February 2021 — Infectious Disease Pathology and Clinical Microbiology
A 70-year-old woman with a history of living-related renal transplant and Crohn’s disease presents shortness of breath, sore throat, a hoarse voice, and weight loss. She is currently receiving immunosuppressive therapy to maintain her transplanted kidney. Routine labs demonstrated elevated leukocytes with a neutrophilic predominance, with imaging highlighting a soft tissue mass in the right posterior pharynx. Diagnosis on frozen section was requested and showed multiple budding yeasts.
What is the most likely identification of the yeast present?
- Blastomyces dermatitidis/B. gilchristii
- Histoplasma capsulatum
- Paracoccidioides brasiliensis
- Coccidioides immitis/C. posadasii
The correct answer is ...
The diagnosis in this case is: Blastomyces dermatitidis/B. gilchristii.
Blastomyces dermatitidis and B. gilchristii are the causative agents of blastomycosis. Blastomycosis is an invasive and sporadic fungal infection that may present as an insidious and sometimes fatal fungal pneumonia throughout regions where it is endemic. It is endemic in select regions of Africa,1 and the central and eastern United States and Canada, surrounding the Ohio and Mississippi river valleys and the Great Lakes. It shares some geographical overlap with histoplasmosis, which is also found along the Ohio and Mississippi river valleys.2 First described in 1894 by Thomas Gilchrist, it can sometimes be found in the literature as “Gilchrist’s disease.”
Blastomyces spp. are thermally-dimorphic fungi, a distinction which signifies growth in a mold form at environmental temperatures, and in a yeast form when grown in a warmer animal host. Of the dimorphic fungi, Blastomyces spp. can be differentiated by their fairly uniform and large size (ranging from 8–15 um), broad-based budding, and a thick, double-layered cell wall. They are readily identifiable on routine hematoxylin/eosin and Grocott’s methenamine silver staining, and are commonly seen in a mixed granulomatous and suppurative inflammatory (i.e., pyogranulomatous) background. Blastomycosis involving the squamous epithelium (such as in this case) is commonly associated with pseudoepitheliomatous hyperplasia, which may be mistaken for squamous cell carcinoma.3 Therefore, a careful search for budding yeasts within areas of neutrophilic inflammation and within multinucleated giant cells is indicated.
Blastomyces dermatitidis and B. gilchristii are morphologically indistinguishable, therefore additional testing such as PCR may be needed to differentiate them. Species identification is not necessary for treatment and is infrequently performed.
The fungus can be found throughout the environment, favoring moist soil and decomposing organic matter (e.g. trees and leaves). Infection can occur after an environmental exposure if the individual breathes in the microscopic fungal spores. Approximately one-half of those infected with the fungus experience symptoms, which typically present with nonspecific signs: fever, cough, muscle pain, shortness of breath, and weight loss. Patients with a long-standing infection and immunocompromised patients can exhibit more severe disease as the fungus disseminates throughout the body.4 The skin is most commonly affected, but can also disseminate to the central nervous system, genitourinary, and skeletal sites.
A combination of clinical features (especially one’s travel history,) biopsy, fungal culture, and morphological assessment are used to diagnose the infection. When possible, histopathological sectioning is helpful in highlighting its association with pyogranulomatous response.5 Commercially available serum and urinary antigen testing is available and has shown to be sensitive in instances where fungal cultures are negative.
- Alvarez G, Burns B, Desjardins M, Salahudeen S, AlRashidi F, Cameron D. Blastomycosis in a young African man presenting with a pleural effusion. Can Respir J. 2006;13(8):441-444.
- Bradsher RW, Chapman SW, Pappas PG. Blastomycosis. Infect Dis Clin North Am. 2003;17(1):21-40, vii.
- Bradsher RW. The endemic mimic: blastomycosis an illness often misdiagnosed. Trans Am Clin Climatol Assoc. 2014;125:188-203.
- McBride JA, Gauthier GM, Klein BS. Clinical manifestations and treatment of blastomycosis. Clin Chest Med. 2017;38(3):435-449.
- Martynowicz MA, Prakash UBS. Pulmonary blastomycosis: an appraisal of diagnostic techniques. Chest. 2002;121(3):768-773.
Nicholas Boire, M.D., M.Sc.
Resident, Anatomic and Clinical Pathology
Bobbi Pritt, M.D., M.Sc., DTMH, FCAP
Consultant, Laboratory of Clinical Microbiology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science