JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
August 2022
I-F07

Signalment (JPC# 1380452):  Adult male Siamese cat

HISTORY:  This cat presented with a small, circular, raised nodule on its head.  Similar, occasionally ulcerated nodules later developed on the head, ears, nose, and forelimbs.  The animal was euthanized and this section taken from the ear at the time of necropsy.

 

HISTOPATHOLOGIC DESCRIPTION: SLIDE A: Haired skin, pinna: Infiltrating, expanding, and effacing the dermis; separating fragmented mature collagen fibers and remaining adnexa; and elevating the multifocally hyperplastic and focally ulcerated epidermis are multiple coalescing nodules of numerous macrophages and neutrophils with fewer perivascular and periadnexal lymphocytes and plasma cells, and rare melanin laden macrophages (pigmentary incontinence). There are numerous intrahistiocytic and extracellular, 4‑10µm diameter, round to oval, lightly eosinophilic yeast that are occasionally surrounded by a clear halo. Epidermal hyperplasia is mild, with rete ridges, acanthosis; there are also prominent intracellular bridges and intercellular edema (spongiosis), and rare neutrophilic exocytosis.

SLIDE B (PAS):  There are numerous intrahistiocytic and extracellular, pleomorphic (round, oval and occasional cigar-shaped), PAS-positive yeast.

MORPHOLOGIC DIAGNOSIS:  Haired skin, pinna:  Dermatitis, pyogranulomatous, nodular, multifocal, moderate, with numerous intrahistiocytic and extracellular PAS-positive yeast, etiology consistent with Sporothrix schenckii, Siamese, feline.

ETIOLOGIC DIAGNOSIS: Aural cutaneous sporotrichosis

CAUSE: Sporothrix schenckii

GENERAL DISCUSSION: 

• An opportunistic, dimorphic, saprophytic fungus found in moist organic debris, sphagnum moss, and hay
• Mycelial (hyphal) form at environmental temperature, yeast in tissue
• Disease is uncommon; seen most frequently in cats, horses, dogs, and humans, with increased incidence in roaming intact male cats and hunting dogs
• Disease occurs more frequently in temperate and tropical zones
• Zoonotic; transmission reported from cats to humans, thus infected cats present a significant public health danger
• Three clinical forms (see gross findings)

PATHOGENESIS: 

• Infection acquired by wound contamination or inoculation by puncture wounds from thorns, wood splinters, contaminated claws, cat bite, etc.
• schenckii organisms are commonly cultured from the blood in cats with both widespread and localized cutaneous lesions
• Pulmonary infections are rare; result from inhalation of the organism

TYPICAL CLINICAL FINDINGS: 

• Typically limited to the skin/subcutaneous fat, but systemic dissemination can occur (more often in cats than dogs)
• Cats with the disseminated form are febrile, depressed, and/or anorexic
• Respiratory signs are the most frequent extracutaneous clinical finding

TYPICAL GROSS FINDINGS: 

• Primary cutaneous form: frequent in dogs and cats
  • Multifocal raised, hairless, crusted, and/or ulcerated nodules or plaques
  • Lesions confined to point of entry of organism
  • May result from a high degree of host immunity which prevents spread
• Cutaneous‑lymphatic form: most common in horses and humans, also reported in dogs
  • Lesions on head, pinnae, and trunk; confined to skin and subcutis
  • Lesions follow the lymphatics proximally from the point of entry; lymphatics become thick and corded
• Extracutaneous/Disseminated form: frequent in cats, rare in dogs (occasionally associated with corticosteroid use)
  • Develops as a sequela to the cutaneous-lymphatic form, or inhalation

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Diffuse and/or nodular pyogranulomatous dermatitis and panniculitis; epidermis is acanthotic or ulcerated, with variable fibrosis and necrosis
• Yeast are pleomorphic, round, oval or cigar-shaped; single or budding cells; 2-6 µm in diameter and 2-10 µm in length; refractile cell wall shrinkage artifact may cause yeast to appear encapsulated
• Organisms are numerous in lesions in cats and rare in dogs and horses
• Found extracellularly with regions of necrosis or within the cytoplasm of macrophages, multinucleate giant cells, and neutrophils
• Yeast may be surrounded by a brightly eosinophilic, stellate, radial corona known as an asteroid body or Splendore-Hoeppli reaction

ADDITIONAL DIAGNOSTIC TESTS: 

• Special/histochemical stains: Yeast are gram-positive and PAS, GMS positive
  • Grocott silver stain more sensitive than cytologic examination or IHCs (Silva JN, et al., J Comp Path 2018)
• Cytology: PAS or GMS stain of exudate highlights yeast; 1-3µm wide, 3-9µm long with light blue cytoplasm, an eccentric nucleus with a thin, clear cell wall and narrow based budding
• Fungal culture: Easy to culture, even when few organisms present
• Indirect immunoperoxidase or direct fluorescent antibody staining with schenckii antiserum
• Polyclonal anti-Mycobacterium bovis (BCG) stain may help identify organisms

DIFFERENTIAL DIAGNOSIS: 

Gross differentials: 

• Cats and dogs, ulcerated and fistulated cutaneous lesions (solitary or multiple):
  • Opportunistic or systemic fungal infections (cryptococcosis (I-F08), histoplasmosis, blastomycosis (I-F06))
  • Bacterial abscesses/severe bacterial pyoderma
  • Leishmaniasis (I-P15, H-P07, U-P03)
  • Foreign body reactions
  • Sterile granuloma and pyogranuloma syndrome (I-M17)
  • Feline leprosy (Mycobacterium lepraemurium, I-B03)
  • Neoplasia
• Horses, cutaneous lymphangitis with draining tracts:
  • Epizootic lymphangitis/pseudoglanders (Histoplasma capsulatum var. farciminosum): Ulcerative, nodular pyogranulomatous lymphangitis usually of hind limbs and neck
  • Glanders/Farcy (Burkholderia mallei): Neutrophilic to pyogranulomatous ulcerative lymphangitis of the head and neck
  • Melioidosis (Burkholderia pseudomallei): Wide host range; often causes an ascending lymphangitis of the distal extremities
  • Ulcerative lymphangitis (Corynebacterium pseudotuberculosis): Ascending neutrophilic to granulomatous ulcerative lymphangitis of the lower limbs (especially fetlock) with intracellular and extracellular diphtheroid bacteria
  • Equine strangles (Streptococcus equi ssp. equi): Regional lymph node abscesses most severely affecting the mandibular and retropharyngeal lymph nodes, which often rupture and contain purulent exudate

Histologic differentials (especially when cigar form of S. schenckii is absent): 

• Histoplasma capsulatum: 2‑4 µm diameter, intrahistiocytic yeast, with single narrow‑based budding (hourglass appearance)
• Cryptococcus neoformans (I-F08): 2-20 µm diameter yeast with thick, mucin-positive, 2 µm thick capsule; forms single or multiple narrow‑based buds; capsule stains well with mucicarmine
• Blastomyces dermatitidis (I-F06): 8‑25 µm diameter, round, multinucleated yeast with double contoured, thick walls, with broad‑based budding
• Cutaneous leishmaniasis (I-P15): Chronic ulcerative dermatitis with 2 µm intrahistiocytic protozoal amastigotes with a vesiculate nucleus and kinetoplast

COMPARATIVE PATHOLOGY: 

• Reported in cattle, mules, donkeys, goats, swine, rats, mice, hamsters, domestic fowl, camels, dolphins, armadillos and chimpanzees
• Occupational hazard for people working closely with vegetation or soil; risk factors include rose gardening, topiary production, hay baling, and Christmas tree farming

REFERENCES:

1. Boes KM. Respiratory system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023: 189-191, 221-222.
2. Coiacetto F, Arthur I, et al. Disseminated sporotrichosis in a bilby (Macrotis lagotis). J Comp Pathol. 2019; 170:74-77.
3. Delaney MA, Treutig PM, Rothenburger JL Ch. 20 Rodentia . In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 512.
4. Fisher DJ. Cutaneous and subcutaneous lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and hematology of the dog and cat. 5th ed. St. Louis, MO: Elsevier; 2020: 80-81.
5. Gross TL, Ihrke PJ, Walder EJ, Affolter, VK eds. Skin Diseases of the Dog and Cat- Clinical and Histopathologic Diagnosis. 2nd ed. Ames, IA: Blackwell Science Ltd.; 2005: 298-301.
6. Hnilica KA, Patterson, AP. Small Animal Dermatology. 4 ed. Elsevier Inc.; 2017:121-122.
7. Jang SS, Walker RL. Fungal and algal diseases. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Elsevier Saunders; 2012:645-650.
8. Kramer JA, Bielitzki J. Integumentary system diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research Volume 2: Diseases. 2nd ed. London, UK: Academic Press; 2012:574.
9. Lane LV, Yang PJ, Cowell RL. Selected infectious agents. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and hematology of the dog and cat. 5th ed. St. Louis, MO: Elsevier; 2020: 48.
10. 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; 2016:655-657.
11. Raskin RE, Conrado FO. Integumentary system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023: 56-57.
12. Silva JN, et al. Comparison of the sensitivity of three methods for the early diagnosis of sporotrichosis in cats. J Comp Path. 2018; 160:72-78.
13. Simmons J, Gibson S. Bacterial and mycotic diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research Volume 2: Diseases. 2nd ed. London, UK: Academic Press; 2012:153-154.
14. Welle MM, Linder KE. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed., St. Louis, MO; 2022: Elsevier; 2022:1177.
15. Wellman ML, Radin MJ. Nasal exudates and masses. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and hematology of the dog and cat. 5th ed. St. Louis, MO: Elsevier; 2020: 125-126.

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