Chapter 68

In contrast to the well-recognized fungal pathogens that cause endemic mycoses (such as Blastomyces, Histoplasma, and Cryptococcus), miscellaneous fungal pathogens comprise large groups of fungi with unfamiliar names that traditionally have caused disease only sporadically. These opportunistic fungi have low inherent virulence and typically cause infection only when normal host resistance mechanisms are compromised. Over the past 30 years, these opportunists have become increasingly important in human patients because immunocompromise associated with chemotherapy, organ transplantation, and HIV infection has become more prevalent. Similarly, over the past 5 to 10 years, the frequency with which opportunistic fungal infections are encountered in small animal patients has increased significantly in association with the use of multiagent immunosuppressive therapy (especially with cyclosporine) to treat immune-mediated disease in dogs. Thus, veterinarians are increasingly likely to encounter patients infected by an opportunistic fungal pathogen with which they are unfamiliar.

Unlike the common endemic fungal pathogens (for which a definitive diagnosis can often be made simply by visualizing the unique morphologic features of the organism in cytologic or histologic samples), opportunistic fungi can only be identified to genus and species level by culture or molecular methods. However, they can be assigned to categories based on their morphologic features in tissue, such as pigmentation, hyphal diameter, and frequency of septation. These categories include phaeohyphomycosis (pigmented hyphal or yeast forms), hyalohyphomycosis (nonpigmented hyphal forms), eumycotic mycetoma (fibrosing granuloma with black or white tissue grains consisting of aggregates of pigmented or nonpigmented fungi, respectively), and zygomycosis (wide, infrequently septate, nonpigmented hyphae associated with pyogranulomatous and eosinophilic inflammation). Because of its similarities to pythiosis and lagenidiosis, zygomycosis is discussed in Chapter 69. Although identification of a specific pathogen after culture is ideal, classification of opportunistic mycoses based on the categories just listed is usually sufficient to allow the clinician to make a reasonable prediction about clinical course and prognosis and to make appropriate treatment decisions. Because many opportunistic fungi are common contaminants and can normally be found on skin, nasal mucosa, and other nonsterile sites, culture- or PCR-based identification of a potential opportunistic fungal pathogen from a skin specimen, nasal swab, or exudate should not be considered evidence of fungal infection unless there is supportive histologic or cytologic evidence of tissue invasion by a morphologically compatible organism.

Diagnosis

Laboratory and Imaging Abnormalities

Results of a CBC, biochemistry panel, and urinalysis in animals with cutaneous phaeohyphomycoses are typically unremarkable. Animals with disseminated disease can have abnormalities associated with underlying immunosuppressive illness or drug treatment. Imaging with computed tomography (CT) or MRI in animals with CNS involvement may reveal focal or multifocal contrast-enhancing lesions that may be associated with hydrocephalus (Figure 68-3).

FIGURE 68-3 Axial T1 postcontrast, T2, and FLAIR magnetic resonance images (A, B, and C, respectively) of the brain of a 6-year-old male neutered Border collie mix that was evaluated for neurologic signs including seizures and progressive obtundation. In the images shown, there is bilateral but asymmetric ventricular dilation that is severe on the right and mild to moderate on the left (asymmetric hydrocephalus). Multifocal regions of contrast enhancement are also present (A). Some of these regions appeared nodular; others had a ring-like appearance. There is also marked contrast enhancement of the ventricular ependymal lining. The regions of contrast enhancement correlate with regions of T2 and FLAIR hyperintensity (B and C) and were isointense on precontrast T1-weighted sequences (not shown). Meningoencephalitis caused by Cladophialophora bantiana and secondary hydrocephalus was diagnosed on brain biopsy and at necropsy (D). Olive-green pigmented masses can be seen on both the left and right sides of the brain. Interestingly, the dog also had cutaneous protothecosis. (Courtesy University of California, Davis, Veterinary Neurology and Anatomic Pathology Services.)

Cytologic and Histologic Findings

On histologic or cytologic examination, fungi that cause phaeohyphomycosis appear as dark-walled, irregularly septate hyphae or as yeast-like cells, solitary or in small groups or chains (Figure 68-4). Pigmentation may not always be apparent on cytologic examination (Figure 68-5). The presence of melanin in the walls of lightly-pigmented hyphae can be confirmed by the examination of unstained sections, by lowering the microscope condenser during examination, or by utilization of a Fontana-Masson stain for melanin.

FIGURE 68-4 Histopathology showing small groups of pigmented, yeast-like fungal organisms in tissue from a nasal mass in a cat with phaeohyphomycosis; H&E stain. (Courtesy Amy Grooters, Louisiana State University, Baton Rouge, LA.)

FIGURE 68-5 Impression smear from the brain of the dog in Figure 68-3.
Septate, branching hyphae are present, but pigmentation is not clearly apparent. Wright’s stain, 1000× magnification. (Courtesy University of California, Davis, Veterinary Pathology Service.)

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