperplastic characterized by acanthosis and mild orthokeratotic hyperkeratosis, and there is increased intercellular clear space with prominent intercellular bridging (spongiosis). 

 

MORPHOLOGIC DIAGNOSIS:  Haired skin and subcutis: Atypical mesenchymal proliferation, focally extensive, marked, with intracytoplasmic eosinophilic viral inclusion bodies, eosinophilic and lymphoplasmacytic dermatitis, and ulceration, baboon (Papio spp.), nonhuman primate.

 

ETIOLOGY:  Yabapox virus

 

ETIOLOGIC DIAGNOSIS:  Dermal yabapox

 

CONDITION:  Yaba disease

 

GENERAL DISCUSSION: 

• Benign, rapidly growing dermal tumors that regress (“pseudotumors”) 
• Genus Yatapoxvirus also includes Yaba-like disease virus (previously “Tanapox virus”)

• Yabapoxvirus infects histiocytes
• Yaba-like disease virus infects epithelial cells and causes lesions similar to monkey pox; disease is termed “benign epidermal monkey pox”

• Previously referred to as histiocytomas
• Natural infections in rhesus monkeys (Macaca mulatta), cynomolgus (M. fascicularis), stump-tailed macaque (M. arctoides), and baboons (Papio anubis)
• Experimental infections in pig-tailed macaque (M. nemestrina), African green monkey (Cercopithicus aethiops), sooty mangabey (Cerocebus atys), and patas monkeys (Erythrocebus patas)
• Virus is thought to be endemic in Africa; widespread infection occurs at an early age in wild caught African monkeys and confers life-long immunity 

• Wild caught African monkeys are resistant
• New world monkeys are resistant
• Captive-born African monkeys are susceptible (they have no immunity) 

 

PATHOGENESIS

• Possible modes of transmission:  Biting insects, inoculation, and trauma
• Virus infects histiocytes and induces proliferation of histiocytes into subcutaneous, tumor-like masses

 

TYPICAL CLINICAL AND GROSS FINDINGS:

• Raised, rapidly growing, ulcerated and hemorrhagic nodules ranging from small papules to nodules up to 6cm in diameter that regress in 6-9 weeks 
• Primarily on head and limbs, including digits 
• Tumors often ulcerate, leaving central crater
• Often spread along lymphatics
• Oral lesions reported in baboons

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Dermis infiltrated by sheets of large, pleomorphic histiocytes that form a unencapsulated and infiltrative mass; histiocytes have granular to finely vacuolated cytoplasm, vesiculate nuclei with a prominent nucleolus and large eosinophilic cytoplasmic inclusion bodies 
• During regression, lymphocytes, plasma cells, macrophages, neutrophils, multinucleate cells, and necrosis are common

 

ULTRASTRUCTURAL FINDINGS:

• Cytoplasm contains many immature to mature pox virions that are large (370 x 150 nm) and brick-shaped to oval
• Outer coat has seven layers and surrounds a dumbbell-shaped core containing double-stranded DNA

 

DIFFERENTIAL DIAGNOSIS:

Dermal nodules in non-human primates:

• Benign epidermal monkey pox (Yaba-like disease virus, genus Yatapoxvirus):  Infects macaques, African nonhuman primates, and humans; causes multiple large, crusted cutaneous nodules primarily on the face, arms and perineum; epidermal hyperplasia and necrosis, with large, granular, eosinophilic inclusions within keratinocytes
• Monkeypox (orthopoxvirus):  Old World monkeys, New World monkeys, great apes, and rarely humans are susceptible; cutaneous rash and pocks, primarily on the hands, feet, legs and buttocks  
• Papillomavirus:  Usually multiple flat to pedunculated cutaneous nodules; intranuclear inclusions within keratinocytes of the stratum granulosum
• African histoplasmosis (Histoplasma capsulatum var. duboisii, I-F13):  Baboons; ulcerated nodules on buttocks, hands, feet and face; pyogranulomatous inflammation; 8-15 um intrahistiocytic yeasts with narrow-based budding
• Mycobacterium leprae (I-B04):  Cutaneous granulomas that may ulcerate; occurs on areas of the body with a lower skin temperature (ears, hands, feet, tail and brow)
• Mycobacterium spp.:  Usually atypical mycobacteriosis; causes subcutaneous fistulas, tracts and abscesses
• Sporotricosis (Sporothrix schenckii, I-F07):  Cutaneous ulcerated nodules and regional lymphadenopathy; granulomas with 3-10 um, spherical to oval yeasts with buds
• Melioidosis (Burkholderia pseudomallei):  Non healing cutaneous fistula with a purulent discharge; bronchopneumonia with abscesses in multiple organs
• Mycotic granulomas; bacterial abscesses; neoplasia; trauma

 

COMPARATIVE PATHOLOGY:

• Human infection with yabapox, tanapox, yaba-like disease virus (zoonotic), cowpox (zoonotic), and vaccinia (orthopox virus used for smallpox vaccination) 
• Mycobacterium avium paratuberculosis in cattle also infects histiocytes and causes histiocytic inflammation.
• Leishmania spp. in dogs, cats, and rodents also infects histiocytes and causes histiocytic inflammation. 
• Numerous poxviruses, usually host specific and cause proliferation and necrosis of the epidermis (not histiocytes)

 

REFERENCES:

1. Mansfield K. Viral diseases. In: Bennett BT, Abee CR, Henrickson R, eds.  Nonhuman Primates in Biomedical Research: Diseases. San Diego, CA:Academic Press; 1998:3-7.
2. 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; 2018:352-353. 

 

 

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