Intraventricular black fungal hyphal masses caused by Cladophialophora bantiana: illustrative case

Abstract

BACKGROUND

CNS fungal infections are rare, life-threatening conditions primarily affecting immunocompromised hosts. While they typically present as brain abscesses, intraventricular proliferation of fungal hyphae is exceedingly rare, and its neuroendoscopic findings have seldom been reported.

OBSERVATIONS

A man in his 80s with a history of malignancies presented with a 1-month history of headache. Brain MRI showed contrast-enhancing lesions along the genu of corpus callosum and lateral ventricles, as well as a nonenhancing lesion protruding into the ventricles. Although these findings were atypical, an endoscopic biopsy was performed because the lesions showed a tendency to enlarge, raising suspicion of a malignant tumor. Neuroendoscopic examination revealed a black-pigmented intraventricular fungal mass, which was partially resected. Shotgun metagenomic analysis identified the pathogen as Cladophialophora bantiana.

LESSONS

C. bantiana exhibits marked neurotropism and is known to cause CNS fungal infections even in immunocompetent individuals. Although intraventricular extension of phaeohyphomycosis is extremely rare and preoperative differential diagnosis remains challenging, a nonenhancing lesion protruding into the ventricles was considered to reflect the presence of fungal hyphae in this case.

https://thejns.org/doi/10.3171/CASE26730

CNS fungal infections are rare entities that predominantly affect immunocompromised individuals, such as those with diabetes mellitus, organ transplantation, or steroid use. Given their association with high morbidity and mortality rates,¹ early diagnosis and prompt therapeutic intervention are imperative. Clinicians occasionally encounter fungal abscesses presenting with radiological findings that are difficult to differentiate from intracranial neoplasms. Furthermore, these lesions may extend into the ventricular system, potentially leading to ventriculitis and meningitis.² However, the formation of a macroscopic fungal mass proliferating within the ventricle is uncommon, and direct endoscopic visualization and sampling of such hyphal structures are exceptionally rare. Herein, we report a case of phaeohyphomycosis in an immunocompetent older male, in which intraventricularly proliferating fungal bodies were directly visualized and sampled under neuroendoscopy, leading to the diagnosis.

Illustrative Case

A man in his 80s with a history of lung, gastric, and colorectal cancer presented with a 1-month history of progressive headaches. He was afebrile, and no other vital sign abnormalities or neurological deficits were identified. Brain MRI revealed an abnormal lesion in the genu of the corpus callosum, and he was referred to our hospital. Diffusion-weighted imaging (DWI) (Fig. 1A) revealed a faintly hyperintense lesion in the genu of the corpus callosum. This lesion showed slightly low signal intensity on both apparent diffusion coefficient (ADC) mapping (Fig. 1B) and T1-weighted imaging (T1WI) (Fig. 1C). On T2-weighted imaging (T2WI) (Fig. 1D) and fluid-attenuated inversion recovery (FLAIR) imaging (Fig. 1E), hyperintensity was noted extending from the genu of the corpus callosum along the walls of the anterior horns of both lateral ventricles. Gadolinium-enhanced imaging showed continuous contrast enhancement extending from the genu along the septum pellucidum (Fig. 1F and G). Regarding the component protruding into the ventricles, a discrepancy was observed between the nonenhancing sequences and gadolinium-enhanced imaging. Arterial spin labeling imaging (Fig. 1H) revealed no significant increase in perfusion. Because enlargement of both the contrast-enhancing lesion and the T2WI/FLAIR hyperintense area was observed over a 1-month period, a malignant brain tumor, such as primary CNS lymphoma or glioblastoma, was strongly suspected, and a histological diagnosis was deemed necessary. Considering that the lesion predominantly involved the ventricular ependymal lining, a neuroendoscopic transventricular biopsy was planned (Video 1). A backup craniotomy was also prepared to allow for immediate open resection if a malignant glioma was suspected on intraoperative pathological examination. Under general anesthesia, a 17.5-Fr peel-off introducer sheath for neuroendoscopy (Medikit Co., Ltd.) was inserted into the anterior horn of the left lateral ventricle. Neuroendoscopy (VISERA ventricular videoscope, Olympus) revealed a dark green, algae-like, pigmented lesion protruding into the anterior horn and the septum pellucidum, which was sampled using biopsy forceps (Fig. 2). The ependymal surface deep to this lesion appeared white and slightly bulging, and this area was also biopsied. Histopathological examination revealed the presence of dematiaceous fungal elements with septate hyphae, leading to a diagnosis of cerebral fungal infection (Fig. 3). The patient was referred to the neurology department for multidisciplinary treatment, and shotgun metagenomic analysis identified Cladophialophora bantiana as the causative organism. The patient was subsequently treated with isavuconazole. Despite aggressive antifungal therapy, the infection remained refractory. Although resection was considered, the residual lesions encasing the fornix and deep veins, as well as their scattered growth throughout the periventricular white matter, led to the decision that effective cytoreduction would be difficult to achieve. The patient died 4 months after the initiation of treatment.

FIG. 1.

A: Diffusion-weighted image showing a high-signal-intensity lesion in the genu of the corpus callosum. B and C:The lesion showed mildly decreased signal intensity on both the ADC map (B) and T1-weighted image (C). D and E: T2-weighted (D) and FLAIR (E) images showing hyperintense lesions extended from the genu of the corpus callosum to the periventricular regions of the bilateral anterior horns of the lateral ventricles. F and G: Gadolinium-enhanced axial (F) and coronal (G) MR images demonstrating continuous enhancement along the ependyma from the genu of the corpus callosum to the septum pellucidum, as well as patchy enhancement within the brain parenchyma. H: No marked increase or decrease in perfusion was observed on arterial spin labeling.

FIG. 2.

A: Endoscopic inspection through the left anterior horn of the lateral ventricle allowed visualization of the left foramen of Monro (asterisk) and revealed black-colored fungal masses (arrow) extending from the anterior horn to the septum pellucidum. The ependymal surface deep to this area appeared whitish and was slightly swollen (arrowhead). B:Gross appearance of the lesion after sampling and fixation in formalin.

FIG. 3.

Hematoxylin and eosin stain revealing fungal masses with hyphal structures (arrow). Inflammatory cell infiltration is also observed (arrowhead). No evidence of malignancy is identified.

VIDEO 1.A sheath was placed in the anterior horn of the left lateral ventricle, and a flexible neuroendoscope was introduced. Dark green, algae-like lesions were observed around the foramen of Monro and along the septum pellucidum. These lesions were sampled using biopsy forceps. In addition, whitish, soft lesions diffusely involving the ependymal surface were identified and sampled. Click here to view.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

Observations

This case report describes an extraordinary case of cerebral phaeohyphomycosis caused by C. bantiana in an immunocompetent older man, in whom an intraventricular fungal mass was directly observed and partially debulked using a neuroendoscopic approach. C. bantiana is a dematiaceous fungus and an extremely rare pathogen known to exhibit marked neurotropism not only in immunocompromised patients but also in immunocompetent individuals. Most reported cases follow a severe clinical course, with a high mortality rate of more than 70%.¹

In the present case, no obvious primary focus of infection was identified, and no underlying condition associated with marked immunosuppression was observed. The route of infection is generally considered to involve inhalation exposure of contaminated soil or inoculation through minor trauma that may go unnoticed by the patient.³ In a report from China, trauma (37%), diabetes mellitus (11%), and corticosteroid exposure (11%) were identified as the most common risk factors for phaeohyphomycosis, with other contributing conditions including malnutrition (6%) and malignancy (5%).⁴ The patient had no history of penetrating trauma, diabetes mellitus, or overt immunodeficiency. However, he engaged in gardening on a regular basis and therefore had frequent exposure to soil. In addition, his history of multiple malignancies may have increased susceptibility to infection through subclinical immune dysfunction. CNS lesions are thought to result from either direct spread from the paranasal sinuses or hematogenous or lymphatic dissemination from primary foci such as the lungs or subcutaneous tissues;⁵ however, no such lesions were identified in the present case.

There are exceedingly few reports describing transventricular endoscopic visualization of intraventricular fungal lesions. In previous reports of phaeohyphomycosis⁶ and Rhizopus-related mucormycosis,⁷ whitish lesions along the ventricular wall were identified. In both cases, tissue samples were obtained and fungal elements were confirmed histopathologically. Recently, Oros et al. reported a highly relevant case featuring an intraventricular mass presenting as a dark-colored abscess that was successfully visualized and sampled via a neuroendoscopic approach.⁸ In our case as well, whitish lesions along the ependymal lining were observed; however, the presence of velvety, dark green to black fungal masses protruding into the ventricular cavity represents a distinctive and previously underreported neuroendoscopic finding. The characteristic pigmentation of C. bantiana is attributed to the high concentration of melanin within its cell walls. Melanin is known to serve as a protective barrier against ultraviolet radiation, oxidative stress, temperature fluctuations, and host immune responses, thereby significantly contributing to the pathogenicity and intrahost survival of the fungus. Particularly in CNS infections, melanin is suggested to enhance resistance against reactive oxygen species and the microbicidal activities of immune cells, potentially facilitating persistent infection and tissue invasiveness.³

Although fungal brain abscesses are rare, specific MRI findings have been reported to assist in preoperative differentiation. A retrospective study of 110 brain abscess cases—consisting of 91 pyogenic, 11 tuberculous, and 8 fungal etiologies—observed that all types typically presented with low signal intensity on T1WI, high signal intensity on T2WI, and clear ring enhancement on contrast-enhanced T1WI. Furthermore, while the outer margins of the abscess walls were smooth or lobulated in nearly all cases of pyogenic and tuberculous abscesses, 50% of the fungal lesions exhibited a characteristic crenated appearance of the wall.⁹ Regarding the diffusion-restricted findings of intracranial abscesses, it has been demonstrated that fungal etiology is characterized by more heterogeneous signal patterns and significantly higher mean ADC values than those of bacterial origin. In terms of lesion distribution, pyogenic abscesses are predominantly solitary and hemispheric, whereas fungal abscesses are more likely to be multifocal and predisposed to involving the basal ganglia region.¹⁰ In the present case, the lesion in the genu of the corpus callosum exhibited slight hypointensity on T1WI and hyperintensity on T2WI, with heterogeneous contrast enhancement and diffusion restriction. These features were compatible with the neuroimaging characteristics of fungal brain abscesses. Importantly, the hyphal component protruding and proliferating within the ventricular system was not delineated on gadolinium-enhanced imaging, but was visualized on nonenhancing sequences such as DWI, T2WI, and FLAIR imaging. It is possible that the structural details of these intraventricular components could have been delineated more clearly if heavily T2-weighted sequences, such as FIESTA or CISS, had been obtained. Although the usefulness of MR spectroscopy has also been reported,⁹ it was not performed preoperatively in the present case.

The efficacy of surgical treatment for C. bantiana brain abscesses has been demonstrated; a systematic review of 124 cases showed that complete excision was an independent predictor of survival in logistic regression analysis (OR 3.36, 95% CI 1.057–10.638; p = 0.04).⁵ On the other hand, reports on the surgical management of intraventricular fungal infections are limited, and no standardized clinical guidelines have been established. Although neuroendoscopic biopsy and debulking were performed in approximately half of the 11 previously reported cases of intraventricular C. bantiana abscesses, achieving complete resection remains extremely challenging due to the extent of the lesions and anatomical constraints.⁸ In our case as well, effective debulking of the brain abscess was impossible, highlighting the clinical difficulty inherent in this pathological condition.

Lessons

Intraventricular C. bantiana infection is extremely rare, yet it must be recognized as a highly lethal disease that can develop even in immunocompetent individuals. In this case, the characteristic black fungal hyphae were visualized on neuroendoscopy, and tissue samples were successfully obtained to establish the diagnosis. A nonenhancing lesion protruding into the ventricles on MRI may reflect the presence of fungal hyphae and could be useful for preoperative prediction. Given the high mortality rate, prompt neuroendoscopic exploration and biopsy are critical, and active resection should also be considered when feasible.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Makino, Saito. Acquisition of data: Makino, Saito, Yonezawa, Higa, Adachi. Analysis and interpretation of data: Makino, Saito, Yonezawa, Higa, Sakiyama, Takashima. Drafting the article: Makino, Saito, Yonezawa. Critically revising the article: Makino, Fujio, Yamahata, Takashima, Hanaya. Reviewed submitted version of manuscript: Fujio, Takashima, Hanaya. Approved the final version of the manuscript on behalf of all authors: Makino. Administrative/technical/material support: Fujio, Yoshimura. Study supervision: Fujio, Hanaya.

Supplemental Information

Videos

Video 1. https://vimeo.com/1221486923.

Correspondence

Ryutaro Makino: Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima-City, Kagoshima, Japan. makinor@m3.kufm.kagoshima-u.ac.jp.