of Nasopharyngeal Carcinoma
Yizhuo Li, Peihong
Wu, Chuanmiao Xie
University Cancer Center, Guangzhou, Guangdong, China
author: Yizhuo Li; Email: firstname.lastname@example.org
Citation: Li YZ, Wu PH, Xie CM. Skull-base
Invasion of Nasopharyngeal Carcinoma. J Nasopharyng Carcinoma, 2014, 1(3):
Competing interests: The
authors have declared that no competing interests exist.
Conflict of interest: None.
the Editorial Department of Journal of Nasopharyngeal Carcinoma. This is an
open-access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in
any medium, provided the original author and source are credited.
Abstract: The nasopharynx is situated just below the base of the skull.
Nasopharyngeal carcinoma (NPC) has a great tendency to invade adjacent regions
fairly early. Due to its deep and hidden anatomical location, the infiltrating
ability of the tumour, and the non-specific nature of the symptoms, it is not
diagnosed until it reaches an advanced stage. So, NPC may present with base of
the skull erosion and/or cranial nerve involvement. Magnetic resonance imaging
(MRI) could provide useful information about the position and quality of NPC
because of its ideal soft tissue contrast and multi-planar imaging capacity.
With gadolinium contrast and fat suppression sequences, it has greater
sensitivity over clinical examination in detecting the base of the skull with
bone erosion and/or perineural invasion. MRI is the choice of imaging modality
for evaluating tumour extension. The aims of this article were to review the
imaging studies of skull-base invasion and its impact on tumour staging and
Key words: nasopharyngeal
carcinoma, magnetic resonance imaging (MRI), imaging diagnosis, tumour stage
Malignant tumours in the nasopharynx often spread intracranial, and the
skull-base and the nerve channels are the main spread pathway. Skull-base was
composed by sphenoid bone, portions of the occipital and temporal bone. The
intracranial surface of the skull-base was divided in to three portions:
anterior cranial fossa, middle and posterior cranial fossa.
The clivus and basisphenoid bone make up the posterior wall and the roof
of the nasopharynx (1). The sphenoid bone is the foundation of the central
cranial base, which is made up of a body, greater and lesser wings and
pterygoid processes (2,3). The anterosuperior surface of the sphenoid body
forms a part of the floor of the anterior cranial fossa. The sella turcica lies
just above the sphenoid sinus, bound anteriorly and posteriorly by the clinoid
processes. Laterally and inferiorly, the greater wings of the sphenoid form the
floor of the middle cranial fossa. The posterior edge of the lesser wing of the
sphenoid delimits the aspect of the middle cranial fossa. Posteroinferiorly,
the anterior aspect of the basiocciput articulates with the posterior part of
the body of the
sphenoid, forming the clivus. The clivus, the anterior tip of the
petrous apex and the basisphenoid bone form the foramen lacerum. Above the
foramen lacerum and lateral to the clivus is the cavernous sinus. The abducens
nerve (VI) passes through the cavernous sinus; the oculomotor nerve (III), the
trochlear nerve (IV) and the first division of the trigeminal nerve are found in
the lateral wall of the cavernous sinus. The optic nerve (II) lies medial to
the cavernous sinus.
Several important foramina traverse the sphenoid bone. The optic canals
are marginated by the roots of the lesser wings of the sphenoid. The optic
nerves and ophthalmic artery go throughout it. The superior optic fissure lies
between the lesser and the greater wings and transmits cranial nerves (CN) III,
IV VI, V1 and ophthalmic vein. The inferior orbital fissure allows
communication between the inferior orbit and the pterygopalatine fossa. The
pterygopalatine fossa is a medial depression of the ptergomaxillary fissure,
which lies between the ptergoid process and the maxillary sinus. It is in free
communication with the infratemporal fossa laterally. The infratemporal fossa
lies lateral to the paranasopharyngeal space. It is bound by the posterior wall
of the maxillary antrum anteriorly, and the deep head of the temporalis muscles
and the zygomatic arch laterally.
Foramen rotundum, foramen ovale and foramen spinosum perforate the
greater wing of the sphenoid bone from anteromedial to posterolateral. Foramen
rotundum is separated from the superior orbital fissure by a thin bar of bone.
Foramen rotundum passes through the space between the back wall of the maxillary
sinus and the body of the pterygiod, and transmits the second division of CN V
(V2). The largest of the foramina, foramen ovale, perforate the sphenoid bone
at the level of the junction of the body and the greater wing. The orifice of
the foramen ovale is surrounded by fat, within which the mandibular branch of
the trigeminal nerve (V3) is transmitted. Posterolateral to the foramen ovale,
the foramen spinosum provides a pathway for the middle meningeal
Figure 1. Photograph of the
normal intracranial surface of skull-base from the downward view showing bone landmarks
and foramina. The right half was distinguished by different colours. From
anterior to posterior are frontal bone (blue), sphenoid (yellow), temporal bone
(orange) and occipital bone (cyan). The left half showing Foramen rotundum,
foramen ovale and foramen spinosum perforate the greater wing of the sphenoid
bone from anteromedial to posterolateral. The clivus, the anterior tip of the
petrous apex and the basisphenoid bone form the foramen lacerum
GW=greater wing of sphenoid; LW=lesser wing of sphenoid; PA=petrous
apex; OB=Occipital bone; FR=foramen rotundum; FO=foramen ovale; FS=foramen
spinosum; FL=foramen lacerum.
Figure 2. CT findings axial
bone window of the skull-base showing several foramina and canals. foramina and
canals are showing relative low density.(PF=pterygopalatine fossa; PP=pterygoid
process; BB=basisphenoid bone; PA=petrous apex; FO=foramen ovale; FS=foramen
spinosum; FL=foramen lacerum; C=clivus; CC=carotid canal).
The bony landmark of the exocranial surface of the skull-base was identified
in relation to the roof of the parapharyngeal space (PPS). The anterior limit
of the PPS roof lies at the apex of the scaphoid fossa. The free border of the
medial pterygoid plate splits superiorly to form the scaphoid fossa. The spine
of the sphenoid bone forms the lateral limit of the roof of the PPS. The
exocranial surface of the petrous temporal bone makes up the major portion of
the bone of the roof of the PPS. The posterolateral border of the roof of the
PPS is the styloid process and the posterior border is the most posterior
aspect of the posterior margin of the jugular foramen.
Clinical examination and endoscopic examination of the nasopharynx can
provide valuable information on mucosal lesion and local tumour extension.
However, it cannot determine deep tumour extension, such as skull-base erosion
and intracranial spread. Cross-sectional imaging has resolved this problem
easily. The primary role of imaging is accurate tumour mapping and display tumour extension to the skull-base and the
spaces. Up to now, there are two scanning instruments used in imaging:
Computed Tomography (CT) and MRI.
CT scanning areas include the
nasopharynx and neck. Axial scans were obtained at 5-mm intervals with the infraorbitomeatal(OM)
line parallel to the gantry(5). The nasopharynx scans were obtained from the
suprasellar cistern to the inferior edge of C2 vertebra. The neck scans were
obtained from the inferior edge of the C2 to the sternal end of the clavicle. The
coronal scans were performed with the hard palate perpendicular to the gantry
(6) and the region from the posterior ethmtoid sinus to the dorsal jugular foramen. After the axial and coronal scans were obtained before injection of
the contrast material, an intravenous contrast injection was used to enhance
the difference between the tumour and other tissues, and for better delineation
of the carotid artery and jugular vein. The coronal scan was not used routinely
The CT findings of skull-base
erosion were classified into three types (7): A, bone destruction, CT
scans show the bone erosion ranged from intensive bone destruction, through
varying degrees of intracranial invasion with CN involvement, to subtle bone
defect without CN involvement (5,6); B, bone sclerosis, CT scans show
the density in the invaded region of the skull-base is higher than that of the
normal area; and C, both of them simultaneously, both the bone defect and abnormal high density area were present.
The region from the suprasellar cistern to the inferior margin of the
sternal end of the clavicle was examined with a combined head and neck coil. T1-weighted
images in the axial, coronal and sagittal planes (repetition time [TR] ms/echo
time [TE] ms, 500-600/10-20) and T2-weighted images in the axial plane
(4000-6000/95-110) were obtained before injection of contrast material. After
intravenous gadopentetate dimeglumine (Magnevist, Schering, Berlin, Germany) at
a dose of 0.1 mmol per kilogram of body weight, T1-weighted axial and sagittal
sequences, and T1-weighted fat saturation axial and coronal images were
acquired sequentially using parameters similar to those used without
gadopentetate dimeglumine. The slice thickness was 5-mm with a 1-mm
intersection overlap for all the sequences. Bone involvement on MRI is
diagnosed when the following could be seen: a defect in the low signal
intensity of the cortex and marrow being replaced by tumour with contrast
enhancement in bone (8) (Figure 3).
Figure 3. NPC in a 51 year-old man.
Pretreatment sagittal (a) T1W images without fat saturation show the erosion of
the clivus (arrow). Contrast-enhanced sagittal (b) T1W images show the erosion
clivus (arrow) with moderate enhancement.
Values comparison between CT and MRI in NPC
Several studies (9-12) demonstrated that MRI could provide useful
information about the position and quality of skull-base because of its ideal
soft tissue contrast and multi-planar imaging capacity. With gadolinium
contrast and fat suppression sequences, it has greater sensitivity over
clinical examination and CT scanning in detecting the base of the skull. MRI
can also avoid the bony artefacts of the skull-base which are very serious in
CT scanning. So MRI is the choice of imaging modality for evaluating local
tumour extension and perineural spread in NPC patients.
Patterns of skull-base erosion
Previous studies (8, 13, 14) reported that skull-base erosion may be
seen in 25–35% of cases. With improvement
in imaging techniques, these percentages will increase. In recent data (15),
the incidence of skull-base invasion was 65.5%, which is higher than previously
reported. This may be because some studies were based on CT scanning, while
others were based on MRI without the use of fat saturation techniques. Li
YZ(15) and Liang SB (16) classified the anatomic sites surrounding the
nasopharynx into three risk grades: high group (≥35%), medium group (≥5%-35%)
and low group (<5%). High risk grade included the base of the sphenoid bone,
pterygoid process, clivus and petrous apex. The base of the sphenoid bone is
the most common erosion site, followed by the pterygoid process, clivus and
petrous apex. These anatomic sites lack any barrier and are only a short
distance from the original tumour. The medium group included the greater wing
of the sphenoid, lateral pterygoid plate, foramen lacerum and cavernous sinus.
These sites are relatively at a longer distance from the original tumour
compared to the high group. The low group include foramen ovale, occipital
condyle, etc. These areas are more distant from the original tumour than the
medium group. These data demonstrate that tumours spread gradually with
decreasing movement from proximal sites to more distant sites surrounding the
nasopharynx. According to the anatomic site, the pathways of skull-base
involvement were classified into five routines (7,15): anterior spread,
superior spread, super-lateral spread, super-anterior spread and
Relationship between skull-base invasion and tumour staging
In the UICC/AJCC staging system
(7th Edition, 2010) (17), bony structure invasion are classified as
T3 lesions. The result is mainly in terms of survival rate. However, Li YZ (15)
et al. proposed another opinion: the MR images showed that the extent of bone
invasion ranged from minimal confined sphenoid base disease through varying
degrees to more extensive bone erosion with or without CN involvement. Most
cases in the low group had T4 lesions (65/74). This may be because the low
group was combined completely with other T4 structure involvements (such as
intracranial extension and/or cranial nerve involvement). Cases in the high and
medium groups did not reveal any intracranial extension or CN involvement on
MRI. The majority of medium group cases also had T4 lesions (154/250). Only in
the high group were T3 cases the majority (190/255). This result indicates the
skull-base invasion in different groups probably impacts the T-staging and
prognosis in NPC patients.
Impact of skull-base
invasion on prognosis
NPC is a tumour that is sensitive
to radiation therapy. However, due to its unique anatomic site, the
dose-limiting organs surrounding the nasopharynx are also damaged during
radiation therapy, which affects the quality of life of the survivors (18). Patients
may suffer from a variety of late complications. These sequelae include
auditory problems (19), oral complications, such as dry mouth (20, 21),
dysphagia (22), CN palsies, memory loss (23), and cognitive (24) and
neuropsychological dysfunction (25). So we suggest that the quality of life
should become a factor of prognosis evaluation in cancer patients.
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