Case 2 -

Cerebral Phaeohyphomycosis, Due to Bipolaris Spicifera Rebecca D. Folkerth - Brigham & Women’s Hosp, Boston, MA

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Introduction: 55yo M with hypertrophic cardiomyopathy, status post orthotopic heart transplant 6 weeks prior - On mycophenylate mofetil, prednisone, and cyclosporine At routine post-op visit, complained of 2 days of frontal headache and lethargy - Headache constant, 8/10, bifrontal, and unaffected by position; alleviated slightly by acetaminophen - No fever, neck stiffness, or vomiting - Wife reported he was less "like himself", with paucity and slowing of speech, and emotional blunting No recent travel or sick contacts; cats at home Employed as a high school woodshop teacher, on leave for several weeks surrounding his heart transplant On examination - T 96.7°F - BP 160/70 mmHg - Alert, oriented, and appropriately interactive, though with a reduced range of affect - Occasional paraphasic errors, and difficulty relaying complex portions of his history - Mild flattening of right nasolabial fold - Strength decreased in right triceps (4+/5) and bilateral ankle dorsiflexion (4/5) - Slight right pronator drift and decreased rapid finger-tapping with the right hand Labs: WBC count 7.36; cyclosporine trough level was 243 ng/mL (therapeutic range: 100-400 ng/mL). Magnetic resonance imaging: - Axial T1 with gadolinium 3cm lesion with nodular signal heterogeneity - Axial FLAIR Increased relative cerebral blood volume, moderate vasogenic edema, and 7mm midline shift Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: Brain biopsy is diagnostic, showing mixed chronic inflammatory reaction, often granulomatous and/or centered around cerebral blood vessels. Pigmented hyphae are readily seen, and can be confirmed with fungal stains (PAS, methenamine silver). Case 2 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 2 - Figure 1 Neuroimaging Case 2 - Figure 2 H&E 400x Case 2 - Figure 3 H&E 400x Case 2 - Figure 4 H&E 400x Case 2 - Figure 5 H&E 400x Differential Diagnoses: Based on the clinical presentation and neuroimaging findings, the differential is: - Abscess (Toxo, Fungus) - Tumor (Lymphoproliferative disorder, Glioma) - Vascular lesion ?? Final Diagnosis: Cerebral Phaeohyphomycosis, Due to Bipolaris Spicifera Case Discussion: Phaeohyphomycosis refers to infection by a pigmented ("dematiaceous") fungus. These organisms have melanin in their cell walls, and may appear grossly pigmented (black) when infecting the skin. Upon microbiologic culture, the colonies also are darkly pigmented. The agent is normally found in soil or decayed wood, and most frequently affects farmers. (In this case, the patient was a woodworker.) The usual route of infection is inhalation, explaining the high incidence of involvement of lungs or paranasal sinuses. (In this case, a route of infection was not identified, but was presumably via inhalation.) It is highly neurotropic, and can involve any part of the brain. It usually forms an abscess with mass effect, and may secondarily involve the meninges, including the dura mater. Importantly, unlike many other fungal infections of the brain, phaeohyphomycosis affects both immunocompetent and immunocompromised hosts (i.e., is not considered opportunistic). On neuroimaging, it appears as a "ring-enhancing" lesion with a core of low- attenuation signal, which can mimic high-grade glioma or metastasis. Because of this radiographic differential, biopsy is usually desired clinically, for definitive diagnosis. Laboratory testing may reveal elevated serum galactomannin levels, however, biopsy with culture is the only means to establish the identity of the infectious agent, and to prescribe appropriate azole antifungal therapy. Review of the Literature/Treatment Options (if applicable): Over 106 orders of fungi have been implicated, and new species are continually being identified. (The agent cultured in this case, Bipolaris spicifera, is relatively uncommon, mentioned in only 4 case reports in the literature. By contrast, Xylohypha (Cladophialophora) bantiana (mentioned in the case report by Dr. Scheithauer, published in 1993) is highly represented, seen in 48% of cases. This infection requires treatment with azole antifungals, despite which a high rate of mortality is associated. Conclusion(s): Cerebral phaeohyphomycosis is a distinctive cerebral infection, occurring in the immunocompetent as well as immunocompromised host, with typical pigmented hyphae in a granulomatous response. References: Hauck EF, McGinnis M, Nauta HJ. Cerebral phaeohypohomycosis mimics high- grade astrocytoma. Journal of Clinical Neuroscience 2008 Sep; 15(9):1061-6. Palaoglu S, Sav A, Basak T, Yalcinlar Y, Scheithauer BW. Cerebral phaeohyphomycosis. Neurosurgery. 1993 Nov;33(5):894-7. Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: A review of 101 cases. Clinical Infectious Diseases 2004; 38:206-16. Rosow L, Jiang JX, Deuel T, Lechpammer M, Zamani AA, Milner DA, Folkerth R, Marty FM, Kesari S. Cerebral phaeohyphomycosis caused by Bipolaris spicifera after heart transplantation. Transpl Infect Dis. 2011 Aug;13(4):419-23.