JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
August 2022
I-F12

Signalment (JPC# 1960546):  Persian cat

HISTORY:  This cat had a nodular skin mass.

HISTOPATHOLOGIC DESCRIPTION:  Haired skin and subcutis: Expanding the deep dermis and subcutis, extending to the deep border, and elevating the overlying epidermis are multiple focally extensive pyogranulomas composed of numerous epithelioid macrophages surrounded by fewer degenerate neutrophils, lymphocytes, plasma cells, and occasional multinucleated giant cells, centered on necrotic debris within aggregates of densely packed, 5-10µm wide, septate fungal hyphae with thick, nonparallel walls, rare irregular non-dichotomous branching, and up to 25µm diameter bulbous swellings. Hyphae are embedded in amorphous, eosinophilic material (Splendore-Hoeppli reaction). Surrounding and separating pyogranulomas are numerous fibroblasts, small caliber blood vessels, and loose fibrous connective tissue (granulation tissue) admixed with mild hemorrhage and edema, progressing to more mature fibrous connective tissue (fibrosis). Multifocally infiltrating the superficial dermis are low numbers of periadnexal to perivascular lymphocytes, plasma cells, and fewer macrophages. There is diffuse, mild, acanthosis and multifocal orthokeratotic hyperkeratosis.

MORPHOLOGIC DIAGNOSIS:  Haired skin and subcutis:  Pyogranulomas (pseudomycetomas), multiple, with granulation tissue, fibrosis, and numerous fungal hyphae embedded in Splendore-Hoeppli material, Persian, feline.

ETIOLOGIC DIAGNOSIS:  Dermal and subcuticular dermatophytosis

CAUSE:  Microsporum canis

CONDITION:  Feline dermatophytic pseudomycetoma

GENERAL DISCUSSION:

• Dermatophytic pseudomycetoma is an atypical, rare form of dermatophytosis that involves the deep dermal and subcutaneous tissues and is typically caused by M. canis
• Feline dermatophytic pseudomycetomas occur almost exclusively in Persian cats, but may be seen in other longhaired breeds
  • Persian cats are predisposed to classic dermatophytosis indicating a potential genetic selective immunodeficiency; inapparent carriers of canis, which may be a reason they are predisposed to dermatophytic pseudomycetoma; one report of a Persian cat with an intra-abdominal dermatophytic pseudomycetoma
• Hyphae within the deep dermis and subcutis cause the formation of mycetoma-like granulomas:
  • These contain fewer hyphal filaments than true eumycotic granules and lack cementing substance with less Splendore-Hoeppli reaction

PATHOGENESIS: 

• Follicular dermatophyte colonization (may be inapparent carriage) > trauma or spontaneous rupture (furunculosis) > release of dermatophytes into the perifollicular and subfollicular dermis > deep dermal and subcutaneous infections > aggregate and induce an immune response (humoral and cell-mediated) > pyogranulomatous/granulomatous inflammation

TYPICAL CLINICAL FINDINGS: 

Pseudomycetoma:

• Has almost exclusively been documented in Persian cats with one or more subcutaneous nodules over dorsal tail or trunk
• May be hyperpigmented and/or ulcerated
• Alopecia, if concurrent typical dermatophytosis

TYPICAL GROSS FINDINGS: 

• Focal to multifocal papules and small to large subcutaneous, often coalescing nodules with occasional ulceration and draining seropurulent to granular material
  • Tissue granules may be seen, which appear grossly as small white grains and are small accumulations of embedded fungal hyphae
  • Overlying skin may be hyperpigmented, if chronic, and alopecic if the pseudomycetoma coexists with more typical dermatophytosis
  • Intra-abdominal and lymph node locations are rare
• Occur most often over dorsal trunk or tail base
• May have lymphadenopathy

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Nodular to diffuse, granulomatous to pyogranulomatous dermatitis and panniculitis surrounding spherical to multilobular fungal aggregates
• Large aggregates of fungal hyphae with the following characteristics: non-pigmented (hyaline), broad (2.5 to 4.5 microns), septate, irregularly branched hyphae; chainlike pseudohyphae; and large (12 micron), thick-walled chlamydospore-like cells that appear as bulbous distentions; hyphae are embedded in amorphous lightly eosinophilic material (Splendore-Hoeppli reaction; antigen-antibody reaction) to form tissue granules
  • Organisms do not resemble dermatophytes found in cornified structures (hair shaft, stratum corneum, or inner root sheaths)
  • Graunles are cuffed by macrophages, MNGC, and neutrophils
• +/- concurrent follicular dermatophytosis with or without inflammation
• Proliferating fibroblastic tissue surrounding outer aspect of lesions or coursing amongst granules creating lobules

ADDITIONAL DIAGNOSTIC TESTS: 

• Fungal stains: Periodic acid-Schiff (PAS), Gomori’s methenamine silver (GMS)
• Culture, after blastomycosis, histoplasmosis, and coccidiomycosis are ruled out since culture can be dangerous
• Immunohistochemistry for canis (limited availability)
• Cytology: Trichogram (microscopic hair examination)
  • Supports diagnosis

DIFFERENTIAL DIAGNOSIS: 

• Eumycetoma: Numerous variably pigmented tissue grains composed of masses of opportunistic, septate, branching, 2-4 um wide, fungal hyphae often embedded in a cementing substance and surrounded by a less intense Splendore-Hoeppli reaction; most fungi isolated are saprophytes (Curvularia geniculata, Madurella grisea, Acremonium hyalinum, Pseudoallescheria boydii, and Phaeococcus)
• Actinomycetoma: center contains gram + bacteria (Actinomyces spp. Nocardia spp.)
• Botryomycosis (Staphylococcus): Gram-positive cocci that can cause a bacterial granuloma or staphylococcal pseudomycetoma; uncommon in the cat
• Other dermatophytic granulomas caused by Trichophyton mentagrophytes: these do not have typical histological features of dermatophytic pseudomycetoma, because they lack grains
• Systemic mycoses such as Cryptococcus can manifest as small soft to firm nodules
• Foreign body granulomas

COMPARATIVE PATHOLOGY: 

Pseudomycetomas in other species:

• Dogs: Called “kerion”; rare; possibly Yorkshire terriers are predisposed; most cases caused by M. canis; one report of dermatophytic granuloma in a Manchester terrier caused by Trichophyton mentagrophytes
  • Dermatophytic pseudomycetoma with lymph node involvement was reported in the Yorkshire terrier with canis
• Ferrets: Rare; instances of infection with Trichophyton spp. and Microsporum spp. in immune suppressed ferrets (Vet Derm. Giner J et al. 2018)

References: 

1. 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: 79-81.
2. Giner J, Bailey J, Juan-Salles C, Joiner K, Martinez-Romero EG, Oster S. Dermatophytic pseudomycetomas in two ferrets (Mustela putorius furo). Vet Dermatol. 2018, 29(5):452-456.
3. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat Clinical and Histopathologic Diagnosis. 2nd ed. Ames, IA: Blackwell Publishing Professional; 2005:272, 288-291, 302.
4. 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: 51.
5. Mauldin EA, Peters-Kennedy J. Integumentary. In: Maxie MG ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol. 1. 6^th Philadelphia, PA: Elsevier Saunders; 2016: 650, 653-654.
6. Miller RI. Nodular granulomatous fungal skin diseases of cats in the United Kingdom: a retrospective review. Veterinary Dermatol. 2010;21:130-135.
7. Miller WH, Griffin CE, Campbell KL. Fungal and algal skin diseases. In: Muller & Kirk’s Small Animal Dermatology. 7th ed. Philadelphia, PA: Saunders Co; 2013: 239.
8. Raskin, RE, Conrado FO. Integumentary system. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A color atlas and interpretation guide. 4th Ed. St. Louis, MO: Elsevier; 2023: 53-55.
9. Welle MM, Linder KE. The integument. In: Zachary JF eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier, Inc.; 2022:1174, 1258.

Click the slide to view.

---