2077

The Accuracy of Head and Neck Carcinoma Sentinel

Lymph Node Biopsy in the Clinically N0 Neck
Taimur Shoaib1
David S. Soutar, Ch.M.1
D. Gordon MacDonald2
Ivan G. Camilleri1
David J. Dunaway1
Henry W. Gray3
Graham M. McCurrach, Ph.D.4
Rodney G. Bessent, D.Phil.4
Torquil I. F. MacLeod, M.R.C.Path.2
A. Gerard Robertson5
1

Plastic Surgery Unit, Canniesburn Hospital,

Bearsden, Glasgow, United Kingdom. Hospital and
School, Glasgow, United Kingdom.

Oral Pathology Unit, Glasgow Dental Hospital and

School, Glasgow, United Kingdom.

Department of Nuclear Medicine, Royal Infirmary,

Glasgow, United Kingdom.

Department of Clinical Physics and Nuclear Medicine, Royal Infirmary, Glasgow, United Kingdom.

Beatson Oncology Centre, Western Infirmary,

Glasgow, United Kingdom.

BACKGROUND. Sentinel lymph node (SLN) biopsy originally was described as a

means of identifying lymph node metastases in malignant melanoma and breast
carcinoma. The use of SLN biopsy in patients with oral and oropharyngeal squamous cell carcinoma and clinically N0 necks was investigated to determine
whether the pathology of the SLN reflected that of the neck.
METHODS. Patients undergoing elective neck dissections for head and neck squamous cell carcinoma accessible to injection were enrolled into our study. Sentinel
lymph node biopsy was performed after blue dye and radiocolloid injection.
Preoperative lymphoscintigraphy and the perioperative use of a gamma probe
identified radioactive SLNs; visualization of blue stained lymphatics identified blue
SLNs. A neck dissection completed the surgical procedure, and the pathology of
the SLN was compared with that of the remaining neck dissection.
RESULTS. Sentinel lymph node biopsy was performed on 40 cases with clinically N0
necks. Twenty were pathologically clear of tumor and 20 contained subclinical
metastases. SLNs were found in 17 necks with pathologic disease and contained
metastases in 16. The sentinel lymph node was the only lymph node containing
tumor in 12 of 16.
CONCLUSIONS. The SLN, in head and neck carcinomas accessible to injection
without anesthesia, is an accurate reflector of the status of the regional lymph
nodes, when found in patients with early tumors. Sentinel lymph nodes may be
found in clinically unpredictable sites, and SLN biopsy may aid in identifying the
clinically N0 patient with early lymph node disease. If SLNs cannot be located in
the neck, an elective lymph node dissection should be considered. Cancer 2001;91:
2077 83. 2001 American Cancer Society.

KEYWORDS: head and neck neoplasms, sentinel lymph node biopsy, radical neck
dissection, lymph node excision.

Presented at the 5th International Conference on

Head and Neck Cancer, San Francisco, CA, July
29, to August 2, 2000.
Funded by Canniesburn Research Trust and the
White Lily Trust.
Address for reprints: Taimur Shoaib, Plastic Surgery Unit, Canniesburn Hospital, Switchback Road,
Bearsden, Glasgow, G61 1QL, UK; Fax: 44-1412115652; E-mail: tshoaib@canniesburn.org
Received June 20, 2000; revision received December 5, 2000; accepted January 29, 2001.
2001 American Cancer Society

he sentinel lymph node concept states that a tumor spreads via

lymphatics to the first echelon lymph node encountered in the
lymph node basin, and this spread is embolic in nature.1 If the
sentinel, or first echelon, lymph node can be identified and examined
for the presence of tumor metastases, the need to perform an elective
staging lymph node dissection is negated.2 The concept has been
applied mainly to breast carcinoma3 and malignant melanoma,4 and
in these carcinomas, sentinel lymph nodes free from tumor suggest a
regional lymph node basin free from tumor with a high degree of
accuracy.
In squamous cell carcinoma of the upper aerodigestive tract, the
investigation and treatment of the patient with a clinically N0 neck
remains controversial.5 Depending on T classification, approximately
30% of patients with head and neck squamous cell carcinoma have
subclinical metastases in the neck,6 and knowledge of lymph node

2078

CANCER June 1, 2001 / Volume 91 / Number 11

disease alters management. Currently, although computed tomography (CT) and magnetic resonance imaging (MRI) scans commonly are used to classify the
neck, their overall accuracy is limited to approximately 70%, and the only highly accurate means of
identifying lymph node disease is to perform a staging
lymph node dissection.7 For early disease, clinicians
are reluctant to perform a neck dissection, because up
to 85% of patients will not benefit, yet adopting a
wait-and-see policy to all necks will result in a high
proportion of patients subsequently developing late
stage regional failure.8
Initial results of the sentinel lymph node procedure in head and neck carcinoma have been reported
with mixed success. In a series of 16 cases, Pitman et
al. were unable to find any blue lymph nodes in patients injected with blue dye alone,9 and in a series of
five cases using radiocolloid alone, Koch et al. remained unconvinced of its role in the management of
patients with head and neck carcinoma.10 The first
case report of a successful sentinel lymph node biopsy
in head and neck carcinoma by using radiocolloid to
trace the first echelon lymph node was performed in
1996 by Alex and Krag on a patient with a supraglottic
carcinoma,11 and in 1998, Bilchik et al. reported the
use of sentinel lymph node biopsy in a variety of
neoplasms, including head and neck carcinoma.12
More recently, we described our method for successful sentinel lymph node biopsy using blue dye and
radiocolloid.13 Werner et al. have had success with the
procedure in the clinically N0 neck,14 and Alex et al.
have published their experience using radiocolloid
alone.15
This study was performed to investigate whether
the sentinel lymph node concept is applicable to patients with clinically N0 necks in oral or oropharyngeal
carcinoma and to map the spread of colloid and dye
from primary site to sentinel lymph node.

METHODS
Patients with oral or oropharyngeal carcinomas were
invited to enter our study. Tumors were amenable to
injection without the need for general anesthesia, and
only patients whose planned primary treatment included a formal elective neck dissection were enrolled.
This comprised patients considered at risk of occult
metastases. Staging of the neck was performed at the
time of clinical examination during general anesthesia
and CT or MRI were not used. Ethical approval was
obtained from the local ethics committee before commencing our study.
Although the method used for sentinel lymph
node biopsy has been described previously,13 it is
summarized briefly here. The day before surgery, pa-

tients attended the Nuclear Medicine Department,

where up to 40 MBq of Tc99m-labeled colloidal human serum albumin either Nanocoll or Albures (Nycomed Amersham, High Wycombe, Bucks, UK) in approximately 0.51 mL of salinewas injected at as
many points as necessary in an attempt to completely
surround the tumor on its deep and lateral aspects. All
patients were offered topical local anesthetic immediately before their injection of radiocolloid. All patients
with oral pain or trismus were strongly encouraged to
accept the offer of local anesthetic, and those patients
with no oral pain or trismus were informed that the
procedure was of only mild discomfort. The needle
used was a size 27F-gauge needle, which was permanently attached to the syringe to avoid inadvertent
separation of the needle from the syringe. The needle
was passed into one to four areas as many times as
necessary in an attempt to completely surround the
tumor with radiocolloid, both on the deep aspect as
well as the lateral aspect to ensure radiocolloid was
present at the metastasizing edge of the tumor.
Initially, Albures (Nycomed Amersham) was the
colloid used in all cases, but after our initial learning
curve, Albures, with a mean particle size of 500 nm,
subsequently was only used for primaries of the
tongue and floor of mouth, and Nanocoll (Nycomed
Amersham), with a mean particle size of 80 nm, was
used for tumors at other sites. Static lymphoscintigraphy was performed at 15 minutes, 30 minutes, and 60
minutes after injection, or until the first appearance of
sentinel lymph nodes within the neck. During surgery,
approximately 0.52 mL of Patent Blue V dye (Laboratoire Guerbet, Aulnay-Sous-Bois, France) was injected into the same site as radiocolloid, and skin flaps
suitable for a neck dissection were raised. The sternomastoid muscle was retracted posteriorly to expose
the deep chain of cervical lymphatics, and attempts
were made at identifying sentinel lymph nodes. Blue
stained lymphatics were followed to blue lymph
nodes, and radioactive lymph nodes were identified
with a Neoprobe 1500 hand-held gamma probe (Neoprobe Corp, Columbus, OH). Sentinel lymph nodes
were identified in their lymph node level and were
labeled according to color and presence of radioactivity. Radioactivity was confirmed within the sentinel
lymph node ex vivo. An appropriate neck dissection
completed the surgical procedure. At the time of surgery, lymph node levels were marked with metal disks.
The sentinel lymph nodes were fixed in 10% neutral
buffered formalin and after fixation were bisected
through their longest axis. If the thickness of the
halves was more than 2 mm, the slices were trimmed
further to provide additional 2-mm-thick blocks. The
remainder of the neck specimen was dissected after

Head and Neck Carcinoma Sentinel Lymph Node Biopsy/Shoaib et al.

fixation, and all lymph nodes greater than approximately 2.5 mm in maximum dimension were identified in their anatomic groups. Each lymph node was
bisected through its longest axis, and one-half was
processed for histologic examination. One hematoxylin and eosin (H & E)stained section was prepared
from each block and was examined for the presence of
lymph node involvement by tumor.

2079

TABLE 1
No. of Sentinel Lymph Nodes Found by Lymph Node Level and
Involvement by Squamous Cell Carcinoma
Lymph node level

No. of sentinel
lymph nodes

No. of sentinel lymph

nodes containing tumor

I
II
III
IV
V

13
50
22
4
1

3
10
3
2
0

RESULTS
Between July 1998 and March 2000, 40 necks were
explored for sentinel lymph nodes in 37 patients with
biopsy proven squamous cell carcinoma. Each neck
side was considered a single case. Ten cases have been
reported previously in our pilot study and are included
in the data.
Thirty-nine cases were classified N0, and one case
was classified clinically as Nx, because of palpable
cervical lymphadenopathy from longstanding nonHodgkin lymphoma. The clinical classification of the
primary tumor was T1 in 14, T2 in 14, T3 in 3, and T4
in 9. The site of the primary squamous carcinoma was
the tongue in 21, floor of mouth in 10, soft palate in 4,
retromolar trigone in 3, the buccal mucosa in 1, and
lower alveolus in 1. The male to female ratio was 2:1.
The mean age of patients was 59 years (range, 29 84).
Sentinel lymph nodes were found in 36 of the 40
necks (90%). In the four necks in which sentinel lymph
nodes were not identified, one was a patient with a T2
anterior floor of mouth tumor undergoing bilateral
neck dissections with palpable lymphadenopathy
from squamous cell carcinoma on one side of the
neck, and no sentinel lymph node was identified in
the uninvolved neck. Three were patients with well
lateralized tongue carcinomas undergoing unilateral
neck dissections. These three tongue carcinomas were
classified as T2 in one case and T4 in two. In all four
cases, the neck dissection specimens were examined
for blue and radioactive lymph nodes ex vivo; however, none was found. In three of four cases in which
sentinel lymph nodes were not detected, the neck was
classified pN. In two cases, the primary tumor was a
T4 tongue carcinoma, and the third was a T2 tongue
tumor. One was classified pathologically as pN2b and
two were pN1. In the case classified N2b, two lymph
nodes were involved with tumor, one of which was
extensively replaced by squamous cells and showed
early extracapsular spread. In the two cases classified
as N1, early lymphatic spread was observed in one
lymph node, and in the other case, one small tumor
deposit of approximately 200 microns in maximum
dimension was observed within a lymphatic channel
in the lymph node capsule.

In 36 cases in which sentinel lymph nodes were

identified, 90 sentinel lymph nodes were found in
total. Forty-one lymph nodes were both radioactive
and blue (hot blue lymph nodes), 35 were hot only,
and 14 were blue only. The median number of sentinel
lymph nodes per neck was 2 with a mean of 2.2 (range,
0 6).
Sentinel lymph nodes were found in lymph node
levels I to V and are summarized in Table 1. Two
sentinel lymph nodes were found in level IIb, in the
triangle bordered by the skull base, sternomastoid
muscle and the spinal accessory nerve. Two patients
had areas of radioactivity, suggestive of sentinel lymph
nodes, identified out with the neck during lymphoscintigraphy. One patient had a T1 left body of tongue
squamous cell carcinoma, and the other had a T2
left soft palate carcinoma. In both cases, lymphoscintigraphy identified the left tonsillar region as the
site, but tonsillectomies were not performed. The
necks of both patients were classified as pN0.
Eight hundred forty-nine lymph nodes, including
sentinel lymph nodes, from 40 necks were examined.
A radical or modified radical neck dissection was performed in 22 cases, a supraomohyoid neck dissection
in 3, and a selective neck dissection excising levels IIV
in 15. In two cases of floor of mouth carcinomas, the
planned procedure of a supraomohyoid neck dissection was converted to one that included level IV, because the sentinel lymph nodes were located inferior to the omohyoid muscle, and in one of these
cases the sentinel lymph node in level IV contained
tumor. Table 2 summarizes the number of lymph
nodes examined and containing tumor from the
neck dissections.
Twenty necks were classified pathologically as N0
and 20 as pathologically N positive (9 were pN1, 8
were pN2b, and 3 were pN2c). In the N positive group
(pN), sentinel lymph nodes were found in 17 and
contained tumor with conventional histology in 16. In
these 16 necks from which sentinel lymph nodes containing tumor were harvested, the sentinel lymph
nodes were the only lymph nodes containing tumor in

2080

CANCER June 1, 2001 / Volume 91 / Number 11

TABLE 2
No. of Lymph Nodes Examined and Containing Tumor by Lymph
Node Level

TABLE 4
Sentinel Lymph Nodes in the pN Neck According to Presence of
Tumor, Dye, and Radiocolloid

Lymph node level

No. of lymph nodes

examined

No. of lymph nodes

containing tumor

Nodal identification
technique

Lymph nodes
with tumor

Lymph nodes
without tumor

Total

I
II
III
IV
V

148
261
188
170
94

7
16
4
2
0

Hot blue
Hot only
Blue only
Total

10
6
2
18

11
9
3
23

21
15
5
41

TABLE 3
Anatomic Location of Nonsentinel Lymph Nodes Containing Tumor,
When Nonsentinel Lymph Nodes Were Found to Harbor Metastases

Case

Anatomic neck level of

pathologically positive
sentinel lymph node

Anatomic level of
nonsentinel lymph
node(s) with tumor

1
2
3
4

II
II
III
IV

II
I
II
II, III

12. Thus, in only four cases, nonsentinel lymph nodes

contained tumor in the presence of pathologically
positive sentinel lymph nodes. In three of these four
necks, one additional lymph node was found to contain tumor, and in one case two nonsentinel lymph
nodes contained tumor. The details of these four cases
are shown in Table 3.
There was one false-negative sentinel lymph node
in a patient with an extensive T4 squamous cell carcinoma of the floor of mouth in whom negative sentinel lymph nodes were found in levels I and II, and
tumor was found within a nonsentinel level II lymph
node.
When a sentinel lymph node was found, the sensitivity of the procedure was 94% (95% confidence
interval, 82100%). All sentinel lymph nodes in patients with pN0 necks were free of tumor (specificity
100%), and the sentinel lymph node correctly predicted the positivity or negativity of the neck in 35 of
36 cases (overall accuracy, 97%). Forty-one sentinel
lymph nodes were harvested in total from the 20 pN
necks, and tumor was found in 18 lymph nodes. Table
4 summarizes the presence of tumor, radioactivity and
blue dye within all sentinel lymph nodes harvested
from pN necks.
Table 5 details the site of the primary tumor, the
number of sentinel lymph nodes found, the pathologic
classification of the neck, and the number of sentinel
lymph nodes containing tumor for each case.

DISCUSSION
This study was performed to determine if the sentinel
lymph node concept was valid for head and neck
squamous cell carcinoma in necks with impalpable
metastases undergoing elective neck dissections. We
conclude that the sentinel lymph node, when identified using a combination of the hand-held gamma
probe and blue dye visualization, reflects the positivity
or negativity of the neck with a high degree of accuracy. We found that sentinel lymph node pathology
using conventional H & E stains reflected that of the
neck dissection in 94% of cases with impalpable disease, but only in those cases when the SLN was found.
Frozen section analysis was not used in this study,
thus avoiding a further variable and ensuring that all
material was available for pathologic analysis. The
accuracy of frozen section has been questioned in
melanoma and breast carcinoma sentinel lymph node
biopsy.16,17
Sentinel lymph node biopsy is technically challenging and difficulties with identifying sentinel
lymph nodes may be encountered during lymphoscintigraphy and surgery. Sentinel lymph nodes may be
too close to the primary injection site to be discernible
by the gamma camera, and this is particularly troublesome for sentinel lymph nodes in level I for a
primary tumor located in the floor of mouth. Although
the use of lead shields and software masking may
highlight level I sentinel lymph nodes, if the procedure
is to find a role in the management of the clinically N0
neck for floor of mouth lesions, we would recommend
exploration of level I in all cases in which the primary
tumor is located in the floor of mouth. During surgical
exploration of level I, the hand-held gamma probe will
detect scatter and shine-through from the primary
site; the use of sterilized lead plates will aid in isolating
radioactivity from lymph nodes. Blue dye visualization
may be the primary means of identifying lymph nodes
in level I, with the hand-held probe being used to
confirm the presence of radiocolloid within the lymph
node ex vivo. Last, removal of the primary tumor does
not remove all radioactivity from the injection site,
despite adequate tumor resection margins, although

Head and Neck Carcinoma Sentinel Lymph Node Biopsy/Shoaib et al.

TABLE 5
Position of Tumor, No. of Lymph Nodes per Case, pN Classification of
Neck and No. of Sentinel-Lymph Nodes Containing Tumor for All
Patients

Case no.

Site of
primary

No. of sentinel
lymph nodes
found

Pathologic
classification of
neck

No. of sentinel
lymph nodes
with tumor

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40

Tongue
Tongue
Tongue
Tongue
FOM
Tongue
Tongue
FOM
FOM
FOM
Buccal
FOM
FOM
Tongue
Tongue
Tongue
Tongue
Tongue
Tongue
Tongue
Alveolus
Tongue
Tongue
Tongue
Palate
FOM
FOM
Tongue
Tongue
Tongue
Tongue
Tongue
RMT
FOM
FOM
RMT
RMT
Palate
RMT
RMT

2
3
2
3
2
2
3
1
1
5
3
0
2
2
3
0
0
3
2
4
6
6
1
1
1
2
2
3
4
3
0
4
2
3
1
2
1
3
2
1

1
2c
1
1
1
0
2b
0
0
2b
0
0
0
2b
0
2b
1
0
0
0
0
0
1
2b
1
2b
0
0
0
1
1
2b
1
1
0
0
0
0
2b
0

1
1
1
1
1
0
1
0
0
2
0
N/A
0
1
0
N/A
N/A
0
0
0
0
0
1
1
1
0
0
0
0
1
N/A
2
1
1
0
0
0
0
1
0

FOM: floor of mouth; RMT: retromolar trigone.

the reduction in radioactivity within the primary site

can aid in the subsequent identification of hot lymph
nodes close to the primary tumor.
Both blue dye and radiocolloid are required for
sentinel lymph node biopsy to be successful. Two
sentinel lymph nodes containing tumor were blue but
contained no radiocolloid, and six sentinel lymph
nodes containing tumor were hot but had no blue dye
within them. In finding the blue lymph nodes, preop-

2081

erative lymphoscintigraphy aided in localizing the

presence of blue dye. Because the pharmacodynamics
of blue dye will be different from radiocolloid, it is not
surprising that some sentinel lymph nodes are identified with one modality only.
Sentinel lymph nodes have been identified in clinically unpredictable sites. Traditional anatomic teaching from cadaveric studies has suggested that lymph
drainage may be sequential from level I to the upper
jugular chain and thence to the lower jugular chain.
This has given rise to the misconception of skip metastases, in which tumor metastases bypass upper
lymph nodes in levels I and II and are found in lower
levels. If the anatomic location of sentinel lymph
nodes is a reflection of direct lymphatic drainage, the
findings that sentinel lymph nodes may be located at
various levels in the neck indicates that tumor drainage is dependent on individual anatomic pathways in
some cases.
In most cases, sentinel lymph nodes have been
the only lymph nodes with tumor in the involved neck
(12 of 16 cases). When nonsentinel lymph nodes also
are involved with tumor, these occasionally have been
identified at higher anatomic levels in the neck. This
phenomenon may be a reflection of tumor spread
from the sentinel lymph node to a second echelon
lymph node at a higher anatomic level.
In one case of a patient with long standing cervical
lymphadenopathy from a low grade non-Hodgkin
lymphoma, the neck was classified clinically Nx. The
primary tumor was a T1 lateral tongue carcinoma, and
the neck was found to contain squamous cell carcinoma in three lymph nodes in levels II, III, and IV.
Three sentinel lymph nodes were found in levels III
and IV, with one of the two cold blue lymph nodes
from level IV containing tumor. Despite the presence
of palpable lymphadenopathy from a different pathologic process, sentinel lymph node biopsy correctly
identified lymph node disease from the squamous cell
carcinoma. In such cases, lymph nodes with increased
hydrostatic pressure may divert lymphatic flow, so
that sentinel lymph nodes are found at clinically aberrant locations. In these cases, the sentinel lymph
node location may reflect the true anatomic drainage
pathway of the primary site. Although this article addresses the use of sentinel lymph node biopsy in the
clinically N0 neck, the use of sentinel lymph node
biopsy in this patient led to noteworthy and significant findings. If sentinel lymph node biopsy finds a
role in the management of patients with head and
neck carcinoma, it will be in the group of patients in
which the presence of tumor metastases within the
lymph nodes is uncertain as in this patient.
On average, more than one sentinel lymph node

2082

CANCER June 1, 2001 / Volume 91 / Number 11

will be found in a single neck. Because the oral cavity

has a rich plexus of lymphatic vessels, these findings
may reflect the diverse lymphatic drainage pathways
to the neck.
Sentinel lymph nodes were not found in 4 cases
(10%), and this is similar to cutaneous melanoma of
the head and neck in which the rate of sentinel lymph
node identification varies between 90% and 96%.18 21
We cannot comment on the learning curve for head
and neck carcinoma sentinel lymph node biopsy, but
in our continuing experience of more than 100 cases,
the rate of failure to identify sentinel lymph nodes
remains much the same.
In this series, sentinel lymph nodes were not identified in four cases. Three cases were tongue tumors:
in all cases, the tumors were indurated and ulcerated.
Blue dye leaked out of the injection site into the oral
cavity at the time of surgery. We presume the colorless
injected colloid followed the same pathway, preventing lymphatic uptake of both dye and radioactivity.
The remaining case was a neck from a patient
undergoing bilateral neck dissections for a tumor
close to the midline. In this case, lymphoscintigraphy
identified drainage to one side of the neck only, and
the lack of sentinel lymph nodes on the contralateral,
clinically clear neck was most likely a reflection of the
true drainage pattern of the tumor. The decision to
perform bilateral neck dissections on patients with
tumors close to the midline can be difficult. Because
the role of sentinel lymph node biopsy has yet to be
defined in patients with head and neck carcinoma, it
seems reasonable to perform the technique on a variety of patient types that are undergoing a neck dissection to address this question, at least in initial studies.
For this reason, we chose to include such patients in
the group studied.
Sentinel lymph node pathology did not reflect that
of the remaining neck dissection in one case. There
thus was one false-negative sentinel lymph node. In
this case, the patient had an extensive T4 tumor of the
floor of mouth, invading into the tongue, mandible,
and skin. In this case, the injection site of colloid and
dye was not at the metastasizing edge of the tumor,
because the small volume of injection was insufficient
to completely surround the tumor on its deep and
lateral aspects. If sentinel lymph node biopsy is to be
used as a staging tool for head and neck carcinomas, it is
important to inject around the whole tumor periphery.
If sentinel lymph node biopsy finds a role in the
management of the clinically N0 neck as a staging
technique, then in cases in which a sentinel lymph
node is not identified a formal elective neck dissection
should be considered for staging purposes. The tech-

nique is only reliable when a sentinel lymph node is

identified.
We propose a multicenter study to investigate
sentinel lymph node biopsy in patients with T1 or T2
lesions of the oral cavity and oropharynx and clinically
N0 necks. If the sentinel lymph node is free of tumor,
no elective treatment of the neck will be undertaken.
Multiple serial sections of the sentinel lymph node will
be examined using routine histology and immunohistochemistry, and if viable tumor is found within the
sentinel lymph node, patients will undergo a neck
dissection and other treatment to the neck according
to local protocols. Sentinel lymph node biopsy can be
a technically challenging procedure, but we believe it
should be investigated further by those clinicians
competent at the procedure, in the context of a multicenter trial. We have commenced such a trial in
Europe, details of which are published on our web site
(http://www.canniesburn.org).

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