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Control #: 1398
Detecting Neck Node Metastases in Head &
Neck Squamous Cell Cancers : How Far Have
We Reached?
eEdE-91-8913
Dr. Supreeta Arya1, Dr. Ameya Kawthalkar1
Dr. J. P. Agarwal2
1. Department of Diagnostic Radiology
2. Department of Radiation Oncology
Tata Memorial Centre
Mumbai, INDIA
Disclosure of Commercial Interest
Neither we nor our immediate family members
have a financial relationship with a commercial
organization that may have a direct or indirect
interest in the content.
Purpose
N - To discuss the various imaging methods
for detecting neck node
metastases in head and neck squamous cell cancers (HNSCC)
E - To review literature on these various imaging methods to evaluate their
efficacy in detecting neck node metastases
C - To discuss the characteristic imaging features of metastatic nodes from
HNSCC on each imaging method
K - To provide the radiologist with a key practice based approach to aid the
clinician in staging the neck.
Imaging methods for neck node
evaluation
• Ultrasound (US)
• Ultrasound guided Fine needle aspiration cytology
(USgFNAC)
• Contrast enhanced Ultrasound
• CT scanning
• MRI & Advanced MRI (diffusion & perfusion MRI)
• Ultra-small particle iron oxide MRI
• PETCT
• Sentinel node biopsy
General principles
• Evaluation of head & neck cancers requires staging of
the primary and staging of the neck
• Metastatic workup is needed only in advanced
cancers ( stage III & IV)
• In staging head & neck cancers, the neck can be
clinically positive with palpable nodes ( cN+ neck) or
clinically negative ( cN0 neck)
Clinically negative neck
• Clinically negative neck can have occult metastases
• Occult metastases are metastatic nodes not detected by
palpation
• Incidence of occult metastases varies according to primary
site, in early stage oral cancers it varies from 27-40% 1
• Average incidence at all sites is 15% 2
• Expectation from imaging is to decrease the number of
undetected occult metastasis
Role of imaging in neck evaluation in HNSCC
Pretreatment
Post treatment
• To detect occult neck node
metastases (in the cN0 neck)
•
To evaluate neck following induction
chemotherapy
• To map the nodal burden prior to
treatment 3
•
To look for recurrence in the neck
following definitive treatment
• To identify necrosis (poor prognosis)
• To identify extra-nodal spread (ENS)
--poor prognostic factor; if ENS + ,
to evaluate relation of the node with
vessels & adjacent structures
General Tips to aid imaging
• Know the expected lymphatic drainage from the primary site of
head & neck cancer  examine these areas critically
• Examine the radiological features  each imaging method can
show typical features in metastatic nodes (described later)
Nodal metastases from various primaries 4
Primary site
Most frequent levels of Nodal metastases
Nasopharynx
II , V, retropharyngeal, supraclavicular ; contralateral
II in 36%
Soft Palate
II, III; contralateral in 29%
Tonsil
II, III; contralateral in 13%
Base tongue
II, III; contralateral in 31%
Gingival , Buccal & Retromolar
trigone
IB, II
Oral tongue
II, I, III; contralateral when crossing midline
Floor of mouth
IA,IB, II; contralateral when crossing midline
Hard palate
Nodal metastases rare
Supraglottic larynx
II, III
Glottic larynx (advanced)
II, III
Pyriform sinus
II, III
Thyroid cancers
VI, VI, III, supraclavicular
Nodal groups 5
Regions of the neck:
1- Submental
2-Submandibular
3
2
1
3-Parotid nodes
4
4-Upper jugular
5
8
6
5-Middle jugular
6-Lower jugular
7
7-Supraclavicular nodes
8-Posterior triangle nodes
AJCC Level based Nodal
Classification 6
IA- Submental
IB-Submandibular
II-Upper jugular
IA
IA
IB
III-Middle jugular
II
IV-Lower jugular
III
V
V-Posterior triangle nodes
IV
VI
VII
VI-Pre/Paratracheal
VII-Upper mediastinal
Other sites of nodal metastases 3
Nodal site
Possible site of primary
1
Parotid nodes
Nasopharyngeal cancers, skin
cancers
2
Retropharyngeal nodes
Nasopharyngeal cancer ,
Thyroid cancer
3
Isolated left supraclavicular
node ( Virchow’s node)
Abdominal /Thoracic primary
or thyroid malignancy
Teaching point
1 & 2 may not be amenable to clinical examination; hence
identification on imaging is important
US features of metastatic nodes 7
1.
2.
3.
4.
5.
6.
7.
8.
9.
Necrosis
Cystic nodes- in HPV +ve cancers & thyroid cancers
Heterogenous internal echotexture
Eccentric cortical hypertrophy ( particularly with abnormal
architecture in hypertrophied part)
Darkly hypoechoic node accompanied with
Absent hilum
Rounded shape
Calcification – in metastases from Thyroid cancer
Abnormal vascularity
-Diffuse intrinsic hypervascularity –in metastases from Thyroid cancer
-Hypovascular or peripheral vascularity- in metastases from squamous cancers
US features - Normal node
Hilum of the node (
Cortex of the node (
)
)
7
US features – Abnormal nodes 7
Node with large area of
necrosis (black region)
Round node without hilum
Darkly hypoechoic node,
no hilum
Node with focus of
coagulative necrosis (arrow)
Node with micro
calcification (arrows)
Node with abnormal
vascularity
USgFNAC
8-12
• Useful tool to needle nodes that are suspicious on
US/ CT/MRI
• Real time method to assess nodes; cost effective, and
gives cytology diagnosis.
Problem• Requires expertise (right needle gauge, right technique, right operator)
• Sampling errors in
 small nodes ( as in the N0 neck)
 nodes compressed against the mandible
 nodes where metastatic focus is localized to one small region
• Negative FNAC is not an entirely reliable method to rule out metastasis
conclusively ( positive FNA is conclusive)
Factors that influence accuracy of USgFNAC
in clinically negative necks 8-12
Author
No of
Site of
patients HNSCC
Clinical T
Stage
USg-FNAC
Sensitivity
specificity
Van den Brekkel
et al , 1991
54
All sites
ALL
76 %
100%
Takes et al.,
1998
64
All sites
All
48%
100%
Righi et al, 1997
25
All sites
All
50%
100%
Borgemeester &
Van den Brekel ,
2008
126
All sites
All
Chaturvedi ,
Datta & Arya,
2014
51
Oral cancers T1 & T2
39% (but was 100%
lowest at
27% in oral
cancers)
14%
100%
Analysis of literature on US g FNAC
8-12
Besides expertise, the accuracy of UsgFNAC is
also dependent on-• Subsite of HNSCC ( lowest reported for oral cancers
and highest for laryngeal cancer)
• ? T stage of primary – Evidence to suggest that lower
the T stage, lower the accuracy of USgFNAC of
suspected neck nodes
Contrast enhanced Ultrasound (CEUS) 13
• Reports suggest that CEUS has a potential role to differentiate
between benign and metastatic nodes
• Heterogeneous enhancement and centripetal enhancement
were features in favor metastatic nodes
CT features of metastatic nodes 6, 14
-Necrosis
•
•
•
Reliable even when seen in subcentimeter nodes
Seen best on contrast enhanced CT; as low density, poorly enhancing foci
Cystic necrosis seen in HPV + cancers; thyroid cancers
-Internal heterogeneity
-Rounded node with lost hilum
-Enlargement
•
•
•
Nodal size criteria varied; short axis/ long axis used.
Short axis > 1.5cm for level II nodes, > 1cm for other nodes = abnormal
Size criteria unreliable and nodes in drainage areas with borderline size should
be viewed with suspicion
-Clustering
3-5 nodes in drainage site of primary – considered abnormal
-Calcification
In thyroid carcinoma
CT features - Abnormal nodes
Necrotic enlarged left level III node
*
Bilateral heterogeneous level
II nodes with necrosis
Normal sized enhancing rounded nonnecrotic node at right level II in the
draining region of posterior pharyngeal
wall primary ( *) ; needs to be viewed
with suspicion
MRI features of metastatic nodes 6, 15
-Necrosis
• Reliable even when seen in subcentimeter nodes
• Seen best on contrast enhanced T1W images; as poorly enhancing foci
/cystic regions
• T2W & STIR images show high signal or hyperintensity
-Internal heterogeneity on T2W sequences
- Spiculated margins
-Rounded node with lost hilum
-Enlargement
• Nodal size criteria similar as with CT
-Clustering
3-5 nodes in drainage site of primary – considered abnormal
MRI- indeterminate and abnormal
nodes
Case of left sided tongue
carcinoma.
Coronal T2W MRI image
showing necrosis in a left level
III node, which was metastatic
on histopathology
Case of right sided tongue
carcinoma. Axial T2W
sequence showing
internal heterogeneity in a
right level II node. On
histopathology there was
one metastatic node at
this level of corresponding
size
A cluster of normal sized
non- necrotic nodes are
seen on the STIR images at
both levels II .
In the presence of a known
primary (such as
nasopharynx) these nodes
are to be viewed with
suspicion
Diffusion weighted MRI ( DW-MRI) 16-18
• Based on the principle that metastatic nodes with
high cellularity have restricted diffusion
• Qualitative- seen as high signal on the high b value image
and dark on the ADC maps
• Quantitative- Metastatic nodes have been reported with
low ADC values while benign nodes have higher ADC values
Fallacy
Recent reports mention overlapping ADC values of
benign and metastatic nodes .
Can DW-MRI help? 16-18
A
B
C
A. White arrow shows a non necrotic unremarkable node at right level II in a known case
of right oral tongue carcinoma ; B. Exponential apparent diffusion coefficient (EADC) image
and C. ADC (apparent diffusion coefficient ) map .
The node (arrows) shows high signal in B & dark signal on C suggesting true restriction of
diffusion . The ADC value measures 0.76 X 10 -3mm2/sec. This node was metastatic on
histopathology.
Fallacy
However overlapping ADC values in non necrotic small nodes have been reported in
HNSCC by Lim et al; also supported by our unpublished data.
Perfusion MRI 19
Using Dynamic contrast enhanced (DCE) MRI
• Early reports mention different characteristics of metastatic
nodes compared to benign nodes
• However conflicting results in various reports ( some report
higher time to peak while others report lower time to peak in
metastatic nodes)
• Currently being investigated to assess control of the neck
following induction chemotherapy.
Ultra-small particle iron oxide MRI (USPIO-MRI)
• Promising early reports with USPIO-MRI for detecting
20
metastatic nodes
• Principle- Normal nodes take up USPIO and appear dark while
metastatic nodes do not take up USPIO and appear bright
• ProblemUSPIO-MRI not available for clinical use as it has not been approved
by recommending agencies. When available in the future, needs
thorough investigation.
FDG PETCT for neck evaluation
• Principle- Metastatic nodes have high uptake with higher SUV
(standard uptake value).
FDG PETCT useful
• As baseline imaging for mapping nodal burden prior to radiotherapy to
compare with post treatment imaging 3
• To characterize nodes if CT or MRI are equivocal
• For evaluation of post treatment neck 3
Fallacy
• Small/ necrotic nodes can be negative 3
• Not useful in the N0 neck where subcm occult metastases is expected 21
• Well differentiated thyroid cancers and medullary thyroid cancers can
be PET negative 3
• Granulomatous and non- specific adenitis can cause false positives
Abnormal nodes on FDG-PETCTon
FDGPET
A
B
Figure A shows intense FDG
uptake in a midline base
tongue primary and a
metastatic left level II node.
The same node appears
unremarkable on the
contrast enhanced CT in B.
B. also shows a subcm right
II node which is rounded ,
but no uptake is seen in A.
Sentinel node biopsy (SNB)
Principle
• A tumor will have preferred nodal drainage basin, with a primary
node. If that node could be identified and biopsied , metastasis could
be ruled out with minimal intervention
• A radioactive dye is injected (99m Tc-labelled Human Serum Albumin
Nanocolloid; maximum 1mci) peritumorally
• Lymphoscintigraphy & SPECT-CT performed, at surgery hot nodes
identified with a hand held gamma probe
• Nodes harvested and histopathological analysis done –with
Hematoxylin & Eosin stain; ideally step serial sectioning and
immunohistochemistry to be performed on the node.
SNB
• A meta-analysis in 847 patients of T1/T2N0 oral & oropharyngeal
SCC revealed an overall sensitivity of 93% for SNB 22
• Dutch multi-institutional trial ( 2014) on sentinel lymph node
biopsy in oral cancer– showed that risk of occult metastasis
reduces from 40% to 8% in T1 T2 oral cancer 23
• SNB being recognized as a viable alternative to
elective neck dissection for staging the neck in early-stage oral
cavity cancer 12, 22-23
• Problem
Elective neck dissection (END) is the standard of care in HNSCC.
No randomized controlled trial exists that compares END and SNB for SNB to
conclusively replace END.
Many methods…
How far have we reached?
Meta-analyses of imaging methods for neck node
evaluation in HNSCC 21, 24-26
Year
Methods studied &
compared
Conclusion
Comment
2007 ( Eur J
radiol) , de
Bondt et al
USgFNAC, US, CT,
MRI, and USPIOMRI
(17 studies)
USgFNAC had the highest
diagnostic
odds ratio with
decreasing performance for
US alone, USPIO MRI, CT,
and MRI in that order.
The meta-analysis included only three
studies with ultrasound-guided FNAC, two
of which had both cNo and cN+ necks. In the
solitary study with cN0 neck,
the sensitivity of USgFNAC was only 48%.
2008 ( J
Natl Cancer
Inst.), Kyaz P
et al
FDG PET ( 32
studies)
FDGPET does not detect
disease in nearly 50% of
patients with neck
metastasis and cN0 in
HNSCC
Both cN+ necks and cN0 necks studied.
Separate subgroup analysis in cN0 neck.
2012, (Acad
Radiol.) ,
Wu et al
MRI ( 16 studies)
With few studies on
DW-MRI .
Also compared with
CT, PET and US
MRI has sensitivity of 76%
and specificity of 76%.
A small number of studies
showed DW-MRI to be
slightly superior
Meta-analysis had both cNo and cN+ necks.
It also found the other methods ( CT, PET &
US) comparable to MRI.
2012, ( BMC
cancer) Liao
LJ et al
CT (7 studies), MRI
(6studies), PET( 11
studies) and US (8
studies)
All methods with similar
sensitivity and specificity,
except for higher specificity
of CT over US
The only meta-analysis till date in the cN0
neck
Discussion
• END is the standard of care for the management of the neck,
particularly in tongue cancers when tumor thickness > 4mm.
• However 2/3rds of the ENDs are unnecessary and can result in
morbidity in 30% 12.
• It would be ideal to have a preoperative imaging method with
high positive predictive value (PPV) and negative predictive value
(NPV) to identify occult metastatic nodes so that unnecessary
END can be avoided .
• However despite advances in imaging, no imaging method has a
100% NPV and high specificity /PPV.
Teaching points
Against such a disadvantage, the radiologist should play a
vigilant role in identifying nodal metastases by
1. Careful imaging technique
2. Knowledge of the primary disease and spread patterns
3. Keen observation of the imaging features of the nodes
4. Suggest appropriate adjunct imaging methods to the clinician for
problem solving if needed
Teaching points
• CT or MRI ordered for imaging the primary are comparable for
evaluating the neck
• There is evidence that DW-MRI may not be useful for
characterizing neck nodes
• Use of DCE-MRI or CEUS may not be cost effective or conclusive
• FDGPET / USgFNA may be added for problem solving
• USgFNAC may not be helpful in early cancers with N0 necks
• When very early lesions ( such as T1 tongue or buccal cancers) are
not imaged with CT/MRI , US may be used to evaluate the cN0
neck to confirm the N0 status, if END is not being planned
Teaching points
• When imaging reveals metastatic nodes, the radiologist should
give a detailed report that includes
 Level of abnormal nodes
 Size & number of abnormal nodes
 Presence of necrosis
 Extracapsular spread
 Relation to common carotid artery and internal carotid artery
(circumferential contact : if < 180° easily resectable,
if > 270°  unresectable)
 Invasion of IJV and other adjacent structures
• FDG PETCT may be ordered and used to map the nodal burden
prior to RT planning
Teaching points
• When imaging does not reveal metastatic nodes despite careful
scrutiny, the clinician might
 Opt for END
 Might observe the neck based on the site of the primary, its
size/ thickness and histological grade. ( In this scenario, no imaging
investigation is 100% accurate , however US may be used as a method of
extended palpation as it is cost effective & involves no radiation exposure)
 Attempt SNB prior to END especially in early stage cancers with
N0 neck (both on clinical examination & imaging)
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