European Journal of Radiology 82 (2013) 773–782

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European Journal of Radiology

journal homepage: www.elsevier.com/locate/ejrad

Review

Retrostyloid parapharyngeal space tumors: A clinician and

imaging perspective
A. Varoquaux a,1 , N. Fakhry b,2 , S. Gabriel c,3 , S. Garcia d,4 , A. Ferretti e,5 ,
S. Chondrogiannis e,6 , D. Rubello e,∗ , D. Taïeb c,7
a
Department of Radiology, La Timone University Hospital, Aix-Marseille University, Marseille, France
b
Department of Otorhinolaryngology-Head and Neck Surgery, La Timone University Hospital, Aix-Marseille University, Marseille, France
c
Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, Marseille, France
d
Department of Pathology, North Hospital, Aix-Marseille University, Marseille, France
e
Department of Nuclear Medicine, PET/CT Centre, “Santa Maria della Misericordia” Hospital, Rovigo, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Although tumors of the parapharyngeal space are rare, they represent a formidable diagnostic and treat-
Received 21 August 2012 ment challenge. The differentiation of a retrostyloid lesion from a prestyloid lesion is critical for guiding
Received in revised form the differential diagnosis. The majority of lesions involving the retrostyloid parapharyngeal space are
17 December 2012
either peripheral nerve sheath tumors, head & neck paragangliomas or metastatic lymph node metastases.
Accepted 2 January 2013
This article provides insights into the many currently available radiological and radionuclide imaging pro-
cedures and guides clinicians toward their appropriate use. In the near future, many patients might also
Keywords:
benefit from new diagnostic approaches such as high resolution integrated PET/MRI and new tracers that
Parapharyngeal neoplasm
Computed tomography
enable “in vivo” assessment of these tumors at molecular level.
Magnetic resonance imaging © 2013 Elsevier Ireland Ltd. All rights reserved.
Radionuclide imaging
Schwannoma
Paraganglioma
Neurofibroma
Diagnostic imaging

∗ Corresponding author at: Director Department of Nuclear Medicine, Medical Physics, Radiology, Interventional radiology, Neuroradiology, Head Service of Nuclear
Medicine & PET/CT Centre, Santa Maria della Misericordia Hospital, Via tre Martiri 140, 45100 Rovigo, Italy. Tel.: +39 0425394428; fax: +39 0425394434.
E-mail addresses: arthur.varoquaux@ap-hm.fr (A. Varoquaux), nicolas.FAKHRY@ap-hm.fr (N. Fakhry), sophie.gabriel@ap-hm.fr (S. Gabriel), stephane.garcia@ap-hm.fr (S.
Garcia), ferretti.alice@azisanrovigo.it (A. Ferretti), chondrogiannis.sotirios@azisanrovigo.it (S. Chondrogiannis), domenico.rubello@libero.it (D. Rubello), david.taieb@ap-hm.fr
(D. Taïeb).
1
Department of Radiology, La Timone University Hospital, Aix-Marseille University, 264 Rue Saint-Pierre, 13385 Marseille Cedex 5, France. Tel.: +33 0491 38 56 69; fax:
+33 0491 38 77 44.
2
Department of Otorhinolaryngology-Head and Neck Surgery, La Timone University Hospital, Aix-Marseille University, 264 Rue Saint-Pierre 13385 Marseille Cedex 5,
France. Tel.: +33 04 91 38 81 13.
3
Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, 264 Rue Saint-Pierre, 13385 Marseille Cedex 5, France. Tel.: +33 04
91 38 55 58; fax: +33 04 91 38 47 69.
4
Department of Pathology, North Hospital, Aix-Marseille University, Chemin des Bourrely, 13915 Marseille cedex 20, France. Tel.: +0 491 965 606; fax: +0 491 965 595.
5
Department of Medical Physics and of Nuclear Medicine, ‘Santa Maria della Misericordia’ Hospital, Via Tre Martiri 140, 45100 Rovigo, Italy. Tel.: +39 0425 39 4430; fax:
+39 0425 39 4434.
6
Department of Nuclear Medicine, ‘Santa Maria della Misericordia’ Hospital, Via Tre Martiri 140, 45100 Rovigo, Italy. Tel.: +39 0425 39 4430; fax: +39 0425 39 4434.
7
Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, 264 Rue Saint-Pierre, 13385 Marseille Cedex 5, France. Tel.: +33
0491 384 406; fax: +33 04 91 38 47 69.

0720-048X/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejrad.2013.01.005
774 A. Varoquaux et al. / European Journal of Radiology 82 (2013) 773–782
1. Normal anatomy of the retrostyloid parapharyngeal
space
The parapharyngeal space (PPS) is located deep within the neck
lateral to the pharynx and medial to the ramus of the mandible.
The superior limit of the PPS is represented by a small portion of the
temporal bone while its inferior limit is represented by the junction
of the posterior belly of the digastric muscle and the greater cornu
of the hyoid bone. The PPS roof is bordered laterally by the medial
pterygoid fascia and medially by the pharyngobasilar fascia. A key
anatomical division of the parapharyngeal space is into prestyloid
and retrostyloid compartments. The stylopharyngeal fascia which
extends from the styloid process to the tensor-vascular-styloid
fascia divides the PPS into an anterolateral or prestyloid, and a
posteromedial, or retrostyloid (post-styloid or carotid artery space)
spaces. The retrostyloid space contains the carotid sheath, sympa-
thetic chain, cranial nerves IX to XII, and lymph nodes. The carotid
sheath contains the internal carotid artery, internal jugular vein,
vagus nerve and glomus vagale (Figs. 1–3).
2. Origin of the primary tumors and pathology
Parapharyngeal space tumors account for 0.5% of all head and
neck neoplasms. The majority of retrostyloid parapharyngeal space
lesions are benign primary tumors that originate from the vagus
nerve. Schwannoma is the most common tumor, followed in fre-
quency by paraganglioma and neurofibroma.
2.1. Schwannoma
Schwannomas most commonly involve the vagus nerve with the
cervical sympathetic chain being the next most common source.
Schwannomas usually occur as a solitary mass. Multiple schwan-
nomas may occur in patients with neurofibromatosis or in a
rare syndrome that has been referred to as schwannomatosis. A
benign schwannoma (neurilemmoma) is generally an encapsulated
mass attached to a nerve. This tumor is composed by alternating
areas with compact zones with spindle cells (Antoni A areas) and
hypocellular zones (Antoni B areas). Cells are arranged in short,
interlacing fascicles and whorling or palisading of nuclei may be
seen (Verocay bodies). Cellularity, cellular pleimorphism, hyper-
chromasia and mitoses can be identified but do not represent
evidence of malignancy. The main differential diagnosis is solitary
neurofibroma. On immunohistochemical studies, S100 protein is
uniformly and intensely positive.
2.2. Paraganglioma
The most common PGL of the retrostyloid compartment is the
glomus vagale that arises at, or just below, the ganglion of the vagus
nerve. Glomus jugulare tumors may infiltrate the post styloid com-
partment secondarily from above, and carotid body tumors may
infiltrate it from bellow. Paraganglioma is a tumor arising from the
neural crest-derived paraganglia. This encapsulated ovoid tumor
exhibits a typical endocrine pattern with chief cells nests (zell-
ballen pattern). Stroma surrounding and separating the nests is
composed of prominent fibrovascular tissue. Sustentacular cells
may be seen at the periphery of the cell nests. There are no definitive
cytological or histological criteria for malignancy. Malignancy is
defined by the presence of metastases rather than local invasion. On
immunohistochemical studies, chief cells express neuroendocrine
markers (chromogranin, synaptophisyn, neuron specific enolase)
while sustentacular cells are positive for S100 protein). Immuno-
histochemical negativity for SDHB has been found to be associated
with germline mutations of the SDHB/C/D genes and might become
in a near future a screening method to select patients for subse-
quent molecular genetic testing.
2.3. Neurofibroma
Cervical vagal neurofibroma is extremely rare. It may occurs as
an isolated or multiple lesions associated with neurofibromatosis
type 1. Neurofibroma is a benign peripheral nerve sheath tumor
principally composed of Schwann cells. It results from a diffuse
increase of the endoneurial matrix with proliferation and distortion
of Schwann cells and axons. Circumscribed but unencapsulated,
neurofibromata expand the nerve in a fusiform manner. Histolog-
ically neurofibroma exhibit interlacing bundles of spindle-shaped
cells. Cellularity can vary and mimic Antoni A and B schwannoma.
Cells are associated with collagen strand separated by a myxoma-
tous and inflammatory stroma. On immunohistochemical studies,
S100 protein is positive but less striking as compared to benign
schwannoma.
2.4. Differential diagnosis
Lymph node metastasis (nasopharynx/oropharynx, thyroid
cancer), lymphoma, other primary tumors (ganglioneuroma, hae-
mangiopericytoma) and a variety of uncommon, miscellaneous
lesions (i.e., abcess, internal carotid artery aneurysm, internal jugu-
lar vein thrombosis, vascular malposition, organizing hematoma)
may arise in the retrostyloid PPS.
3. Molecular genetics classification
The current genetic classification of PHEO/PGL include ten dif-
ferent susceptibility genes for the entire paraganglial system. The
succinate dehydrogenase subunit D (SDHD), B (SDHB) and C (SDHC)
are the three main susceptibility genes (collectively named SDHx)
of hereditary head and neck PGLs (HNPGLs). The prevalence of
SDHx mutations is also very high in apparently sporadic HNPGLs
(up to 35%). Patients with SDHx mutations may also develop
PHEO and extra-cervical PGLs. SDHB mutations are associated with
higher rates of malignancy. Predictors for a positive SDH muta-
tion test included family history, previous adrenal or extra-adrenal
pheochromocytoma, multiple HNPGLs and age <40 years [1]. PNSTs
which include schwannoma, neurofibroma, ganglioneuroma and
their malignant variants may occur as a manifestation of the NF1
syndrome. NF1 is characterized by the presence of multiple neu-
rofibromas, café-au-lait spots, Lisch nodules of the iris and other
rare disorders. In these patients, multifocal PNSTs and malignant
transformation occur more frequently than sporadic cases as well
as synchronous benign and malignant PNSTs. NF1 patients may also
develop PHEO.
Another hereditary disease, neurofibromatosis type 2 (NF2), is
associated with schwannomas but they are typically of vestibular
nerve, and classically bilateral. SMARCB1 germline mutations have
recently been identified as an underlying cause of schwannomato-
sis.
4. Approach to the patient with a parapharyngeal space
tumor
4.1. Clinical evaluation
History of the present illness: A parapharyngeal space tumor
most commonly presents as a bulging mass of the oropharynx or a
cervical mass sometimes with subtle signs such as pharyngeal dis-
comfort or foreign body sensation. In a significant number of cases,
tumors are discovered as an incidental finding when the patient
 A. Varoquaux et al. / European Journal of Radiology 82 (2013) 773–782 775

Fig. 1. Relationship of retrostyloid parapharyngeal space with adjacent cervical spaces. Axial planes of the PPS on T2-weighted spin-echo (A), T1-weighted spin-echo
(B), Contrast-enhanced T1-weighted spin-echo (C), Fat-suppressed spoiled gadolinium enhanced gradient recalled T1 (D). (1) Retro-styloid parapharyngeal space (carotid
space), (2) Pre-styloid parapharyngeal space, (3) Pharyngeal mucosal space, (4) Retropharyngeal space, (5) Pre vertebral space, (6) Parotid space, (7) Masticator space, (8)
Posterior triangle space. Components of retrostyloid parapharyngeal space: (9) Retrostyloid parapharyngeal space fat, (10) Stylo pharyngeal fascia and muscle, (11) Pars
nervosa of retrostyloid parapharyngeal space, (12) Internal carotid artery, (13) Internal jugular vein, (14) Posterior belly of digastric muscle adjacent to mastoid notch, (15)
Sternocleidomastoid muscle.

is examined for an unrelated problem. Dysphagia, hypernasality,
hoarseness of voice or snoring, sleep apnea may indicate a bulky
tumor. Otologic symptoms may also occur in cases of eustachian
tube orifice obstruction. Horner’s syndrome may be associated with
cervical sympathetic schwannoma. Pain, trismus, multiple nerve
palsies and rapid tumor growth should raise concern about the
possibility of malignancy. HNPGL may rarely cause symptoms of
catecholamines oversecretion (e.g., sustained or paroxysmal ele-
vations in blood pressure, headache, episodic profuse sweating,
palpitations, pallor, and apprehension or anxiety).
Past and familial medical history: Personal history of cancer (pha-
ryngeal, thyroid), PHEO/PGL or lymphoma should be obtained.
Personal or familial history for hereditary disease can be of great
value. Alcohol and tobacco use, and general medical health should
also be obtained.
Physical examination: Physical examination usually is poorly
informative. It can find an oropharyngeal mass usually located
back to the posterior palatal arch by contrast to prestyloid tumors
located anteriorly in the soft palate. Examination of the oral cav-
ity and oropharynx is essential to rule out primary cancer with

Fig. 2. Retrostyloid parapharyngeal space. Axial planes of post contrast fat saturated 3D T1 MRI (A) and post contrast CT scanner (B) showing components of retrostyloid
parapharyngeal space (1) Internal carotid, (2) internal jugular vein, (3) distal part of temporal styloid process, (4) insertion of stylo-hyoid muscle and ligament, stylo-glossus
muscle, stylo-pharyngeus muscle and non retrostyloid anatomical structures (5) digastric muscle in mastoid groove, (6) pre-styloid parapharyngeal fat, (7) pre-vertebral
longus capiti muscle, (8) deep lobe of parotid gland.
776 A. Varoquaux et al. / European Journal of Radiology 82 (2013) 773–782
Fig. 3. Muscular insertions of the styloid process. Reformatted parasagittal 3D T2 along stylo-hyoid muscle (A), stylo-pharyngeal muscle (B), stylo-gloss muscle (C) showing
distal part of temporal styloid process (1), stylo-hyoid muscle and ligament (2), stylo-pharyngeal muscle (3), stylo-gloss muscle (4), digastric muscle (5), mastoid (6),
stylomastoid foramen (7), medial pterygoid muscle (8), lateral pterygoid muscle (9), superior constrictor muscle (10), hyo-gloss muscle (11).
lymph node involvement. A pulsating lump that can be felt in the
neck may be indicative of vascular tumor such as PGL. The physical
examination should include a full assessment of the cranial nerves
and flexible laryngoscopy. Biochemical testing: Patients in whom
a HNPGL is suspected require measurements of 24-hour urine or
plasma metanephrines and plasma chromogranin A. Since HNPGL
are almost always non-secreting tumors and benign, elevations in
urine or plasma metanephrine levels are more frequently indica-
tive of extra-cervical PGL that may coexist with HNPGL. Plasma
chromogranin A may be elevated in biochemically silent tumors.
4.2. Diagnostic imaging
Computed Tomography (CT) and Magnetic Resonance Imaging
(MRI) are the cornerstone in the initial evaluation. Radionuclide
imaging is complimentary to radiological imaging and provides
specific information about the tumour’s functional and molecular
characteristics. Positron emission tomography (PET) has a higher
sensitivity than single-photon emission computed tomography
(SPECT) and provides images of better resolution.
The main goals of modern imaging are:
1. Locate the tumor to retrostyloid vs. prestyloid on CT and MRI
studies. A retrostyloid tumor can easily be identified when there
is an anterior and/or medial displacement of the ICA, an antero-
lateral displacement of the prestyloid parapharyngeal fat pad
(between the mass and the pterygoid muscles) and an extension
of the mass posteriorly to the styloid process. Carotid and jugular
vessel displacement can be useful to predict the likely nerve of
origin (splaying of the IJV and ICA predicting vagal nerve origin
vs. no separation for sympathetic chain origin) [2].
2. Find clues for making the differential diagnosis between lesions.
3. Characterize of the pathologic conditions as aggressive or non
aggressive in nature.
4. Assess intracranial extension.
4.2.1. Radiological imaging
4.2.1.1. Ultrasound. Using high frequency (above 7.5 MHz) linear
transducers, ultra sonography (US) can reveal the cervical vagal
nerve in healthy individuals [3]. This can be helpful for determining
the vagal origin of some tumors in the parapharyngeal spaces [3],
and allows sonographic-guidance for fine needle aspiration cytol-
ogy [4].
4.2.1.2. Multidetector computed tomography. Mutidetector CT
(MDCT) allows rapid acquisition of volumetric data in high
resolution and multiplanar reformation. With actual technology,
the voxel size (which affects the spatial resolution) can be as small
as 0.082 mm3 (vs about 4.4 mm3 for T1 weighted gadolinium MR
angiography and 1.1 mm3 for time of flight MR angiography).
With less than 30 seconds acquisition time, MDCT is less affected
by motion artifacts than MRI. Recently, MDCT angiography was
found to be more sensitive than MRI (83% vs 78%) in differentiating
paragangliomas from other mimicking lesions [5]. CT may also
guide fine-needle aspiration (see Fig. 4) Table 1.
4.2.1.3. Magnetic resonance imaging. MRI offers a high contrast-
to-noise ratio within soft tissue and is particularly useful in the
localization and characterization of head and neck lesions. The most
common MRI protocols are detailed in Table 2. Conventional MR
imaging using spin-echo T2-weighted and pre and post contrast
spin-echo T1-weighted imaging allows precise anatomical local-
ization of the lesions. Tumor spread, infiltration or T2-low signal
intensity are predictors of malignancy [6]. Flow voids within the
tumor indicate high-velocity flow in dilated tumor vessels and
are typical of PGL [7]. MR angiography is useful to assess vascu-
lar neoplasm. Several sequences are available with and without
gadolinium contrast enhancement. Among these sequences, phase
contrast angiography, gadolinium-enhanced MR angiography and
time-of-flight (TOF) are the most widely used [7]. Three dimen-
sional (3D) TOF MR angiography has been found to be one of the
more sensitive technique in PGL patients (sensitivity 90%, speci-
ficity 92%). Diffusion weighted imaging (DWI) which is dependent
on tissue cellularity might be of particular interest for distinguish-
ing benign from malignant masses [8] and might provide additional
information in the diagnosis of PGL [9]. MR perfusion imaging might
provide prognostic information but requires further evaluation in
the clinical setting.
4.2.1.4. Angiography. The use of conventional angiography is most
often performed for pre-operative endovascular embolization and
is intended to minimize the blood loss intraoperatively.
4.2.2. Radionuclide imaging
4.2.2.1. 18 F-FDG PET imaging. 18-fluoro-2-deoxy-glucose (18 F-
FDG) uptake reflects glucose uptake and, indirectly, the energy
metabolism. 18 F-FDG is taken up by tumor cells via glucose
membrane transporters (mainly GLUT-1 and GLUT-3) and phos-
phorylated by hexokinase into 18 F -FDG-6P. Interestingly, most
PGLs are FDG avid despite their relative indolence. This finding con-
trasts with the observation that other endocrine tumors generally
exhibit glucose metabolism phenotype in the later stages of the
 A. Varoquaux et al. / European Journal of Radiology 82 (2013) 773–782 777

Fig. 4. Retropharyngeal lymph node metastasis. Axial plane of spin echo T1 (A), spin echo T2 (B), Fat-suppressed spoiled gadolinium enhanced gradient-recalled T1 (C),
18 gauge core biopsy under CT fluoroscopy (D). Presence of two retropharyngeal metastatic lymph nodes (large arrows) from a soft palate mucoepidermoïd carcinoma
(previously treated with surgery radiotherapy and chemotherapy) mimicking a retrostyloid parapharyngeal space primary tumors. The diagnosis was proved by core biopsy
performed under general anesthesia. Note the stylopharyngeal fascia and muscle on MRI (small arrows).

disease. Patterns of FDG uptake are variable among PNSTs. 18 F -
FDG PET and PET/CT imaging have been used to distinguish benign
from malignant PNSTs.
4.2.2.2. Somatostatin receptor-based SPECT and PET imaging. SST2
is the most prevalent SST subtype in PGLs. SPECT imaging with
111 In-pentetreotide is the current classical scintigraphic modal-
ity of reference for SST imaging. SPECT/CT has now become more
widely available and has the advantage of simultaneous acquisi-
tion of both morphological and functional data, thus increasing
diagnostic confidence in image interpretation and enhancing sen-
sitivity. However, SPECT imaging has practical constraints such as
long imaging times. Based on experience with conventional scintig-
raphy using 111 In -radiolabeled pentetreotide, PET imaging using
68 Ga-labeled somatostatin agonists has been evaluated. All HNPGL
can be virtually detected by high resolution SST imaging.
4.2.2.3. 18 F-DOPA PET imaging. 18 F -DOPA binds to LAT1 (trans-
porter for neutral aminoacids) and is converted into 18 F-FDA by
cytosolic AADC. Like other tumors that originate from the APUD
system, PGL can trap and decarboxylate amino acids such as DOPA.
Since 18 F -DOPA is quickly converted into 18 F-dopamine in the
proximal renal tubule and eliminated in the urine, premedication
with carbidopa (an AADC inhibitor) is used by some authors to
improve bioavailability of the tracer and increase tumor uptake.
18 F-DOPA PET has been proved to be the highest sensitive func-
tional imaging method for detecting HNPGLs [10].
5. Fine-needle aspiration cytology
Transoral or transcervical fine-needle aspiration cytology
(FNAC) may be performed after imaging and after excluding HNPGL
if the results may influence the therapeutic strategies (i.e., elderly,
poor medical condition, non-typical imaging findings of schwan-
noma or HNPGL). The accuracy of the FNAC depends greatly on the
quality of the collection and may reach 99% [11].
6. Treatment
Surgery is the primary treatment of choice of retrostyloid para-
pharyngeal space tumors. A number of surgical access routes to
this region are possible (i.e., transcervical, transcervical/parotid,
transcervical/parotid/mandibular, infratemporal approach in cases
of skull base invasion) depending on multiple factors such as
tumor size, location and invasiveness. Mini-invasive surgery
approaches (endoscopic and/or robotically-assisted) may be an
option in well-encapsulated tumors. A lymph node dissection
may also be performed in malignant tumors. Surgical resec-
tion of PNSTs (enucleation) often necessitate sacrifice of the
involved nerve. Treatment of PGL syndromes would be to
remove first the hypersecreting tumors (PHEO and/or sympa-
thetic extra-adrenal PGL). Surgical risks include nerve and vascular
injury (adhesion to the internal carotid artery). In selected
cases, tumor embolization can be performed 24-hours prior to
surgery of HNPGL. Surgeons have to explain all risks for poten-
tial post-operative morbidity. The risk of post-operative cranial
nerve deficit increases when tumors are aggressive and have
grown upward toward the skull base. Gastrostomy and tra-
cheotomy may be required in patients with multiple cranial nerve
involvement. In selected cases, external radiotherapy or care-
ful observation could be the best option. Some patients with
aggressive HNPGL might also benefit from radionuclide internal
radiotherapy.
778 A. Varoquaux et al. / European Journal of Radiology 82 (2013) 773–782

Table 1
Signal patterns of post-styloid retropharyngeal mass: comparison of relevant radiological imaging modalities.

Paragangliomac Nodal metastasisa Schwannomab Neurofibromad

Echo-doppler (linear 12–15 Mhz probe) Well circumscripted Un-circumscripted Well Similar to
hypoechoic mass; extensive hypoechoic mass; circumscripted schwannoma
arterial feeders with low mild hilar arterial hypoechoic mass
resistance wave form at pulsed feeder and high with posterior
doppler resistance wave enhancement;
form at pulsed cystic component
doppler possible; no
arterial feeder
MRI SE T1 Similar signal than muscle Similar signal than Lower signal than Lower signal than
with flow voids (“salt and to muscle, absence muscle, flow voids muscle, absence of
pepper” appearance) of flow voidsa are exceptionalb flow voidsd
MRI SE T2 Mildly higher than muscle Lower than muscle Higher than Very hyperintense
or heterogeneous muscle, cystic parts signal with central
(necrosis)a are seenb dark dot area
(target sign) d
MRI 3D TOF Similar signal to muscle with Rare hilar arterial No arterial feeders No arterial feeders
rich arterial feeders feeders
MRI 3D gadolinium angiography Signal higher than muscle with Rare enhancement Exceptionally mild No arterial
rich arterial feedersc and rare hilar arterial feeders are enhancement; no
arterial feeders seen arterial feeders
seen
MRI 3D TOF gadolinium Similar to MRI 3D gadoliniumc Similar to MRI 3D Similar to MRI 3D Similar to MRI 3D
gadolinium gadolinium gadolinium
MRI 3D T1 FATSAT gadolinium Strong and homogeneous Heterogeneous Uniform Mild enhancement
enhancementc enhancement a enhancement without rimd
without rim, cysts
does not enhanceb
CT (pre-contrast and angio-CT) Pre-contrast density similar to Pre-contrast Pre and post Pre and post
muscle, with avid density similar to contrast density contrast density
enhancementc muscle, without lower to muscleb lower to muscle
avid enhancement
Conventional angiography Intense tumor blush, Mild tumor blush Rare tumor blush No tumor blush
preoperative hemostatic
embolization possible
a
Fig. 4.
b
Fig. 5.
c
Fig. 6.
d
Fig. 8.

7. Imaging features of primary tumors
7.1. Schwannoma
7.1.1. Radiological imaging
US shows a solitary, oval, hypoechoic mass with poste-
rior enhancement and absence of an echogenic hilum. The
direct visualization of a contiguity between the nerve and the
tumor on longitudinal scan, is the only pathognomonic sign
of nerve sheath tumor origin. CT shows a low density well
circumscribed fusiform mass with homogeneous enhancement.
Large lesion (>3 cm) can show benign degenerative changes
consisting in intratumoural cystic areas or hemorrhages with
fluid-fluid levels and calcifications [12,13]. MRI shows a non-
specific begin tumor pattern consisting in a high intensity T2
with encapsulation [14]. Pre and post contrast T1-weighted MR
images show an homogeneous low-signal-intensity mass. Large
tumors may exihibit benign degenerative changes consisting

Table 2
Technical parameters of relevant radiological imaging modalities used in practice for imaging parapharyngeal masses.

Slice thicknessa Matrixa Field of viewa Mean estimated

effective radiation
dosea

Echo-doppler (linear 12–15 Mhz probe) 5 mm 768 × 1024 4 × 7 cm none

MRI SE T1 [5] 4 mm 160 × 256 20 × 20 cm none
MRI SE T2 [5] 4 mm 128 × 256 20 × 20 cm none

MRI 3D TOFb [5] 1.5 mm 256 × 256 20 × 20 cm none

MRI 3D gadolinium angiography [21] 4 mm 320 × 224 20 × 20 cm none
MRI 3D TOFb gadolinium [22] 1.5 mm 256 × 256 20 × 20 cm none
MRI 3D T1 FATSAT gadolinium 1 mm 256 × 256 20 × 20 cm none
CT (pre-contrast and angio-CT) [32] 1 mm 512 × 512 20 × 20 cm 8 mSv (3 mSv for
unenhanced CT and
5 mSv for CT
angiogram)
Conventional angiography [7,33] Projection 1024 × 1024 From 10 × 10 cm to 5 mSv
30 × 30 cm projections
a
All values are user-defined parameters.
b
Time of flight.
 A. Varoquaux et al. / European Journal of Radiology 82 (2013) 773–782
Fig. 5. Vagal schwannoma. Axial T1-weighted spin-echo (A), Axial T2-weighted spin-echo (B), 3D gadolinium-enhanced fat-saturated T1-weighted MR image in (C), Axial
18F-FDG PET/CT (D), Whole-body 18FFDG PET (MIP image) (E). Well circumscribed 4 cm fusiform mass with heterogeneous enhancement related to degenerative changes
(A, C, arrows), moderate to high T2 signal (D, arrows), low density on CT (D) and no significant FDG uptake (D, E). Note the anterior displacement of internal carotid artery
(A, B, C, small arrows).
in cystic (non enhanced) and pseudocystic areas (enhanced)
(Fig. 5).
7.1.2. Radionuclide imaging
Reubi et al. did not demonstrate significant amounts of somato-
statin receptors in schwannomas [15] which is consistent with the
negativity of 111 In-pentetreotide scintigraphy in the clinical setting.
Acquiring PET/CT imaging with 18 F-FDG, the standardized uptake
value (SUV) showed wide variations among tumors [16,17]. 18 F-
FDG uptake might be heterogeneous in larger tumors which exhibit
frequent cystic changes and necrosis. Malignant tumors have sig-
nificant higher SUVmax than benign tumors, even if high SUV might
be observed in benign cases [17–19].
7.2. Paraganglioma
7.2.1. Radiological imaging
PGL are characterized by their topography, hypervasculariza-
tion and possible bony erosion related to tumor growth. Vagus
nerve PGL displace ICA anteromedially and separates it from IJV.
Color and pulsed Doppler US show hypervascular mass with exten-
sive intra-tumoural arterial vessels. CT angiography demonstrates
a marked enhancement following contrast administration with
intra-tumoural vessels. Fow signal voids in the tumor seen on
spin-echo sequences are typical of PGL with a “salt and pepper”
appearance on spin-echo T2-weighted MR images. The “pepper”
component represents the multiple areas of signal void, inter-
spersed with the “salt” component, which is seen as hyperintense
foci (due to slow flow) [20]. MR angiography using TOF, phase
contrast, or gadolinium enhancement also demonstrates intra
tumoural arterial vessels [21,22]. CT provides better visualization
of bone erosion.
7.2.2. Radionuclide imaging
Considering HNPGLs, several studies have demonstrated a high
sensitivity (89–100%) of 111 In-pentetreotide scintigraphy. How-
ever, its sensitivity needs to be revised downwards in patients
with hereditary syndromes because some additional lesions can
be at the millimeter stage and not detectable by conventional
779
scintigraphy (overall sensitivity 75%) [23]. Currently, DOTATATE
(Tyr3-octreotate) has the highest affinity for SST2 with very
promising results in small series [24]. There is insufficient data to
draw conclusions regarding sensitivity. In a recent meta-analysis
performed on 11 studies (275 patients), the pooled sensitivity and
specificity on a per lesion-based analysis of 18 F-DOPA PET/CT in
detecting PCC/PGL were 79% and 95%, respectively [25]. To date,
18 F-DOPA PET/CT has been proved to be highly sensitive in differ-
ent series and may be considered a good imaging technique for
HNPGLs (sensitivity >95%) and it might also detect abdominal PGL
that may coexist with HNPGL in SDHx-related syndromes (Fig. 6)
[1]. 18 F-FDG PET/CT is also very sensitive in these patients and may
be added to the work-up (Fig. 6) [10,26]. 18 F-DOPA is more specific
than SST2-analogs in the diagnosis of PGL (Fig. 7).
7.3. Neurofibroma
7.3.1. Radiological imaging
The imaging features of solitary neurofibroma overlap those of
schwannoma, and often they are indistinguishable. Neurofibroma
tends to be more hypodense/less enhanced on CT; more hyperin-
tense (T2-weighted images)/less enhanced on MRI in comparison
to schwannoma. The target sign which appears on transverse T2-
weighted MR images as a central area of low signal intensity
surrounded by an area of high signal intensity is most commonly
encountered in neurofibromas [27]. Peripheral enhancement pat-
tern, perilesional edema-like zone, and intratumoural cystic lesions
are suggestive of malignant tranformation [28] (Fig. 8).
7.3.2. Radionuclide imaging
Benign neurofibroma usually exihibit a low metabolic pattern.
Malignant tumors had significant higher 18 F-FDG SUV [18,19].
18 F-FDG can be useful in predicting malignant transformation in
patients with NF1 with a sensitivity nearing 100% [29]. However,
it is important to recognize the potential limitations of 18 F-FDG
PET because there are very few false-negative reports. In malig-
nant tumors, SUVmax level did not predict tumor grade but low
SUV is associated with higher survival time [30,31].
780 A. Varoquaux et al. / European Journal of Radiology 82 (2013) 773–782

Fig. 6. Multicentric SDHD-related paraganglioma syndrome (4 HNPGL, 1 extraadrenal. abdominal PGL: arrows). Three dimensional (3D) CT angiography in axial plane (A),
3D gadolinium-enhanced fat saturated T1-weighted MR image in axial plane (B), coronal plane (C), sagittal plane (D); Coronal MIP planes of 4D time-resolved gadolinium
MRI angiography at arterial phase (E), 18 F-FDG PET/CT (MIP image) (F) and 18 F-DOPA PET/CT (MIP image) (G). ICA is displaced anteriorly and medially by the vagus nerve
PGLs (small arrows). Tumors exihibit an arterial enhancement and a high avidity for 18 F-FDG and 18 F-DOPA.

Fig. 7. Parapharyngeal hypervascularized nodal metastases from papillary thyroid carcinoma. Axial fat suppressed T2 weighted spin echo (A, C, D), axial T1 contrast-
enhanced fat-saturated T1-weighted spin-echo (B), axial angio-CT (E), coronal reconstructions of angio-CT (F), coronal reconstructions of gadolinium enhanced angio-MR
(G), ultrasonography with doppler (H) Well circumscripted ovoid mass, arising from left retrostyloid para-pharyngeal space: anterior displacement parapharyngeal fat (A, B,
E, white arrows), and lateral displacement of internal carotid artery (A, B, E, black arrows). Mass signal intensities are not consistent with paraganglioma nor sheath nerve
tumor: no flow voids are seen on spin echo T1, T2 signal is mildly high, strong and homogeneous enhancement is shown but not synchronous to carotid arteries. MRI and CT
demonstrate 6 other lesions in nodes (C, F, G, arrows) and one in thyroid (D, arrow). Thyroid neoplasm was detected on ultrasonography (H) and confirmed by fine-needle
aspiration (papillary thyroid carcinoma). 123 I-MIBG (I) 18 F-FDG PET (K) and 18 F-FDOPA PET (L) were negative which was not consistent with paragangliomas. Octreoscan (J)
was positive which is not an uncommon finding in lymph node metastases from papillary thyroid carcinoma.
 A. Varoquaux et al. / European Journal of Radiology 82 (2013) 773–782
Fig. 8. Vagal neurofibroma. Axial T1-weighted spin-echo (A), Axial T2-weighted spin-echo (B), Contrast-enhanced axial T1-weighted spin-echo (C). Coronal T1-weighted spin-
echo (D), Coronal T2-weighted spin-echo (E), Coronal contrast-enhanced fat-saturated T1-weighted spin-echo retarded (15 min) (F). Well circumscribed solitary 8 cm ovoid
an elongated mass (large arrows) with delayed homogeneous enhancement (F), liquid like T2 signal with target sign (B, E, small arrows) is very suggestive of neurofibroma.
This mass displace anteriorly internal carotid artery. Note the anterior displacement of digastric muscle (A, C, small arrows) and superior displacement of parapharyngeal
fat (D, small arrow).
8. Conclusion and perspectives
Diagnosis and treatment of retrostyloid parapharyngeal space
tumors need a multidisciplinary team. From a surgical point of view,
mini-invasive approaches open new perspectives in certain clini-
cal settings. In the near future, new tracers that are targeted to
angiogenesis as well as MR perfusion imaging might be of particu-
lar interest in the detection and characterization of HNPGLs and in
the evaluation of responses to anti-angiogenics. Diagnostic imaging
may gain advantage of PET/MRI by using an integrated system with
simultaneous acquisition of both techniques. Excellent results from
molecular profiling studies now provide important and promising
information in the identification of new tracers that are targeted
to apoptosis or hypoxia and enable “in vivo” assessment of these
tumors at molecular level. Finally, some patients with aggressive
HNPGLs might also benefit from new targeted therapies including
radionuclide internal radiotherapy.
Conflict of interest statement
The authors declare no conflict of interest.
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