eEdE-89
PET-CT and MRI Unusual
Findings of Perineural Tumor
Spread in Head and Neck Cancer
and Review of the Literature
Bachir Zoghbi, Marques Bradshaw, Roshan Arjal, and
M. Gisele Matheus
Conflict of Interests: None
Learning Points
• Definition of perineural tumor spread (PNTS)
• Clinical Presentation
• Imaging findings of distinct modalities
• Usual and unusual patterns of PNTS
• Treatment implications
• Discussion
PNTS & PNI-Definition
• Ability of a tumor to grow within and along nerve layers, away from the primary
site, using the nerve as a route of spread (metastatic process)
• Histologically, at a microscopic level, extension of tumor in the nerve
compartments is called perineural invasion (PNI). The original definition of PNI
by Batsakis is tumor cells in, around, and through the nerves which leads to
some controversial interpretations
• Some pathologists define PNI as at least 33% of the circumference of the nerve
surrounded by tumor to differentiate from focal abutment of the primary tumor,
but the criteria to define small PNI near the primary tumor or spread through
perineural tissue is still debatable
• Imaging wise ( CT, MRI , and PET-CT) identification of tumor within the nerve
pathway is defined as PNTS
PNTS & PNI-Definition
• The tumor can invade any of the layers of the nerve (epineurium,
perineurium, or endoneurium)
Epineurium
Perineurium
Tumor
Endoneurium
• The tumor spread may be
retro or antegrade and may
not be detectable in its
entire extension or pathway
creating skip lesions
PNTS -Definition
Head & neck tumors
Tumor
in any compartments, from skin to mucosal space,
may disseminate via
Tumor
Direct invasion
Frank Netter- Atlas of Human Anatomy
Hematogenic
Lymphatic
PNTS
PNTS - Facts
• The mechanisms of dissemination remains incompletely understood
• Early theories
• Direct invasion and spread through loose collagenous network of the nerve sheath
• Lymphatic channels associated with the nerve
• Latest theories
• Complex interaction between specific tumor cell types, supporting stroma, and nerves
• Neurotrophic growth factors and axonal guidance molecules are involved
• Increase activity of proteinases and increase expression of specific cell surface receptors
The earliest theories have fallen out of favor because there are no
lymphatic network within the nerve sheath and perineurium actually
creates a tight high resistance zone with multiple layers of collagen and
basement membrane.
PNTS -Facts
• Theoretically any tumor can use this method of dissemination
• Some tumors are more commonly associated to PNTS than others
• SCCa (mucosal or cutaneous) shows significant number of PNTS due its high
prevalence
• Adenoid cystic carcinoma is associated with PNTS in about 60% of cases
• Mucoepidermoid carcinoma has a high association with PNTS
• Melanoma, lymphoma, and even basal cell carcinoma had been reported in
isolated case reports
• PNI implies poor prognosis
Clinical Findings
• More than two thirds can be asymptomatic
• Those having symptoms may complain of pain, paresthesia,
numbness and motor weakness in the involved nerve distribution
• As most involve the facial and the trigeminal nerve: facial paralysis,
trigeminal neuralgia, and masticator muscle weakness is common
• In unusual cases, where the metastatic deposition is far from the
primary site, the clinical symptoms are usually underestimated
Imaging Findings
Direct
• Abnormalities of the nerve and
adjacent structures
Indirect
• Muscular asymmetry due to
denervation atrophy
• Accuracy of the PNTS identification increases with improving tissue contrast
MRI>>>>>>>> CT
• Sensitivity and specificity of PET-CT is unknown, but brings metabolic
information to the imaging assessment, which is identifiable in some cases
even with size below the expected resolution of PET (about 8 mm)
Imaging Findings-CT
• Early, subtle imaging finding
• Loss of the fat attenuation in the
neural foramen or expected neural
pathway
Example: Axial Face CT image with
contrast shows loss of normal fat
attenuation in the right greater
palatine foramen (arrow) in
comparison to normal fat
attenuation(arrowhead) on the left.
Case of PNTS from right palate SCCa.
Imaging Findings-CT
• Late imaging finding
• Asymmetric enlargement of the nerve
pathway filled by soft tissue mass which may
or may not enhance
• Remodeling or erosion of the adjacent bone
Example: Face CT image with contrast shows
enlargement of the right pterygopalatine fossa
(arrowhead) occupied by abnormal soft tissue
mass in comparison with normal appearance
left pterygopalatine fossa (arrow). Case of PNTS
from right tonsillar fossa SCCa.
Imaging findings-MRI
• The intrinsic high tissue contrast of T1W
sequences without fat suppression allows
visualization of the affected nerve which is
usually abnormally thick
• Fat-suppressed T1WI with contrast easily
reveals the abnormally enhancing nerve (a
finding that is not specific to PNTS but can
also be seen with inflammatory processes)
• T2WI may show asymmetrically abnormal
increased signal
Examples of PNTS on T1WI with contrast and without fat-sat,
show abnormally enlarged and enhancing V2(arrow) and V3 (arrowhead)
Imaging Findings-Challenge Case
• Patient with multiple previous small SCCas
of the retroauricular skin with a new
preauricular mass (arrow)
• All neural foramina appeared symmetrical
And intact (not displayed in this picture)
Imaging Findings-Challenge Case
• PET-CT reveals hypermetabolic activity near the pterygoid
plate, which was interpreted as artifactual given low level SUV
in comparison to patient’s known tumor
• Retrospective assessment
shows a 8 mm round,
nonenhancing soft tissue mass
(arrow) at the same location
of the subtle metabolic activity
Imaging Findings-Challenge Case
• 6 months latter, after resection and radiotherapy, MRI T1WI reveals PNTS with thickness of
auriculotemporal nerve (arrow) and V3 (arrowhead)
Imaging Findings-Challenge Case
• MRI T1WI post contrast without fat-sat reveals PNTS (arrows) with thickness of the
auriculotemporal nerve (left figure), cavernous sinus (center), and V2 within the foramen
rotundum (right figure)
Challenge Case-Discussion
Although not strongly described in the current literature and
limited to a few case series and case reports, PET-CT may reveal
hypermetabolic activity in PNTS, even with small lesions that are close
to the method’s lowest limits of resolution.
This particular case showed a skip lesion in the left mandibular
segment of the 5th CN, as the earliest imaging findings of the PNTS. The
lesion was visible on the PET-CT, and most likely the result of
retrograde tumor dissemination through facial and auriculotemporal
nerve.
The radiation coverage did not include the 5th CN and follow up
MRI revealed retro and antegrade progression of the PNTS into the
cavernous sinus and rotundum, respectively.
Imaging Findings- PET-CT
• Linear or round hypermetabolic
activity in a nerve pathway
• CT images may or may not show
asymmetric thickness of the nerve and
destruction or remodeling of the
adjacent structures
Example: Previously treated
periauricular/scalp SCCa with parotid
invasion and PNTS through facial and
fifth cranial nerve with neck pain. PETCT reveals hypermetabolic ativity along
the cervical nerve root C3 (arrows)
Imaging Findings- Unusual Cases
• MRI and PET correlation- same case of the previous slide
Cervical spine MRI axial T2WI (left), T1WI (center), and T1WI C+ (right) reveals,
asymmetry of the longus colli muscles, left being smaller than right (arrowhead)
with subtle thickness and post contrast enhancement (arrow).
Imaging Findings- Unusual Cases
Great auricular nerve
Lesser occipital nerve
C1
C2
C3
C3
Frank Netter- Atlas of Human Anatomy
• Diagram shows the presumable unusual, but feasible, pattern of PNTS discussed in the previous slide
with skip lesions most likely via GA nerve or LO nerve to C2 and C3 nerve roots
Imaging Findings- Unusual Cases
After left neck radiation the same patient shows worsening of the
neurological symptoms now with apparent brachial plexus topography.
STIR
T1WI C+
MRI and PET-CT show thickness of the left brachial plexus and focal
hypermetabolic activity (arrows). The findings may be the result of PNTS
progression, post radiation brachial plexitis, or a combination of both.
Imaging Findings- Third Illustrative Case
• Patient previously treated for right oral tongue SCCa shows interval
recurrence in the left paraspinal muscles
• PET-CT reveals a mass lesion with hypermetabolic activity in the left paraspinal
muscles (arrowhead) with linear hypermetabolic activity following the left cervical
spine nerve root (arrow), which is most likely associated with PNTS
Imaging Findings- Third Illustrative Case
• Patient progressed with worsening neurological symptoms and MRI (T1WI C+)
revealed leptomeningeal dissemination of the tumor via PNTS (arrows)
Treatment Implication
In these three patients with different distributions of PNTS over the course of
their disease, the combination of varied imaging methods, such as PET-CT and MRI
was a key factor for identification of the tumor deposition over the neural
pathway and the treatment implications were distinct and markedly significant.
•
In the first case, change in the radiation coverage could potentially offer
better control of the PNTS, which showed rapid intracranial progression
•
In the second case, radiation treatment covering the PNTS area was
immediately initiated after PNTS identification
•
In the third case, leptomeningeal spread was suggested as a potential
complication during clinical discussion based on PET-CT images
Discussion
The last few decades have shown increased awareness of PNTS as
a potential route of metastatic dissemination. The most common pattern
of PNTS through facial and trigeminal cranial nerve have been extensively
demonstrated and discussed. The marked improvement of diagnostic
imaging quality have allowed us to master cranial nerve anatomy and
look for findings of tumor involvement. However, neuroradiologists have
to keep in mind that this route of tumor dissemination may show
uncommon alternative routes of spread that can also be identified with
careful and meticulous evaluation of nerve pathways in the head and
neck region.
Discussion
The hypermetabolic activity visible on PET-CT can be subtle and
easily confused with artifact or pitfalls such as muscular activity, misregistration, or vascular structure. Therefore, linear or punctate/round
metabolic activity should be prudently evaluated as a potential site of
PNTS. Anatomic and morphological review of the adjacent nerve
pathways should be integrated in the imaging evaluation algorithm.
The accuracy of PET-CT for identification of PNTS is unknown.
There are however, sporadic case reports and case series showing that
detection of PNTS via PET-CT appears to be a feasible and most likely
reliable. Therefore, further investigation for the sensitivity and specificity
of PET-CT detection of PNTS, is necessary.
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