Contributed by Stephen E. Mason MD, Nathaniel D. Dueker MD, Charles W. Stratton MD, William O. Whetsell, Jr. MD
DIAGNOSIS: CEREBRAL PHAEOHYPHOMYCOSIS
DISCUSSION:
The term "phaeohyphomycosis" was originally coined as a histopathologic term to designate subcutaneous and deep-seated infections by dematiaceous fungi, i.e., infections caused by any species of the mycotic genus Dematium. More recently, the term has come into broader use to describe infections at any site cause by species within the genus Dematium (1) including Xylohypha bantiana (previously known as Cladophialophora bantiana) (2, 3, 4), Wangiella dermatitidis (previously known as Exophiala dermatitidis) (5, 6), Onchronoconis gallopavum (7, 8) and Ramichloridium mackenziei (9, 10). An interesting characteristic of these organisms is neurotropism in humans, which, though well documented, is not understood (11).
Cerebral phaeohyphomycosis is a rare but well-delineated disease entity. It is a clinical syndrome diagnosed in those patients with deep-seated cerebral infections secondary to dematiaceous fungi. Such infections have been attributed to multiple species of dematiaceous (darkly pigmented) fungi, but Xylohypha bantiana (previous known as Cladophialophora species) is the most common (11). The pigmented nature of this organism has been shown to be due to melanin, which it produces, and this feature may assist this organism in evading host defenses (12). Wangiella dermatitidis and
C. neoformans Melanin-negative mutants show reduced virulence when compared to their wild-type counterparts. This may be, in part, secondary to melanin's inherent quality as a buffer against host oxidation killing mechanisms. The melanin specific stain, Fontana-Masson, can be used for further identification of the organism. Other dematiaceous fungi known to cause cerebral infection include Ramichloridium mackenziei, Wangiella dermatitidis and Bipolaris sp. (13). R. mackenziei is the only organism showing a recurrent geographic distribution with all but one reported case occurring in the Middle East. The majority of cases reported in North America have occurred secondary to Xylohypha bantiana (11).
Localized superficial infections with dematiaceous fungi are not uncommon and produce subcutaneous involvement, otitis and sinusitis (14). Cerebral phaeohyphomycosis is the most common as well as the most serious and devastating of the deeper forms of dematiaceous fungal infection though other deep localized infections such as arthritis and endocarditis have been described (13).
Several dematiaceous fungi are known for their neurotropism including Xylohypha bantiana, the causative organism in this case (12). While it seems logical that CNS infections may occur from direct spread from paranasal sinuses, only one case recorded in the literature had concomitant colonization of paranasal sinuses (15). It therefore seems likely, though yet unproved, that central nervous system seeding occurs by the hematogenous route, probably initiated by a respiratory colonization consequent to inhalation. However, the low frequency of CNS infections by Xylohypha bantiana has thus far obviated elucidation of this mechanism. In our case, overwhelming acute broncho-pneumonia obscured clear assessment or confirmation of pulmonary fungal colonization.
Successful treatment regimens for cerebral phaeohyphomycosis have been described to combine early, aggressive surgical debridement with long-term anti-fungal therapy. Despite these therapies, however, the mortality rate is dismal approaching approximately 75% in reported cases (11).
A typical but particularly confounding and peculiar feature of this infection is that it occurs primarily in immunocompetent males with no obvious risk factors, whereas most other deep-seated fungal/mold infections occur in immunosuppressed individuals. It should be noted, however, that a few cases of cerebral Xylohypha bantiana infection have been described in immunocompromised individuals (11).
In the microbiology lab, the differential diagnosis for Xylohypha bantiana by culture-plate morphology is primarily Aspergillus Niger because of the velvety-black growth. However, in Aspergillus Niger, the reverse side of the plate should be creamy-tan and not black like that seen in dematiaceous fungal growth. In carrying out laboratory analysis of specimens from ring-enhancing CNS lesions in immunocompetent patients (especially males), it is important to consider cerebral phaeohyphomycosis in the differential diagnosis, and particular laboratory precautions are recommended when dematiaceous fungal infection is suspected. Specimens should be handled with Biosafety Level 2 containment because of the known pathogenesis of these organisms in immunocompetent hosts and their ability to be aerosolized, and when cerebral phaeohyphomycosis is suspected or considered, slide cultures should not be made.
REFERENCES
Contributed by Stephen E. Mason MD, Nathaniel D. Dueker MD, Charles W. Stratton MD, William O. Whetsell, Jr. MD
International Society of Neuropathology