Phaeohyphomycosis is the collective term for infections caused by dematiaceous or darkly pigmented fungi. They derive their black color by generating melanin in their cell walls.
A 64-year-old male, chronic smoker, construction worker, and avid hunter presented with a one-week history of confusion and staggering gait leading to a fall. He also complained of cough productive with black sputum. Family and travel histories were unremarkable; however, social history was remarkable for a recent devastating flood in the town where he lived that sustained a large amount of water and mud damage. On presentation, his vital signs were normal. On examination, the patient was alert but not oriented. On chest auscultation, decreased breath sounds were noted in the left lower lobe. Neurological, cardiovascular, and abdominal examinations were otherwise within normal limits. His initial set of labs revealed mild leukocytosis, a negative procalcitonin, and hyponatremia. Chest X-ray (CXR) demonstrated left lower lobe pneumonia. With this information, he was therefore thought to have community-acquired pneumonia and was initiated on azithromycin 500 mg intravenous (IV) daily, ceftriaxone 1 g IV daily, and IV hydration.
Due to his initial neurologic complaints, a brain computed tomography (CT) was completed (Figure
CT brain axial view demonstrating left frontal lobe mass concerning for glioblastoma.
MRI brain axial view demonstrating multiple enhancing masses coalescing into a larger mass with surrounding edema resulting in midline shift involving anterior corpus callosum.
CT chest demonstrating multifocal pneumonia in the left lung base with areas of suspected internal necrosis. No mediastinal lymphadenopathy is visible.
With the possibility of the brain lesion still being a glioblastoma, a stereotactic brain biopsy was performed first instead of a bronchoscopy. This biopsy revealed numerous light brown, long sparsely branching septated hyphae with dilated spores positive on Gomori methenamine silver (GMS) stain and periodic acid-Schiff (PAS) light green stains. Cultures were unfortunately not sent from this tissue at this time. Based on these pathology results, infectious disease consultation was sought, and empiric liposomal amphotericin 5 mg/kg IV daily with concurrent voriconazole 300 mg IV every 12 hours was initiated. At this time with a possible disseminated fungal disease on the differential, bronchoscopy was pursued. There were no endobronchial lesions present. Fungal culture of lung biopsies was completed at 35°C and revealed
With the still unidentified fungal brain abscess and the size of the lesion portending a poor prognosis if treated only medically, neurosurgery team performed a craniotomy with the intention of complete resection. Unfortunately, only a partial resection was achievable due to the location and size of the mass. Fungal culture of the brain tissue was completed on BBL™ Sabouraud Dextrose Agar, BBL™ Inhibitory Mold Agar, and BBL™ Brain Heart Infusion Agar with 5% Sheep Blood (BD Biosciences: Becton, Dickinson and Company, Sparks, MD) with mold isolated after 6 days after inoculation at 35°C. The isolates were described as velvety green-brown in color with very long chain length, minimal branching, and oval conida. Visual identification was made as
The presence of two rare infections in an otherwise immunocompetent individual prompted an immunological evaluation including immunological levels of Immunoglobulin (Ig) A, E, G, and M, Herpes Simplex virus PCR, CD4 counts, T4/T8 ratio, B cell count, and Natural killer cell count and however did not reveal a cause of low IgG. He was therefore treated with human IV immunoglobulin (IVIG) Octagam® 5% 500 mg/kg IV. His 6 week hospital course was complicated by cachexia, physical deconditioning, poor neurological status, and aspiration pneumonia with recurrent episodes of sepsis. Considering his poor overall state of health and grim prognosis with incomplete resection, palliative services were consulted and family decided to withdraw further medical care and transfer to hospice for comfort care.
Fungal infections account for less than 2% of brain abscesses [
Several environmental factors and nature of occupation appear to have some role, and the pathogen commonly inoculates through the skin after laceration. Inhalation of spores, direct extension from paranasal sinuses, and penetrating trauma to the brain are among the other suggested modes of infection [
In fact, the most common manifestation of CNS phaeohyphomycosis is a solitary brain abscess which occurs in approximately two-thirds of cases, but multiple easily identifiable abscesses can also be seen on CT scan or MRI [
Radiographically,
Despite the opportunistic nature of fungal infections, more than half of patients affected with primary cerebral phaeohyphomycosis are immunocompetent individuals [
Mortality rate of cerebral phaeohyphomycosis is 70% or more despite aggressive measures including neurosurgical intervention and long-term systemic antifungal therapy [
Although invasive treatment of bacterial brain abscesses has evolved in an era of minimally invasive neurosurgical management, surgical resection is still recommended as adjunctive therapy in brain abscesses particularly in fungal infections [
Several distinctive aspects exist to our case. The presence of both lung and brain masses in a high-risk patient in an area of high lung cancer incidence and with radiographic characteristics of glioblastoma with possible pneumonia prompted only consideration of malignancy on the differential of the brain abscess. This diagnosis was delayed by not sending culture data from the initial brain biopsy. The presence of a completely separate lung infection also contributed to delay. Based on the limited existing evidence and experience from our case, it is easy to conclude that outcomes depend on early and accurate diagnosis. We suggest multidisciplinary approach involving neurology, neurosurgery, infectious disease, microbiology, and pathology for accurate diagnostic confirmation and minimizing delay. Confirmatory molecular testing of molds is now recommended for accurate identification and susceptibility testing. Multimodal therapy with two to three antifungals along with surgical resection may improve outcomes. However, there is a paucity of data and guidelines to determine a standardized approach to infections from these rare black molds. Cases should be handled with care not only for proper diagnosis but also for prevention of infecting individuals involved in the patient’s case.
Central nervous system
Computed tomography
Chest X-ray
Gomori’s methenamine silver
Intravenous
Intravenous immunoglobulin
Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry
Minimum inhibitory concentrations
Brain magnetic resonance
Periodic acid-Schiff
Polymerase chain reaction
Rolling circle amplification.
The case was presented as a poster in American Thoracic Society Conference 2018. Abstract can be found at
The authors declare that they have no conflicts of interest.
MFK collected medical information and drafted the manuscript. REI and CPS participated in the care, reviewed the available literature, and contributed to critical review of the literature. All authors read and approved the final manuscript.