Three-year-old ovariohysterectomized female domestic shorthair cat (Felis catus).This cat had a history of tail chewing, hair loss and recurring dermatitis over the tail and caudodorsum, occurring since this cat was acquired as a kitten from Florida. Affected areas of skin were alopecic with erythema, crusted papules, plaques, and nodules. There was limited to no clinical response to treatment with fluoxetine, topical antibiotics and regular flea prevention and the cat deteriorated following injections of depomedrol and cefovecin. Following biopsy and initial diagnosis, the cat underwent tail amputation; however, the cat had recurring dermatitis over the caudodorsum 3 weeks postoperatively and was euthanized and submitted for necropsy.

Gross Description:  

At necropsy, there were two reddened, ulcerated areas over the caudodorsum with variable brown crusts and dried red-brown exudate. The caudal, larger area of ulceration and crusting was overlying a healing scar within the skin (interpreted as part of the surgical site from the previous tail amputation). The cranial, smaller area of ulceration was not associated with the previous surgical wound. On cut section, these areas extended into and expanded the subcutis, with poorly demarcated, tan to pink, firm, multifocal to coalescing nodules. There was no gross involvement of the underlying vertebrae and no gross evidence of spread to lymph nodes or visceral organs.

Histopathologic Description:

The section examined was taken from the cranial, smaller area of skin ulceration not associated with the previous surgical wound. Underlying a locally extensive area of ulcerated epidermis and expanding the dermis and subcutis, there is a poorly demarcated, nonencapsulated infiltration of large numbers of eosinophils, moderate lymphoplasmacytic and histiocytic infiltrates and fewer neutrophils, with extensive, multifocal areas of eosinophilic necrotic and karyorrhectic cellular debris. Within areas of necrosis, there are small to moderate numbers of predominantly negatively stained, extracellular, 10-15 µm diameter hyphae with variably prominent round or bulbous dilatations and intermittent right angle branching. Areas of necrotic cellular debris and inflammatory cellular infiltrate surround and isolate small aggregates of irregular, eosinophilic collagen fibers (collagenolysis).

Special Stains: Staining with Grocott’s methenamine silver (GMS) yielded moderate numbers of broad, thick-walled hyphae of varying diameters that are occasionally septate. Staining with PeriodicAcid-Schiff (PAS) highlights hyphae with similar morphology, albeit less prominently.

Morphologic Diagnosis:  

1. Skin, caudodorsum: Dermatitis, panniculitis, steatitis and myositis, eosinophilic and histiocytic, with lymphoplasmacytic infiltrates, marked, locally extensive, chronic with multifocal necrosis and hyphae
2. Skin, caudodorsum: Ulceration, multifocal, moderate to marked, chronic

Lab Results:  

Previous biopsy and culture of the affected areas yielded scant mold; further identified as Lagenidium sp. by 18S/ITS (internal transcribed spacer) nucleic acid amplification and sequence analysis. Culture of necropsy samples was unable to repeat isolation of Lagenidium spp.


Fungal dermatitis/Lagenidium sp.

Contributor Comment:  

The fungal hyphae present in this case are consistent with a recurrence of dermatitis associated with Lagenidium sp., previously confirmed in this cat by 18S/ITS nucleic acid amplification and sequence analysis. Members of the genus Lagenidium sp. are a group of the Oomycetes, closely related to Pythium sp. and often referred to as ‘water molds’. Oomycetes are frequently pathogens of plants, nematodes, and insect larvae; however, they are occasionally associated with disease in mammals.2 The most widely known Lagenidium species is Lagenidium giganteum, a pathogen of mosquito larvae that has previously been implemented as a biologic control agent.2 Although stages of oomycetes may be morphologically similar to fungal hyphae, oomycetes are phylogenetically distinct from fungi.7,8 In contrast to fungi, the cell wall of oomycetes contains cellulose and β-glucan rather than chitin8 , and the cell membranes lack ergosterol.7 Oomycetes also differ from fungi with respect to life stages produced, including the production of sporangia and biflagellate zoospores.7 Most case reports of lagenidiosis involve dogs; however, there have been several recent reports in cats.7 Infection with Lagenidium sp. in dogs typically occurs in young to middle-aged dogs and most frequently occurs in southeastern United States.2,3,7 Exposure to water bodies such as lakes and ponds is frequently, but not always, reported.3 Recent molecular work has led to the description of two closely related pathogens in dogs; Lagenidium giganteum forma caninum and Paralagenidium karlingii. 5 Lagenidium giganteum forma caninum causes cutaneous or subcutaneous disease with frequent widespread dissemination, involving visceral organs, lymph nodes and/or great vessels.3 Paralagenidium karlingii infection in dogs results in chronic ulcerative and/or nodular dermatitis that does not typically disseminate.5 Recommended treatment for lagenidiosis is wide surgical resection where possible.1,3,7 Prognosis is poor for disseminated disease, with lagenidiosis poorly responsive to medical therapy.2,9

Differential diagnoses for lagenidiosis on clinical presentation and histopathology may include pythiosis, resulting from infection with the oomycete, Pythium insidiosum; and zygomycosis, involving infection with fungal organisms such as Basidiobolus ranarum and Conidiobolus spp..1,2,5 All may result in granulomatous and/or eosinophilic inflammation and morphologically appear as broad, irregular branching hyphae that are rarely to occasionally septate.1 Differentiation is clinically important due to differing treatment and prognosis7,8.

Diagnosis of lagenidiosis can be challenging. Cytology and histopathology yield hyphae with similar morphology to pythiosis and zygomycosis.4 Although there may be subtle differences in size and/or morphology of hyphae, histopathology cannot be used for definitive differentiation.3 Fungal culture is possible but can be difficult due to the fastidious nature of Lagenidium sp. (particularly the sexual stages). Definitive diagnosis requires confirmation through molecular assays on tissue or cultured isolates.3,7,9 Lagenidium sp. should be considered a differential in cats with granulomatous to eosinophilic, nodular to ulcerative dermatitis.

JPC Diagnosis:  

Haired skin and subcutis: Dermatitis, panniculitis and myositis, eosinophilic and gran-ulomatous, and eosinophilic, focally extensive, marked, with multifocal necrosis, ulceration, and fungal hyphae, domestic shorthair, Felis catus.

Conference Comment:  

The contributor provides an excellent example and overview of the pathogenic Oomycete water mold, Lagenidium sp. As mentioned above, Lagenidium sp. is strikingly similar in geographic distribution, clinical, and histologic appearance to the more commonly diagnosed Oomycete, Pythium insidiosum. 6 As a result, the majority of conference participants had pythiosis as their top differential for this lesion.

Infection with both Pythium insidiosum and Lagenidium spp. typically, but not always, occurs when the host has prolonged contact with standing or stagnant water containing the motile aquatic flagellate zoo-spores.2,3,6 This infectious form of the organism is attracted by animal fur, damaged skin, and intestinal mucosa. As a result of contact with standing water, infections in domestic animals are most commonly reported in the limbs, ventral thorax, and abdomen. When a mammalian host with a skin injury enters a contaminated pond, the oomycete zoospores of will encyst upon contact with the injured skin and mechanically penetrate the tissue, causing clinical disease.6

Like pythiosis, this disease is typically highly aggressive and lesions in the great vessels, mediastinum, lungs, and esophagus have been reported in dogs. However, unlike pythiosis, gastrointestinal disease has not been reported in Lagenidium spp.6Both entities are associated with a poor to grave prognosis even with wide surgical excision of cutaneous masses because the majority of animals infected with this pathogen have occult, non-resectable, disease in regional lymph nodes or distant sites when initially diagnosed. 2,3 In dogs infected with the less aggressive species, Paralagenidium karlingii mentioned by the contributor, surgery that achieves three cm margins is often curative.7 Medical therapy for lagenidiosis is typically ineffective because ergosterol, the target for most antifungal drugs, is lacking in the Oomycete cell membrane. 6,7

Conference participants discussed this lesion as a great example of chronic-active inflammation. Chronic-active inflammation occurs when the inciting inflammatory stimulus has not been removed from the chronic inflammatory process and continues to elicit an acute inflammatory response.1

1. Ackermann M. Inflammation and healing. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 4th ed. St. Louis, MO:Mosby Elsevier; 2012:127.

2. Grooters AM. Pythiosis, lagenidiosis and zygomycosis. Vet Clin Small Anim. 2003; 33:695-720.

3. Grooters AM, Hodgin EC, Bauer RW, Detrisac CJ, Znajda NR, Thomas RC. Clinicopathologic findings associated with Lagenidium spp. infection in 6 dogs: Initial description of an emerging oomycosis.J Vet Intern Med. 2003;17:637-646.

4. Grooters AM, Foil CS. Miscellaneous fungal infections. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. Philadelphia, PA: WB Saunders; 2012:681-683.

5. Hartfield JN, Grooters AM, Waite KJ. Development and evaluation of an ELISA for the quantification of anti-Lagenidium giganteum forma caninum antibodies in dogs. J Vet Intern Med. 2014; 28:1479-1484.

6. Mauldin E, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA:Elsevier; 2016:657-660.

7. Mendoza L, Vilela R. The Mammalian pathogenic oomycetes. Curr Fungal Infec Rep. 2013; 7:198- 208.

8. Raffaele S, Kamoun S. Genome evolution in filamentous plant pathogens: why bigger can be better. Nature Reviews Microbiology. 2012; 10:417-430.

9. Znajda NR, Grooters AM, Marsella R. PCR-based detection of Pythium and Lagenidium DNA in frozen and ethanol-fixed animal tissues. Vet Dermatology. 2002; 13:187-194.

Click the slide to view.

3-1. Haired skin, cat.

3-2. Haired skin, cat.

3-3. Haired skin, cat.

3-4. Haired skin, cat.

3-5. Haired skin, cat.

3-6. Haired skin, cat.

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