A 39 year old African American male presents to the Emergency Department with a three day history of headaches and fatigue. The patient describes his headache as a sharp, constant pain that is exacerbated by movement. He also has been experiencing blurred vision and feeling unstable on his feet. His past medical history is significant for HIV diagnosed 8 years ago. On admission, his absolute CD4 count is 104 with a viral load of 150 vc/ml. He is compliant with his anti-retroviral therapy and Bactrim prophylaxis. Physical exam is unremarkable except for oral thrush. Imaging reveals multifocal areas of enhancement throughout the brain and cerebellum with associated vasogenic edema, which was thought to most likely represent an infectious process. The patient was taken to the operating room for a brain biopsy. Tissue was sent to surgical pathology and the microbiology laboratory for evaluation.
The histology results were reviewed first and the H&E stain showed a pyogranulomatous inflammatory response with budding yeast forms. These findings were better visualized on the GMS stain which illustrated numerous yeast forms ranging in size with frequent broad based budding. In the microbiology laboratory, a white-tan mold grew on Sabouraud dextrose, SAB with chloramphenicol and Mycosel agar slants after 18 days of incubation at 30°C. On microscopic examination, the lactophenol cotton blue prep revealed narrow septate hyphae with round conidia at the end of fine conidiophores (characterized as a lollipop appearance). These finding are consistent with a diagnosis of Blastomyces dermatiditis and were confirmed with a DNA probe. Other pertinent laboratory results included urinary antigens positive for both Blastomyces and Histoplasma and a negative cryptococcal antigen in the serum.
Blastomyces dermatiditis is a thermally dimorphic fungus found in the Midwest, Ohio and Mississippi River valleys and the south central portion of the United States. The infection is obtained by inhalation of spores from decaying wood along rivers and patients typically show symptoms consistent with pneumonia. In some cases, particularly in immunocompromised patients, dissemination to the skin, bone and central nervous system can occur.
Morphologic diagnosis can be made from surgical pathology specimens which show broad based, budding yeast forms with a double contoured cell wall, ranging in size from 8-15 µm. In the microbiology laboratory, the mold form grows slowly (2-3 weeks) and is characterized by narrow septate hyphae with delicate conidiophores bearing round to oval conidia which are described as lollipop-like. Due to that fact that Blastomyces is not able to be differentiated from the mold form of Paracoccidioides brasiliensis and Chrysosporium spp., confirmation of the identification is necessary. Traditionally, this was done by temperature induced culture conversion of the mold form to the yeast form but due to the availability of rapid, commercially available DNA probes specific for the exoantigen of Blastomyces dermatiditis, this test is more commonly utilized currently.
Other supplemental tests used in the diagnosis include a Blastomyces urinary antigen which shows good sensitivity in both pulmonary and disseminated disease. In our case, the positive urinary antigen for Histoplasma was considered to be a false positive result due to known cross reactivity with Blastomyces as a result of shared polysaccharides.
Cryptococcus neoformans was also included in the differential diagnosis due to the patient’s HIV status, presenting symptoms and the fact it is a common cause of fungal meningitis in individuals with CD4 counts below 200. This infection was ruled out due to a negative serum cryptococcal antigen. In addition, in tissue Cryptococcus would show variably sized (2-20 µm), narrow based yeast forms with a prominent polysaccharide capsule and grow quickly as a yeast in fungal culture.
In the case of our patient, he was started on Amphotericin B based on the histology results. He experienced resolution of his headaches and recovered well following surgery. His was discharged to an extended care facility for 6 weeks of continued IV antifungal therapy before being placed on oral voriconazole.
-Srinivasa Chekuri, MD, is a 4th year Anatomic and Clinical Pathology resident at the University of Mississippi Medical Center.
-Lisa Stempak, MD, is an Assistant Professor of Pathology at the University of Mississippi Medical Center in Jackson, MS. Currently, she oversees testing performed in both the Chemistry and Microbiology Laboratories.