JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
August 2022
I-F05 (NP)

Signalment (JPC# 1629462):  Four-year-old, female, rhesus monkey (Macaca mulatta)

HISTORY:  Nodular lesions were present in the subcutaneous tissues near the right scapula and within the pharynx.

HISTOPATHOLOGIC DESCRIPTION:

SLIDE A:  Haired Skin: Expanding the dermis and subcutis, multifocally elevating the ulcerated epidermis, and extending to surgical margins is a 1 x 3cm nodule composed of haphazardly arranged multinucleated giant cells admixed with moderate numbers of reactive fibroblasts. Multinucleated giant cells are primarily Langhans’ type (horshoe-shaped nuclear arrangement), with occasional foreign-body type (central aggregate of nuclei), and contain up to 20 nuclei. Multifocally, multinucleated giant cells surround variably sized foci of large, foamy, epithelioid macrophages. Surrounding smaller caliber subcutaneous and dermal vessels there are accumulations of numerous lymphocytes, scattered plasma cells, neutrophils, and eosinophils. Rarely, within the giant cell cytoplasm, there are 2‑4µm wide, parallel, thick-walled, septate fungal hyphae with non-dichotomous branching, and 8‑12µm diameter yeast. Overlying the ulcerated dermis is a serocellular crust composed of necrotic debris, degenerate neutrophils, and fibrin. Subjacent to the ulceration, there are small caliber blood vessels arranged perpendicular to plump fibroblasts (granulation tissue).

SLIDE B:  Haired skin (PAS):  Multinucleated giant cells contain variable numbers of PAS-positive, 2-4µm diameter, parallel, thick-walled, septate fungal hyphae with non-dichotomous branching and occasional bulbous swellings. Multifocally, there are irregularly round, 8-12µm diameter spheres with blue central 3-7µm cores surrounded by a clear halo (yeast).

MORPHOLOGIC DIAGNOSIS:  Haired skin:  Dermatitis, granulomatous, nodular, focally extensive, moderate, with epidermal ulceration, and intrahistiocytic fungal hyphae and yeast, rhesus monkey (Macaca mulatta), nonhuman primate.

ETIOLOGIC DIAGNOSIS:  Dermal paecilomycosis

CAUSE:  Paecilomyces sp.

CONDITION:  Cutaneous hyalohyphomycosis (paecilomycosis)

GENERAL DISCUSSION:

• Ubiquitous saprophytic fungi related to Penicillium and Aspergillus, found in soil and decaying organic matter, and are common contaminants of laboratory cultures
• Disease is extremely rare
• Hyalohyphomycosis is both a subcutaneous or systemic mycotic infection caused by fungal hyphae in tissue that are nonpigmented (non-dematiaceous)
• Causes of hyalohyphomycosis (paecilomycosis) include Paecilomyces, Pseudoallescheria, Geotrichum, Acremonium, Chrysosporium, Colletotrichum, Geomyces, Geosmithia, Metarhizium, Schizophyllum commune, and Fusarium spp.

PATHOGENESIS:

• Opportunistic infection via entry into a cutaneous wound or ear canal
• Wide dissemination to include:
  • CNS
  • Pneumonia (dogs, horses, reptiles)
  • Keratitis (horses) and chorioretinitis (dogs)
  • Discospondylitis (dogs)

TYPICAL CLINICAL FINDINGS:

• Signs vary with the organ system affected
• Lethargy, weight loss, diarrhea, chorioretinitis
• Signs associated with infection of the central nervous system: deafness, ataxia, vestibular signs, seizures

TYPICAL GROSS FINDINGS:

• Cutaneous nodule, +/- ulceration of overlying epidermis, non-healing abscess, draining fistulous tracts
• Focal or generalized lymphadenopathy
• Disseminated infection, diskospondylitis, chorioretinitis, keratitis

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Nodular to diffuse granulomatous to pyogranulomatous inflammation
• Abundant multinucleate giant cells (Langhans’ and foreign body type), large foamy macrophages
• Thick-walled, regularly septate, non-dichotomous branching hyphae with sporadic bulbous dilations
• Large and small (2-15µm) eosinophilic ellipsoid yeast forms with broad based budding

ADDITIONAL DIAGNOSTIC TESTS:

• GMS, PAS
• Culture

DIFFERENTIAL DIAGNOSIS:

• Other mycotic granulomas: Sporothrix, Blastomyces, Mycobacterium, Cryptococcus, phaeohyphomycosis (I-F04; Alternaria, Drechslera, Exophiala, Philophora spp.)
• Other granulomatous diseases including foreign body reaction, sterile granuloma, pyogranuloma syndrome
• Cutaneous neoplasia
• Diseases causing a generalized lymphadenopathy: Lymphoma, ehrlichiosis, Toxoplasma

COMPARATIVE PATHOLOGY:

• Described in dogs, cats, guinea pigs, horses, various reptiles, and humans
• Fly River turtles: Fatal superficial dermatomycoses has been reported
• Texas tortoises: Necrotizing scute disease (NSD) due to infection with Fusarium incarnatum resulting in blemishes on the shell confined to the superficial epidermal keratin layers; does not result in systemic disease or death
• Giant tortoises: Results in systemic mycoses that manifests as fungal pneumonia with caseous, firm nodular masses within the lung and as fungal plaques on mucosal or coelomic surfaces; dissemination to spleen, kidneys, liver or other viscera possible
• Loggerhead sea turtles: Fusarium solanispecies complex (FSSC) lineages commonly isolated from shell lesions; Calcofluor and potassium hyfroxide nor useful in diagnosis (Cafarchia, Vet Pathol 2020)
• American alligator: Emphysematous bullae with black or white fungal mats ( farinosus) or caseating pneumonia (P. farinosus and P. lilacinus, respectively)
• Nile crocodile: Pink plaques lining airways ( lilacinus)
• Estuarine and freshwater crocodiles: Gray, gelatinous lesions in the skin due to Fusarium
• Spectacled caiman: Casts of airways in the lung ( lilacinus)
• Snakes: Dermatomycoses common in snakes (Paecilomyces and Fusarium spp.)
• Captive chondrichthyans: Paecilomyces present as skin and/or gill necrosis, erosion, ulceration, and systemic infection.
• Chondrichthyans: Fusarium spp., particularly Fusarium solani species complex (FSSC) most common fungal pathogen of chondrichthyanx. Results in well-demarcated, ulcerative and/or hemorrhagic lesions in areas of the lateral line organs of the head and torso.
• Captive amphibians: Fusarium commonly isolated in fungal dermatitis which result in brown to red skin discoloration, excessive skin shedding, cutaneous nodules and ulcers.
• Horseshoe crabs: Fusarium spp. consistently isolated from Cutaneous ulceration, bronchitis, and ophthalmitis associated with fungi (LaDouceur, Vet Pathol 2020)
• Horses: Pulmonary mycosis secondary to enterocolitis and mycotic rhinitis and sinusitis have been associated with paecilomycetes (Hensel, J Comp Pathol 2020; More, Vet Pathol 2018)
• Mice: Chronic granulomatous disease, particularly in the lungs
  • Mice with lack of function of NADPH oxidase due to null mutation gp91(phox) developed pulmonary infections with variotii

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell Publishing; 2016:79.
2. Cafarchia C, Paradies R, Figueredo LA, et.al. Fusarium spp. in Loggerhead Sea Turtles (Caretta caretta): From Colonization to Infection. Vet Pathol. 2020;57(1):139-146.
3. Conley KJ and Shilton CM. Crocodilia. In: Terio K, McAloose D, St. Leger J, eds, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:864-866.
4. Grooters AM, Carol SF. Miscellaneous fungal infections. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Elsevier Saunders; 2012: 676-7, 684-5.
5. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Oxford, UK: Blackwell; 2005: 301-303.
6. Hensel M, Meason-Smith C, Plumlee QD, et.al. Retrospective Analysis of Aetiological Agents Associated with Pulmonary Mycosis Secondary to Enteric Salmonellosis in Six Horses by Panfungal Polymerase Chain Reaction. J Comp Pathol. 2020;174:1-7.
7. LaDouceur EEB, Mangus L, Garner MM, Cartoceti AN. Histologic Findings in Captive American Horseshoe Crabs (Limulus polyphemus). Vet Pathol. 2019;56(6):932-939.
8. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016: 653.
9. More SN, Hernandez O, Castleman WL. Mycotic Rhinitis and Sinusitis in Florida Horses. Vet Pathol. 2019;56(4):586-598.
10. Osslboff RJ. Serpentes. . In: Terio K, McAloose D, St. Leger J, eds, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 913-914.
11. Pessler AP. Amphibia. . In: Terio K, McAloose D, St. Leger J, eds, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:940.
12. Rodriguez CE, Henao Duque AM, Steinberg J, and Woodburn DB. Chelonia. In: Terio K, McAloose D, St. Leger J, eds, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:845-846.
13. Simmons J and Gibson S. Bacterial and Mycotic Diseases of Nonhuman Primates. In: Abee CR, et al, eds. Nonhuman Primates in Biomedical Research. Vol 2. 2^nd San Diego, CA: Elsevier; 2012: 157.
14. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1176.

Click the slide to view.

---