15

Management of Cervical Metastasis

PETER E. ANDERSEN, MD, FACS
SCOTT SAFFOLD, MD

Head and neck cancer represents less than 5 percent

of all cancers in the United States and will be
responsible for approximately 11,800 deaths in
2001.1 However, worldwide it ranks as the sixth most
common cancer,2 thus making head and neck cancer
a major health problem. While the term head and
neck cancer refers to tumors of myriad sites of origin and histologic types, over 90 percent of these are
squamous carcinomas arising from the epithelium of
the upper aerodigestive tract (oral cavity, oropharynx, hypopharynx and larynx) and for the purposes
of this discussion the term shall refer exclusively to
these tumors.
The status of the regional lymphatics is one of
the most important prognostic indicators in patients
with head and neck cancer. Head and neck cancers
that are localized to the primary site without
regional lymph node metastasis have excellent cure
rates with either surgery or radiation therapy. The
presence of regional metastases results in cure rates
that are approximately half of those obtainable if
metastasis to the regional lymphatics is not present.
Thus the treatment of the neck has become one of
the most actively debated topics in the field of head
and neck oncology. Treatment of the neck in patients
with clinical evidence of nodal metastasis has traditionally been surgical. In recent decades this has
been extended to include a combination of surgery
and radiation therapy. The role of chemotherapy in
the management of neck disease remains controversial and is currently being actively investigated.
Butlin3 was the first surgeon to systematically
address the cervical lymph nodes by excising the

274

nodal tissue of the submandibular triangle in continuity with the primary lesion in patients with cancer
of the tongue. This did not remove all of the lymphatic tissue in the neck that was at risk for metastasis and it was not until the radical neck dissection
(RND) described by Crile4 and later popularized by
Martin5,6 that systematic removal of all of the lymphatic tissue in the lateral neck became routine.
Radical neck dissection, however, is cosmetically
deforming and produces a characteristic shoulder
disability that has been termed the shoulder syndrome.7 In an effort to lessen the morbidity of classic RND, various modifications have been proposed
that preserve non-lymphatic structures that are normally sacrificed during this procedure but still
remove all of the nodal tissue excised in RND. These
modifications in general include preservation of the
spinal accessory nerve (SAN) and can also involve
preservation of the internal jugular vein (IJV) and/or
the sternocleidomastoid muscle (SCM). More
recently, further modifications of neck dissection
have been proposed which preserve all of the nonlymphatic structures removed in then-RND but do
not remove all of the lymphatic tissue on the
involved side of the neck. These operations, which
have been termed selective neck dissections, are
based on observations that cancers of the head and
neck tend to metastasize in predictable patterns
based on the location of the primary tumor. Whether
these modifications avoid all of the morbidity of
RND is ambiguous, however there is evidence that
shoulder function is retained when the spiral accessory nerve is preserved.8,9,10

Management of Cervical Metastasis

Anatomy of Cervical Lymphatics

The lymphatics of the head and neck are a rich plexus
of vessels whose anatomy was described by Rouviere
and others.11,12 There are many methods of clinically
describing locations of lymph nodes; however the
method that is in widest use and most reproducible is
the system described by the Head and Neck Service
at Memorial Sloan-Kettering Cancer Center. This
system divides the neck into 5 nodal groups or levels,
which are described in Figure 151.13
Classification of Neck Dissections
With the development of the many modifications of
the classic RND there has been a proliferation of
terms to describe these various procedures. This has
resulted in a nomenclature that is non-uniform and
confusing. To facilitate communication and to ensure
standardization, the American Academy of Otolaryngology, Head and Neck Surgery has proposed a classification scheme for neck dissection.13 In this

275

scheme, RND, which is defined as the removal of

nodal groups I to V with the SCM, IJV, and SAN, is
considered to be the standard basic neck dissection,
while all other procedures are considered to be modifications of RND. Modified radical neck dissection
(MRND) consists of preservation of one or more of
the non-lymphatic structures normally removed in
RND. Selective neck dissection consists of removal
of one or more regional lymph node groups with
preservation of the SAN, SCM, and IJV. This nomenclature is described in greater detail in Table 151
and Figure 152. The typical postoperative appearance of patients after various neck dissections are
shown in Figure 153, Figure 154, Figure 155, and
Figure 156. The routine use of a standardized system will greatly reduce the confusing nomenclature
currently used in describing neck dissections.
Patterns of Lymphatic Flow
The entire concept of selective or limited neck dissection is based on the clinical observation that

Figure 151. System for describing location of cervical lymphatic metastases. IJV = internal jugular vein; SAN = spinal accessory nerve; SCM = sternocleidomastoid.

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CANCER OF THE HEAD AND NECK

Table 151. Classification of Neck Dissections

Nodal Levels
Dissected

Structures
Preserved

Radical neck dissection (RND)

Type I modified radical
neck dissection (MRND I)
Type II modified radical
neck dissection (MRND II)
Type III modified radical
neck dissection (MRND III)

IV
IV

None
SAN

IV

Supraomohyoid neck
dissection (SOHND)

IIII

Lateral (jugular) neck

dissection (LND)

IIIV

Anterolateral neck
dissection (ALND)

IIV

Posterolateral neck
dissection (PLND)

IIV

SAN
SCM
SCM
IJV
SAN
SCM
IJV
SAN
SCM
IJV
SAN
SCM
IJV
SAN
SCM
IJV
SAN

Type of Neck Dissection

IV

SAN = spinal accessory nerve; SCM = sternocleidomastoid; IJV = internal

jugular vein.

Figure 152.

squamous cell carcinomas of the upper aerodigestive tract metastasize to the cervical lymph nodes in
a predictable pattern. Strong experimental evidence
of this concepts validity is provided by Fisch,14 who
performed lymphography using oil-based contrast
media injected into postauricular lymphatics.
Twenty-four hours after injection the patients underwent complete neck dissection and filling of the
lymph nodes was verified in almost every one of his
100 cases. The flow of the contrast material was
observed with radiography. From observations
obtained from 8 cases that were free of lymph node
metastases, Fisch was able to document the normal
pattern of flow in the cervical lymphatics.
After injection in the postauricular lymphatics,
contrast first flowed into a group of nodes just
below and behind the angle of the mandible. These
nodes were called the junctional nodes by Fisch
and probably represent either high level V or high
level II nodes. From the junctional nodes, contrast

Cervical lymph node groups removed in various types of neck dissection.

Management of Cervical Metastasis

277

Figure 153. Cosmetic and functional deformity resulting from radical neck dissection. A, Anterior view demonstrating anterior and inferior
displacement of shoulder and trapezius muscle (arrow). B, Anterior view demonstrating decreased shoulder abduction. C and D, Posterior
view demonstrating winging of scapula. (Photos courtesy of James I. Cohen, MD, PhD.)

flowed first into both the lymphatics along the

spinal accessory nerve and the internal jugular
vein. Contrast in the lymphatics along the spinal
accessory nerve then flowed into the transverse
cervical chain, and through this medially into the
low jugular chain. Of particular interest is the
observation that contrast contained within the lymphatics of the spinal accessory chain could reach
the jugular chain lymphatics by connecting vessels
which occurred at many places along the spinal
accessory chain. Contrast contained within the
jugular chain could not, however, reach the spinal
accessory chain by retrograde flow along the same
route. Flow to contralateral lymphatics or retrograde lymphatic flow was not observed. These patterns are shown in Figure 157. A critical question

left unanswered by the studies of Fisch is the precise location of the junctional nodes he described.
If these nodes are commonly involved by head and
neck cancer metastasis, it is possible virtually anywhere in the neck, and the concept of selective
neck dissection would seem to be unsound. However, as will be shown in the section on patterns of
nodal metastasis from squamous carcinomas of the
upper aerodigestive tract, these junctional nodes
are probably uninvolved in most cases of head and
neck cancer since metastasis to level V is uncommon, except in nasopharyngeal carcinoma.

Figure 154. Postoperative appearance of neck after modified

radical neck dissection, type I.

Figure 155. Postoperative appearance of neck after supraomohyoid neck dissection.

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CANCER OF THE HEAD AND NECK

Figure 156. Postoperative appearance of neck after bilateral

modified radical neck dissections, type III.

Incidence and Pattern of Nodal Metastasis

The rational use of modifications of RND, especially selective neck dissection, is based upon work
describing the patterns of lymphatic metastasis.
These studies have shown that patterns of metastasis
can be predicted based upon knowledge of the primary tumor location. Without such validation the
concept of selective neck dissection would be
invalid, since by definition nodal tissue at risk for
metastasis would be left behind in the neck.
Lindberg published the location of nodal metastases in patients with squamous carcinoma of the
upper aerodigestive tract as determined by clinical
examination15 in 1972. This review consisted of
2,044 previously untreated patients with squamous
carcinoma of the head and neck. The presence of
nodal metastasis and their location was assessed
and correlated with the location and stage of the
primary site. Primary sites were divided into oral
tongue, floor of mouth, retromolar trigone/anterior
faucial pillar, soft palate, tonsillar fossa, base of
tongue, oropharyngeal walls, supraglottic larynx,
hypopharynx and nasopharynx. Fifty-seven percent

of patients presented with clinical evidence of

metastasis in the cervical nodes. Lindberg showed
that for lesions of the oral tongue, floor of mouth,
retromolar trigone/anterior faucial arch and soft
palate, the incidence of cervical nodal metastasis
increased with the size of the primary tumor. However, the incidence of nodal metastasis did not correlate with the size of the primary in tumors of the
tonsillar fossa, base of tongue, supraglottic larynx,
and hypopharynx.
Lindberg demonstrated that squamous cell carcinomas of the upper aerodigestive tract tend to
metastasize to the neck in a predictable pattern. By
far the most common site of metastasis by all
tumors is to the ipsilateral level II nodes. Tumors
that lie within the oral cavity anterior to the circumvallate papillae have a propensity to metastasize to
levels I through III, with levels IV and V seldom
involved. Tumors of the oropharynx have a low
propensity to metastasize to level I; metastasis is
most common to level II with decreasing incidence
of metastasis in levels III and IV. These tumors have
a higher rate of metastases to level V than oral cavity tumors but the rate is still low. Tumors of the
supraglottic larynx and hypopharynx rarely metastasize to level I, again metastases were most com-

Figure 157. Pattern of lymphatic flow as demonstrated by Fisch.

Data from Fisch UP, et al. Cervical lymphatic system as visualized by
lymphography. Ann Otol Rhinol Laryngol 1964;73:869-82.

Management of Cervical Metastasis

mon to level II with a decreasing incidence in levels III and IV and metastases to level V were infrequent. Tumors of the nasopharynx are unique
among squamous cell carcinomas of the upper
aerodigestive tract in that they metastasize widely
to levels II through V. Contralateral metastases were
uncommon in cancers of the floor of mouth, oral
tongue, hypopharynx, and retromolar trigone/anterior faucial arch. In contrast, tumors of the
nasopharnyx, base of tongue, oropharyngeal walls,
soft palate, supraglottic larynx, and tonsil have substantial rates of contralateral metastases.
Lindbergs data clearly showed that in cases of
squamous cell carcinoma of the upper aerodigestive
tract, with the exception of nasopharyngeal carcinoma, nodal metastasis occurs in a predictable pattern and it may, in certain instances, be sound to
exclude dissection of the level V lymph nodes. However, this study provides only information on clinically positive nodal metastasisit provides no information on the incidence and location of occult nodal
metastasis. Such information on microscopic metastasis can only be obtained from a surgical specimen.
Byers and colleagues published one such study16 in
1988. They examined the specimens of 428 patients
undergoing 648 modified neck dissections and correlated the location of the pathologically positive
lymph nodes with the primary site. The majority of
these neck dissections were selective neck dissections and therefore not all of the lymph node levels at
risk were examined in each patient. This study essentially confirms the clinical data of Lindberg,15 that
lesions anterior to the circumvallate papillae are most
likely to metastasize to lymph nodes levels I through
III and lesions within the hypopharynx and larynx to
levels II through IV. It must be pointed out, however,
that the majority of these dissections were less than
comprehensive and therefore the low incidence of
metastasis to certain nodal levels may simply reflect
the lack of sampling of those levels.
In order to fully assess all the lymph node levels
at risk for a particular primary site, surgical specimens should include all lymph node levels (comprehensive neck dissection). Just such information is
provided in a series of studies by Shah and colleagues,17,18,19 which involved 1,081 previously
untreated patients who underwent 1,119 classic

279

RNDs for squamous carcinoma of the upper aerodigestive tract. The operations consisted of 343 elective RND in the clinically N0 setting and 776 therapeutic RND in the clinically N+ setting.
The results of Shahs studies are shown in Figure
158. Each lymph node level shows the percentage
of patients with pathologically N+ neck dissections
who had metastasis at that level. In patients with primary tumors of the oral cavity undergoing therapeutic RND, the majority of metastatic nodes were
located in levels I to III; level IV was involved in 20
percent of specimens and level V in only 4 percent.
In those with primary oropharyngeal tumors, the
majority of metastases were located in levels II to IV;
levels I and V were involved in 17 percent and 11
percent of the specimens respectively. Therapeutic
neck dissection in hypopharyngeal tumors showed
that the majority of metastases were located in levels
II to IV, while levels I and V were involved in 10 percent and 11 percent of the specimens respectively.
Primary tumors of the larynx metastasized to levels
II through IV with levels I and V being involved in 8
percent and 5 percent of the specimens respectively.
In the setting of elective RND in patients with
primary tumors of the oral cavity, the majority of
metastases were located in levels I to III; levels IV
and V were involved in 9 percent and 2 percent of
the specimens respectively. In patients with primary
tumors located in the oropharynx, the majority of
metastases were located in levels II to IV; levels I
and V were involved in 7 percent of the specimens
each. Patients with tumors of the hypopharynx
undergoing elective RND had the majority of metastases in levels II to IV, while levels I and V were not
involved in any of the specimens. Primary tumors of
the larynx metastasized primarily to levels II
through IV, while levels I and V were involved in 14
percent and 7 percent of the specimens respectively.
The question of metastasis to level V was
addressed by another study from Memorial Hospital
by Davidson and colleagues.20 They examined the
specimens of 1,123 patients undergoing 1,277 RNDs
and found metastases to level V in only 3 percent of
patients. Level V metastases were highest in patients
with hypopharyngeal and oropharyngeal primary
sites (7% and 6% respectively). Only 3 of the 40
patients with level V metastases had these in the face

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CANCER OF THE HEAD AND NECK

Figure 158. Incidence of metastasis to lymph node levels by primary site in N+ and N0 patients. (Data from Shah
JP, et al. The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer
1990;66:10913, and Shah JP. Patterns of cervical lymph node metastasis from squamous carcinomas of the upper
aerodigestive tract. Am J Surg 1990;160:4059.)

of a clinical N0 stage. They concluded that the incidence of metastases to level V was small in general,
and extremely unlikely in the clinically N0 patient.
Evaluation of the Neck
Pre-surgical staging of the neck has become more
complex over the years. Clinical assessment of the
neck by palpation, while providing critical information, is inadequate in its sensitivity for detecting
metastatic disease to the cervical nodes. Error rates
as high as 40 percent have been reported when physical examination alone is used to evaluate the neck.21
Patient factors such as a short, obese neck, as well as
prior irradiation play a role in decreasing the accuracy of this technique. Clearly, radiologic assessment of the neck adds to the sensitivity and specificity of preoperative neck evaluation.

Computerized tomography (CT) and magnetic resonance imaging (MRI) have become the workhorses
of imaging modalities in head and neck squamous cell
carcinoma (HNSCC). Size criteria are frequently used
as indicators of metastatic involvement. Other features
such as central necrosis or ring-enhancement aid in
specificity but are relatively infrequent findings. Generally, a subdigastric node measuring > 15 mm, a submandibular node > 12 mm, and other nodes > 10 mm
are suspicious for involvement. Using criteria such as
these, the accuracy of detecting neck disease
approaches 90 percent.22,23 Size, however, is certainly
not pathognomonic for cancerous involvement of
lymph nodes. Even in the patient with an identified
squamous cell carcinoma of the upper aerodigestive
tract, a myriad of alternative causes of enlarged lymph
nodes exist. Further, microscopic foci of disease may
exist in nodes of normal size. As CT or MRI is often

Management of Cervical Metastasis

employed to evaluate the primary lesion, inclusion of

the neck in the area of study incurs nominal additional
expense and no morbidity. Although CT and MRI provide excellent anatomic detail and are the current
modalities of choice, they provide little information on
the biology of the lymph node.
Due to its non-invasiveness and affordability,
ultrasound (US) has been investigated as a potential
tool in evaluating neck disease. Factors such as size,
irregular margins, and echo characteristics of lymph
nodes have been shown to have predictive value in
assessing involved nodes. The overall sensitivity of
this approach, however, is limited due to the operatordependent nature of ultrasound.24 Some authors have
proposed ultrasound in combination with ultrasoundguided fine needle aspiration as an approach to diagnosis. Takes and colleagues25 examined, with ultrasonography, 64 necks staged N0 based on physical
examination. Those with nodes greater than 5 mm in
size underwent ultrasound-guided needle biopsy.
Results were further verified with histopathologic
examination and the findings compared with CT of
the neck for detection of involved nodes. They found
a 48 percent sensitivity, 100 percent specificity, and
79 percent accuracy for ultrasound versus 54, 92, and
77 percent respectively for CT. These results demonstrate that, in experienced hands, ultrasound can be a
useful tool. Its widespread application, however, is
limited by the technical expertise required for accurate interpretation.
Positron emission tomography (PET) has been
employed to assess metabolic changes in a variety of
tissues including those of the head and neck. PET
localizes regions of increased glucose metabolism by
using the radionuclide 2-[18F]-fluoro-2-deoxy-Dglucose. Hanasono26 and colleagues demonstrated a
potential role of this technique in evaluating unknown
primaries, distant metastases, and for tumor surveillance. They suggest that it may be effective as an adjuvant to CT and MRI in selected cases. Another study,
however, found sensitivity of 78 percent and specificity of 100 percent when PET was used to evaluate
patients clinically staged N0.27 Although their numbers were small, the results compare favorably to other
imaging modalities. Another interesting approach
attempts to combine the sensitivity of PET with the
anatomic detail of CT and MRI. Wong and col-

281

leagues28 used computer-combined imaging to evaluate primary lesions in the head and neck. They found
enhanced detail and accuracy as compared to clinical
exam or single modality imaging alone. Whether this
approach can be extended to evaluation of nodal disease is unclear, and cost-benefit issues may preclude
its widespread utilization.
Selection of Surgical Therapy
The proliferation of different types of modified neck
dissection has the potential to lead to confusion
regarding what type of neck dissection is appropriate for a particular clinical situation. This is complicated by the lack of data from randomized studies
comparing the effectiveness of the variations of neck
dissection. The goal of any neck dissection, however, should be: to remove all clinically obvious
metastatic disease, to sample the lymph node levels
at highest risk for metastasis in order to detect the
presence of occult metastasis, and to perform this in
such a way as to minimize the morbidity of the procedure without compromising the 2 previous goals.
With this in mind, 2 dominant clinical scenarios
emerge: the clinically N0 and the clinically N+ neck.
A general algorithm is presented in Figure 159.
In the clinically N0 setting, the first decision to be
made is whether to perform a neck dissection at all or
to simply observe the neck for the development of
metastasis. There is no firm data to suggest that elective neck dissection improves survival; in fact the
only randomized trial addressing this question failed
to find any survival advantage to elective neck dissection.29 However, some authors have reported
improved survival in patients treated during a time
period when elective neck dissection is frequently
performed as compared to earlier periods where
observation of the neck was more common.30 It
seems likely, however, that if elective neck treatment
is to improve survival, that it will be of most benefit
to those patients with a high risk of occult metastasisthus some authors have recommended elective
neck treatment in patients with a greater than 20 to
25 percent risk of occult metastasis.31 In addition it is
often assumed that if the neck is observed closely,
any metastatic disease that occurs will be detected at
an early stage. This assumption is, in fact, erroneous,

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CANCER OF THE HEAD AND NECK

as Andersen and colleagues32 reported on a series of

47 patients who recurred in the neck during observation. In these patients, 60 percent were pathologically
N2 or greater and extracapsular spread was present in
half when the failure was detected.
Due to the high rates of occult metastasis in
patients with primary tumors located in the hypopharynx, oropharynx, and supraglottic larynx, elective
treatment of the neck (with neck dissection if surgical
resection of the primary tumor is planned, or with
radiotherapy if the primary tumor is to be irradiated
for cure) is indicated.15 Occult metastasis from tumors
of the oral cavity (specifically tongue and floor of
mouth) has been correlated with tumor stage15 and
tumor thickness33 (Figure 1510). Therefore, elective
treatment of the neck is indicated in patients with
tumor greater than 2 mm thick or in T3 or T4 primaries. Other indications for elective neck dissection
include the need to enter the neck, either to resect the

Figure 159.

primary tumor (eg, mandibulotomy, lateral pharyngotomy, supraglottic laryngectomy), or for reconstruction (eg, free tissue transfer). In these situations it is
convenient to electively dissect the neck. Another factor, which may lead the surgeon to electively dissect
the neck, is the case of the patient is believed unlikely
to return for the close follow-up that is necessary if
observation of the neck is to be employed.
When deciding the type of neck dissection to perform in the elective setting, 2 factors must be considered: the likelihood of occult metastasis, and the
most likely location of the metastases based on the
location of the primary tumor. Since in the clinically
N0 patient the majority of neck dissections are likely
to be negative for occult metastasis,21,34,35 the neck
dissection chosen must be the least morbid possible.
Selective neck dissections are ideally suited for the
elective setting. On examining Figure 158, the operations that remove the nodal levels most at risk are

General algorithm for selection of neck dissection.

Management of Cervical Metastasis

283

Figure 1510. Risk of occult nodal metastasis with increasing thickness of oral cavity cancers
(tongue and floor of mouth). Data from Spiro RH, et al. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth.33

obvious. Primary tumors in the oral cavity should

undergo supraomohyoid neck dissection (SOHND);
oropharyngeal tumors would best be treated with lateral neck dissection (LND). However, since surgical
resection of the primary often involves an approach
through level I, anterolateral neck dissection
(ALND) may be a better choice, while tumors
located in the hypopharynx or larynx should undergo
LND. If the surgeon desires only one operation that
is appropriate in all situations (for proficiency or for
instruction of residents) then ALND is an excellent
operation for the elective treatment of the neck in
patients with head and neck cancer.
In the clinically N+ patient, the existence of lymphatic metastasis is established and therefore it is
acceptable to perform a neck dissection with a greater
potential for morbidity. It has been shown that preservation of the spinal accessory nerve in the N+ neck is
not associated with increased risk of recurrence in the
neck as long as the nerve is not involved by the
tumor,36 therefore even in this setting it is possible to
potentially ameliorate some of the morbidity of RND.
As Figure 158 demonstrates, the incidence of metastasis at all levels in the neck increases in the setting of
clinically obvious neck metastasis. Therefore in the
N+ patient, an acceptable and safe neck dissection to
perform is a comprehensive neck dissection that
spares the spinal accessory nerve if it is not involved
with tumor (MRND I).
The use of selective neck dissections in the N+
patient is controversial. While Shahs study17 shows
that the rate of metastasis to all levels increases in the
N+ neck, it also shows that the pattern of metastasis

still follows the general pattern seen in the N0 neck.

There is in fact some evidence that selective neck dissection in the N+ neck yields control rates similar to
more comprehensive neck dissections.37,38 The efficacy of selective neck dissection in the N+ neck is still
a matter of debate; however, its use in low-stage neck
disease such as the N1 neck is not unreasonable. The
type of selective neck dissection employed should be
based on the patterns of nodal metastasis shown in
Figure 158. Given the low risk of metastasis to level
V reported by Davidson20 and the increased risk of
involvement of level IV in the N+ neck, the ALND
might be the selective neck dissection of choice if one
is to perform this type of operation in the N+ setting.
Radiation Therapy
The ability of radiotherapy to improve outcomes in
squamous cell carcinoma of the head and neck is well
demonstrated. Its efficacy in early T1 and T2 lesions
of the upper aerodigestive tract approaches that of
surgical management. Treatment of disease metastatic
to the neck with radiation has also shown benefit.
Studies have shown that, in the N0 neck, radiotherapy
is as effective as elective neck dissection (END) in
reducing locoregional recurrence.39 Surgery combined with radiation has been shown to reduce local
failure rates to 18 percent in N1 necks.40 The timing
of neck irradiation, however, has been a subject of
debate. Preoperative radiation had been favored in the
past due to the theoretical advantage of treating while
the vascular supply of the tumor was undisturbed.
Preoperative therapy may also help to reduce bulky

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CANCER OF THE HEAD AND NECK

disease and thus facilitate surgical extirpation. However, the increased incidence of radiation-related surgical complications following high-dose preoperative
radiotherapy has led to the currently accepted practice
of administering radiotherapy in the postoperative
period. Typically, surgeons prefer postoperative radiation to avoid the wound healing difficulties encountered in operating on previously irradiated tissue. Further, Leemans et al has shown that histopathologic
evaluation of the neck specimen can be used to select
those patients who are more likely to benefit from
combined therapy.41 Patients with neck disease found
to be metastatic to multiple nodes or extending
beyond the lymph node capsule have been shown to
have better locoregional control and survival with the
addition of postoperative radiotherapy.42 Delaying
radiation allows the surgeon to select patients with
these risk factors for further treatment. In fact, an
RTOG study with long-term follow-up showed that
patients treated with postoperative radiation had
lower locoregional failure rates than those treated preoperatively. Due to a higher incidence of distant disease, however, they demonstrated no difference in
survivals.43
More recently, neoadjuvant chemotherapy has
shown some promise in management of advanced
head and neck squamous cell carcinoma. Various
organ preservation protocols have been proposed in
which combined chemotherapy and radiation have
been used as initial therapy of the primary lesion and
neck metastases. These approaches reserve surgery
for salvage in patients failing to develop a complete
response. Their proponents suggest that for partial
responders, following neoadjuvant multi-modality
therapy, an oncologically sound surgical procedure
can be performed that has a greater chance of preserving speech or swallowing. This potential benefit
must be weighed against the increased risk of surgical
complications that has been associated with preoperative therapy. Chemoradiotherapy protocols designed
at preserving function at the primary site often fail to
eradicate disease in the neck. This necessitates posttreatment surgical management of the neck even for
those achieving a dramatic response at the primary
site. Lavertu44 and colleagues demonstrated a 46 percent complication rate in patients treated with neoadjuvant chemotherapy. Only 12 percent of these, how-

ever, were major complications, and they found no

increased risk in those patients undergoing chemoradiotherapy. Other studies have shown similarly low
wound-related complication rates; this is consistent
with historically reported rates of neck wound complications following neck dissection alone.45
Controversies
A key controversy in management of the neck in head
and neck squamous cell carcinoma relates to which
and how much therapy is appropriate. In management
of the N0 neck, it is generally accepted that a metastatic risk in excess of 20 percent warrants elective therapy. Although some advocates of a watchful waiting
policy exist, current data supports liberal use of prophylactic therapy. Though little information in regard
to impact on survival exists, a study from Memorial
Sloan-Kettering Cancer Center demonstrated that,
despite close follow-up, patients who were observed
rather than electively treated presented with advanced
neck disease. Sixty percent of patients who recurred
in the neck presented with N2 or greater disease and
77 percent had evidence of extracapsular spread.32
Such patients required more extensive therapy than if
they had undergone elective treatment.
What therapy is indicated for treatment of the N0
neck is an issue of some debate. Advocates of elective radiotherapy suggest that its ability to control
microscopic foci of disease render it comparable to
neck dissection in control of neck disease. Its sequelae, including often-debilitating xerostomia, however, make it a more morbid treatment option, as
compared to selective neck dissection. Certainly,
selective lateral or supraomohyoid neck dissection
can be performed quickly, safely and with minimal
postoperative morbidity. The oncologic efficacy of
selective neck dissection has been discussed earlier,
and those factors make it the treatment of choice for
the clinically uninvolved neck, unless radiotherapy is
to be employed for the treatment of the primary site.
Management of the N1 neck is more controversial. Conventionally, radical neck dissection (RND)
has been the treatment of choice for patients presenting with disease in the neck. Modifications of
RND, including those sparing the eleventh nerve, in
the past were criticized for their violation of tradi-

Management of Cervical Metastasis

tional surgical oncologic principles. An en bloc

resection is not possible and lymphatic channels
must be cut to preserve such structures. It is now
accepted that tumor metastasizes in an embolic fashion and therefore, effective treatment can still be
rendered. This has been borne out by the work of
Bocca.46 An extensive review of functional neck dissection, preserving the eleventh nerve, sternocleidomastoid muscle, and internal jugular vein routinely
showed a recurrence rate comparable to RND even
in N1 disease in 171 patients. So long as nodes are
not adherent to the structures of concern and a connective tissue plane of dissection can be established,
it may be possible to preserve these structures. That
the important structures traversing the neck are
maintained within their own aponeurotic sheaths is
validated by the work of Byers.47 In an extensive
review of functional and selective neck dissection,
he found a 4.7 percent local recurrence rate for
patients with pathologically positive jugulodigastric
nodes despite preservation of the eleventh nerve, so
long as postoperative radiotherapy was used.
As it has become more accepted to preserve
important structures in the neck, the concept of
removing only at-risk nodal groups even in the N+
neck has been considered. Spiro and colleagues48
reviewed the Memorial Sloan-Kettering Cancer Center experience with supraomohyoid neck dissection
and found that in 31 patients undergoing therapeutic
dissection and radiotherapy, there was a 6 percent
local failure rate. Traynor and colleagues49 examined
29 patients with N1-N2C neck disease treated with
various forms of selective neck dissection (SND) and
found local recurrence rates of only 4 percent. Their
group emphasized the importance of careful selection
of patients. Shah demonstrated that, even in patients
with clinically evident neck disease, of 776 pathologically evaluated RNDs only 3.7 percent had involvement of the level V nodes.36 This data, in addition to
early studies of patterns of lymphatic spread of head
and neck squamous cell carcinoma, have led to
broader application of selective neck dissection
(SND) in management of the N1 neck, particularly if
postoperative radiotherapy is utilized. Those with
massive adenopathy, fixed nodes or gross extracapsular spread should be treated with classic radical neck
dissection. They suggest, however, that the type of

285

neck dissection can be individualized: nodal groups

resected as well as structures of the neck to be preserved are based on known patterns of lymphatic
spread as well as findings at the time of surgery.
FUTURE DIRECTIONS
As with many neoplastic diseases, the future of head
and neck squamous cell carcinoma management
likely will include emerging treatments such as
immunotherapy. Novel approaches such as gene
therapy, T cell manipulation, and cytokine therapy
have been employed in experimental treatment of
other solid tumors with limited success. While the
application of such strategies is based on a limited
understanding of tumor immunology at the primary
site, even less is known about the immunoregulatory
role of the draining lymphatics. Current treatment
protocols focus on the goal of complete extirpation
of the tumor. As Collins points out, however,
HNSCC is more likely a systemic disease with a
predilection for sites in the head and neck.50 The role
of lymph nodes in this process is unclear. Extrapolating conventional immunology to tumor biology,
tumor antigens are transported from the primary site
either by antigen-presenting cells (macrophages,
dendritic cells, B cells) or by tumor cells themselves
to the regional lymph node where an immunologic
response is initiated. The propagation of this
response is systemic rather than local. It follows,
then, that lymph nodes are biologic rather than
mechanical barriers to tumor advancement. Several
investigators have found evidence of increased antitumor activity in lymph nodes draining HNSCC.
Vetto and colleagues51 found higher expression of
the T cell activation marker OX40 on cells from
draining lymph nodes than in the peripheral blood.
Other studies have also shown that the draining
lymph nodes have been exposed to tumor antigens.52,53 Clearly, through tolerance or immunosuppression, this systemic immune response is ineffective in controlling disease. One study demonstrated
a tumor-induced inhibitory effect on lymph node
cells that was more pronounced in first echelon
nodes than in nodes outside the primary drainage
basin.54 As our understanding of the immunologic
interactions between the tumor and the host pro-

286

CANCER OF THE HEAD AND NECK

gresses, therapy guided at manipulating and enhancing the immune response may be developed. It is
possible that the key to understanding this relationship lies within the draining lymph nodes.
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