JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
August 2022
I-F13 (NP)

Signalment (JPC# 2749408):  Female baboon (Papio spp.)

HISTORY:  This baboon had multiple, raised, firm, often ulcerated skin nodules on the face, hands, feet, and tail areas.  The lesions recurred following surgical removal and did not respond to medical therapy.

HISTOPATHOLOGIC DESCRIPTION:  Haired skin:  Expanding the dermis and subcutis, compressing adnexa and underlying panniculus muscle, and elevating or abutting the overlying moderately hyperplastic and focally ulcerated epidermis, are multifocal to coalescing nodular infiltrates composed of numerous epithelioid macrophages and multinucleated giant cells (Langhans’ type) often containing numerous intracytoplasmic, round to ovoid, pale eosinophilic, 8-15µm diameter yeast, with a 2-3µm thick wall and a single, 2µm diameter round, peripheral nucleus; yeast occasionally exhibit narrow-based budding. Within these areas are viable and degenerate neutrophils, cellular debris (lytic necrosis), fewer lymphocytes, and low numbers of plasma cells and eosinophils and scattered areas of hemorrhage. There is diffuse mild acanthosis, orthokeratotic hyperkeratosis, and spongiosis.  The focal ulcer is covered by a serocellular crust composed of necrotic and keratin debris, hemorrhage, and many yeast.

MORPHOLOGIC DIAGNOSIS:  Haired skin:  Dermatitis, pyogranulomatous and eosinophilic, nodular, multifocal to coalescing, moderate, with numerous intrahistiocytic yeast, ulceration, epidermal hyperplasia, and hemorrhage, baboon (Papio spp.), nonhuman primate.

ETIOLOGIC DIAGNOSIS:  Cutaneous histoplasmosis

CAUSE:  Histoplasma capsulatum var. duboisii

CONDITION:  African histoplasmosis

SYNONYMS:  Large-form histoplasmosis

GENERAL DISCUSSION: 

• Chronic granulomatous disease that primarily affects the skin and bone; natural infections have been reported only in baboons and humans
• The agent is indigenous to Africa; soil is the natural reservoir
• Few cases have been reported in Texas since 1986, involving wild-caught and native-born baboons

PATHOGENESIS: 

• Transmission is by inhalation, ingestion, or direct dermal contact
• Most infections are thought to be the result of inhalation or ingestion with development of local minor primary lesions subsequent hematogenous dissemination to the skin and bones
• Direct contact with affected baboons through grooming and licking of cutaneous lesions may be a viable mode of transmission for captive animals
• Incubation period is variable and long, approximately one to three years

TYPICAL CLINICAL FINDINGS: 

• Solitary or multiple, raised, firm nodules, papules, pustules, or ulcerated granulomas
• Affects sparsely haired areas that are in contact with the ground: hands, feet, buttocks, and tail; may also occur on the face, ears
• Enlarged peripheral lymph nodes that drain areas with skin lesions, also liver and scrotum

TYPICAL GROSS FINDINGS: 

• Lesions are usually confined to the skin and dermis, but may involve subjacent bone (with resultant osteomyelitis), draining lymph nodes, testis,
• Lesions are typically nodular or ulcerated with reddish-brown purulent exudate
• Common sites affected include: Hands, feet, buttocks, tail, face, ears, scrotum
• Enlarged regional lymph nodes

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Pyogranulomatous inflammation in the dermis and subcutaneous tissue with numerous histiocytes, multinucleate giant cells (both foreign body and Langhans types), and small aggregates of neutrophils
• Yeast: Round to ovoid, pale-staining, basophilic, 8-15 um in diameter (at least 2x bigger than other Capsulatum spp.) with thick walls, and single, narrow-based budding; a single, small, round to elongate, nucleus; often in pairs (“hourglass” shape) and short chains within histiocytes and giant cells
• Bone lesions: Osteolysis with minimal osteoid and marrow fibrosis

ULTRASTRUCTURAL FINDINGS:

• Yeast: Variable round, oval, crescent, or biconcave disks; thick cell wall, no capsule, single nucleus and a large nucleolus

ADDITIONAL DIAGNOSTIC TESTS: 

• Organisms are often easily found on skin scrapings and have characteristic histomorphology
• Gomori’s methenamine silver or Gridley’s fungal stain
• Immunodiffusion and complement fixation tests cannot differentiate between the different varieties of Histoplasma
• Difficult to morphologically differentiate capsulatum var. capsulatum from H. capsulatum var. duboisii in culture

DIFFERENTIAL DIAGNOSIS:

For histologic findings:

• Zygomycosis (Entomophthorales): fungal hyphae; causes pyogranulomatous inflammation with eosinophils and multinucleated giant cells in skin, subcutis, and muscle
• Actinomyces: Gram-positive rod; causes pyogranulomas of the skin, pancreas, peritoneum, and various mucosal surfaces
• Coccidioides immitis: yeast with variable size endospore; causes pyogranulomas in multiple organs; spleen, liver, kidneys, LN, esophagus, vertebrae
• Blastomyces dermatidis: Yeast with broad-based budding, multiple nuclei; causes pyogranulomas in the brain, lungs, tracheobronchial lymph node, liver and spleen
• Oesophagostomum: nematode; causes pyogranulomas in colon, kidney, prostate, pancreas and heart

COMPARATIVE PATHOLOGY: 

• Histoplasma capsulatum var. duboisii reported only in baboons and humans

 

Organism	Histoplasma capsulatum var. duboisii	Histoplasma capsulatum var. capsulatum	Cryptococcus neoformans	Coccidioides immitis	Blastomyces dermatiditis
Tissue response	Pyogranulomatous with MNGC	Histiocytic	Histiocytic, min. to mod.	Pyogranulomatous	Pyogranulomatous
Size (μm)	8-15	2-4	2-10	5-100	8-15
Cell wall thickness	Thick	Thin	Thin	Thick	Thick
Number of nuclei	Single	Single	Single	None (endospores)	Multiple
Bud and attachment	Single bud; narrow-based	Single bud; narrow-based	Single bud; narrow-based	None	Single bud; broad-based
Capsule	None	None	Mucicarmine-positive	None	None
Endospores	None	None	None	Yes	None
Dimorphic	Yes	Yes	Yes	Yes	Yes
Common species affected	Baboons Humans	Dogs Cats	Cats	Many species	Dogs
Common sites affected	Skin Bone	Lung Disseminated	Lung CNS	Lung	Lung Skin Disseminated

Modified from Migaki G, et. al., 1993

REFERENCES: 

1. Abee, C., Mansfield, K., Tardif, S. et al. Nonhuman Primates in Biomedical Research Volume 2: Diseases. 2nd ed. Waltham: Elsevier, 2012:151-154.
2. Migaki G, Hubbard GB, Butler TM. Histoplasma capsulatum duboisii infection, baboon. In: Jones TC, Mohr U, Hunt: Nonhuman Primates II: Monographs on Pathology of Laboratory Animals. New York, NY: Springer-Verlag; 1993:19-23.
3. Maxie MG, Miller MA. Bones and Joints. In: Maxie MG,ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders. 2016:104.
4. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023: 53-54, 158-161, 189, 220-221, 254, 490.
5. Robinson WF, Robinson NA. Cardiovascular System. In: Maxie MG,ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders. 2016:97.
6. Rosol TJ, Grone A. Endocrine Glands. In: Maxie MG,ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders. 2016:340.
7. Schlemmer SN, Fratzke AP, Gibbons P, et al. Histoplasmosis and multicentric lymphoma in a Nubian goat. J Vet Diagn Invest. 2019;31(5):770-773. doi:10.1177/1040638719868810
8. Simmons J, Gibson SV. Bacterial and mycotic diseases. In: Bennett BT, Abee CR, and Henrickson R. Nonhuman Primates in Biomedical Research: Diseases. 2nd ed. London, UK: Academic Press; 2012:153.
9. Uzal FA, Plattner BL, Hostetter JM. Alimentary System. In: Maxie MG,ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier Saunders. 2016:98, 202-203.
10. Valenciano AC, Cowell RL, eds. Diagnostic Cytology and hematology of the dog and cat. 5th ed. St. Louis, MO: Elsevier; 2020: 49, 50, 52, 80, 133, 217, 238, 290-294, 315, 371-373, 460.
11. Valli VEO, Kiupel M, Bienzle D. Hematopoietic System. In: Maxie MG,ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier Saunders. 2016: 186-187.
12. Wilcock BP, Njaa BL. Special Senses. In: Maxie MG,ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders. 2016:449-450.

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