JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
August 2022
I-F09

Signalment (JPC# 1397818):  Atlantic bottle-nosed dolphin

HISTORY:  This dolphin had extensive white, crusting, cutaneous lesions.

HISTOPATHOLOGIC DESCRIPTION:  Slide A:  Non-haired skin: Within the superficial dermis along the epidermal junction, effacing the normal dermal architecture and compressing adjacent collagen fibers, are there are multifocal to coalescing nodular infiltrates composed of numerous epithelioid macrophages and fewer multinucleate giant cells (Langhans’ and foreign body type) which frequently contain numerous round to oval, 6 - 12 µm diameter, clear yeast with a 1 µm thick wall and, infrequently, a 2 - 4 µm eosinophilic center. These infiltrates are admixed with abundant extracellular previously-described yeast arranged individually or occasionally in a linear “string of pearls” arrangement, occasional lymphocytes and plasma cells, rare neutrophils, eosinophilic cellular and basophilic karyorrhectic debris (necrosis), eosinophilic fibrillar material (fibrin), increased clear space (edema). Tendrils of epithelioid macrophages with a granular, amphophilic cytoplasm infiltrate into the deeper dermis where they separate and surround collagen fibers. The overlying epidermis is diffusely and irregularly hyperplastic with prominent rete ridges. There is diffuse, mild, parakeratotic hyperkeratosis with multiple small colonies of 1 x 3 µm bacilli along the epidermal surface. There are colonies of mixed bacteria present within a few dermal vessels (postmortem overgrowth).

Slide B (Gridley's stain):  There are abundant purple intrahistiocytic and extracellular, 6 - 12 µm, round to oval, occasionally budding yeast located singly or forming variably long chains. Adjacent macrophages contain light purple finely granular material (digested fungal walls).

MORPHOLOGIC DIAGNOSIS:  Non-haired skin: Dermatitis, granulomatous, chronic, multifocal to coalescing, marked, with epidermal hyperplasia, parakeratotic hyperkeratosis, and abundant intrahistiocytic and extracellular yeast, etiology consistent with Paracoccidioides brasiliensis, Atlantic bottlenose dolphin (Tursiops truncatus), cetacean.

ETIOLOGIC DIAGNOSIS:  Cutaneous paracoccidioidomycosis

CAUSE:  Paracoccidioides brasiliensis (Vilela, Emerg Infect Dis 2016; St. Leger, Cetacea 2018; Sarcistan, Diseases of Aquatic Organisms, 2016)

CONDITION:  Lobo-like disease (prev. lobo’s disease)

SYNONYMS:  Lobomycosis-like disease, lacaziosis-like disease

GENERAL DISCUSSION: 

• Molecular data suggest a novel, noncultivable strain of Paracoccidioides brasiliensis is the cause of this disease in dolphins; closely related to (and previously thought to be) Lacazia loboi which causes similar cutaneous lesions in humans
• Indolent cutaneous infection with no systemic involvement; only rare reports of regional lymphadenopathy in humans and dolphins (Atlantic bottlenose, Guiana, and Indian ocean humpback dolphin)
• World-wide distribution

PATHOGENESIS: 

• Thought to follow exposure to contaminated soil or vegetation via a local penetrating injury (including shark bites) with lesion spread via auto-inoculation
• Animals may become debilitated and die usually from secondary bacterial infections and malnutrition

TYPICAL CLINICAL FINDINGS: 

• Smooth swelling progresses slowly to a nodular or verrucous, crusting, white lesion
• Lesions in areas frequently exposed to the air such as top of head, dorsal fin, and top of dorsal peduncle and flukes, but may also be present on flanks and ventrum
• Occasional regional lymphadenopathy, but dissemination does not occur

TYPICAL GROSS FINDINGS: 

• Multiple, elevated, well demarcated, nodular to verrucous, whitish, crusty lesions up to 40 cm in diameter
• Cut surface exhibits either:
  • Small, soft, beige, glassy foci just beneath the epidermis
  • Large, circumscribed nodules extending into the deep dermis with possible ulceration of the overlying epidermis

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Histopathologic features are characteristic and diagnostic
  • Cutaneous lesions: Large, discrete granulomas confined to the dermis; periphery of lesion commonly has foamy macrophages with PAS and Gridley's positive material believed to represent debris from digested fungi
  • Epithelial hyperplasia with marked acanthosis, hyperkeratosis, and irregular down growth of rete ridges
• Yeasts are 5 – 12 µm, round to oval to or crescentic (secondary to collapse of the wall); with a 1 µm thick, double-contoured cell wall
  • Stains poorly with H&E; outline visible with homogenous, faintly basophilic internal contents
  • Budding produces chains of three or more uniform cells connected by a tubular isthmus in a characteristic 'string of pearls' pattern, branching chains are possible by secondary budding

 ULTRASTRUCTURAL FINDINGS:

• Organisms consist of a highly electron dense outer rim lining a relatively homogenous electron dense cell wall
• Organisms are often connected by a narrow, tubular portion of the cell wall

 ADDITIONAL DIAGNOSTIC TESTS: 

• Special/histochemical stains: Gridley's fungal stain, Gomori’s Methenamine Silver, Periodic Acid Schiff (PAS)

DIFFERENTIAL DIAGNOSIS: 

• Dermatitis in dolphins:
  • Erysipelothrix rhusiopathiae: Gram-positive bacterium that causes a peracute septicemia with vasculitis & dermal infarcts; “diamond skin disease”
  • Nocardia: Gram-positive rod bacterium, cutaneous abcessation, commonly manifests systemic dissemination
  • Pox virus: Cutaneous “tattoo” lesions; solitary or coalesced circular grey blemishes with eosinophilic intracytoplasmic inclusions
  • Herpesvirus (Gammaherpesvirinae): Dermatitis, proliferative genital plaque-like lesions; necrotizing with eosinophilic intranuclear inclusion bodies
  • Papillomavirus: Proliferative lesions on mucous membranes (frenulum, tongue, penis, vagina); metastatic spread possible
• Other cutaneous fungal infections:
  • Histoplasma capsulatum: 2 - 4 µm intrahistiocytic yeasts with basophilic centers and peripheral clear zones
  • Cryptococcus neoformans: 2 - 10 µm, spherical, yeasts with an eosinophilic center and a clear, 5 µm wide capsule
  • Blastomyces dermatitidis: 15 - 20 µm broad-based budding yeasts

COMPARATIVE PATHOLOGY: 

• Lobomycosis only occurs naturally in humans, and is caused by Lacazia loboi (initially thought to be causative agent of lacaziosis-like disease/lobo-like disease in dolphins)
• Paracoccidiodes braziliense occurs in dolphins and humans (termed South American blastomycosis); one possible case of transmission between dolphin and human documented (Sacristan)

References: 

1. Bossart GD. Marine mammals as sentinel species for oceans and human health. Vet Pathol. 2011; 48(3): 676-690.
2. Dold C. Cetacea (whales, dolphins, porpoises). In: Miller RE, Fowler M, eds. Fowler's Zoo and Wild Animal Medicine. Vol 8. St. Louis, MO: Elsevier; 2015:431.
3. Migaki G, Jones SR: Mycotic diseases in marine mammals. In: Pathology of Marine Mammal Diseases. Vol II., Boca Raton, FL: CRC Press Inc; 1983: 8-9.
4. Refi JS, et al. Lobomycosis: Risk of zoonotic transmission from dolphins to humans. Vector Borne Zoonotic Dis. 2013; 13(10):689-693.
5. Leger JA, Raverty S, Mena A. Cetacea. In: Terio KA, McAloose D, St. Leger JA, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:559-560.

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