Introduction

Phaeohyphomycosisis a term used to describe infections caused by fungi that contain melanin in their cell walls and was described in 1974 by Ajello et al.(1-3) These ubiquitous organisms have been isolated as plant parasites or saprophytic fungi from soil, water, and air.(4) The fungi are also referred to as phaeoid, dematiaceous, darkly pigmented, and they elicit an array of clinical syndromes, spanning solitary subcutaneous nodules associated with local trauma to life-threatening infections, such as brain abscess and disseminated disease.(5-8)

Bulk of the fungi are molds, and frequently cause infection in immunocompetent individuals, contrary to infection with other more common molds like Aspergillus, which typically involves highly immunocompromised patients.(9)

Fungal brain abscesses are usually related to immunocompromised state. An exception to this rule is, cerebral phaeohyphomycosis (CP) caused by darkly pigmented fungi owing to the fact that around one-half of these were seen in patients with no underlying disease or risk factors. Despite that CP is an extremely uncommon cause of brain abscess, it is often fatal irrespective of the immune status.(10-12)

Characteristic features of dematiaceous fungus, attributable to the presence of melanin in its cell wall distinguishes it from the other common fungi affecting the CNS. The melanin apart from imparting a brown colour to this fungus,contributes to its neurotropic nature andis responsible for its virulence as it interferes with the microglial cells. It probably extends a defence by scavenging free radicals and hypochlorite that are generated during oxidative burstin phagocytic cells. Furthermore, melanin by binding, mayprevent the action of hydrolytic enzymes and antifungal drugs on the plasma membrane.(9,13) These collective functions assists in explaining the pathogenic potential of some dematiaceous fungi in a immunocompetent host.(9)

We hereby present a case of cerebral phaeohyphomycosis.

Case Report

A 45-year-old male, farmer by occupation, was referred from an outside hospital in an unconscious state with one day history of multiple episodes of seizures. Patient was on mechanical ventilation. On examination, patient was afebrile and vital signs were stable. Haematology reports showed neutrophilic leucocytosis. Procalcitonin levels were in the upper limits of normal range.Serological tests for Hepatitis B,Hepatitis C and Human immunodeficiency virus/HIV were negative.

Computed Tomography/CT scan of the head showed a well-defined heterodense lesion in the right parieto-occipital lobe (parasagittal in location) with perilesional vasogenicedema and mass effect. Magnetic Resonance Imaging/ MRI of brain (plain and contrast) with Magnetic Resonance Spectroscopy showed a well-defined intra-axial irregular ring enhancing solid lesion measuring 2.7 x 2.5 x 2 cm in the right parietal lobe with adjacent white matter infiltration and mass effects. (Figure 1)

High-grade glioma or caseating tuberculoma was initially presumed based on his age, progressive symptoms and radiological findings. Right parieto-occipital mini craniotomy and total excision of mass lesion was done under neuronavigation.

Pathological examination revealed large areas of necrosis, chronic inflammatory cell infiltrate composed of lymphocytes, plasma cells, epithelioid histiocytes, and many multinucleate giant cells. Brown pigmented fungal septate hyphae were seen amidst necrosis. Septate hyphae with melanin pigments were confirmed by positive staining with special stains (Grocott-methenamine silver/GMS stain, Fontana-Masson stain and Periodic acid Schiff/ PAS stain). The final diagnosis of Phaeohyphomycosis was rendered. (Figure 2, 3)

Patient was initiated on Itraconazole and Tinidazole. Patient is doing well with no complaints after 1 year of surgery.

Figure 1: 45 year old male with cerebral Phaeohyphomycosis presenting with seizures and altered sensorium. MRI of brain showed a well-defined intra-axial irregular ring enhancing solid lesion measuring 2.7 x 2.5 x 2 cm in the right parietal lobe with adjacent white matter infiltration and mass effects.

Figure 2: 45 year old male with cerebral Phaeohyphomycosis presenting with seizures and altered sensorium. Histopathological examination.(A) Large areas of necrosis, chronic inflammatory cell infiltrate composed of lymphocytes, plasma cells, epithelioid histiocytes, and many multinucleate giant cells seen. [H&E Stain, x100] (B) Brown pigmented fungal septate hyphae were seen amidst necrosis. [H&E Stain, x400] (C)Septate hyphae with melanin pigments were confirmed by positive staining with special stain [PAS Stainx400] (D) Septate hyphae with melanin pigments were confirmed by positive staining with special stain (GMS Stain x400)

Discussion

The term “Pheohyphomycosis” is used to describe a diverse group of fungal infections caused by dematiaceous fungi with characteristic presence of melanin pigment in their cell walls. Based on the anatomical site involved, it is classified as cutaneous, subcutaneous, paranasal sinus and cerebral types.(10) Among these, cerebral pheohyphomycosis is the most dangerous, but a very rare form, commonly caused by Cladophialophora bantiana (C. bantiana).(10,11) Other infrequent fungi responsible are Ramichloridium mackenzei, Ochroconis gallopavum, Thielavia subthermophila and Fonsecaea species.

Infections are common in second and third decade of life (unlike our patient who is 45 years of age). Occupations involving exposure to plants/vegetations like agricultural workers, botany students and infants born in rural agricultural families have increased risk of infections.(12)

Inhalation of spores into the lung with colonization, followed byhematogenous spread has been suggested although the exact portal of entry is unknown.(10) Cerebral type commonly presents as brain abscess with meningitis and myelitis being rare presentation. The most common clinical manifestations are hemiparesis and headache followed by seizures and altered sensorium.(12) Our patient presented with seizures and altered sensorium. Cerebral Phaeohyphomycosis mimics high grade glioma, caseating tuberculoma and metastasis clinically and radiologically.(10) Histopathological examination plays a significant role in the final diagnosis.

In spite of the fact that, life-threatening fungal infections are usually related to severe immuno-compromised states, primary cerebral pheohyphomycosis appears to be an exception, as it is increasingly recognized to cause serious disease in immuno-competent individuals with no known underlying disease.

Melanin in these fungi may contribute for its pathogenicity as it provides a protective advantage in eluding the host defenses.(10) It is characterized by darkly pigmented hyphae, which can be observed with hematoxylin-and-eosin (H&E) stain, but more clearly with Masson-Fontana melanin staining. Nonetheless, this stain can also be positive for hyaline fungi, suggesting a low specificity.(9,14) Gomorimethenamine silver (GMS) stain may be helpful in the visualization of hyphae as dark elements against a green background.(9) PCR amplification and molecular sequencing play a crucial role in the identification and classification of black molds. There have been no reports of application of serology in the diagnosis of phaeohyphomycosis.(14)

Despite the fact that there is no standard therapy, combining medical treatment (amphotericin B and triazoles) with surgical excision of the abscess is the preferred management for cerebral phaeohyphomycosis.(10,12,14)

Conclusion

Primary cerebral phaeohyphomycosis is a rare, fatal fungal infection which often infects immunocompetent individual and is to be considered in the differential diagnosis of cerebral abscess. Early diagnosis and an aggressive therapeutic approach are essential to improve the patient’s outcome and reduce mortality.

References

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