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We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales.

A 47-year-old diabetic man with chronic renal failure presented with a 1-month history of complete ptosis of the left upper eyelid, left proptosis, and left-sided headache. During the course of the patient's care, other significant diagnoses were excluded, such as orbital inflammatory syndrome, carotid-cavernous syndrome, and cavernous sinus thrombosis. Neuroimaging revealed only minimal left sphenoid sinus disease. Sphenoid biopsy revealed the presence of septate hyphae on Gram staining and produced a fungal culture characteristic of Schizophyllum commune. Minimal sphenoid sinus infection in a patient with chronic medical issues and probable immunosuppression predisposed this patient to fungal rhino-orbital infection. Several weeks of intravenous liposomal amphotericin treatment on an outpatient basis yielded resolution of clinical symptoms.

Among species of the heterobasidiomycetous yeasts, Filobasidiella neoformans is the only serious pathogen that causes fatal infections in both immunocompromised as well as immunocompetent patients. Three phenotypic characteristics, including growth at 37 degrees C, extracellular polysaccharide capsule and laccase activity, of F. neoformans are known to play major roles in the pathogenicity of the fungus. Several CAP genes involved in polysaccharide capsule formation, as well as the CNLAC1 gene encoding a laccase, have previously been cloned and characterized. To analyse the presence of these Cryptococcus neoformans virulence factors in other heterobasidiomycetous yeasts, numerous species of heterobasidiomycetous yeasts were screened for the presence of laccase activity and a polysaccharide capsule. Species exhibiting laccase activity and possessing a glucuronoxylomannan (GXM) capsule were screened for homologues of both the CAP59 gene and the CNLAC1 gene of F. neoformans. Southern blots of genomic DNA from GXM capsule-producing species exhibited no discernible hybridization to the CAP59 DNA sequence except for the two varieties of F. neoformans and Cryptococcus podzolicus. Although discernible, the hybridization band observed with the DNA of C. podzolicus was faint. Oligonucleotide primers constructed using the CAP59 gene sequence also failed to yield PCR products from DNAs of these yeasts except for the two varieties of F. neoformans. These results, coupled with the absence of a CAP59 homologue in the database, suggested the CAP59 gene to be unique to F. neoformans. C. podzolicus was the only species besides F. neoformans that possessed a capsule and expressed strong laccase activity on various media containing phenolic compounds. A CNLAC1 homologue was isolated from C. podzolicus while it was not detected in the species producing beige to faint tan colonies on media with phenolic compounds. Compared to the CNLAC1 sequence of four serotypes of F. neoformans, the CNLAC1 homologue of C. podzolicus showed the highest homology to that of serotype B/C strains and the lowest homology to that of serotype A strains.

We report the first case of invasive disease caused by Fusarium chlamydosporum. The patient had aplastic anemia with prolonged neutropenia and was treated with immunosuppressive therapy. While she was receiving empirical amphotericin B, a dark crusted lesion developed on her nasal turbinate. Histologic analysis revealed invasive hyaline hyphae and some darkly pigmented structures that resembled conidia of dematiaceous molds. Only after the mold was grown in culture were characteristic colonial morphology, phialides, conidia, and chlamydospores evident, thus permitting the identification of F. chlamydosporum. This case illustrates the ever-increasing spectrum of pathogenic Fusarium spp. in immunocompromised patients and emphasizes the potential pitfalls in histologic diagnosis, which may have important treatment implications.

Genetic engineering is an important tool in helping us to define the molecular basis of pathogenicity and is also useful in helping us to identify new therapeutic targets in pathogenic fungi. Molecular genetic manipulation of micro-organisms requires the development of plasmid-mediated transformation systems that include: (i) infusion of exogenous DNA into recipient cells, (ii) expression of genes present on the incoming DNA, and (iii) stable maintenance and replication of the inserted DNA leading to expression of the desired phenotypic trait. Transformation systems have been developed for only a handful of fungi that are pathogenic to humans including several species of Candida, Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces derrmatitidis, Aspergillus fumigatus, Wangiella dermatitidis (Exophiala dermatitidis) and Coccidioides immitis. Except for Candida species and A. fumigatus, where passage of exogenous DNA into recipient cells has been achieved readily using methods developed for transformation of Saccharomyces cerevisiae and Aspergillus nidulans, respectively, development of transformation systems in other pathogenic fungi has been delayed considerably and has only been possible recently with the introduction of electroporation and biolistic methods. Conventional spheroplasting methods or cell wall permeabilization methods using lithium acetate have not been successful for transformation of C. neoformans and work with only low efficiency in H. capsulatum. The fate of incoming DNA varies greatly in these pathogenic species regardless of their phylogenetic relationships. Understanding the fate of incoming DNA is critical for the construction of transforming vectors and the molecular manipulation of the organisms. In this symposium, recent advances in molecular genetic systems including transformation systems, the fate of incoming DNA and strategies for targeted integration are discussed in relation to four pathogenic fungi.

An 8-year-old boy who had chronic granulomatous disease developed a soft tissue infection of the right heel after riding on a motor scooter. Infection was insidious, and minor heel pain and fevers occurred only on the day interferon-gamma was injected. Soft tissue biopsy showed hyphal elements, and Paecilomyces varioti grew in culture. The infection was treated with amphotericin B for 7 weeks (total dose, 40 mg/kg) followed by 1 year of therapy with itraconazole (100 mg twice daily). Complete cure was achieved during the follow-up period of 10 months.

Exophiala dermatitidis, one of the saprophytic dematiaceous fungi, is a rare cause of human infection that, when invasive, is nearly always fatal. Besides the more common subcutaneous infection usually caused by traumatic inoculation, infection can also spread hematogenously, in which case the organism has a distinct neurotropism. A patient with autosomal recessive chronic granulomatous disease of childhood who was found to have a progressive pulmonary and central nervous system infection with E. dermatitidis responded to an aggressive, multifaceted therapeutic approach. Scanning electron microscopy of the cultured conidiogenous cells confirmed that the manner of conidiogenesis is typical of the genus Exophiala. We report the first successful treatment of an infection involving the lungs and central nervous system by a combination of surgical resection of the pulmonary source and medical therapy with amphotericin B, flucytosine or ketoconazole, and transfused white cells, followed by a prolonged course of fluconazole.

We report two cases of allergic bronchopulmonary fungal disease (ABPFD) caused by Curvularia sp and associated with allergic fungal sinusitis (AFS). Curvularia lunata was cultured in one case and Curvularia senegalensis was cultured in the other. Based on these cases and a review of the literature, we discuss unusual clinical and pathologic features that can occur in ABPFD. Unusual clinical aspects of ABPFD include associated AFS, absence of asthma, progression to Churg-Strauss angiitis and granulomatosis, concomitant hypersensitivity pneumonitis, and underlying cystic fibrosis. Atypical pathologic features that may occur in ABPFD include follicular bronchiolitis, xanthomatous bronchiolitis, limited tissue invasion, fungus balls, and association with unusual fungi. Prominent follicular bronchiolitis and xanthomatous bronchiolitis were misleading histologic features in one of our cases and led to a delay in recognition of the diagnosis. Both patients presented primarily with AFS; ABPFD was detected subsequently. This suggests that a small subset of patients with AFS may be at risk for ABPFD. The goal of this review is to increase awareness of unusual clinical and pathologic manifestations of ABPFD. It is hoped that this will result in accurate diagnosis and proper therapy, especially for patients who present with atypical features. Unusual fungal species should be considered in patients who have clinical findings compatible with ABPFD but who do not demonstrate immunologic reactivity to Aspergillus sp, especially Aspergillus fumigatus. In addition, ABPFD should be considered in patients with AFS who develop new pulmonary lesions.

This is the first reported infection by the saprophytic fungus, Phialophora repens. The infection was a solitary granulomatous nodule in the scalp of a Zaïrian man with advanced lepromatous leprosy. The patient was being treated by long-term prednisolone therapy. In tissue sections there were nonpigmented microcolonies composed of irregularly branched septate hyphae. A darkly pigmented fungus was isolated on Sabouraud's medium. The mycologic features of the etiologic agent were typical of P. repens. The infection was treated successfully by excision of the nodule.

A case of recurrent systemic infection caused by Phialophora parasitica occurred in an elderly woman and over a 4-year period was documented (either clinically or at autopsy) to involve two sites on the chest wall, the hip, the vertebral body, and the aorta. The infection was treated with intravenous amphotericin B and a subsequent course of terbinafine. To our knowledge, this is the first reported case of disseminated infection by P. parasitica with systemic involvement as well as of its treatment with terbinafine. The literature on human infection caused by P. parasitica, which is rare and has occurred in both normal and compromised hosts and with and without antecedent trauma, was reviewed; problems encountered both in the laboratory identification of P. parasitica and in therapy were assessed.

Disseminated infection caused by Fusarium moniliforme is described in a 32-year-old granulocytopenic man with malignant lymphoma being treated with cytotoxic drugs and corticosteroids. Infected skin denuded by antecedent severe varicella-zoster infection was the probable source of fungemia. F. moniliforme grows rapidly on common mycological media as a lavender- to violet-colored mold at 25 to 37 degrees C. Its aerial hyphae produce fusoid macroconidia and characteristic fusiform microconidia in chains. The morphology of hyphae in tissue closely resembles species of Aspergillus and is not diagnostically specific. Morphological characteristics which distinguish cultures of F. moniliforme from other medically important species of Fusarium are discussed.

A zygomycotic (phycomycotic) orbital cellulitis developed in a healthy 9-year-old boy. Because of the involved tissue's unfamiliar histopathologic features, an initial diagnosis of eosinophilic granuloma was made and appropriate treatment was delayed for more than six months. The patient's slowly progressive form of zygomycosis was clinically and morphologically similar to that described in previously recorded cases. All three cases occurred in otherwise healthy children living within the United States. Their involved tissues had mixed histopathologic features of chronic granulomatous entomophthoramycosis and acute necrotizing mucormycosis; however, unlike entomophthoramycosis, the fungi in these cases may invade the walls of blood vessels and cause severe tissue necrosis. We believe that these three cases represent a distinct clinicopathologic variant of facial-cranial zygomycosis not previously delineated in the literature. Although they are aggressive, these infections are not as fulminant as in classic mucormycosis, but can nevertheless be lethal.

Anthopsis deltoidea was found to be the cause of an olecranon bursitis in a 79-year-old golfer. Serial histological sections of the olecranon bursa showed faintly stained, brown-walled, septate, hyphal elements in the centers of the necrotic debris. The combination of bursectomy and flucytosine treatment cured the infection.

A brain abscess caused by a new variety of Cladosporium trichoides occurred in a previously healthy man. A reversed T-suppressor/helper cell ratio was noted as the only immunologic abnormality. He required three surgical procedures, the last an occipital lobectomy, and antifungal chemotherapy to control his disease. He received 2,068 mg of amphotericin B and one year of flucytosine at 6 g per day. Ten months after the last surgery he is without evidence of disease. C. trichoides var. chlamydosporum was isolated from the abscess. It differed from C. trichoides by producing chlamydospores in vitro and only hyphae in the brain abscess. On modified Sabouraud agar, the fungus did not grow at 25 degrees C and grew poorly at 30 degrees C and 37 degrees C. Histologic sections revealed necrosis, no encapsulation, and no epitheliod cells.