Ultrasonographic Evaluation of Malignant and Normal

Cervical Lymph Nodes

Craig P. Giacomini, BS,* R. Brooke Jeffrey, MD,† and Lewis K. Shin, MD†,‡

Head and neck malignancies, including squamous cell carcinoma, lymphoma, and thyroid
cancer, are a major cause of morbidity and mortality worldwide and frequently present with
cervical lymphadenopathy. Distinguishing normal from malignant lymph nodes is critical for
accurate staging, prognosis, and determination of optimal therapeutic options. Gray-scale,
power, and color Doppler ultrasonography offers an inexpensive yet effective method in
identifying abnormal cervical lymph nodes. Sonographic nodal features that should be
assessed include size, shape, echotexture (including microcalcifications and cystic changes),
presence of an echogenic hilus, and vascularity. Although no single sonographic feature can
accurately distinguish malignant from normal nodes, a combination of these characteristics
can help to make this determination.
Semin Ultrasound CT MRI 34:236-247 Published by Elsevier Inc.

V arious malignancies arise in the head and neck region.

The incidence, risk factors, and mortality rates associ-
ated with these cancers vary. For example, it is estimated that
there would be 56,460 new cases of thyroid cancer in the
United States in 2012 with an estimated 1780 deaths.
Thyroid cancer risk factors include female gender, age, family
history, radiation exposure, and certain genetic syndromes
including familial adenomatous polyposis and multiple
endocrine neoplasia type 2.1 Head and neck squamous cell
carcinomas (HNSCC) make up approximately 3% of all
malignancies in the United States, with an estimated 52,000
new cases in 2012.2 These cancers are nearly twice as
common among men as they are among women and are
diagnosed more often in individuals older than 50 years.
Primary tumors arise in various mucosal surfaces of the head
and neck including but not limited to the tongue, orophar-
ynx, nasopharynx, piriform sinuses, nasal cavity, and larynx.
Major risk factors include tobacco and alcohol use as well as
human papillomavirus infection for certain cancer subtypes.3
Malignant involvement of local lymph nodes is a common
feature of many head and neck cancers. Nodal involvement is
the most important prognostic factor in HNSCC.4 Unilateral
cervical node metastases have been shown to reduce the 5-year
*Stanford University School of Medicine, 291 Campus Drive, Li Ka Shing
Building, Stanford, CA 94305.
†Department of Radiology, Stanford University Medical Center, Stanford, CA.
‡Department of Radiology, VA Palo Alto Health Care System, Palo Alto, CA.
Address reprint requests to Lewis K. Shin, MD, Department of Radiology, VA
Palo Alto Health Care System, 3801 Miranda Ave, MC 114, Palo Alto, CA
94304. E-mail: lewis.shin@va.gov
survival rate of patients by nearly 50%, and bilateral metastases
reduce survival by an additional 50%.5,6 In papillary thyroid
cancer (PTC), nodal microscopic metastases have been
reported in as many as 80% of the patients undergoing
prophylactic lymph node dissection.7 The clinical significance
of these micrometastases is unclear. In addition, metastatic
cervical lymph nodes detected after thyroidectomy can remain
stable for years in many patients.8 Nevertheless, macroscopic
cancer involvement of cervical lymph nodes is associated with
tumor recurrence and diminished overall survival.9,10 Hence,
evaluation of cervical lymph nodes for malignant spread is
critical for determining patient prognosis and optimal ther-
apeutic options. High-resolution ultrasound offers a fast,
noninvasive, and inexpensive approach.
Nodal sonographic features can offer a clue for whether a
lymph node contains cancer. Ultrasound provides detailed
information about the internal and external features of a lymph
node and demonstrates superior sensitivity and specificity in
detecting malignant nodes compared with physical examina-
tion. For example, sonography has become the imaging
method of choice to evaluate cervical lymph nodes in patients
with PTC, both in the initial staging and in their subsequent
surveillance following thyroidectomy.11-15 Other imaging
modalities, including computed tomography (CT), magnetic
resonance imaging, and positron emission tomography, have
also shown utility in evaluating cervical lymphadenopathy.
However, these approaches are comparatively expensive, with
ultrasound demonstrating higher sensitivity for detecting
cancer.16-18 No single sonographic feature can accurately
distinguish a normal or reactive lymph node from a malignant

236 0887-2171/$-see front matter Published by Elsevier Inc.

http://dx.doi.org/10.1053/j.sult.2013.04.003
Ultrasonographic evaluation of malignant and normal cervical lymph nodes 237

one; rather, a combination of characteristics including nodal

size, shape, location, echotexture, and vascularity character-
ization can help make this determination. As a result,
ultrasound-guided fine-needle aspiration biopsy with cytologic
analysis is frequently used for the confirmation (or exclusion)
of malignancy in suspicious lymph nodes. In this article, we
review the anatomy of normal cervical lymph nodes and the
role of ultrasound in the characterization of abnormal
(eg metastatic) nodes.

Cervical Lymph Node Structure

and Anatomy
Lymph nodes are encapsulated and highly organized struc-
tures that are interposed along regional vessels of the lympho-
vascular system. Lymph nodes are surrounded by a
collagenous capsule and contain a highly cellular cortex of
densely packed lymphoid follicles. Afferent lymphatic vessels
pierce the capsule and extend through the cortex where they
converge with a network of broad interconnected channels
called medullary sinuses. The sinuses ultimately extend to the
central concavity of the node termed the hilum that contains
the lymph node artery and vein. Lymph drains from the hilum
into efferent lymphatic vessels, which eventually join the
bloodstream via the thoracic duct or right lymphatic duct.19,20
Various systems have been devised for the anatomical
classification of cervical lymph nodes. The American Joint
Committee on Cancer (AJCC) devised a commonly used
system that divides the head and neck into 7 regions.5,21-23
However, this classification scheme has limitations in ultra-
sonographic evaluation because it excludes certain lymph
nodes in the head and neck (Fig. 1A). A more useful system
was developed by Hajek et al.24 that divides cervical lymph
nodes into 8 anatomical regions (Fig. 1B) that are readily
amenable for sonographic evaluation.21,25

Ultrasonography Technique
Various sonographic modalities can be used for lymph node
evaluation, including gray-scale, color Doppler, power Dop-
pler sonography (PDS), and 3-dimensional PDS. Gray-scale
ultrasound can characterize features including lymph node
location, size, shape, border, echogenicity, calcifications,
necrosis or cystic change, and adjacent soft tissue edema.
Vascular features of lymph nodes can be evaluated by color or
power Doppler ultrasound. Spectral analysis is used to
measure blood flow velocity and vascular resistance. PDS has
increased sensitivity compared with standard color Doppler
sonography in visualizing small vessels or the vascular supply
of smaller lymph nodes. The 3-D PDS allows for reconstruc-
tion of images in 3 dimensions.26,27
The choice of transducer is an important consideration
when evaluating cervical lymph nodes as higher frequen-
cies provide better resolution for superficial structures,
whereas lower frequencies are more effective at imaging
deep nodes. A linear transducer of at least 7.5 MHz is
Figure 1 (A and B). Anatomical schematics. (A) The AJCC classification
of pathologic cervical lymph nodes. I—submental and submandib-
ular nodes. II—anterior cervical and internal jugular lymph node
chain from the skull base to the level of the hyoid bone. III—internal
jugular chain nodes from the hyoid bone to the cricoid cartilage. IV—
nodes in the internal jugular chain between the cricoid cartilage and
clavicle. V—lymph nodes along the spinal accessory chain posterior to
the sternocleidomastoid muscle. VI—nodes from the hyoid bone to
the suprasternal notch with the medial border of the carotid sheath
bilaterally forming its lateral borders. VII—nodes in the superior
mediastinum. (B) Classification developed by Hajek et al. classifiying
nodes readily amenable to ultrasound evaluation. Anatomical bound-
aries depicted (Reprinted with permission21). (Color version of the
figure is available online.)
generally recommended, although higher frequency trans-
ducers of 10–18 MHz are often used. In certain circum-
stances, the convex surface of a curvilinear or sector probe
238
offers the advantage of a more expansive viewing field, that
may be particularly useful when examining supraclavicular
lymph nodes.21,26,27
Although there is no single correct approach for
evaluating neck nodes, one should employ a method that
is both comprehensive and systematic. The patient should
be placed in the supine position with the neck in a neutral
or slightly hyperextended position. One approach is to
first evaluate the submental area, followed by the sub-
mandibular and parotid regions. Next, the upper, middle,
and lower cervical levels should be evaluated. Lastly, the
supraclavicular fossa and posterior triangle should be
assessed.
Sonographic Features of Normal
and Malignant Cervical Lymph
Nodes
Number and Distribution
Normal cervical lymph nodes are generally detectable by
ultrasound in 4 anatomical locations including the parotid
(20%), submandibular (20%), upper cervical (20%), and
posterior triangle (35%-37%) regions. Elderly patients tend
to have fewer nodes than younger patients, although the
mechanism underlying this decrease is not well under-
stood.21,28,29 Thus, detection of lymph nodes outside these
4 regions or the finding of increased numbers of lymph nodes
in an elderly patient should raise suspicion for a pathologic
process.
Head and neck malignancies tend to metastasize to specific
lymph node clusters depending on the subtype and location of
the primary tumor. For example, in 1 study evaluating
sonographic features of cervical lymph nodes in patients with
thyroid cancer, 66.52% of the metastatic nodes were found to
be situated in the lower third, 20.36% were found in the
middle third, and only 13.12% were found in the superior
third of the neck. In contrast, benign lymph nodes were found
more often in the superior (45.94%) and middle (39.53%)
third of the neck.30 In non-Hodgkin's lymphoma, metastatic
lymph nodes are typically located in the submandibular and
upper cervical regions.31,32
In 2%-9% of all head and neck cancers, the primary
tumor cannot be identified, in which case the malignancy
is termed a cancer of unknown primary origin.33 Evaluat-
ing the location of metastatic lymph nodes can offer clues
regarding the origin of these malignancies. For example,
cancers of the tongue and larynx along with thyroid
carcinomas commonly metastasize to lymph nodes within
the internal jugular chain.34,35 The laterality of the
malignant lymph nodes is another important consider-
ation, as the primary lesion should be sought in ipsilateral
mucosal or cutaneous structures. Bilateral neck masses
can suggest the occult primary lesion is from a midline
structure, such as the base of the tongue or nasopharynx.
Isolated left supraclavicular adenopathy, the “Virchow
node,” should raise suspicion of a primary malignancy
C.P. Giacomini et al
outside of the neck; the classic primary is gastric carci-
noma but others include esophageal and pancreatic
origins.36-39 Posterior triangle adenopathy in a high-risk
patient population (ie Southern Chinese) should raise
concern for nasopharyngeal carcinoma.40
Lymph Node Size
Although size has traditionally been used to distinguish
malignant from normal nodes, it has been shown to be an
inaccurate sole criterion.41 Several reasons exist for this
unreliability including the observation that normal cer-
vical lymph nodes vary in size depending on their
anatomical location. In a study using ultrasound to
compare normal cervical lymph nodes between Chinese
and Caucasian subjects, Ying et al. demonstrated that the
largest lymph nodes in both ethnicities are located in the
submandibular region (0.6 cm), whereas the middle
cervical nodes were found to be the smallest (0.2 cm).42
In addition, when lymph nodes become reactive from
local infection and inflammation, their increased size from
hyperplasia can equal that of metastatic nodes. Brancato
et al. used ultrasonography to discover that patients with
chronic autoimmune thyroiditis have increased numbers
of enlarged hyperplastic neck nodes, especially in levels II,
III, and IV.43 Therefore, using the patient's clinical history
in combination with changes in cervical lymph node size
can help assess metastatic involvement. An increase in
nodal size on serial examinations in a patient with a
known malignancy is highly suspicious for cancer.
Another confounding factor is the finding that for older
patients, normal cervical lymph nodes tend to be larger
compared with those of younger patients, presumably
owing to increased fat content with advancing age.29
Defining the upper size limit of a normal lymph node
remains controversial. Wide variations in the techniques
applied and in the nodal dimensions measured have made
it difficult to draw conclusions from the literature. In a
seminal study published in 1998, van den Brekel et al.
attempted to define the optimum size cutoff for identify-
ing malignant cervical lymph nodes in different anatom-
ical regions based on the AJCC classification.44 The study
used ultrasound to measure the minimum axial diameter
of nodes from a series of 184 surgically treated patients
with HNSCC. For the group of patients as a whole, a
threshold of 10 mm had a sensitivity of 63% and specific-
ity of 92%. However, the study shows that different
criteria work better for the different AJCC regions, and
they demonstrate that adjusting the size criteria even
slightly significantly affects sensitivity and specificity. In
a recent study, Moghaddam et al. used 7 mm and 13 mm
as cutoffs for minimal and maximal nodal diameter,
respectively, for assigning a cervical lymph node as
malignant.45 The 7-mm minimal diameter cutoff corre-
sponded to a sensitivity and specificity of 85% and 79%,
respectively, and the 13-mm maximal diameter cutoff
achieved 85% sensitivity and 59% specificity. As other
studies propose different criteria, lymph node size should
Ultrasonographic evaluation of malignant and normal cervical lymph nodes 239

be correlated with patient history and other sonographic

characteristics.

Shape
Shape is another criteria frequently used to distinguish
malignant and normal lymph nodes. Quantifying the shape
of a lymph node is performed by examining the short axis to
long axis ratio (S:L). Round nodes (S:L 4 0.5) are considered
to be suspicious for malignancy (Fig. 2), whereas flat, oval-
shaped nodes (S:L o 0.5) (Fig. 3) are generally considered
normal or reactive.46 One caveat is that normal lymph nodes in
the submandibular and parotid regions can often have a round
shape.47 Conversely, malignant nodes may have an oval shape
when they are in the early stages of development.

Figure 3 (A and B). Normal lymph node. (A) Gray-scale sonogram

demonstrates a normal, flat lymph node with an echogenic hilus
(arrow). (B) Color Doppler image demonstrates absence hilar flow.
(Color version of the figure is available online.)

Although several studies demonstrate a correlation

Figure 2 (A and B). Abnormal lymph node from breast carcinoma
metastasis. (A) Gray-scale sonogram demonstrates abnormal, rounded
lymph node morphology. (B) Color Doppler image demonstrates
abnormal peripheral flow. (Color version of the figure is available
online.)
between nodal shape and the presence of malignancy,
this association is not perfect. Tohnosu et al. used ultra-
sound for cervical lymph node evaluation in 58 patients
with established esophageal cancer.48 This study demon-
strated that in 126 evaluated lymph nodes, the presence of
metastasis was significantly higher among those nodes
having a round shape (S:L 4 0.5) and a long axis
exceeding 10 mm; among the 77 metastatic lymph nodes
evaluated, oval-shaped nodes (S:L o 0.5) harbored a 26%
cancer content on histologic examination, whereas round
nodes contained a 59.1% cancer content. More recently,
in a study evaluating cervical lymph nodes in patients with
thyroid cancers, Kuna et al. demonstrated that 11.8% of
240 C.P. Giacomini et al

with confirmed papillary thyroid carcinoma, 86% of nodes

were found to be hyperechoic compared with the adjacent
muscles on gray-scale ultrasound.13 This hyperechogenicity is
presumed to be due to intranodal deposition of thyroglobulin
by neoplastic cells.34,40 Hence, the incidental finding of
hyperechoic cervical lymph nodes should prompt evaluation
of the thyroid gland for cancer. Lymphomatous lymph nodes
can exhibit a pseudocystic appearance, defined as hypoecho-
genicity with posterior enhancement.34,35

Echogenic Hilus
On ultrasound, the hilum of a normal lymph node appears
as an eccentric, echogenic intranodal structure (Fig. 3) that is
continuous with adjacent perinodal fat. Approximately
90% of nodes with a maximum transverse diameter greater
than 5 mm show an echogenic hilum on high-resolution
ultrasound.40,53 This appearance is thought to be secondary
to the medullary sinuses that act as acoustic interfaces that
Figure 4 Abnormal lymph node from papillary thyroid carcinoma
metastasis. Gray-scale sonogram demonstrates focal echogenic regions
(long arrows) with irregular and unsharp borders (short arrow)
suspicious for extracapsular spread.

the 296 benign nodes examined had a round shape.30

Among the 221 malignant lymph nodes they examined,
34.4% were oval shaped.

Border
There have been mixed reports and controversy regarding
nodal border and its correlation with malignancy. Some
studies suggest that cancerous nodes tend to have a sharp
border on ultrasound, whereas benign nodes appear to have
ill-defined borders.49,50 This sharp border has been proposed
to be secondary to intranodal tumor infiltration, which causes
an increase in the acoustic impedance difference between the
lymph node and surrounding tissues.50 However, it is known
that extracapsular spread of malignant cells frequently results
in an irregular nodal border on ultrasound (Fig. 4). Further-
more, others have reported that lymph nodes with irregular
borders tend to be malignant whereas those with well-defined
borders are benign. Toriyabe et al. found that 84.6% of cervical
lymph nodes with irregular margins were metastatic, and
82.6% of nodes with regular margins were benign.51 Similarly,
Moritz et al. report that the majority of benign, enlarged
cervical lymph nodes had well-defined boundaries, and 54%
of lymph node metastases were poorly defined.52 Caution
should be used when interpreting nodal border in relation to
metastatic disease.

Echogenicity
Normal, reactive, and most malignant nodes have a predom-
inantly hypoechoic appearance on ultrasound relative to
adjacent musculature. One exception is metastases from PTC
that can have a hyperechoic appearance (Figs. 5–7). One study
demonstrated in 198 metastatic lymph nodes from patients
Figure 5 (A and B). Abnormal lymph node from papillary thyroid
carcinoma metastasis. (A) Gray-scale sonogram demonstrates absence
of the echogenic hilus. (B) Color Doppler image demonstrates
abnormal peripheral flow. (Color version of the figure is available
online.)
Ultrasonographic evaluation of malignant and normal cervical lymph nodes 241

partially reflect the ultrasound waves. The absence of an

echogenic hilus may indicate that infiltrating malignant cells
have obliterated this structure, although tuberculous nodes
can also exhibit this appearance. Notably, early metastatic
nodes frequently have a normal echogenic hilus on
ultrasound.54,55

Calcifications
Cervical lymph node calcification is an uncommon find-
ing, but its presence may suggest infiltration by thyroid
cancer, specifically papillary subtypes (Figs. 6, 8, 9 and
10).21 These calcifications are thought to correspond to
psammoma bodies, which are identifiable on histologic
evaluation.35 When present, a thorough evaluation of the
thyroid gland for an underlying malignancy is indicated.

Figure 7 (A and B). Abnormal lymph node from papillary thyroid

carcinoma metastasis. (A) Transverse and (B) Longitudinal gray-scale
sonograms demonstrate marked, abnormally increased lymph node
echotexture (arrows).

Medullary thyroid cancer can also present with calcifica-

Figure 6 (A and B). Abnormal lymph node from papillary thyroid
carcinoma metastasis. (A) Gray-scale sonogram demonstrates hetero-
geneous lymph node with abnormal, nonhilar, hyperechoic foci
(arrow), and microcalcifications (arrowheads). (B) Gray-scale sono-
gram (different plane) demonstrates additional abnormal hyperechoic
foci (arrow) and microcalcifications (arrowheads).
tions within metastatic lymph nodes, but this finding is
less common in comparison.
The distribution of nodal calcifications is another important
consideration. Thyroid cancer–associated calcifications tend to
have an irregular distribution. In contrast, outside of the neck,
peripherally distributed or “egg-shell” calcification typically
signifies a nonmalignant etiology.56 For example, in the
mediastinum, nodal egg-shell calcification is classically asso-
ciated with silicosis but can also be present in patients with
sarcoidosis or tuberculosis.57-59 Silvers et al. reported CT
detection of egg shell–type calcifications within cervical lymph
nodes in a patient with sinus histiocytosis after treatment with
interferon.60 Other less common causes of cervical lymph
node calcifications include metastatic mucinous adenocarci-
nomas, granulomas, fat necrosis, and previously treated
lymphomas.
242
Figure 8 Abnormal lymph node from papillary thyroid carcinoma
metastasis. Gray-scale sonogram demonstrates predominantly cystic
lymph node (long arrow) with mural soft tissue nodularity (short
arrows) and microcalcifications (arrowheads).
Intranodal Necrosis
When tumor cells within a lymph node outgrow its blood
supply, necrosis results. This necrosis most commonly
manifests as cystic changes within the node that appear as
echolucent regions on ultrasound, corresponding to cystic
or liquefaction necrosis. Less commonly, coagulation
necrosis can occur, which appears as echogenic foci not
continuous with surrounding perinodal fat and not
exhibiting acoustic shadowing. Although ultrasound has
been shown to be useful for detecting necrotic changes,
studies have demonstrated that magnetic resonance imag-
ing and CT imaging modalities have superior sensitivity.
Figure 9 Abnormal lymph node from papillary thyroid carcinoma
metastasis. Gray-scale sonogram demonstrates small, flat lymph node
with abnormal microcalcifications (arrowheads).
C.P. Giacomini et al
Figure 10 Abnormal lymph node from papillary thyroid carcinoma
metastasis. Gray-scale sonogram demonstrates heterogeneous, hyper-
echoic lymph node with abnormal microcalcifications (arrowheads).
However, no differences in specificity have been reported
between these platforms.61
Cystic necrosis of lymph nodes (Fig. 11) is commonly
associated with metastatic squamous cell carcinoma (Figs. 12
and 13) and PTC (Figs. 8, 14, 15 and 16).62 Kessler et al. found
that 14 of 20 patients with PTC had sonographic evidence of
cystic changes, whereas no cystic changes were found in
patients without cancer.63
Vascular Pattern and Resistance
Color and power Doppler ultrasonography can readily assess
lymph node vascularity. In normal or reactive lymph nodes,
Figure 11 Abnormal lymph node from melanoma metastasis. Color
Doppler image demonstrates mixed cystic (short arrow) and solid
node with abnormal color Doppler flow (arrowheads); note: posterior
acoustic enhancement of cystic regions (long arrow). (Color version of
the figure is available online.)
Ultrasonographic evaluation of malignant and normal cervical lymph nodes
Figure 12 Abnormal lymph node from squamous cell carcinoma
metastasis. Color Doppler image demonstrates cystic changes (arrow-
heads) and solid components (arrows). (Color version of the figure is
available online.)
the vasculature cannot be appreciated (Fig. 3) or is confined to
the hilar branches (Fig. 17).6 Metastatic lymph nodes can
exhibit distinct patterns of vascularity. For example, metastatic
lymph nodes have characteristically more peripheral
(Figs. 2 and 5) or mixed (exhibiting both peripheral and hilar)
vascular patterns (Fig. 16); a disorganized intranodal vascular
flow has also been described with metastatic PTC, melanoma
metastases, and lymphomatous nodes (Figs. 11, 15
and 18).26,64-67 One potential pitfall is a carotid body
Figure 13 Abnormal lymph node from squamous cell carcinoma
metastasis. Color Doppler image demonstrates cystic changes (arrow-
heads), avascular (long arrow), and vascularized (short arrow) solid
components. (Color version of the figure is available online.)
243
Figure 14 Abnormal lymph node from papillary thyroid carcinoma
metastasis. Gray-scale sonogram demonstrates complex, cystic lymph
node with thick, irregular septations (arrowheads) and mural
nodularities (arrows).
paraganglioma that can appear like an abnormal, vascularized
cervical lymph node. The classic location of a mass situated at
the “Y” of the carotid bifurcation splaying the internal and
external carotid arteries is highly suggestive of this diagnosis
(Fig. 19). Some argue that biopsy should be avoided owing to
the risks of bleeding and scarring when classic imaging features
are present,68 and biopsy should be reserved in atypical cases.
With the use of spectral Doppler ultrasound, the nodal
vascular resistance can be quantified in terms of a resistive
index and a pulsatility index. The limits of vascular resistance
Figure 15 Abnormal lymph node from papillary thyroid carcinoma
metastasis. Color Doppler image demonstrates abnormal disorganized
internal (arrowheads) and peripheral (arrow) flow. Abnormal cystic
change is present (C). (Color version of the figure is available online.)
244
Figure 16 Abnormal lymph node from papillary thyroid carcinoma
metastasis. Power Doppler image demonstrates abnormal, increased
hilar (arrowheads) and peripheral (arrow) flow. Abnormal cystic
change is present (short arrow). (Color version of the figure is available
online.)
for normal vs malignant lymph nodes remain controversial,
and conflicting reports have been published.69 For example,
some studies show increased vascular resistance in meta-
static nodes compared with normal or reactive nodes,
whereas others report the opposite. In addition, different
cutoff values of resistive index and pulsatility index have
been published in differentiating metastatic and reactive
nodes.70,71 In view of the inconsistency among various
reports and the technical difficulties involved in obtaining
suitable or repeatable values, the role of intranodal vascular
resistance in routine clinical practice is felt to be limited.
Contrast-Enhanced Ultrasound:
Microbubbles
Contrast-enhanced ultrasound (CEUS) is a method that uses
traditional sonography and the application of contrast agents
Figure 17 Abnormal lymph node with biopsy-proven reactive changes
only. Color Doppler image demonstrates mildly increased hilar flow
extending to node periphery (arrows). (Color version of the figure is
available online.)
C.P. Giacomini et al
Figure 18 Abnormal lymph node from papillary thyroid carcinoma
metastasis. Color Doppler image demonstrates abnormal disorganized
internal (arrowheads) and peripheral (arrows) flow. (Color version of
the figure is available online.)
that enhance the quality of images. Microbubble contrast
agents are emerging as a promising medical imaging modality.
These micrometer-sized, gas-filled bubbles are stabilized by
thin encapsulating shells and administered intravenously to the
systemic circulation. They provide enhanced resolution and
increased contrast of sonographic images because of the high
degree of echogenicity difference between the gas in the
microbubbles and the surrounding soft tissue in the body.
CEUS has been shown to be effective in differentiating
benign and malignant lymph nodes. In a study involving 32
patients presenting with carcinoma of the oral cavity, the
geometric dimension, margin, location, and vascular
Figure 19 Abnormal lymph node mimic owing to a carotid body
paraganglioma. Color Doppler image demonstrates a vascular mass
(arrowheads) with a heterogenous echotexture located at the carotid
bifurcation; mass is “splaying” the external carotid artery (short arrow)
and the internal carotid artery (long arrow). (Color version of the
figure is available online.)
Ultrasonographic evaluation of malignant and normal cervical lymph nodes
architecture of 94 enlarged cervical lymph nodes were
examined using unenhanced and contrast-enhanced color
Doppler sonography. Contrast enhancement correctly identi-
fied 86% of histologically confirmed malignant nodes com-
pared with 79% identification without enhancement.52 In
another study, 56 lymph nodes from 45 patients were
examined using conventional ultrasonographic techniques or
CEUS with an injection of sulfur hexafluoride microbubbles to
determine malignant involvement. Lymph nodes examined
included axillary, inguinal, and cervical nodes from patients
with suspected metastasis or de novo lymphadenopathy of
uncertain nature. The specificity (76%), sensitivity (80%), and
accuracy (78%) of differentiating between benign and malig-
nant lymph nodes increased significantly (93%, 92%, and
92.8%, respectively) with the addition of CEUS.72 The
improved diagnostic accuracy and value of diagnostic infor-
mation from CEUS have been demonstrated in other studies,
including enhanced detection of sentinel lymph nodes in
breast cancer.73,74
The concept of targeted CEUS is yet another promising
technology for nodal evaluation. This technique involves the
injection of microbubbles conjugated with ligands that target
specific molecular markers expressed by an area of interest.
This method has shown promise in visualizing malignancies in
mouse studies and is currently in use in various preclinical
trials.75
Ultrasound Elastography (UE)
Malignancies are generally stiffer than surrounding tissue, and
this property can be assessed by a relatively novel approach
known as UE. In particular, specialized transducers apply
pulses of acoustic energy to assess tissue stiffness based on its
degree of deformation. An image known as an elastogram is
generated (eg stiff regions are displayed in blue and softer areas
in red). In addition, an index termed the strain ratio can be
calculated to objectively quantify the degree of tissue stiffness.
Although this technique is not used routinely in clinical
practice, it has demonstrated utility in diagnosis of thyroid,
breast, and prostate cancers as well as other disease states such
as liver fibrosis.76-79 In addition, several studies have
attempted to use UE to discriminate benign from malignant
cervical lymph nodes.80-83 Lyshchik et al. reported that a
strain ratio 4 1.5 corresponded to 98% specificity and 85%
sensitivity in metastatic lymph node classification, whereas
Tan et al. demonstrated 92.5% sensitivity and 53.4% specific-
ity.80,81 Both of these studies found that UE performed
significantly better than gray-scale ultrasound for malignant
lymph node determination. However, UE has certain limi-
tations. For example, motion of surrounding tissues and
vessels during compression scanning can create artifacts, and
when analyzing large lymph nodes, surrounding tissue may
need to be left out, which may affect strain measurements.81
Conclusions
Ultrasonography is an imaging modality that is favored
worldwide because of its precision, portability, practicality,
245
and cost. Here, we have described the use of this technology
to distinguish metastatic from benign cervical lymph nodes.
This determination has implications for diagnosis, staging,
prognostication, and determining optimal treatment regimens
for cancer patients. No single sonographic feature can accu-
rately distinguish malignant from normal nodes. Rather, one
should assess a combination of features including lymph node
size, shape, distribution, echogenicity, intranodal necrosis,
calcifications, and the pattern of vascularity in combination
with the patient's clinical history when evaluating cervical
lymphadenopathy. Emerging sonographic technologies
including microbubble contrast enhancement and elasto-
graphy would likely improve our ability to noninvasively
assess cervical lymphadenopathy.
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