Glioblastoma multiforme with transdural extension to the external auditory canal via the tegmen tympani—Clinical report with review of the literature

Glioblastoma multiforme (GBM) is the most aggressive and invasive malignant glioma, accounting for 45.2% of all cases with an annual incidence of 3.19 cases per 100,000 individuals and a median survival of 15 months [1]. Transdural extension of GBM is rare, particularly without previous surgical intervention [2]. Few reports have described cases of GBM propagating through the skull base [3]. Here, we report a case of a patient presenting with a temporal lobe GBM extending to the external auditory canal (EAC) through the tegmen tympani. This case is reported as a descriptive study of a 60-year-old female with an extradural GBM. A literature review of the phenomenon was conducted and reported. This study was executed with ethical considerations, including informed consent. The participant provided consent after receiving an explanation of the procedures, potential risks and benefits, and right to withdraw. A 60-year-old female with a history of Eustachian tube dysfunction presented with right ear otorrhea for several months. She required insertion of multiple tympanostomy tubes for the Eustachian tube dysfunction previously. Physical examination revealed decreased right-sided hearing, a 10% tympanic membrane perforation, local erythema, and serous fluid accumulation with a clear and normal EAC. She was prescribed antibiotics and scheduled for follow-up with audiometry results. In the interim, she developed bloody right ear drainage. A friable, smooth, vascular lesion obscuring the right ear’s EAC was discovered, biopsied, and returned as GBM. A CT brain demonstrated a 2.5 cm temporal lobe mass with midline shift and vasogenic edema. Dehiscence of the right tegmen tympani was noted with abnormal soft tissue density throughout the right EAC, middle ear, and mastoid cells. MRI brain revealed a right temporal lobe mass with peripheral enhancement, central necrosis and vasogenic edema (Figure 1). There was contiguous enhancement in the right temporal bone and middle ear cavity, extending laterally towards the EAC and anteromedially towards the Eustachian tube. Coronal (A and B) and axial (C) sequences of the CT of the temporal bone showing dehiscence of tegmen tympani (arrows). Cadaveric anatomic demonstration of the tegmen tympani (D) as illustrated from the Rhoton Collection. Axial T1 with gadolinium (E) and coronal (F) preoperative MRI sequences demonstrating a homogeneously enhancing right temporal lesion (yellow arrow) extending into the middle ear cavity, external auditory canal, and the anteromedial region of the Eustachian tube (red arrow). MRI T1 with gadolinium sequences showing gross total resection of the mass and no evidence of tumor recurrence at the 6 months (G and H) postoperative follow up. The patient underwent resection via a combined approach. The surgery involved excision of the tumor from right EAC with middle ear exploration and tympanomastoidectomy. The tumor caused erosion of the incus and involved sectioning of the chorda tympani nerve. The following step included an infratemporal approach to the middle fossa and temporal lobe. Elevation of the dura revealed a subtemporal dural defect with tumor extending through the tegmen tympani into the middle ear without involvement of the Eustachian tube. The tumor in the middle ear, dura, and temporal lobe was resected, achieving gross total resection. Initial histopathology revealed hypercellularity, nuclear atypia, and necrosis concerning for high grade glioma (Figure 2). Pathology was significant for IDH1-wildtype GBM, WHO grade IV with KRAS mutation, PTEN mutation with loss of heterozygosity, CDKN2A homozygous loss and TERT promoter mutation, and molecular subgroup G1/EGFR. After an unremarkable post-operative course, she received external beam radiotherapy at a dose of 60 Gy in 30 fractions utilizing intensity modulated radiation therapy and daily image guidance. This therapy was followed with a 1-month break, and then she received maintenance temozolomide and Tumor Treating Fields daily for 6 months. On follow-up at 17 months since diagnosis, she remained neurologically intact, with improved hearing and no evidence of recurrence (Figure 1). On follow-up at 20 months, MRI imaging revealed inoperable recurrence of GBM in her corpus callosum and midline structures. She has developed short-term memory issues but has remained on maintenance temozolomide and Tumor Treating Fields at last follow-up, 29 months since initial diagnosis. Histopathological analysis with H&E staining shows areas of hypercellularity, nuclear atypia and mitotic figures (A), as well as pseudopalisading necrosis (B). Immunohistochemistry showed the tumor cells to be positive for GFAP (C), confirming the diagnosis of GBM. GBM, glioblastoma multiforme. Transdural extension of GBM through the skull base is rare with few reports in the literature, making this the third ever reported case [3]. While the pathophysiology of GBM extraneural spread remains unclear, surgical procedures can precipitate this dissemination via vessel and blood brain barrier disruption [4, 5]. Other factors such as hypertension causing dural and vascular slits in the middle fossa and skull base foramina can propagate spread of GBM [4]. The tegmen tympani is a low-resistance plate of the petrous part of the temporal bone, separating the intracranial space from the middle ear [4]. This unique case involves tegmen tympani dehiscence stemming from tumor protruding from the temporal lobe into the temporal bone through the EAC. The dehiscence may result from increased intracranial pressure from tumor infiltration, and is associated with cerebrospinal fluid (CSF) leaks [6]. Less CSF decreases brain cushioning, allowing brain pulsations on a specific bone area, resulting in bone remodeling and tumor infiltration [7]. Metastases to the tegmen tympani itself are reported as Belal et al., assessing metastatic lesions involving the temporal bone, reported the tegmen tympani to be the second most common site of metastasis [8]. Although this patient has a history of multiple tympanostomy tube placements and Eustachian tube dysfunction, it is unlikely that the recurrent tube placements could have caused the tegmen defect leading to the GBM extension into the EAC. Literature review yielded two reports of GBM extending to the extracranial compartment through the tegmen (Table 1). Nager et al. reported a 41-year-old presenting with a mass protruding from the right EAC, demonstrating a right frontotemporal GBM extending through the tegmen and protruding through the tympanic membrane into the right EAC [2]. Thrull et al. reported a 61-year-old presenting with left-sided hemiparesis and right sided impaired hearing, with imaging revealing a mass in the right temporal lobe infiltrating the temporal bone through the tegmen mastoideum into the mastoid cells. The tumor was resected via temporal craniotomy, with final pathology consistent with GBM IDH-1 wild type with MGMT methylation [3]. Arba Cecia: Conceptualization; formal analysis; methodology; validation; visualization; writing—original draft; writing—review and editing. Emal Lesha: Conceptualization; data curation; investigation; methodology; supervision; writing—original draft; writing—review and editing. David G. Laird: Data curation; formal analysis; methodology; validation; visualization; writing—original draft; writing—review and editing. Elsa Nico: Data curation; formal analysis; investigation; validation; visualization; writing—original draft; writing—review and editing. Kaan Yagmurlu: Conceptualization; investigation; methodology; supervision; validation; visualization; writing—original draft; writing—review and editing. Bruce L. Fetterman: Conceptualization; investigation; methodology; resources; writing—original draft; writing—review and editing. L. Madison Michael II: Conceptualization; methodology; project administration; resources; supervision; validation; visualization; writing—original draft; writing—review and editing. The authors have nothing to report. Informed consent was obtained from all participants. The authors declare no conflicts of interest. Given the nature of this case study, IRB approval was not required. All ethical standards of the institution were strictly followed for the creation of this work. The data that supports the findings of this study are available within the article.