History
A 6-year-old neutered male domestic shorthair cat had a history of lethargy, trembling, stumbling, and falling over once. The cat had a decreased appetite of 1 day's duration. The cat had access to the outdoors for the last 2 months, and its vaccination status was not current.
Clinical and Gross Findings
At the initial evaluation, physical examination findings were unremarkable, excluding results of the neurologic examination. The cat was ataxic but did not have postural deficits. It was ambulatory without assistance. Absence of deep pain sensation was evident on the medial aspect of each pelvic limb. Bilateral direct and indirect pupillary light responses were considered normal. No signs of pain were elicited via neck manipulation. Clinicopathologic analyses revealed leukopenia (4.11 × 103 WBCs/μL; reference range, 5.1 × 103 WBCs/μL to 13 × 103 WBCs/μL) characterized by mild neutropenia (2.49 × 103 cells/μL; reference range, 2.9 × 103 cells/μL to 12 × 103 cells/μL).
The cat was hospitalized for a period of 5 days, during which time its neurologic status deteriorated. Initially, the cat remained bright, alert, and responsive but had worsening ataxia. The cat later became anorectic. On the fourth day, the cat was laterally recumbent, trembling, and nonambulatory. Pupillary light responses were decreased. The withdrawal reflexes were absent in both left limbs and decreased in both right limbs. The patellar reflex of the left pelvic limb was exaggerated, and anal tone was decreased. Because of the deterioration of the cat's condition, the owner elected euthanasia on the fifth day and necropsy was performed.
On gross examination, the cerebellum (particularly, the right lateral hemisphere and the vermis) was swollen with flattening of the cerebellar folia. The surface had multiple to coalescing gray-black areas overlaid by hyperemic leptomeninges (Figure 1). The brain was bisected along the midline, revealing a poorly circumscribed, 2-cm-diameter, gray-black mass. It effaced 60% of the white matter and the cerebellar folia within the ventrocaudal portion of the cerebellum.
Photographs of the caudolateral view of the cerebellum (A) and longitudinal cut surface of the brain (B) of a cat that had ataxia and was euthanatized because of progressively deteriorating neurologic function. Notice that the cerebellum is swollen with multiple to coalescing green-brown areas that are overlaid by hyperemic leptomeninges. On cut surface, a green-brown mass (2 cm in diameter) effaces approximately 60% of the ventrocaudal portion of the cerebellum.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Photographs of the caudolateral view of the cerebellum (A) and longitudinal cut surface of the brain (B) of a cat that had ataxia and was euthanatized because of progressively deteriorating neurologic function. Notice that the cerebellum is swollen with multiple to coalescing green-brown areas that are overlaid by hyperemic leptomeninges. On cut surface, a green-brown mass (2 cm in diameter) effaces approximately 60% of the ventrocaudal portion of the cerebellum.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Photographs of the caudolateral view of the cerebellum (A) and longitudinal cut surface of the brain (B) of a cat that had ataxia and was euthanatized because of progressively deteriorating neurologic function. Notice that the cerebellum is swollen with multiple to coalescing green-brown areas that are overlaid by hyperemic leptomeninges. On cut surface, a green-brown mass (2 cm in diameter) effaces approximately 60% of the ventrocaudal portion of the cerebellum.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic and Microbiologic Findings
Histologic examination of tissue sections revealed that the cerebellar white matter and cerebellar folia were effaced by a focally extensive area of inflammation and necrosis, which extended into the leptomeninges. The inflammatory infiltrate was composed of a large number of epithelioid macrophages, a moderate number of lymphocytes, fewer neutrophils and plasma cells, and occasional multinucleated giant cells. Pigmented brown hyphae were detected within macrophages and multinucleated giant cells, but most hyphae were free within the neuroparenchyma (Figure 2). The hyphae were 5 to 7 μm in diameter with septate parallel and nonparallel walls and occasional branching. Single-celled, ovoid to round (10 to 20 μm in diameter), thick-walled dilations appeared to be budding in chains from the hyphae. The remaining vessels had severe hypertrophy of the endothelial cells, surrounded by prominent lymphoplasmacytic perivascular cuffing. The leptomeninges were expanded by similar inflammation and fungal elements. Fungal hyphae with the same characteristics were visible in unstained sections of the cerebellum (Figure 3). Fungal culture of the cerebellum yielded Cladophialophora bantiana.
Photomicrograph of a section of the cerebellum of the cat in Figure 1. Multiple golden brown to black fungal hyphae are evident in epithelioid macrophages and multinucleated giant cells. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Photomicrograph of a section of the cerebellum of the cat in Figure 1. Multiple golden brown to black fungal hyphae are evident in epithelioid macrophages and multinucleated giant cells. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Photomicrograph of a section of the cerebellum of the cat in Figure 1. Multiple golden brown to black fungal hyphae are evident in epithelioid macrophages and multinucleated giant cells. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Photomicrograph of an unstained section of the cerebellum of the cat in Figure 1. Multiple aggregates of fungal hyphae with arboreal processes are evident. The hyphae are brown and range from 5 to 7 μm in diameter with septate parallel and nonparallel walls and occasional branching. In this view, numerous ovoid to round (10 to 20 μm in diameter) dilations are budding in a chain (ie, conidial chain) from a hypha (arrow). Bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Photomicrograph of an unstained section of the cerebellum of the cat in Figure 1. Multiple aggregates of fungal hyphae with arboreal processes are evident. The hyphae are brown and range from 5 to 7 μm in diameter with septate parallel and nonparallel walls and occasional branching. In this view, numerous ovoid to round (10 to 20 μm in diameter) dilations are budding in a chain (ie, conidial chain) from a hypha (arrow). Bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Photomicrograph of an unstained section of the cerebellum of the cat in Figure 1. Multiple aggregates of fungal hyphae with arboreal processes are evident. The hyphae are brown and range from 5 to 7 μm in diameter with septate parallel and nonparallel walls and occasional branching. In this view, numerous ovoid to round (10 to 20 μm in diameter) dilations are budding in a chain (ie, conidial chain) from a hypha (arrow). Bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 236, 3; 10.2460/javma.236.3.295
Morphologic Diagnosis
Severe, focally extensive, necrotizing pyogranulomatous meningoencephalitis with intralesional dematiaceous fungal hyphae, consistent with C bantiana.
Comments
Cladophialophora bantiana is a pigmented fungus in the phylum Ascomycota.1 Cladophialophora bantiana has had several names, including Torula bantiana, Cladosporium bantianum, Xylohypha bantiana, Cladosporium trichoides, and Xylohypha emmonsii.1–6 It is typically found in soil and decomposing plant material worldwide, particularly in tropical and subtropical regions.1,2,5,6 It is the most common cause of cerebral phaeohyphomycosis in humans and cats.3,6 Phaeohyphomyocosis is defined as an infection that is caused by a fungus that contains melanin in its cell walls (ie, dematiaceous fungi).3–6 Cladophialophora bantiana can affect animals other than humans, of which cats appear most susceptible.4 Melanin is thought to be a factor in the virulence of C bantiana, although the exact pathogenesis of infection is not completely understood.1,6 Approximately 15 agents have been identified as causes of phaeohyphomycosis in cats7; most are plant pathogens, laboratory contaminants, and saprophytes.4
For most affected animals, it is not known how C bantiana infects the brain. The most accepted hypothesis is that an animal inhales the spores, which subsequently enter the lungs1,2,5,6; from the lungs, the organisms enter the bloodstream and spread hematogenously to the brain.6 Cladophialophora bantiana is considered neurotropic and has the ability to invade the CNS in immunocompetent and immunocompromised animals.1–5 In cats, C bantiana causes granulomatous or pyogranulomatous lesions in the CNS, which are often accompanied by meningitis.2
Neurologic signs of this disease vary, depending on which part of the brain is affected. An affected animal may have altered mentation, ataxia, postural reaction deficits, seizures, or cranial nerve abnormalities.5 Magnetic resonance imaging or computed tomography typically reveals areas in the brain that are suggestive of a space-occupying mass.5
Grossly, tissue lesions caused by C bantiana may be gray, green, or brown of varying intensity,5 although the pigmentation of the organisms cannot always be observed in tissues.7 The lesions are typically well defined but nonencapsulated, and the meninges can be adherent to the lesion. Distribution can be focal or multifocal; multifocal lesions are more common.3 Lesions of similar appearance (eg, hematomas, melanomas, and other pigmented lesions) can confuse the diagnosis.2
To definitively diagnose phaeohyphomycosis, histologic examination and mycologic culture of affected tissues are required.1–3,6 Granulomatous inflammation and necrosis are major histologic features that are typically associated with brown to black intralesional septate fungal hyphae.2,4,5 However, the pigment may only be visible in culture conditions and not evident in tissue sections.2,5,7 The hyphae are 2 to 7 μm in diameter and occasionally septate and can be branched or nonbranched.2,5 Long, oval, and single-celled sparsely branching conidial chains are characteristic of C bantiana.1,3,4
Because C bantiana can cause life-threatening disease in humans, the organism should only be handled with biosafety level 2 containment; when samples from animals for which C bantiana infection is a differential diagnosis are submitted for analysis, the diagnostic laboratory should be alerted to that fact.1,6 In fungal culture, the colonies appear olive green, brown, or black.1–4 Cladophialophora bantiana can be slow growing and frequently requires > 4 days to form visible colonies.1,2,4 The identification of C bantiana relies primarily on lesion characteristics, growth of the organism at 42° to 43°C, and PCR assay results.1–4
There is no definitive treatment for this disease in humans and cats, although most physicians and veterinarians agree that an aggressive approach must be taken.1–3,6 Surgical resection, if possible, and treatment with antifungal agents are effective in some cases, but no 1 regimen is consistently successful.1,2 Several antifungal agents, including amphotericin B, flucytosine, fluconazole, and itraconazole, have been used to treat C bantiana infections, but the fungus is frequently refractory to 1 or multiple treatment options.1–3,5,6 Administration of combinations of these drugs may result in improved survival rates, but no research has been done to evaluate that possibility to the authors' knowledge.6 In cats, initial improvement may be evident immediately following corticosteroid treatment but administration of that drug is not recommended because of the concern of worsening the infection.5
For cats with cerebral phaeohyphomycosis, overall prognosis is poor, especially in animals with multiple lesions.5 Even if the initial focal lesion is removed and treated, relapse is likely.1,2,5 The main prognostic indicator seems to be the ability to completely resect the lesion.1,3,5,6 Unfortunately, the outcome in most cases is death.
References
- 1.↑
Coldrick O, Brannon CL, Kydd DM, et al. Fungal pyelonephritis due to Cladophialophora bantiana in a cat. Vet Rec 2007;161:724–727.
- 2.↑
Abramo F, Bastelli F, Nardoni S, et al. Feline cutaneous phaeohyphomycosis due to Cladophyalophora bantiana. J Feline Med Surg 2002;4:157–163.
- 3.↑
Deb S, Khan AK, Debasish B, et al. Intracranial necrotizing granuloma caused by Cladophialophora bantiana. Neurol India 2005;53:335–336.
- 4.↑
Elies L, Balandraud V, Boulouha L, et al. Fatal systemic phaeohyphomycosis in a cat due to Cladophialophora bantiana. J Vet Med A Physiol Pathol Clin Med 2003;50:50–53.
- 5.↑
Mariani CL, Platt SR, Scase TJ, et al. Cerebral phaeohyphomycosis caused by Cladosporium spp. in two domestic shorthair cats. J Am Anim Hosp Assoc 2002;38:225–230.
- 6.↑
Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: a review of 101 cases. Clin Infect Dis 2004;38:206–216.
- 7.↑
Armed Forces Institute of Pathology Web site. Wednesday Slide Conference 2006–2007, Case II, conference 15. Available at: vp4.afip.org/wsc/wsc06/06wsc15.pdf. Accessed Mar 12, 2009.
