Clinical Radiology xxx (2014) e1ee15

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Clinical Radiology
journal homepage: www.clinicalradiologyonline.net

Oral cavity squamous cell carcinoma: Role of

pretreatment imaging and its influence on
management
S. Arya a, *, P. Rane b, A. Deshmukh b
a
Department of Radio-diagnosis, Tata Memorial Centre, Mumbai, India
b
Head Neck Services, Department of Surgical Oncology, Tata Memorial Centre, Mumbai, India

art icl e i nformat ion

Squamous cell carcinoma (SCC) is the commonest malignancy in the oral cavity. The oral cavity
Article history: has several subsites. Knowledge of the patterns of disease spread at each subsite with the
Received 5 November 2013 impact on treatment and prognosis provides a deeper understanding of the role of imaging.
Received in revised form Information from imaging helps accurate staging, assess resectability, and plan multimodality
31 March 2014 treatment. Mandibular erosion, posterior soft tissue extent, and perineural spread influence
Accepted 15 April 2014 treatment and prognosis in gingival, buccal, and retromolar trigone (RMT) cancers. Multi-
detector computed tomography (MDCT) with multiplanar reformations and bone and soft
tissue algorithms provides the highest specificity for bone erosion. Hard palate SCC is optimally
imaged with contrast-enhanced magnetic resonance imaging (MRI) to detect perineural
spread. In oral tongue and floor of the mouth (FOM) SCC, extrinsic muscle invasion, extension
across the midline, extent of posterior and inferior spread, and proximity to the hyoid are
issues that impact therapeutic options. Contrast-enhanced MRI is the optimal imaging method
for staging the primary due to its superior soft tissue resolution. In oral tongue SCCs with
tumour thickness
4 mm, elective neck dissection can be avoided. For nodal staging (N-
staging), all imaging methods are comparable, but fall short of surgical staging. Sentinel lymph
node biopsy has a promising role in N-staging. Positron emission tomography (PET)/integrated
PET/CT has no role in evaluating the clinically negative neck. PET/CT has a role in pretreatment
evaluation of advanced oral cavity SCC for depicting distant metastases and for mapping nodal
extent in the clinically positive neck. Diffusion-weighted MRI, dynamic contrast-enhanced
MRI, and CT perfusion have a potential role as baseline pretreatment studies for response
assessment to chemoradiation in advanced oral cavity SCC.
Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction
Oral cancer is the sixth most common cancer worldwide,
with the highest incidence in South Asia.1 Although tobacco
* Guarantor and correspondent: S. Arya, Department of Radio-diagnosis,
Tata Memorial Centre, Mumbai, India. Tel.: þ91 22 24177000, þ91
9820524150 (mobile); fax: þ91 22 2414 6937.
E-mail address: supreeta.arya@gmail.com (S. Arya).
and alcohol are the major causes with a documented syn-
ergistic effect, a link also exists with a diet lacking in anti-
oxidants. Areca nut chewing is another factor in Indo-Asian
populations. The other less frequent causes include human
papilloma virus (more frequently implicated in oropha-
ryngeal cancers), poor dental hygiene, chronic mechanical
irritation by sharp tooth or denture, as well as genetic
susceptibility.2

0009-9260/$ e see front matter Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.crad.2014.04.013

Please cite this article in press as: S.Aryaa,*supreeta.arya@gmail.comP.RanebA.Deshmukhb, Oral cavity squamous cell carcinoma: Role of pre-
treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
e2 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15

Approximately 90% of the malignancies arising from the covered upper and lower alveolus, buccal mucosa, and
various subsites of the oral cavity are squamous cell carci- retromolar trigone (RMT). The lips form the anterior
nomas (SCC).1,2 The primary aim of this article is to discuss boundary of the oral cavity. The anterior two-thirds of the
the role of imaging in the management of oral cavity SCC tongue form the oral tongue, while the posterior one-third,
(OCSCC). The principles of treatment are briefly described also called the base of tongue (BOT), is part of the
followed by anatomy of the oral cavity, the patterns of oropharynx (Fig 1).
spread of OCSCC, the influence of imaging findings on The oral cavity can be divided into an oral cavity proper
therapy, the optimal imaging methods for comprehensive and the vestibule. The oral cavity proper consists of the oral
staging at each subsite, along with deficiencies in the 7th tongue and FOM and is bounded by the hard palate supe-
edition American Joint Committee on Cancer (AJCC) staging riorly (Fig 2a). The gingiva-covered upper and lower alve-
of OCSCC. olus form the boundary separating the oral cavity proper
from the vestibule. The outer boundary of the vestibule is
formed by the buccal mucosa that is closely apposed to the
Principles of treatment of oral cancers
buccinator forming the buccal mucosaebuccinator com-
plex, lateral to which lies the fat-filled buccal space that
OCSCC from all subsites have a propensity not only to
leads posteriorly to the masticator space (Fig 2b). Posteri-
spread locally but also to the lymphatics of the neck. The
orly the vestibule leads into the RMT, which is a triangular
goals of therapy in OCSCC are (1) treatment of the primary
mucosal area behind the last mandibular molar contiguous
tumour and neck and (2) preserving form and function with
above with the maxillary tuberosity (Fig 3). Behind this
appropriate reconstruction.1 Based on the combination of T,
mucosa lies the pterygomandibular raphe to which the
N, and M stages, OCSCC is further divided into stages I, II, III,
superior pharyngeal constrictor and the buccinator muscles
IVA, IVB, and IVC. Stages I and II (T1eT2, N0, M0) are treated
are attached.
with a single modality, surgery or radiotherapy. Surgery is
The oral tongue consists of the intrinsic muscles just
the preferred method in OCSCC, although the overall sur-
beneath the dorsum and the extrinsic muscles (genioglosus,
vival and local control with both modalities is similar.
hyoglossus, palatoglossus, and styloglossus). The sling-like
Radiotherapy has disadvantages of prolonged treatment,
mylohyoid along with the paired geniohyoid on its upper
xerostomia, mucositis, and osteoradionecrosis. It is partic-
surface and the anterior belly of digastric on its lower sur-
ularly not preferred in lesions close to the bone and in
face form the radiological FOM. The genioglossus, hyo-
young patients.3
glossus, mylohyoid, and digastric are well seen on T2W MRI
Approximately 40e60% of OCSCC present in advanced
sequences (Fig 4a and b). The sublingual space is a fat-filled
stage (III and IV). The prognosis and loco-regional control in
space between the genioglossus located medially and the
these cases is poor. These are treated with multimodality
mylohyoid situated inferiorly and laterally. The lingual ar-
therapy, standard practice being radical ablative surgery
tery is seen as a flow void at MRI (Fig 4b) or enhancing
followed by postoperative radiotherapy or chemo-
structure at CT within this space, but the lingual and
radiotherapy (also called concurrent chemoradiation).2 In
order to preserve quality of life, there has been a paradigm
shift towards organ preservation in other head and neck
SCC (HNSCC) with concurrent chemo-irradiation offered as
primary treatment.4 However, surgery has remained the
mainstay of treatment in OCSCC.
Metastases to neck nodes in OCSCC at presentation are
seen in up to 45% depending on the subsite.2 Cervical nodal
metastasis is the single most important prognostic factor in
OCSCC reducing survival by 50%.5 When metastatic nodes
are detected on clinical examination confirmed with im-
aging, it is referred to as the Nþ neck (N1- N3 of AJCC stage).
The neck that is negative for nodes on clinical examination
and imaging is called N0. The Nþ neck is treated with
modified radical neck dissection involving dissection of
levels IeV nodes.2 There are three approaches to the man-
agement of the N0 neck in OCSCC: (1) elective neck
dissection/irradiation, particularly recommended in T3 and
T4 lesions; (2) watchful waiting (observation); or (3)
sentinel lymph node biopsy 3,6.
Figure 1 Sagittal reformation on 16 section MDCT shows the
boundary between oral cavity and oropharynx as a circular line
Anatomy of oral cavity extending from junction of hard palate and soft palate (*) along each
anterior tonsillar pillar to the dorsum of tongue in the region of
The oral cavity has several subsites, namely the oral circumvallate papillae (not seen on imaging). BOT, base of tongue; OT,
tongue, floor of the mouth (FOM), hard palate, gingiva- oral tongue (extent shown by horizontal line); FOM, floor of mouth.

Please cite this article in press as: S.Aryaa,*supreeta.arya@gmail.comP.RanebA.Deshmukhb, Oral cavity squamous cell carcinoma: Role of pre-
treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15 e3

Figure 2 Subsites of oral cavity. (a) Coronal reformation on a 16 section MDCT with puffed-cheek technique shows oral cavity proper containing
oral tongue (OT), floor of mouth (FOM), and hard palate (vertical arrow). Dotted arrow shows distended buccal vestibule with air separating
buccal and gingival mucosa that meet at upper and lower gingivobuccal sulcus (arrowhead). (b) Axial MDCT section with puffed-cheek tech-
nique. Short arrow shows the buccal mucosaebuccinator complex. Dotted arrow shows buccal space posterior to which is the masticator space
containing masseter (M).

hypoglossal nerves (lateral to the artery) are not visualized
on imaging.
Spread patterns and influence on
management
Oral tongue cancers usually arise from the lateral border
and occasionally from the ventral surface. They can invade
Figure 3 RMT anatomy. Schematic diagram showing mucosa of RMT
(arrowhead pointing to shaded region), pterygomandibular raphe
behind (arrow) attached to the pterygoid hamulus (*) and mylohyoid
line (dotted line) below. The raphe is a conduit for superior spread to
masticator space and pterygopalatine fossa. Reproduced with
permission from Arya S et al. Retromolar trigone squamous cell
cancers: a reappraisal of 16 section MDCT for assessing mandibular
invasion. Clin Radiol. 2013; 68:e680ee688.
the extrinsic muscles, extend into the sublingual space,
encase the neurovascular bundle, and spread across the
midline (Fig 5). Extension to the FOM can erode mandible
(in <10%) and may also reach up to the hyoid. Invasion of
the opening of the Wharton’s duct in the FOM can result in
dilated submandibular ducts (Fig 6a and b). Posterior spread
can occur into the BOT, valleculae, and pre-epiglottic space
(Fig 6c and d). Extension across the BOT into the anterior
tonsillar pillar can reach the RMT or the tonsil, posterior
tonsillar pillar, and lateral oropharyngeal wall. Small tu-
mours along the lateral border may be treated by wide
excision glossectomy with adequate margins. More exten-
sive spread requires partial to total glossectomy. Recon-
struction is planned if there is an expected 30% or more
volume loss following excision.
Gingival, buccal, and lip cancers can erode the mandible,
invade tongue muscles, and spread laterally up to the
overlying skin. Advanced gingivo-buccal cancers can spread
posteriorly into the RMT and masticator space. SCC of the
RMT can spread circumferentially in multiple directions to
invade the BOT, FOM, tonsil, buccal mucosa, body and ver-
tical ramus of mandible, and muscles of masticator space
(Fig 7a). Maxillary erosion is less frequent than mandibular
erosion. The pterygomandibular raphe can be a route of
superior spread of RMT SCC to the masticator space without
eroding the mandible. RMT SCC reaching the superior limit
near the pterygoid hamulus can also ascend into the pter-
ygopalatine fossa (Fig 7b). A combination of increased signal
on T2W and short tau inversion recovery (STIR) MRI se-
quences with enhancement on gadolinium-enhanced se-
quences is indicative of tumour spread. Hard palate SCC can
spread into the nasal vault, maxillary sinus, and through the
greater palatine foramen and canal (Fig 8) into the pter-
ygopalatine fossa.
The 7th edition AJCC tumor staging of SCC of the oral
cavity and lips is provided in Table 1. Imaging delineates the

Please cite this article in press as: S.Aryaa,*supreeta.arya@gmail.comP.RanebA.Deshmukhb, Oral cavity squamous cell carcinoma: Role of pre-
treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
e4 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15

Figure 4 Tongue anatomy. (a) Axial T2W MRI image clearly depicts genioglossus (paired short arrows), hyoglossus (dashed arrow), and
mylohyoid (long arrow). (b) Coronal T2W MRI image shows lingual artery (horizontal arrow) in the hyperintense sublingual space, mylohyoid
(arrowheads), genioglossus (vertical arrow), and anterior belly of digastric (oblique arrow).

deep extent of the tumour not amenable to clinical exami-
nation, which is needed for accurate staging. Imaging also
provides information not incorporated in the TNM staging
that impacts treatment and prognosis. Table 2 describes the
spread patterns and their influence on therapeutic options.
The issues that need further discussion include mandibular
erosion; extent of soft tissue invasion of masticator space in
gingival, buccal, and RMT cancers; perineural spread;
tumour thickness in tongue cancers; and evaluation of the
neck for nodes.
Mandibular erosion
Mandibular invasion influences management, which can
vary from the conservative marginal mandibulectomy (that
preserves function and cosmesis) to the more destructive
segmental mandibulectomy.1,3,7 Clinical examination alone
is insufficient to predict bone invasion. The status of the
surgical resection margins impacts survival.2 Bone resection
margins are difficult to assess by clinical examination or
frozen section and hence accurate preoperative imaging
assumes a vital role.2,3
Segmental mandibulectomy is performed when there is
significant cortical erosion with invasion of the marrow;
hemimandibulectomy is offered when the inferior alveolar
canal and mandibular foramen are invaded.3,7 Segmental
mandibulectomy is also offered in edentulous and irradi-
ated mandibles or when a bulky soft-tissue component of
the OCSCC abuts a large surface area of the mandible, in
order to obtain tumour-free resection margins (Fig 9a).
Marginal mandibulectomy involves rim resection of the
mandible and is offered when there is minimal erosion of
the alveolar margin or when a small soft-tissue component
abuts the alveolar crest of the mandible to obtain onco-
logically safe resection margins (Fig 9b).3,7,8 It can be ach-
ieved when at least 1 cm of the height of the body of the
mandible can be preserved (to prevent fracture). Hence,
imaging should ideally record the presence or absence of
cortical, marrow, and inferior alveolar canal invasion; the
depth and length of erosion; the height of the intact
mandible at the site of erosion and/or the height of the
mandible free from paramandibular soft tissue. The latter
information is obtained by measuring the height from the
inferior border of the mandible to the inferior limit of the
paramandibular soft-tissue component (Fig 9b).
Mandibular invasion has been extensively evaluated by
orthopantomography (OPG), bone scintigraphy, conven-
tional CT, single photon emission computed tomography
(SPECT), integrated positron emission tomography (PET)/CT,
MRI, multidetector CT (MDCT), and cone-beam CT.9e21 The
goal has been to identify an imaging method with the
highest sensitivity for detecting invasion without reducing
specificity. OPG has a reported low specificity for mandib-
ular erosion,10,11 presumably due to periodontitis and
odontogenic infections (particularly in quid-chewing pop-
ulations) that can mimic malignant erosion. Detection of
erosion requires at least 30% mineral loss and midline ero-
sions can be missed.11 The role of OPG in OCSCC is mainly in
planning dental treatment prior to definitive treatment
with irradiation to prevent osteo-radionecrosis and to
assess the distance between dental roots prior to
mandibulotomy.
SPECT bone imaging showed the highest sensitivity of
100% for mandibular invasion in OCSCC, but at the expense
of very low specificity (29%).12 Planar bone imaging had low
specificity and lower sensitivity than SPECT.9 Mukherji
et al.13 demonstrated that conventional CT with 3 mm
sections in bone and soft-tissue algorithms had a high
specificity of 87% for mandibular invasion in OCSCC without
compromising sensitivity (96%).13 Subsequently, Brock-
enbrough et al.14 using Dentascan, a CT software originally
designed to evaluate dental implants, reported a sensitivity

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treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15 e5

Figure 5 Spread patterns of oral tongue SCC on MRI. (a) Axial contrast-enhanced MRI best shows the tumouretongue contrast in SCC of the right
anterior tongue (*) also seen as a hyperintense lesion (*) in (b). (b) T2W axial MRI image best depicts the genioglossus (short arrow), which is
hyperintense s/o invasion. The invaded right hyoglossus is not seen separate from the tumour (compare with the contralateral hyoglossus shown
by long arrow). (c) Coronal STIR MRI image shows the tumour (*) invading the sublingual space lateral to the lingual artery (arrow) suggesting
invasion of the lingual and hypoglossal nerves (located lateral to artery). (d) Coronal contrast-enhanced MRI in another patient shows the
tumour (*) crossing the midline that is more likely to have bilateral metastatic nodes. Arrows show bilateral levels IB nodes that need to be
viewed with suspicion.

of 95% and specificity of 79% for mandibular invasion in
OCSCC. Goerres et al.15 concluded that [18F] -fluoro deoxy
glucose (FDG) uptake seen on PET/CT images does not add
to CT information for identification of bone infiltration.15
Bolzoni et al.16 reported high sensitivity and specificity
with MRI for mandibular invasion in OCSCC. However,
Imaizumi et al.17 comparing CT with MRI in 51 patients of
OCSCC found MRI to overestimate cortical erosion and
inferior alveolar canal involvement. Dental CT was used in
35 of their 51 patients that resulted in 100% sensitivity and
accuracy of 94% for CT. Multidetector scanners have ushered
in a new era in CT imaging. Vidiri et al.18 compared four-row
MDCT with MRI in OCSCC and found no statistically sig-
nificant difference in accuracy for mandibular invasion (86%
and 81% respectively). Handschel et al.19 using six-row
MDCT reported 82.6% sensitivity and 86.9% specificity for
mandibular invasion with good interobserver variability
between three observers.
Although the positive predictive value of CT for
mandibular invasion is considered satisfactory, the sensi-
tivity is still considered inadequate by some who advocate
intraoperative periosteal stripping when CT is negative.2,3,19
MRI in contrast has high negative predictive value, but less
specificity. Major reasons for inadequate sensitivity or
specificity of imaging methods are failure to visualize the
alveolar crest of the mandible and coexistent odontogenic
infections, respectively. Although there have been rapid
advances in CT technology, the full potential of MDCT has
not been exploited for mandibular invasion with few
studies reporting on 16 or higher section CT scanners.21

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treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
e6 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15

Figure 6 Spread patterns of oral tongue SCC. (a) Contrast-enhanced sagittal T1W MRI image showing tumour along ventral surface of anterior
tongue (arrow) invading opening of the right Wharton’s duct with resultant dilated duct (arrowhead). (b) Axial T2W MRI image shows the linear
hyperintense dilated duct (arrow). (c) Axial contrast-enhanced MRI image shows enhancing tumour in the right base tongue reaching the lingual
tonsil (arrow) that shows greater enhancement than the normally enhancing contralateral lingual tonsil (dashed arrow). (d) Sagittal contrast-
enhanced MRI shows tumor in the vallecula and pre-epiglottic space (arrow).

Arya et al.22 using 16 section MDCT recently reported 94%
sensitivity and 90% specificity for assessing mandibular in-
vasion in RMT SCC.22 This study emphasized the importance
of optimal MDCT technique that includes thin sections and
multiplanar reformations along with bone and soft-tissue
algorithms for increasing accuracy and interobserver
concordance in assessing mandibular invasion.22
Combinations of imaging methods and diagnostic algo-
rithms have been proposed by some to exploit the high
sensitivity and specificity of different imaging methods. Abd
El-Hafez et al.23 reasoned that a negative MRI is reliable to
rule out mandibular invasion, but a positive MRI should be
complemented with PET/CT to increase specificity.23 Van
Cann et al.24,25 proposed initial imaging with CT followed by
SPECT when CT was negative to reduce unnecessary man-
dibulectomies. Gu et al.26 compared CT, PET/CT, and MRI
alone with their combined use and found that combined
use increases specificity to 100%, but the sensitivity was
83.3%. In practice, the cost effectiveness of these combina-
tions needs to be factored.
There are two reports of cone-beam CT for mandibular
invasion with high sensitivity (91%) and specificity
(100%).20,21 Subtle alveolar crest invasion was still declared
a problem due to severe dental artefacts and image noise.
Other problems with cone-beam CT include limited scan-
ning volume, limited contrast, and limited soft-tissue in-
formation.27 A systematic review found no evidence-based
data to support the low radiation dose claimed for cone-
beam CT.27 Moreover, OCSCC requires complete staging
evaluation with contrast-enhanced CT/MRI. Hence, 16 sec-
tion and higher MDCT technology with thin sections and
multiplanar comprehensive imaging capabilities need

Please cite this article in press as: S.Aryaa,*supreeta.arya@gmail.comP.RanebA.Deshmukhb, Oral cavity squamous cell carcinoma: Role of pre-
treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15 e7

Figure 7 Spread patterns of RMT SCC. (a) Axial CT section showing an enhancing tumour extending into the buccal space (white arrow); the
masticator space at the level of the medial pterygoid (dashed arrow) and tonsil (black arrow). (b) Axial CT section at a superior level shows
tumour spread into the right pterygopalatine fossa as a soft-tissue density (arrow).

reappraisal. The advantage of 16 section and higher MDCT is
that it can provide sections as thin as 0.625 or 0.75 mm. This
enables isotropic multiplanar reformations in any plane and
when used with bone algorithms, makes possible high-
resolution views of buccal, lingual, and occlusal cortices,
increasing the sensitivity for detecting cortical erosion
(Fig 9c and d). Correlating findings on clinical examination
with imaging has the potential to improve specificity.
Masticator space spread
The 6th edition AJCC staging of head and neck cancers
subclassified T4 in OCSCC into T4a (resectable) and T4b
(unresectable) depending on regions of spread and impact
on resectability. The 7th edition AJCC staging has relabelled
T4a cancers to “moderately advanced” and T4b cancers to
“very advanced”28 and a subset of T4b maybe amenable to
treatment. The precise extent of posterior soft tissue spread
is important for planning resection in gingival, buccal, and
RMT SCC. Posterior spread can involve the masseter and
medial pterygoid muscles or extend higher to involve lateral
pterygoid and temporalis muscles. Few reports correlate
imaging findings and the outcomes of resection in advanced
OCSCC with posterior spread. Liao et al.29,30 described sur-
gical outcomes of buccal, gingival, and RMT cancers that
extended to the masticator space. Using CT or MRI, a line of
demarcation passing through the mandibular (or sigmoid)
notch (between the condyloid and coronoid processes) was
used to divide posterior disease spread above and below the
level of notch into supra-notch and infra-notch T4b disease,
respectively. Infra-notch T4b had a favourable outcome
with a superior local control rate of 74% compared to greatly
increased surgical morbidity, poorer local control, and
overall survival in supra-notch T4b disease.29 CT and MRI
can both demonstrate masticator space involvement above
and below the mandibular notch. The infra-notch masti-
cator space contains the medial pterygoid, whereas the
supra-notch masticator space contains the lateral pterygoid
and bulk of temporalis (Fig 10). In RMT SCC, Crecco et al.31
reported an MRI accuracy of 90% for T-staging in 22
patients.
Perineural spread
Perineural spread refers to macroscopic tumour spread
beyond the primary site separate from the main bulk of the
tumour by travelling along the perineural sheath or along
the endoneurial plane.32 Perineural invasion (PNI) in
contrast refers to microscopic invasion of small nerves
confined to the main tumour bulk; is not seen on imaging
and is an adverse prognostic factor.32e34 In oral cancers, the
reported incidence of perineural spread varies from
5e10%.33,35 Vural et al.36 found an association of perineural
spread and neural cell adhesion molecule (N-CAM)
expression in 93% patients of HNSCC.36
In lip cancers, perineural spread can occur through the
mental foramen along the mental nerve and upstages dis-
ease to T4a.34 In oral tongue and FOM cancers, perineural
spread can course along the lingual nerve to the mandibular
nerve and thence to the inferior alveolar nerve.33 In hard-
palate cancers, perineural spread occurs through the
greater palatine foramen and canal (Fig 8) along the greater
palatine nerve into the pterygopalatine fossa.34 In RMT SCC,
perineural spread can occur by tumour extending posteri-
orly into masticator space35 with further lateral spread to
the mandibular foramen and thence along the inferior
alveolar nerve. In advanced gingival, buccal, and RMT can-
cers, perineural intracranial spread can occur along the
mandibular nerve through the foramen ovale and contra-
indicates resection.34
MRI is superior to CT for imaging perineural spread.
Disruption of the bloodenerve barrier leads to leakage of
contrast agents that causes nerve enhancement (depicted
better on MRI than CT) before nerve enlargement (seen

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treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
e8 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15

Figure 8 Hard palate SCC. (a) Axial CT section shows a widened left greater palatine foramen (black arrow). (b) Axial T2W MRI shows a
hyperintense mass (arrows) in the left greater palatine foramen. (c) Coronal CT section, bone window shows extension of the mass into the left
greater palatine canal (arrow). Note the calibre of the contralateral normal canal (dashed arrow). (d) Coronal contrast-enhanced MRI in the same
patient depicts the mass better due to the striking enhancement.

with both CT and MRI).33,34 CT may depict perineural spread
as loss of normal fat density or as excessive enhancement in
various foramina. Foraminal widening or erosion is seen in
more advanced cases.34 Coronal fat-suppressed post-gado-
linium T1W MRI best demonstrates perineural spread along
foramen ovale or greater palatine canal as increased
enhancement.33,34 Nemzek et al.32 reported a sensitivity of
95% of MRI for perineural spread, but Imaizumi et al.17 re-
ported overestimation of inferior alveolar canal invasion on
MRI due to surrounding inflammation.17 Liao et al.29 in their
series of gingival, buccal, and RMT cancers found that nerve
invasion was the sole adverse factor to predict local control
and disease-free survival in infra-notch T4b gingivo-buccal
and RMT SCC. However, in their series, preoperative MRI
could not reliably predict perineural invasion. Other series
report an imaging accuracy approaching 70% for prediction
of perineural invasion in HNSCC.34 Long-standing features
of perineural spread include denervation atrophy of the
masticator muscles (preceded by denervation oedema)
seen as reduced bulk and hyperintensity on T1W and T2W
images due to fatty replacement.33
Tumour thickness
In early tongue cancers, tumour thickness is the single
best prognostic factor for predicting survival (more than the
T stage).5 The terms “tumour thickness” and “tumour
depth” have been used synonymously in different re-
ports.5,37 T stage is dependent on maximum tumour
dimension, but tumour thickness (or more correctly
“tumour depth”37) is defined as the deepest invasion of
tumour in the tissue from the mucosal surface.5 The meta-
analysis by Huang et al.5 has shown an association of
tumour thickness >4 mm on histopathology with signifi-
cant increase in neck node metastases.5 Hence, elective
neck dissection has been recommended when the tumour
thickness exceeds 4 mm.28 For tumours seen as ulcers on
the lateral border of the tongue, the maximum lateral-to-
medial dimension is the tumour thickness, whereas for
tumours on the superior or inferior surface, the craniocau-
dal dimension is the tumour thickness. In a proliferative
tumour, tumour thickness does not include the exophytic
part beyond the surface and in an ulcerative tumour,

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treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15
Table 1
American Joint Committee on Cancer (7th edition) TNM staging for SCC of
oral cavity and lips.
Tumor
 TXe Primary tumor cannot be assessed
 T0- No e/o primary tumor
 Tise Carcinoma in situ
 T1 e
2 cm
 T2 e >2 cm but
4 cm
 T3 e >4 cm
 T4a e Moderately advanced local disease
(Oral cavity) Tumor invades cortical bone, deep (extrinsic)
muscles of tongue, maxillary sinus, or skin of face
(Lip) Tumor invades cortical bone, inferior alveolar
nerve, floor of mouth, or skin of face
 T4b e Very advanced local disease
Tumor involves masticator space, pterygoid plates, skull base, or
encases internal carotid artery
Node
 NX e Cannot be assessed
 N0 e No regional lymph node metastasis
 N1 e Single ipsilateral lymph node,
3 cm in greatest
dimension
 N2
B N2a e Single ipsilateral lymph node, >3 cm &
6 cm in
greatest dimension
B N2b e Multiple ipsilateral lymph nodes,
6 cm in greatest
dimension
B N2c e Bilateral or contralateral lymph nodes,
6 cm in
greatest dimension
 N3 e Lymph node(s) >6 cm in greatest dimension
Metastasis
 M0 e none
 M1 e yes
tumour thickness is best measured from the adjacent intact
mucosa.5,37
Tumour thickness has been prospectively evaluated by
preoperative MRI and intraoperative ultrasound with
satisfactory accuracy.38e43 Lam et al.39 reported that
contrast-enhanced T1W images had higher accuracy than
T2W images for tumour thickness when compared with
histopathology.39 Despite the efforts to correlate tumour
thickness on imaging with histopathology, in practice there
are two limitations with imaging-derived measurements.
First, in a proliferative tumour, MRI with closed mouth
would be unable to distinguish between the exophytic and
deep parts, impacting accuracy of tumour thickness esti-
mation. Second, the use of imaging-based tumour thickness
for decision making for neck dissection is limited by the fact
that MRI is often not ordered by the clinician for early tu-
mours (where frozen section histopathology-derived
tumour thickness is relied upon).
Choice of imaging methods
T-staging
Diagnosis of OCSCC is made with clinical examination
and biopsy. Imaging is used for staging disease. Few retro-
spective and prospective studies exist comparing CT and
MRI for imaging oral cavity with emphasis on tongue
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treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
e9
cancers. They favour MRI over CT for T-staging, particularly
for oral tongue and FOM SCC where the soft-tissue resolu-
tion is important.44e49 At our institute, we perform
contrast-enhanced CT on a 16 section MDCT scanner for
gingival/alveolar, buccal, lip, and RMT SCC where evaluation
of mandibular erosion is a priority. The advantage of speed
of imaging ensures greater patient throughput in resource-
constrained settings while providing staging accuracy for
relevant issues. Contrast-enhanced MRI is reserved for oral
tongue, FOM, and hard-palate SCC. The advantages and
disadvantages of these imaging methods for staging various
subsites are discussed in Table 3.
CT and MRI protocols
Contrast-enhanced CT is performed from the skull base
to the upper border of manubrium sterni. We acquire sec-
tions at 2.5 or 3 mm thickness on our GE and Siemens 16
section MDCT scanners. Multiplanar reformations are then
generated ad hoc from 0.625 or 0.75 mm retro-
reconstructed images. Both soft-tissue and bone algo-
rithms are obtained and the reformations are studied for
the mandible and soft-tissue extent on an integrated vol-
ume viewer or workstation using triangulation.22 Narrower
windows are used to study soft-tissue extent. The puffed-
cheek technique50 is routinely used, asking the patient to
puff the cheeks with air and hold it while breathing quietly.
This helps delineate the epicentre and tumour relationships
with confidence. In the few cases where dental amalgam
interferes with image quality, gantry tilt is employed to
obtain satisfactory sections. However, gantry tilt is not
possible with all modern MDCT machines.
Optimal MRI requires a 1.5 T magnet with a neck coil and
imaging performed from the skull base to the upper border
of the manubrium sterni. Multiplanar imaging in the axial,
coronal, and sagittal planes using T1W, T2W, and STIR se-
quences are obtained with 4 mm thickness and a field of
view (FOV) of 18e20 cm. Fat-suppressed gadolinium-
enhanced T1W sequences in all three planes and diffusion-
weighted (DW) imaging with b0e1000 are also performed.
Contrast-enhanced T1W sequences51 best display the
tumouretongue contrast and perineural spread. The
extrinsic muscle involvement is best appreciated on axial
and coronal T2W sequences combined with gadolinium-
enhanced images.51,52 Cortical bone erosion is studied on
unenhanced T1W sequences (although Imaizumi et al.17 re-
ported chemical shift artefacts resulting in false-positive re-
sults) and T2W sequences. Marrow involvement is studied
on unenhanced T1W, STIR, and gadolinium-enhanced T1W
sequences.17 Nodes are evaluated on T2W, coronal STIR,
contrast-enhanced T1W, and DW sequences with apparent
diffusion coefficient (ADC) maps.
Neck node evaluation (N-staging)
Tongue cancers usually spread to ipislateral level I and II
nodes, but skip metastases could occur to levels III and IV and
contralateral metastases are also known. Midline FOM SCC
can spread to bilateral nodes.3 Nodal metastases are frequent
from gingival, buccal, and RMT SCC and occur to level IA, IB
e10 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15
Table 2
Imaging findings in oral cavity squamous cell carcinomas (OCSCC) and their impact on treatment.
Site of squamous cell Spread pattern
carcinomas
Oral tongue & FOM Tumour thickness >4 mm
Extrinsic muscle (genioglossus and
hyoglossus) invasion
Extension across midline OR
Midline tumours (especially in FOM)
Extension into sublingual space
Invasion of floor of mouth
Encasement of both neurovascular
bundles
Posterior extent to base tongue,
tonsil or lateral oropharyngeal wall
Postero-inferior extent to vallecula,
pre-epiglottic space and hyoid
Posterosuperior spread to masticator
space (rare)
Gingival, buccal & RMT Invasion of skin, maxillary sinus,
tongue muscles
Gingival, buccal, RMT, lip, oral Mandible
tongue & FOM Significant lateral segment invasion
Bulky para-mandibular soft-tissue
component abutting large surface
of mandible
Mid-third mandible invaded
Subtle lingual plate erosion
(except tooth socket)
Gingival, buccal, RMT, Spread to masticator space below
hard palate mandibular notch (to low masticator
space containing medial pterygoid)
Masticator space above mandibular
notch (contains lateral pterygoid and
bulk of temporalis)
Pterygopalatine fossa, skull base & ICA
invasion
All subsites Bulky nodes at multiple levels with
extranodal disease
All subsites Large nodal mass encasing carotid
artery 270
RMT, retromolar trigone; FOM, floor of mouth.
*Rþ resection e When microscopic or macroscopic residual disease is left behind after attempted curative surgery.
and II regions. Hard palate SCC is less likely to present with
adenopathy. CT and MRI used for staging the primary have
comparable accuracy for evaluating neck nodes and extra-
nodal spread.53 The most important feature indicative of
metastasis is necrosis. However, as not all metastatic nodes
present with macroscopic necrosis, various size criteria have
Please cite this article in press as: S.Aryaa,*supreeta.arya@gmail.comP.RanebA.Deshmukhb, Oral cavity squamous cell carcinoma: Role of pre-
treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
Implication Influence on therapy
Increased incidence of neck node Elective neck dissection recommended5,28
metastases5
Upstaging (clinical T2/T3 disease a) Excision of FOM muscles for clear
to T4a) margins. Reconstruction needed along with
b) Multimodality treatment2,3;
Bilateral neck metastases (close Planning therapy of both sided neck
scrutiny of both sides of neck on
imaging)
Possibility of neurovascular bundle Influences extent of resection
involvement; Adverse prognosis
Loss of bulk More extensive reconstruction; commonly
with anterolateral thigh flap, along with
Multimodality treatment2,3
Extensive disease Total glossectomy; possibility of
Rþ resection* þ adjuvant (postoperative)
radiation
Alternately concurrent chemoradiation
offered
Advanced disease Extensive surgery needed; alternately
concurrent chemoradiation may be
offered
Poor prognosis; Relative surgical Morbid surgery requiring hyoid removal
contraindication and supraglottic laryngectomy with
extensive reconstruction; alternately
treated with chemoradiation
T4b Unresectable
Treated with chemo-irradiation
T4a Resectable
T4a stage Segmental mandibulectomy
No upstaging to T4a if bone not Segmental mandibulectomy
eroded
T4a stage Mid-third segmental mandibulectomy
with removal of genial tubercle and
muscle attachments
Requires bone and soft-tissue replacement,
commonly free fibular microvascular
reconstruction
T4a stage Lingual plate/oblique marginal
mandibulectomy
T4b Resectable
T4b Poor local control and prognosis if resected
T4b Unresectable
Adverse prognosis Postoperative radiotherapy/definitive
treatment with chemoradiation2,3
Inability to dissect vessel Unresectable disease;
from node treatment with radiotherapy/
chemoradiation
been used. A minimum axial diameter of >11 mm for level II
nodes and 10 mm for all other nodes is considered abnormal.
For a group of nodes in the drainage area of the primary, the
minimum axial diameter criteria decreases to >9 mm for
level II nodes and 8 mm for other nodes.54 Despite these, the
false-positive and false-negative rates vary between
 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15 e11

Figure 9 (a) Coronal reformat on 16 section MDCT (puffed-cheek technique) shows right buccal SCC (*) abutting a large area of mandibular shaft
(vertical line) without erosion. Segmental mandibulectomy still required for oncologically safe resection margins. (b) A left buccal SCC (*)
reaching the lower gingivo-buccal sulcus and abutting a smaller surface of the mandible. The height of the mandible measured (vertical line)
from the inferior limit of paramandibular soft tissue (horizontal line) to the lower border of mandible is sufficient to ensure marginal man-
dibulectomy (that requires an at least 1 cm post-surgery height of mandible to prevent fracture). (c) Bone-window and (d) bone-algorithm
images of oblique reformations (16 section MDCT) in a case of RMT SCC showing bone erosion (arrows). Oblique reformation best depicts
the curved RMT in its entirety. Note the superior resolution in (d).

15e20%.54 Endemic granulomatous disease in populations
where oral cancer has the highest incidence also diminishes
the value of size criteria.
The incidence of occult neck node metastases in the
clinically negative neck varies from 6e46%.3 Expectations of
imaging to detect these occult metastases continue, but
there is no pretreatment imaging method to detect micro-
scopic metastasis. The choice between elective neck
dissection and watchful waiting for the clinically negative
neck in oral cancers has long been a subject of controversy. A
recent meta-analysis concluded that elective neck dissec-
tion should be performed in all,55 but this meta-analysis has
been criticized.56 Hence, imaging has a role in surveillance
when watchful waiting of the neck is the chosen strategy.
Imaging methods other than CT or MRI used for evaluating
the neck have been ultrasonography, ultrasound-guided
fine-needle aspiration cytology (FNAC), contrast-enhanced
ultrasound, DW MRI, dynamic contrast-enhanced MRI (DCE
MRI), and PET/CT. Several meta-analyses have compared
various imaging methods for detecting neck node metastases
in head and neck cancers.57e60 None of these meta-analyses
has been exclusively in OCSCC. A meta-analysis by deBondt
et al.57 comparing ultrasound-guided FNAC, ultrasound, CT,
MRI, and ultra-small particle iron oxide MRI (USPIO MRI) has
shown that ultrasound-guided FNAC had the highest diag-
nostic odds ratio for detecting metastatic neck nodes with
decreasing performance for ultrasound alone, USPIO MRI, CT,
and MRI in that order. However, this meta-analysis included

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treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
e12 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15

in small studies.61e65 A meta-analysis by Wu et al.58 ana-

Figure 10 Left buccal SCC with superior spread above mandibular
notch; note invaded left temporalis (*), lateral pterygoid (þ) and
retroantral fat (arrowhead); compare with normal right lateral pter-
ygoid (LP) and temporalis (arrow). Left hemimandible is destroyed by
the mass. Supra-notch T4b disease is a surgical contraindication.
three studies with ultrasound-guided FNAC, two of which
had both clinically positive and negative necks. In this meta-
analysis, in the solitary study with clinically negative necks,
the sensitivity of ultrasound-guided FNAC was only 48%.
Advances in MRI, such as DW MRI with b 0e1000 with ADC
maps, as well as DCE MRI reported encouraging results in
differentiating subcentimetre benign and metastatic nodes
lysing the performance of MRI for N-staging and comparing
it with other methods in head and neck SCC found a
sensitivity and specificity of 76% and 86%, respectively,58
comparable with PET, CT, and ultrasound. In this meta-
analysis, studies with DW MRI showed slightly superior
performance to conventional MRI.58 Several reports using
PET/CT in the N0 neck have shown no proven value.66e68
This is due to the high false-positive rate from infective or
inflammatory nodes and limited sensitivity in picking small
nodes. A meta-analysis by Kyzas et al.59 evaluating PET/CT
in HNSCC found that it did not detect disease in half the
patients with N0 neck. Hence, the current role of PET/CT in
HNSCC for pretreatment nodal evaluation lies in detecting
the extent of regional nodal metastases in the N-positive
neck that could alter radiation therapy fields or extent of
neck dissection.69 The most recent meta-analysis by Liao
et al.60 in the N0 neck concludes that modern imaging
methods (ultrasound, PET, CT, and MRI) offer similar diag-
nostic accuracy to detect nodal metastases. Pooled sensi-
tivity and specificity of CT, MRI, PET, and ultrasound were
52% and 93%; 65% and 81%; 66% and 87%; and 66% and 78%,
respectively.60 Software-based fusion PETeMRI with DWI
has been evaluated in OCSCC for nodal metastases in a small
series and did not perform better than PET or ultrasound.
Hence, the promise of imaging replacing surgical staging of
the neck in OCSCC appears distant.70
Sentinel node biopsy (SNB) in OCSCC is at an experi-
mental stage with promising early results. Civantos et al.6 in
a prospective multi-institutional trial involving 140 patients
with T1 or T2 oral cavity cancers reported a negative pre-
dictive value of 96% and a true-positive rate of 90.2% with

Table 3
Choice of imaging methods for T staging at various subsites of oral cavity squamous cell carcinomas (OCSCC).

Site of SCC Imaging method Advantages Disadvantages

of choice
Oral tongue & floor CE-MRI A. Superior soft-tissue characterization44,45 for A. MRI* can overestimate inferior alveolar
of mouth U Extrinsic muscle invasion canal involvement and mandibular cortical
U Posterior & inferior soft tissue extent erosion (due to chemical shift artefacts)17
B. Highly sensitive for bone erosion16,17 B. Swallowing artefacts
(that occurs in <10% cases in tongue cancers) Problem solving for bone erosion -May add:
a) CT (has increased specificity13,17e22) OR
b) SPECT24,25 (has increased sensitivity)
Gingival &buccal CE-MDCT with A. Bone erosion (high positive predictive value13,17e22) A. Dental amalgam artefacts
cancers puffed-cheek B. Speed of scanning B. May miss early perineural spread
techniquea C. Adequate for posterior soft tissue extent to
decide resectability (can display infra and
supra-notch T4b disease29)
RMT CE-MRI* Accurate T staging and relations31 A. Overestimation of mandibular invasion17
*comparable B. Swallowing artefacts
CE-MDCT * with High accuracy for bone erosion13,17e22; adequate May miss early perineural spread
puffed cheek for soft-tissue extent29
techniquea
Hard palate CE-MRI A. High accuracy for marrow & perineural invasion Cortical erosion less well depicted
B. Complete soft-tissue extent depicted (CE-MDCT is therefore complementary)
Lip CE-MDCT with High accuracy for bone erosion13,17e22; adequate CT may miss early perineural spread32e34,
puffed-cheek for soft tissue extent but MRI could overestimate perineural
techniquea spread17

CE-MRI, contrast-enhanced magnetic resonance imaging; CE-MDCT, contrast-enhanced multidetector computed tomography; CT, computed tomography;
SPECT, single photon emission computed tomography.
a
Preferred in the authors’ institute.

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 S. Arya et al. / Clinical Radiology xxx (2014) e1ee15
SNB. A diagnostic meta-analysis of SNB in 847 patients of
clinically T1/T2N0 OCSCC and oropharyngeal SCC patients
revealed an overall sensitivity of 93%.71
Metastatic workup (M-staging)
In untreated OCSCC, there is no additional value of PET/
CT over CT or MRI in evaluating the primary or the clinically
negative neck.47e49,66e68 The National Comprehensive
Cancer Network (NCCN) guidelines recommend use of PET/
CT only in stage III or IV cancers when management may be
altered due to detection of distant metastases.28 If PET/CT is
not employed, a chest CT is used to rule out pulmonary
metastases in higher T stage cancers and particularly when
abnormal nodes are seen at level IV/supraclavicular region.
CT of the abdomen is ordered only when the clinical index
of hepatic metastasis is high.2
Deficiencies of TNM staging in OCSCC
T-staging
T4b disease in gingival, buccal, and RMT SCC
The AJCC 7th edition staging of head neck cancers has
defined soft-tissue extending to masticator space from any
subsite of oral cavity as T4b or very advanced. Staging sys-
tems should reflect differences in prognosis and survival.
Yet Liao et al.30 reported similar 5-year local control, neck
control, disease-free survival, and overall survival in 58
patients of T4a disease as compared to 45 patients with T4b
disease. Another study by Liao et al.29 differentiated be-
tween T4b extending below and above the mandibular
notch and concluded that infra-notch disease was resect-
able with good local control if nerve invasion was absent.29
Imaging could have a role in re-categorization of T4 b dis-
ease in gingival, buccal, and RMT SCC into resectable and
unresectable disease.
T4a disease in oral tongue and FOM SCC
In oral tongue cancers, disease reaching into extrinsic
muscles is T4a. However, disease extending into base
tongue, valleculae, or even hyoid bone is T4a. Yet the
morbidity of surgery in these groups differs widely
(Table 2). Genden et al.3 suggest that in selected T4 lesions,
primary chemoradiotherapy may be as effective as primary
surgery and postoperative radiotherapy, helping avoid
morbid surgery.3 Imaging could have a potential role of to
substratify T4a oral tongue SCC. Alternately imaging infor-
mation could be used to re-assign invasion of base tongue/
valleculae/pre-epiglottic space, and hyoid bone to T4b when
the disease originates from the oral tongue.
N-staging
The AJCC N-staging for OCSCC is dependent on number,
size, and laterality of nodes. In metastatic nodes with
extranodal spread, a circumferential contact 270 with
internal carotid artery indicates unresectability.72 Extra-
nodal spread is an adverse prognostic criterion.6 The
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treatment imaging and its influence on management, Clinical Radiology (2014), http://dx.doi.org/10.1016/j.crad.2014.04.013
e13
present 7th edition AJCC N-staging system does not incor-
porate extranodal spread and resectability status of nodes.
Ongoing research
Pretreatment imaging with DW MRI, perfusion CT, and
DCE-MRI have been used for early prediction of response to
chemoradiation in HNSCC.73e77 Baseline perfusion CT dis-
played either constant significant reduction in blood flow
(BF) or initial reduction in blood volume (BV) in responders
in one study.73 Kim et al.74 reported that pretreatment ADC
values with DW MRI were significantly lower in complete
responders and this had a sensitivity of 65% and specificity
of 86% in predicting response to chemoradiation in HNSCC.
DW MRI and DCE-MRI have also been used in combination
to predict response of the primary as well as nodes to
chemoradiation.77
Conclusion
Information from imaging helps assess resectability, plan
surgical resection, reconstruction, and multimodality
treatment; and indicate prognosis. Mandibular erosion,
posterior soft tissue extent, and perineural spread are
relevant issues in gingival, buccal, and RMT cancers. In oral
tongue and FOM SCC, involvement of extrinsic muscles,
extent across midline, extent of posterior and inferior
spread, and proximity to hyoid are issues that impact
therapy. In oral tongue SCCs with tumour thickness
4 mm,
elective neck dissection can be avoided. For N-staging, all
imaging methods are comparable, but fall short of surgical
staging. PET has a role in pretreatment evaluation of
advanced OCSCC for depicting distant metastases and for
mapping nodal extent in the Nþ neck.
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