Tension pneumocephalus related to nasopharyngeal carcinoma: A case report

Abstract

Tension pneumocephalus associated with nasopharyngeal carcinoma is an exceptionally rare but potentially fatal condition. We report a case of tension pneumocephalus associated with nasopharyngeal carcinoma treated by radiochemotherapy. Three-month follow-up computed tomography (CT) and positron emission tomography-computed tomography (PET-CT) showed significant tumor regression but moderate intracranial pneumocephalus. Four days later, the patient was found in a comatose state and emergency brain CT showed extensive pneumocephalus with transtentorial descending and right temporal herniations. The patient died 5 days later. A summary of tension pneumocephalus is presented and the mechanism of fistula formation is discussed. This case enlightens tension pneumocephalus as a possible early complication of nasopharyngeal carcinoma treatment.

Introduction

Tension pneumocephalus is an accumulation of air confined to the intracranial space that compresses the brain structures, leading to neurological deterioration. Most cases are caused by trauma and surgery [1]. Rare cases are due to tumors [2], the most frequent being paranasal sinus osteomas [3]. Pathogenesis involves a ball valve effect where air is forced into the cranial cavity through an osteodural defect during Valsalva maneuver but is trapped due to the defect being covered by the brain [1,4]. Another mechanism, which may be combined with the first one, is the negative intracranial pressure that occurs secondary to loss of cerebrospinal fluid [3,4].

Clinical findings include headache, neurologic deficit, and an altered level of consciousness [1]. Diagnosis is made when clinical signs correlate with imaging findings, particularly computed tomography (CT) detection of intracranial air appearing as very low attenuation areas (-1000 Hounsfield units) [5]. The Mount Fuji sign on brain CT, described by presence of air causing posterior displacement and separation of frontal lobes, is specific for tension pneumocephalus (Fig. 3A). Treatment includes oxygen therapy, dural defect closure, and decompressive craniostomy [6].

Fig. 3.

Brain computed tomography (CT) without contrast showed (A) severe holocranial pneumocephalus with Mont Fuji sign (white arrows with red borders). There is (B) a significant increase in pneumocephaly compared to Figure 2C (white arrows with orange borders) associated with transtentorial descending herniation as shown by the effacement of perimesencephalic cistern (white arrowheads with orange borders). CT bone windows with coronal reconstructions (C) depict well the large defect on right middle cranial fossa floor related to previous tumor invasion connecting the intracranial space and the pharynx (white arrows with blue borders).

Pneumocephalus associated with nasopharyngeal carcinoma (NPC) is exceptionally rare. We present a rare case of tension pneumocephalus associated with NPC treatment by radiochemotherapy.

Case report

In August 2021, a 48-year-old Moroccan man was diagnosed with stage IVa (T4N0M0, American Joint Committee on Cancer 8th Edition) nonkeratinizing squamous cell differentiated NPC. Initial cervicofacial CT with contrast showed a large enhancing mass in the right parapharyngeal space with skull base destruction and intracranial extension (Figs. 1A and B). Fluorodeoxyglucose-positron emission tomography (FDG-PET) CT showed significant FDG-avidity (Fig. 1C).

Fig. 1.

Computed tomography (CT) with contrast showed (A) a large enhancing mass in the right parapharyngeal space (white arrows with red borders). Top down view from a 3-dimensional (3D) CT reconstruction (B) showed large skull base destruction (white arrows with green borders). Fluorodeoxyglucose-positron emission tomography (FDG-PET) CT showed (C) significant FDG-avidity (white arrows with black borders).

Between September 6, 2021, and October 19, 2021, the patient received concurrent chemoradiotherapy: 3 cycles of cisplatin (100 mg/m²) every 3 weeks combined with a total dose of 69 Gray of Intensity modulated radiation therapy (33 fractions).

On January 27, 2021, follow-up CT showed significant tumor regression, leaving a large defect on the right middle cranial fossa floor, and benign intracranial pneumocephalus (Figs. 2A-C). A PET-CT performed the next day showed a very good partial metabolic response, with the tumor remaining moderately active in its posterior-superior part immediately below the skull base (Fig. 2D).

Fig. 2.

Three-month follow-up computed tomography (CT) showed (A) significant tumor regression, leaving a large defect on the right middle cranial fossa floor (white arrows with red borders), better depicted (B) in a top down view from a 3-dimensional CT reconstruction (white arrows with green borders), and (C) benign intracranial pneumocephalus (white arrows with orange borders). A Fluorodeoxyglucose-positron emission tomography (FDG-PET) CT performed the next day showed (D) a very good partial metabolic response, with the tumor remaining moderately active in its posterior-superior part immediately below the skull base (white arrows with black borders).

On January 31, 2022, the patient was admitted to the emergency department with general deterioration, altered mental status, and dyspnea. He was pale, cachectic, dehydrated, and tachypneic with major airway obstruction. The patient's Glasgow Coma Scale score was 5 (E2M2V1). Vital signs were: blood pressure at 120/80 mmHg, respiratory rate of 30 breaths/min, heart rate of 140 beats/min, and oxygen saturation of 90% using a nonrebreathing mask. Physical examination showed decreased air entry on both sides of the chest with diffuse rhonchi. Laboratory investigations were notable for neutrophilia of 18.250/µL, C-reactive protein of 375,2 mg/L, and D-dimer levels of 1205 ng/mL. A SARS-CoV-2 test was performed and the result came out positive.

Emergent CT pulmonary angiography showed bilateral bronchopneumopathy but no pulmonary embolism. Brain CT showed severe holocranial pneumocephalus with transtentorial descending herniation (Figs. 3A and B). A large defect on the right middle cranial fossa floor (related to a previous tumor invasion) was connecting the intracranial space and the pharynx (Fig. 3C).

Given the patient's clinical condition, neurosurgery was not considered. Antibiotherapy for bronchopneumopathy was started. The patient died 5 days later.

Discussion

Pneumocephalus associated with NPC is exceptionally rare. In most reported cases, proposed mechanisms to explain the formation of a fistula enabling the entry and entrapment of air into the skull are tumor invasion, osteoradionecrosis (ORN), or a combination of both [[7], [8], [9], [10], [11], [12], [13], [14], [15], [16]].

In 1951, Dr. Raider [7] reported the first case of pneumocephalus due to NPC by way of extension through the base of the skull. Bone necrosis related to radiation therapy was already brought up at least as a partial cause (along with neoplastic invasion) for the occurrence of pneumocephalus. In 1995, Ng et al. [8] presented a case in which pathological findings supported ORN as the cause of skull base fistula, no residual NPC tumor cell being identified. Similarly, in the cases reported by Wu and Lee [17], and Wang et al. [13], skull base bone biopsy demonstrated ORN changes and no tumor cells. Risso et al. [16] is the only reported case in which both ORN and tumor infiltration were pathologically found.

ORN is considered to be linked to a disruption of bone metabolism due to bone fibrosis-atrophy. Imaging is limited regarding distinction between ORN, osteomyelitis and tumor recurrence, and thus histology is crucial for diagnosis, showing an absence of osteoblastic activity, inflammatory, and tumor cells [19]. Incidence of skull base ORN in patients with NPC following a single course of radiation therapy (RT) is reported to be around 1%. There is a latency period of about 3.5-4 years from the end of RT to the diagnosis of skull base ORN [18].

Regarding our case, pneumocephalus occurred only 3 months after the completion of radiotherapy. This quite short time led us to believe that the fistula was not caused by ORN but by the shrinking of the tumor (following radiochemotherapy) which had previously invaded the skull base. The main limitation of our work is the lack of biopsy or autopsy specimens to support our hypothesis. Our case is nevertheless noteworthy in that the delay in the onset of serious neurological symptoms was particularly short (3 months), leading to a fatal outcome directly related to tension pneumocephalus. Additionally, it demonstrates how quickly benign pneumocephalus can progress to tension pneumocephalus, as evidenced by 2 consecutive imaging studies taken just 4 days apart (Figs. 2C and 3B). This could be explained by the abundant coughing from the patient during this interval due to his bronchopneumonia.

In conclusion, tension pneumocephalus associated with nasopharyngeal carcinoma is exceptionally rare but potentially fatal. The physician should be aware of tension pneumocephalus as a possible early complication of nasopharyngeal carcinoma treatment, which can lead to skull base fistula formation by ORN and/or tumor melting. In this context, physicians should also keep in mind that benign pneumocephalus can rapidly progress to fatal intracranial hypertension especially when conditions associated with Valsalva maneuver are present.

Patient consent

The patient passed away before we could obtain their consent. Despite efforts to reach out to their next of kin and legal representative, they were untraceable. Approval for publication has been granted by my organization, its legal representative, and an ethics committee, in accordance with local legislation.