Acrophialophora fusispora brain abscess in a child with acute lymphoblastic leukemia: review of cases and taxonomy

Abstract

A 12-year-old girl with acute lymphoblastic leukemia was referred to King Faisal Specialist Hospital and Research Center. The diagnosis without central nervous system (CNS) involvement was confirmed on admission, and chemotherapy was initiated according to the Children Cancer Group (CCG) 1882 protocol for high-risk-group leukemia. During neutropenia amphotericin B (AMB) (1 mg/kg of body weight/day) was initiated for presumed fungal infection when a computed tomography (CT) scan of the chest revealed multiple nodular densities. After 3 weeks of AMB therapy, a follow-up chest CT revealed progression of the pulmonary nodules. The patient subsequently suffered a seizure, and a CT scan of the brain was consistent with infarction or hemorrhage. Because of progression of pulmonary lesions while receiving AMB, antifungal therapy was changed to liposomal AMB (LAMB) (6 mg/kg/day). Despite 26 days of LAMB, the patient continued to have intermittent fever, and CT and magnetic resonance imaging of the brain demonstrated findings consistent with a brain abscess. Aspiration of brain abscess was performed and the Gomori methenamine silver stain was positive for hyphal elements. Culture of this material grew Acrophialophora fusispora. Lung biopsy showed necrotizing fungal pneumonia with negative culture. The dosage of LAMB was increased, and itraconazole (ITRA) was added; subsequently LAMB was discontinued and therapy was continued with ITRA alone. The patient demonstrated clinical and radiological improvement. In vitro, the isolate was susceptible to low concentrations of AMB and ITRA. A. fusispora is a thermotolerant, fast-growing fungus with neurotropic potential. We report the first case of human infection involving the CNS. Acrophialophora resembles Paecilomyces but differs in having colonies that become dark and in the development of phialides along the sides or at the tips of echinulate brown conidiophores. Conidia are borne in long chains and are smooth or ornamented with fine-to-coarse echinulations, sometimes in spiral bands. The taxonomy of the genus Acrophialophora is reviewed, and Acrophialophora nainiana and Acrophialophora levis are considered as synonyms of A. fusispora.

FIG. 1

Chest CT showing nodular lung lesions with cavitation.

FIG. 2

(A) CT of the brain with contrast demonstrating the brain lesion in the left parieto-occipital region. (B) Brain magnetic resonance imaging with contrast showing the ring-enhancing lesion in the left parieto-occipital region with minimal surrounding edema.

FIG. 3

GMS stain of the brain abscess aspirate showing multiple fungal elements.

FIG. 4

Lung biopsy. (A) Cavitary lesion in the right lobe; (B) hematoxylin and eosin stain showing necrotizing cavitating pneumonia.

FIG. 5

Microscopic morphology. (A) Basally inflated phialides of case isolate, UTHSC 99-2508, occurring along the sides of thin-walled, hyaline-to-pale brown septate hyphae (magnification, ×306). (B) Proliferating phialides of the case isolate, UTHSC 99-2508 (magnification, ×306). (C) Long chains of limoniform-to-fusiform, one-celled, smooth, hyaline conidia of the case isolate, UTHSC 99-2508 (magnification, ×613). (D) Echinulate, brown, prostrate conidiophore of isolate UTHSC 96-2378, anchored by a definite basal hyphal cell (magnification, ×580). (E) Basally inflated phialides of dog isolate R-3122, borne along the sides of brown, echinulate conidiophores (magnification, ×306).

FIG. 6

Colonial morphology after 7 days of incubation on PDA at 37°C. (A) Colony of the case isolate, UTHSC 99-2508; (B) colony of dog isolate R-3122.

FIG. 7

Electron microscopy. (A) Scanning electron micrograph of smooth-to-slightly roughened conidia, soil isolate R-2942 (magnification, ×10,000). (B) Scanning electron micrograph of conidia with fine spirals, from human corneal isolate R-2944 (magnification, ×10,000). (C) Scanning electron micrograph of conidia with coarse spirals, from human bronchial washing isolate R-2943 (magnification, ×10,000).