Tension pneumocephalus — A rare complication of radiotherapy in nasopharyngeal carcinoma

Pathology (1995), 27, pp . 204-208

Case Report TENSION PNEUMOCEPHALUS - A RARE COMPLICATION OF RADIOTHERAPY IN NASOPHARYNGEAL CARCINOMA WAI F. NG*, KAI

H.

FUNGt AND JONATHAN S.

T.

SHAM:j:

Department of Pathology * and Department of Radiologyt, Caritas Medical Centre, Hong Kong and Department of Radiation Oncologyt, The University of Hong Kong

Summary A patient with nasopharyngeal carcinoma (NPC) treated by radiotherapy developed tension pneumocephalus due to a naso-cranial fistula. The fistula was due to a pathological fracture at the base of skull affected by bone necrosis. The clinical features, neuro-radiological and post-mortem findings are presented. This is the first case report of pneumocephalus in association with NPC. The brain showed florid subarachnoid and intraventricular air collection under tension, low grade meningitiS, foreign body giant cell reaction in the arachnoid membrane and multifocal cerebral infarction. Late radiation necrosis was also found in the left temporal lobe. The cause of the tension pneumocephalus in relation to radiation bone necrosis and the possible role of pneumocephalus in producing the multifocal cerebral infarction are discussed. The more common radiation necrosis of brain is also discussed. The pathogenesis of the pneumocephalus in this patient is distinctly different from the more common causes such as head injury and surgery. Key words: Nasopharyneal carcinoma, pneumocephalus, radiation bone necrosis, radiation brain necrosis.

Accepted 9 March 1995

INTRODUCTION

Pneumocephalus most commonly occurs as a complication of head injury, often with associated cerebrospinal fluid rhinorrhea and meningitis. 1 . 2 •3 It could also occur as a complication of surgery, eroding infection or neoplasia. When it occurs in association with neoplasia, radiotherapy may have been given. 4.5 'We report a patient with nasopharyngeal carcinoma (NPC) treated with radiotherapy and developed a naso-cranial fistula due to necrosis of skulll base. This resulted in tension pneumocephalus. The patient also had radiation necrosis of the left temporal lobe. The neuropathology ofthe tension pneumocephalus is presented and the possible pathogenetic mechanism discussed. The rarity of this complication in patients with NPC treated with radiotherapy is discussed. CASE REPORT Clinical Summary The patient was a 60-yr-old Chinese male. He was diagnosed to have nasopharyngeal carcinoma (NPC) stage IV T3d (infratemporal fossa) N,Mo in 1987. Computerized tomography (CT) showed that the tumor had involved the left infratemporal fossa , left middle cranial fossa, left

parapharyngeal space and the left pterygomaxillary fissure. A course ofradiotherapy (64 Gy/32 fractions/6 V2 wks) was given and completed on 23 December 1987. Complete remission was documented post treatment with endoscopy and biopsy. He defaulted follow-up after November 1988 and returned in November 1989 with headache and multiple cranial nerve palsy (left sixth and fifth cranial nerves palsy and impairment of left eye vision). CT showed a recurrent tumor involving the left infratemporal fossa and the middle and posterior cranial fossa. Endoscopy and biopsy however were negative. In view of the concordant clinical features and CT findings, he was treated for relapse with chemotherapy employing eis-platinum and 5 flurouraeil , with a total of 7 courses given. There was some clinical response in terms of improvement of headache. CT in September 1990 showed that the tumor in the middle cranial fos sa had diminished in size. The patient refused further intravenous chemotherapy and he was started on oral cyclophosphamide. He was last seen on 15 January 1991 in the Oncology Department and there was complete blindness and ophthalmoplegia of left eye. On 18 April 1991, about 3.5 yrs after the radiotherapy, he was found unarousable in bed by his workmate. On admission to hospital, he was in poor general condition, dehydrated, incontinent and with temperature of 39.4 °C. He was drowsy with spontaneous eye opening and response to pain but aphasic. Cranial nerves could not be properly assessed. Reflexes were normal. Blood pressure was 150/100 mmHg. Decreased air entry was noted on the left side of the chest. Other findings were unremarkable. Renal function was normal apart from raised urea (14.1 mmoIlL) . Blood gas showed respiratory alkalosis. Complete blood count was normal apart from leucocytosis of 16.1 x 109 / L (polymorphs 850/0). Chest roentgenogram showed bilateral early bronchopneumonia. Blood culture was negative. Lumbar puncture failed due to technical difficulty. The skull radiograph showed the presence of multiple areas of intracranial gas collections and air-fluid level in ventricles. The base of the skull appeared sclerotic, consistent with the history of radiotherapy. Postcontrast axial CT showed multiple pockets of gas collections along the basal cisterns, Sylvian fissures and insulae, interhemispheric cisterns, left parietal convexity and over the left frontal lobe (Fig. 1). Intraventricular gas was noted within the asymmetrically dilated frontal and temporal horns of the lateral ventricles . Air-fluid levels were noted within some of the collections. Sclerotic changes in the skull base in the clivus and left greater wing of sphenoid was shown using bone window settings . A linear fracture line was detected in the left side of the body of sphenoid in the parasellar region (Fig. I). A wedge shaped unenhanced hypodense area was noted in the 'right parietal cortex. He was diagnosed to have cerebral infarction, bronchopneumonia, pneumocephalus and probably recurrent NPC. He was treated with intravenous fluid, broad spectrum antibiotics and Ryle's tube feeding . The clinical course was marked by initial improvement but complicated by further aspiration. There was progressive bilateral pneumonia resistant to therapy despite change of antibiotics . He died about 5 wks after admission.

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Fig. 1 Axial cranial eT showing a linear fracture line (arrow) in the body of sphenoid on the left side extending medially to involve the sphenoidal sinus. Intracranial gas collections are also present in anterior and middle cranial fossae. (r-right)

POST MORTEM FINDINGS The major finding was in the brain and skull apart from bilateral confluent bronchopneumonia which was· the immediate cause of death. The bone of the cranial vault was normal. The dura was markedly thickened, fibrotic and adherent over the base of both middle cranial fossae, especially on the left side medially which was about 0.8cm thick. The left optic nerve, left trigeminal nerve and left abducent nerve were entrapped by the thickened dura on the site. The basi-occipital bone which forms the roof of the nasopharynx and the squamous temporal bone corresponding to the medial floor of the left middle cranial fossa were soft. The fracture in the sphenoid evident on the CT scan and the possible naso-cranial fistula could not be identified grossly. However, no specimen radiograph was taken for correlation. Microscopy showed extensive bone necrosis involving the left squamous temporal bone, left sphenoid bone and the basi-occipital bone (Fig. 2). Reactive new bone formation, fibrosis, chronic inflammatory infiltrate and fibrinoid change of vessels were also evident. The nasopharynx was lined by a smooth surface with no visible tumour. Microscopy revealed extensive mucosal ulceration with hyaline fibrosis and focal chronic inflammatory cells infiltrates. No residual NPC was identified in the nasopharynx, the adjacent bone or dura. The brain was 1400 g, pale and moderately swollen. There was some disruption to the left hippocampal gyrus during removal due to adhesion to the fibrous dura (Fig. 3, second slice). There was no grossly discernable subarahnoid exudate to indicate meningitis and culutre was not taken at autopsy. There was no uncal or tonsillar

Fig. 2 Section of bone from medial part of left squamous temporal bone and left sphenoid bone showing bone necrosis, fibrosis and chronic inflammatory cells infiltrate. (Haematoxylin and eosin stain, original magnification x 40).

hernia. The Circle of Willis was moderately to severely atherosclerotic. The internal carotid arteries on both sides showed fibrous plagues causing up to 30% of luminal obstruction. In the anterior, middle and posterior cerebral arteries and the vertebrosbasilar artery, fibrous plagues causing up to 30-60070 luminal obstruction were noted. The most severely affected part was the proximal part of left middle cereral artery with 80% luminal obstruction. There was however no thromboembolism noted. There was also no evidence of radiation vasculitis affecting the Circle of the Willis and the major cerebral arteries. On comparison, the degree of atherosclerosis in the brain was more severe than that in the coronary arteries and aorta, which showed mild atherosclerosis (upto 30% luminal obstruction in the coronary arteries). The heart was normal with no concentric hypertrophy. The brain was cut in standard coronal sections after fixation. There was multiple irregular cystic dilation of the subarachnoid space, most prominent in the medial frontal and left insular area (Fig. 3, first and second slice). The adjoining cortical gyri showed thinning and shaggy irregular surfaces. A large infarct was present in the right parietal region about 5 X 4 x 3 cm, in the territory of the right middle cerebral artery. (Fig. 3, third slice). The left temporal lobe showed rusty discoloration in the white

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Fig. 4 An area from the frontal lobe showing emphysematous distension of the subarachnoid space (Haematoxylin and eosin stain, original magnification x 40). Inset: An area of the arachnoid membrane showing mild lymphocytic infiltrate and foreign body giant cells. (Haematoxylin and eosin stain, original magnification x 200)

Fig. 3 Coronal sections of brain. Note multiple gas-P?ckets in the parasagittal frontal gyri, right cingulate gyrus an~ left ll~sula. The anterior horns of the lateral ventricles are asymmetrIcally dilated. Note infarct in the right parietal lobe. (r-right)

matter about 8 mm across. The lateral ventricles were distorted and asymmetrically dilated. The cerebellum was normal. The anterior pontine surface was rough and irregular. On microscopy, there was emphysematous distension of the subarachnoid space (Fig. 4). These changes were generalized, affecting the cerebrum, cerebellum and brain stem. A low grade chronic meningitis marked by mononuclear inflammatory cells and occasional foreign body giant cells reaction were also noted (Fig. 4, inset). The right parietal lobe showed features of established recent ischaemic infarct beneath the emphysematous arachnoid membrane (Fig. 5). Multifocal small recent cortical brain infarcts were also noted in area associated with the pneumocephalus. The left temporal lobe showed evidence of old radiation necrosis affecting the white matter. It was marked by spongiosis, microcystic degeneration, aggregate of hemosiderin - laden macrophages, astrocytosis, telangiectasia and fibrinoid change of arteries (Fig. 6). The ventricles were focally disrupted. No tumour was noted in the brain. The pituitary showed no evidence of radiation necrosis. DISCUSSION

This is the first case report of pneumocephalus in association with NPC in the literature. The mechanism of formation of the communication between intra-cranial

content and outside in this case was quite different from previous reported cases of pneumocephalus in association with neoplasms. In earlier reports, the communication was due to the presence of tumour 6 or trans-sphenoid surgical intervention which by itself would have the risk of CSF rhinorrhoea. 5 This patient presented multiple neuropathological findings that needed to be analysed. This included tension pneumocephalus, low grade chronic meningitis, necrosis of skull bone, radiation necrosis of the left temporal lobe and multi focal recent ischemic brain infarction. The pneumocephalus was most likely due to a naso-cranial fistula developing in the area of bone necrosis and the fistula was probably marked by the pathological fracture line seen on the CT scan. CSF rhinorrhoea, was not documented in the present case due to a lack of clinical information preceding the terminal illness. The alternative of gas-forming bacteria as the major cause of pneumocephalus was not supported due to a lack of florid meningitis on gross and microscopic examination. The low grade meningitis may be due to the presence of air for sometime evident by the presence of foreign body giant cells (Fig. 4, inset). However, contribution by nasal bacterial flora could not be excluded when a fistula was present. The term 'tension' is used to describe the pneumocephalus because it was severe and multi focal with involvement of the lateral ventricles and tension disruption of the arahnoid membrane was noted in multiple area (Fig. 4 and 5). This patient also had late radiation necrosis of the left temporal lobe and the skull bone. Late radiation necrosis of the brain selectively involves the temporal lobe and occurs in about 10,10 of NPC patient treated by radiotherapy.7 The latent interval in this patient of about 3.5 yrs lies within the reported range of 9 mths to 16 yrs (median 33 mths). Radiation necrosis of temporal lobe may be asymptomatic (160,10) or presents with classical temporal lobe epilepsy (310,10), vague symptoms of temporal lobe damage (390,10) or nonspecific features of intracranial lesions (140,10). For the present patient, we

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Fig. 5 Recent ischemic infarct of right parietal lobe. Note emphysematous distension of the subarachnoid space and a normal artery on the top left (Haematoxylin and eosin stain, original magnification x 40).

Fig. 6 White matter of left temporal lobe showing oedema, telangiectasia, collection of hemosiderin-Iaden macrophages, gliosis and an artery with fibrinoid change (upper middle). (Haematoxylin and eosin stain, original magnification x 100).

are not .sure of the symptoms present due to a lack of clinical information preceeding the terminal illness. On the other hand, there is no documented incidence for radiation necrosis of skull in NPC. Radiation as the cause of the skull bone necrosis in this patient was supported by the radiological finding of diffuse sclerosis involving the base of skull and the presence of fibrinoid vasculopathy. However, a co-existing contribution by chronic infection could not be excluded. The presence of multifocal recent ischemic brain infarct in this patient is interesting. The pathological features were that of ordinary ischemic infarct and distinctive from that of late radiation necrosis selectively involving the white matter of the temporal lobe. 7 This patient had moderate to severe atherosclerosis involving the major arteries with no evidence of radiation vasculitis. The multifocal brain infarctions might have been precipitated by the tension pneumocephalus acting on arteries compromised by atherosclerosis. It is interesting to note that venous infarction had not occurred. This might be accounted for by a better collateral circulation of smaller veins and that the larger veins were protected within dura sinuses which was not the principal anatomical plane of pneumocephalus in this patient. The association of tension pneumocephalus in the subarachnoid space and ventricles and multifocal cerebral infarction in this patient

is unique and no previous documented case could be found in the literature. The more common differential diagnosis for a NPC patient in remission after radiotherapy presenting with impairment of conscious state or impairment of limb movement are temporal lobe radionecrosis and hypothalamic-pituitary dysfunction, the definitive diagnosis of which require CT and hormonal studies. 8 For the management of patients with such presentation, especially if there is associated fever, even in the absence of CSF rhinorrhoea, simple investigation like plain radiograph of the skull is indicated to exclude pneumocephalus. The authors wish to thank Dr KO Cheung, Consultant Physician, Caritas Medical Centre, Hong Kong for allowing us to use the clinical material. The manuscript is expertly prepared by Ms Irene Hui, Department of Pathology, Yan Chai Hospital, Hong Kong;

ACKNOWLEDGEMENTS

Addressjorcorrespondence: W.F.N., Department ofPatho]ogy, Yan Chai Hospital, 7-11 Yan Chai St, Tsuen Wan, Hong Kong.

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Pathology (1995), 27, April 6. Isler RJ, Weber AL. Pneurnocephalus from paranasal sinus carcinoma. Ann Otolo Rhinol Laryngol 1978; 87: 142-3. 7. Lee WMA, NOSH, Ho HCJ et aI. Clinical diagnosis of late temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma. Cancer 1988; 61: 1535-42. 8. Woo E, Lam K, Yu YL et al. Temporal lobe and hypothalamicpituitary dysfunctions after radiotherapy for nasopharyngeal carcinoma: a distinct clinical syndrome. J Neurol Neruosurg Psych 1988; 51: 1302-7.