Académique Documents
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Editors
A. Ferlito, Udine, Italy
W. Arnold, München, Germany
ABC
Fax+ 41 61 306 12 34
E-Mail karger@karger.ch
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Vol. 62, No. 4, 2000
Contents
177 Preface
Ferlito, A. (Udine); Arnold, W. (München)
178 The Biology of Tumor Invasion, Angiogenesis and Lymph Node Metastasis
Petruzzelli, G.J. (Maywood, Ill.)
Preface
Acquisition of the Malignant Phenotype ronment may favor the expansion of more aggressive
clones in the formation of metastases. Hence the clinical
HNSCC, like all solid tumors, is thought to arise after a observation that supraglottic tumors will present more
series of genetic events resulting in accumulation of DNA frequently with metastasis than comparable stage glottic
damage. Targets of these mutations include inactivation tumors. Although the size of the subpopulation of metas-
of growth-regulating tumor suppressor genes, or the acti- tasizing cells in any given tumor may be quite large, a very
vation of oncogenes, which drive cellular proliferation by small percentage (! 0.01%) of circulating tumor cells will
a variety of mechanisms. initiate metastatic colonies.
Our current understanding of cancer supports the hy- Epithelial tumors represent excellent systems in which
pothesis that the development of malignant tumors is due to study the stepwise progression resulting in an invasive
to alterations in normal mechanisms of cellular prolifera- malignancy. Fearon and Vogelstein [6] were the first to
tion, differentiation, and a failure of programmed cell present compelling evidence identifying a sequence of
death (apoptosis). These genomic changes result in partic- reducible cytogenetic events in the development of colo-
ular phenotypic changes such as defects in terminal differ- rectal tumors and metastases. It is likely that a similar
entiation, loss of response to normal growth controls, series of cytogenetic alterations exist in the development
defects in response to intracellular signals for apoptosis of HNSCC as well. Many investigators have begun to
and resistance to cytotoxicity, all of which provide cancer examine the molecular pathogenesis of HNSCC in terms
cells a particular growth advantage. These genetic altera- of alterations in cytogenetic, proto-oncogene activation,
tions may be spontaneous or inherited but are most often growth factor production loss of tumor suppressor genes,
due to the actions of viral or chemical mutagens or direct and failure of apoptosis [7–9] Although no specific pat-
radiation-induced DNA damage [2, 3]. Recently is has tern of genetic events in the development of HNSCC has
been demonstrated that differential epigenetic mecha- been accepted, a recent comprehensive review by Myers
nisms may account for the development of HNSCC in [9] has proposed a hypothesis for HNSCC resembling the
individuals without traditional exposures to mutagens multi-step colorectal carcinogenesis model (fig. 1).
[4].
Not all cells within a given tumor will contain identical
cytogenetic abnormalities. First proposed by Fidler and The Biology of Invasion
Hart [5], this concept of tumor heterogeneity proposes
that tumors are composed of subpopulations of cells, and Essential characteristics of cancer are the ability to
these subpopulations will differ with respect to their invade surrounding tissues and metastasize to regional
immunogenicity, invasiveness, growth kinetics, sensitivi- and distant sites. The events attendant to local invasion
ty to cytotoxic drugs and ability to metastasize. While by an epithelial tumor include loss of adhesion to sur-
neoplasms may be heterogeneous, the local tumor envi- rounding tumor cells and basement membrane, produc-
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Abstract
For over five decades, the principle landmarks used in Introduction and Historical Review
cervical nodal classification were clinical and defined
either by palpation or found at the operative table. How- In the first four decades of the 20th century, Charpy
ever during the past two decades, sectional imaging has [1], Trotter [2], and finally Rouvière [3] developed the
consistently improved its quality and resolution and it basis of our present understanding of cervical lymphatic
has been shown that imaging can identify deep struc- anatomy [1–3]. These authors mapped the location and
tures and adenopathy not amenable to palpation. Such drainage of the cervical lymph nodes and referenced the
disease can alter planned operative or radiation fields. In location of these nodes to landmarks assessed by palpa-
the April 1999 issue of the Archives of Otolaryngology – tion and anatomy seen at surgery. Such surgical land-
Head Neck Surgery, for the first time an imaging-based marks included the carotid bifurcation, the inferior belly
classification was published that gave precise anatomic of the omohyoid muscle, the posterior belly of the digast-
landmarks for use in classifying metastatic cervical ade- ric muscle, the common facial vein, and the spinal acces-
nopathy. This classification was developed in consulta- sory nerve. These authors noted the importance of the
tion with head and neck surgeons so that the nodal levels nodal chain surrounding the internal jugular vein and
classified by this imaging-based system would corre- these nodes were divided into upper, middle, and lower
spond closely with the nodal levels determined by utiliz- jugular subgroups.
ing the most commonly employed clinically-based clas-
Level I These nodes lie above the hyoid bone, below the mylohyoid muscle and anterior to the back of
the submandibular gland (previously classified as the submental and submandibular nodes)
Level IA These nodes lie between the medial margins of the anterior bellies of the digastric muscles
above the hyoid bone and below the mylohyoid muscles (previously known as submental
nodes)
Level IB On each side of the neck, these nodes lie lateral to the level IA nodes and anterior to the back of
each submandibular gland
Level II These nodes extend from the skull base to the level of the bottom of the body of the hyoid bone.
They are posterior to the back of the submandibular gland and anterior to the back of the
sternocleidomastoid muscle
Level IIA These nodes are level II nodes that lie either anterior, lateral, medial, or posterior to the inter-
nal jugular vein. If posterior to the vein, the nodes are inseparable from the vein (previously
classified as upper internal jugular nodes)
Level IIB These are level II nodes that lie posterior to the internal jugular vein with a fat plane separating
the nodes and the vein (previously classified as upper spinal accessory nodes)
Level III These nodes extend from the level of the bottom of the body of the hyoid bone to the level of
the bottom of the cricoid arch. They lie anterior to the back of the sternocleidomastoid muscle
(previously known as the mid-jugular nodes)
Level IV These nodes extend from the level of the bottom of the cricoid arch to the level of the clavicle.
They lie anterior to a line connecting the back of the sternocleidomastoid muscle and the
posterior-lateral margin of the anterior scalene muscle. They are also lateral to the carotid
arteries (previously known as the low jugular nodes)
Level V These nodes lie posterior to the back of the sternocleidomastoid muscle from the skull base to
the level of the bottom of the cricoid arch. From the level of the bottom of the cricoid arch to
the level of the clavicle as seen on each axial scan, they lie posterior to a line connecting the
back of the sternocleidomastoid muscle and the posterior-lateral margin of the anterior scalene
muscle. They also lie anterior to the anterior edge of the trapezius muscle
Level VA Upper level V nodes extend from the skull base to the level of the bottom of the cricoid arch.
They are posterior to the back of the sternocleidomastoid muscle
Level VB Lower level V nodes extend from the level of the bottom of the cricoid arch to the level of the
clavicle as seen on each axial scan. They are posterior to a line connecting the back of the
sternocleidomastoid muscle and the posterior-lateral margin of the anterior scalene muscle
Level VI These nodes lie between the carotid arteries from the level of the bottom of the body of the
hyoid bone to the level of the top of the manubrium (previously known as the visceral nodes)
Level VII These nodes lie between the carotid arteries below the level of the top of the manubrium and
above the level of the innominate vein (previously known as the superior mediastinal nodes)
Supraclavicular These nodes lie at or caudal to the level of the clavicle as seen on each axial scan and lateral to
nodes the carotid artery on each side of the neck. They are also above and medial to the ribs
Retropharyngeal These nodes lie within 2 cm of the skull base and they are medial to the internal carotid arter-
nodes ies
The parotid nodes and other superficial nodes are referred to by their anatomic names
Reproduced and modified with permission of the Archives of Otolaryngology – Head Neck Surgery [26].
How to Use the Imaging-Based Classification should be evaluated separately. That is, the ‘lines’ that are
used to define the boundaries of the levels should be
The classification was designed to be easily and readily ‘drawn’ separately for each side of the neck. The lines
usable (fig. 1–6 illustrate the classification and table 1 need not actually be drawn, as when one becomes familiar
summarizes the classification). Each side of the neck with the classification, they can be easily visually approxi-
Fig. 1. Diagram of the neck in the lateral projection outlining the level of the bottom of the cricoid cartilage and the clavicle, they are
landmarks of the imaging-based classification. Level I nodes are cau- posterior to the oblique plane described above. The region of the lev-
dal to the mylohyoid muscle and extend down to the bottom of the el VII nodes is outlined, extending from the top of the manubrium
body of the hyoid bone and to the posterior edge of the submandibu- down to the innominate vein. These nodes essentially lie at or anteri-
lar gland. Level II nodes extend from the skull base to the bottom of or to the level of the carotid arteries. Level VI nodes are not indicated
the body of the hyoid bone and from the posterior edge of the sub- on the diagram. They are located below the bottom of the body of the
mandibular gland to the posterior edge of the sternocleidomastoid hyoid bone and above the top of the manubrium, situated between
muscle. Level III nodes extend from the inferior margin of the level II the carotid arteries.
nodes to the bottom of the cricoid arch. They also extend back to the
posterior edge of the sternocleidomastoid muscle. Level IV nodes Fig. 2. Diagram of an axial slice of the neck at the level of C2. The
extend from the inferior margin of the level III nodes to the upper internal carotid artery (C) and internal jugular vein (J) are identified
margin of the clavicle as described in the text. Their posterior margin on each side. Within 2 cm of the skull base, if a node is medial to the
is an oblique plane that extends from the posterior lateral aspect of inner aspect of either internal carotid artery, that node is classified as
the anterior scalene muscle (dotted line) to the posterior edge of the a retropharyngeal node. Nodes anterior, lateral and behind the inter-
sternocleidomastoid muscle. This plane is represented by oblique nal jugular vein are level IIA nodes. At this level of the neck, there
lines in the figure. Level V nodes extend from the skull base to the rarely are nodes posterior to (J) and anterior to back edge of the ster-
clavicles and are anterior to the front edge of the trapezius muscle. nocleidomastoid muscle. However, such a node would be a level IIA
Above the level of the bottom of the cricoid cartilage they are posteri- node. Nodes posterior to the back of the sternocleidomastoid muscle
or to the back edge of the sternocleidomastoid muscle. Between the are level VA nodes (see text).
mated or a straight-line guide or ruler can be placed on the fied. The supraclavicular fossa is defined on each axial
film or monitor. Whenever a lymph node is transected by scan whenever any portion of the clavicle is identified on
one of the ‘lines’ that define the levels, the side of the line one side of the neck. That is, if the scan level is cranial to
on which the majority of the nodal cross-sectional area any portion of the clavicle, the nodes in the lower lateral
lies is the level in which the lymph node should be classi- neck should be classified as being in either level IV or lev-
el VB. Once any portion of the clavicle is seen on the scan, dibular nodes. Level I nodes can be subclassified into lev-
such nodes are classified as supraclavicular nodes (fig. 6). els IA and IB.
If nodes are seen below the level of the clavicle and lateral Level IA represents those nodes which lie between the
to the ribs, they are axillary nodes (fig. 7). The clinically medial margins of the anterior bellies of the digastric mus-
important internal jugular nodes described by Rouvière cles, above the hyoid bone and below the mylohyoid mus-
[3] are now classified as level II, III, or IV nodes, depend- cle (previously classified as submental nodes) (fig. 3).
ing on their location with reference to the axial scan levels Level IB represents the nodes which lie below the mylo-
of the bottom of the body of the hyoid bone and the bot- hyoid muscle, above the hyoid bone, posterior and lateral
tom of the arch (anterior rim) of the cricoid cartilage. to the medial edge of the anterior belly of the digastric
muscle, and anterior to a transverse line drawn on each
axial image tangent to the posterior surface of the sub-
The Imaging-Based Classification mandibular gland on each side of the neck (previously
classified as submandibular nodes) (fig. 3).
Level I includes all of the nodes above the hyoid bone, Level II extends from the skull base, at the lower level
below the mylohyoid muscles, and anterior to a transverse of the bony margin of the jugular fossa, to the level of the
line drawn on each axial image through the posterior edge lower body of the hyoid bone (fig. 1–3). Level II nodes lie
of the submandibular gland (fig. 1, 3). Thus, level I nodes anterior to a transverse line drawn on each axial image
include the previously classified submental and subman- through the posterior edge of the sternocleidomastoid
muscle and lie posterior to a transverse line drawn on Level IIB nodes are level II nodes that lie posterior to
each axial scan through the posterior edge of the subman- the internal jugular vein and have a fat plane separating
dibular gland. If a node situated within 2 cm of the skull the nodes and the vein (previously classified as upper spi-
base lies anterior, lateral or posterior to the carotid sheath, nal accessary nodes) (fig. 3).
it is classified as a level II node. If the node lies medial to Level III nodes lie between the level of the lower body
the internal carotid artery, it is classified as a retropharyn- of the hyoid bone and the level of the lower margin of the
geal node (fig. 2). Caudal to 2 cm below the skull base, cricoid cartilage arch (fig. 1, 4). These nodes lie anterior to
level II nodes can lie anterior, lateral, medial and posteri- a transverse line drawn on each axial image through the
or to the internal jugular vein. Level II nodes can be sub- posterior edge of the sternocleidomastoid muscle. Level
classified into levels IIA and IIB. III nodes also lie lateral to the medial margin of either the
Level IIA nodes are level II nodes that lie posterior to common carotid artery or the internal carotid artery. On
the internal jugular vein and are inseparable from the vein each side of the neck, the medial margin of these arteries
or they are nodes that lie anterior, lateral or medial to the separates level III nodes (which are lateral) from level VI
vein (previously classified as upper internal jugular nodes (which are medial). Level III nodes were previously
nodes) (fig. 2, 3). known as the mid-jugular nodes.
Level IV nodes lie between the level of the lower mar- scan (fig. 1–5). Level V nodes all lie anterior to a trans-
gin of the cricoid cartilage arch and the level of the clavi- verse line drawn on each axial scan through the anterior
cle on each side as seen on each axial scan. These nodes lie edge of the trapezius muscle. Between the levels of the
anterior and medial to an oblique line drawn through the skull base and the bottom of the cricoid arch, these nodes
posterior edge of the sternocleidomastoid muscle and the are situated posterior to a transverse line drawn on each
lateral posterior edge of the anterior scalene muscle on axial scan through the posterior edge of the sternocleido-
each axial image (fig. 1, 5, 6). The medial aspect of the mastoid muscle (fig. 1, 2–4). Between the axial level of the
common carotid artery is the landmark which separates bottom of the cricoid arch and the level of the clavicle,
level IV nodes (which are lateral) from level VI nodes level V nodes lie posterior and lateral to an oblique line
(which are medial) to this artery (fig. 5, 6). Level IV nodes through the posterior edge of the sternocleidomastoid
were previously known as the low jugular nodes. muscle and the lateral posterior edge of the anterior scal-
Level V nodes extend from the skull base, at the poste- ene muscle (fig. 5, 6). The level V nodes can be subdivid-
rior border of the attachment of the sternocleidomastoid ed into VA and VB nodes.
muscle, to the level of the clavicle as seen on each axial
Level VA (upper level V) nodes lie between the skull edge of the sternocleidomastoid muscle and the lateral
base and the level of the lower margin of the cricoid carti- posterior edge of the anterior scalene muscle (fig. 5).
lage arch. They are behind the posterior edge of the ster- Level VI nodes lie inferior to the lower body of the
nocleidomastoid muscle (fig. 1–4). hyoid bone, superior to the top of the manubrium, and
Level VB (lower level V) nodes on each side lie between between the medial margins of the left and right common
the level of the lower margin of the cricoid cartilage arch carotid arteries or the internal carotid arteries. They are
and the level of the clavicle as seen on each axial scan. the visceral nodes (fig. 5, 6).
They are behind an oblique line through the posterior
As the imaging-based nodal classification encompasses Today, CT and MR imaging form an integral part of
all of the cervical lymph nodes, it is easy to apply the clas- the assessment of the majority of cases of head and neck
sification when describing lymph node metastases from cancer. The imaging findings clearly compliment the
laryngeal cancer. Ogura [27] found that positive nodes physical examination and the imaging-based classifica-
from laryngeal cancers can occur in all triangles of the tion provides the radiologist with clinically acceptable
neck except in the submental triangle. Translating this guidelines with which to classify the cervical nodes and
into the imaging-based nodal classification means that all communicate these findings to the clinicians in a mutual-
nodal levels except level IA are at risk [28]. Although sub- ly acceptable way. This new classification provides added
mandibular nodes (level IB) may uncommonly be in- precision and reproducibility to nodal localization and it
volved in advanced supraglottic cancers, this appears to is hoped that imaging will now become a necessary com-
occur only in cases with extensive internal jugular chain ponent of patient classification and staging. It is also
disease (levels II, III and IV). In general, supraglottic can- hoped that this classification can add precision and repro-
cers metastasize to levels II and III, however, there is ducibility to the nodal localization required in the accu-
some discrepancy in the literature regarding metastasis of mulation of data in planned multi-institutional studies
these tumors to the posterior triangle nodes [29, 30]. involving laryngeal cancer [34].
When the spinal accessory nodes are involved, it is most
commonly to the nodes in the superior portion of this
nodal chain [31]. Thus, while level IIB (and rarely level Acknowledgement
VA nodes) may be affected in supraglottic cancers, level
The authors want to thank Bradley Delman, MD, for the line
VB are usually not involved.
drawings that he created for this paper.
In cases of glottic and subglottic cancers, the prelaryn-
geal nodes and occasionally the pretracheal nodes may be
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Color Doppler Ultrasound marker of tumor viability, based upon the increased gly-
colysis that is associated with malignancy as compared
Color flow imaging allows simultaneous two-dimen- with normal tissues. It has been proven that head and
sional imaging and evaluation of blood flow. CDUS is a neck carcinomas have high glycolytic activity and in-
sensitive noninvasive imaging technique capable of de- creased FDG uptake (fig. 2) [21].
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a prospective study, 63 untreated patients with palpable that a short PET protocol, which is suitable for routine
cervical lymph node enlargement underwent examination clinical use, is superior to morphologic procedures (CT or
with CDUS. Reactively enlarged lymph nodes showed MRI) for lymph node staging of HNSCCs [15]. PET
characteristically intense hilar perfusion, whereas nodal investigation revealed a higher sensitivity (87%) and spec-
metastases had mainly peripherally located flow [19]. ificity (94%) compared with CT values of 65 and 47% and
Lymph nodes invaded by malignant lymphoma were MRI values of 88 and 40%, respectively [15].
highly perfused, showing color signals in the center as well
as in the nodal periphery [19]. Perfusional patterns may
provide therefore useful additional information in the dif- Conclusions
ferential diagnosis of cervical lymphadenopathy. Further-
more, in experimental studies the value of US contrast At present, we are unable to establish lymph node
medium is ongoing investigated to improve the accuracy involvement accurately using current available noninva-
of US and to give additional information about tumor sive methods. Nevertheless, imaging procedures like CT
patterns [20]. and MRI do have clearer roles in evaluating lymph nodes
that are not easily accessible to clinical and US examina-
tions such as the retropharyngeal, upper mediastinal and
Positron Emission Tomography paratracheal lymph nodes. They are also valuable tools in
defining the relation of metastases to critical structures
Imaging procedures as described above are used for the such as carotid artery, cervical spine or brachial plexus.
detection and localization of the primary tumor, regional Despite the high accuracy of the invasive US-guided
lymph node involvement and their relationship to adja- FNAC, there remains an uncertainty of false results
cent anatomical structures. Differentiation between reac- (110%). PET has also a high accuracy in detecting malig-
tive enlargement of lymph nodes and tumor-infiltrated nant lymph nodes, however, since this investigation is
nodes may be difficult on the basis of radiological criteria expensive and limited to certain locations, the use in a
[16]. Fluorine-18 fluorodeoxyglucose (18F-FDG) is a routine clinical setting is at present not practicable.
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7 American Joint Committee on Cancer: Flem- node metastasis. Arch Otolaryngol Head Neck 21 Jabour BA, Choi Y, Hoh CK, Rege SD, Soong
ing ID, Cooper JS, Henson DE, Hutter RPV, Surg 1991;117:663–673. JC, Lufkin RB, Hanafee WN, Maddahi J,
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8 Ferlito A, Rinaldo A: False negative conven- 18 F-fluorodeoxyglucose in a routine clinical
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Relat Spec 2000;62:112–114.
Abstract
Cancer of the larynx is a common problem in a head and Introduction
neck oncological surgical practice; as such, pathology
departments supporting such surgical practices will ex- Surgical therapy is an essential element in the compre-
amine cervical lymph node dissection specimens with hensive treatment of many patients with laryngeal cancer
some frequency. Issues to be settled among pathologists [1, 2]. As understanding of the modes of spread of primary
and surgeons include – How precise an anatomic dissec- laryngeal cancer has crystallized, the routine practice of
tion of the specimen is called for? What histological fea- cervical lymph node dissection as an adjunct to treatment
tures of the specimen will be of most use to the clinicians of the primary tumor has likewise assumed an essential
who are devising a course of postoperative therapy for role in the care of many of these patients [3–10].
the patient? What sorts of methods are needed to identi- A robust surgical literature discusses the relative merits
fy the maximum number of micrometastases which may and demerits of a host of techniques for cervical node dis-
be lurking within the lymph nodes of the specimen? Is section – particularly in the patient with either low stage
there a role for routine application of special techniques – disease or a clinically negative neck [11–22]. At the same
such as immunohistochemistry or molecular biology – in time, the radiological literature is filled with studies of the
the analysis of these specimens? While the answers to efficacy of imaging methods at detecting occult cervical
these questions are likely to vary somewhat from one node disease [23–29]. At present, it appears as though nei-
center to another, patients are best served when these ther clinical examination (including even intraoperative
References
1 Shah JP, Lydiatt W: Treatment of cancer of the 12 Stringer SP: Current concepts in surgical man- 21 Breau RL, Suen JY: Management of the N0
head and neck. CA Cancer J Clin 1995;45:352– agement of neck metastases from head and neck. Otolaryngol Clin North Am 1998;31:
368. neck cancer. Oncology (Huntingt) 1995;9:547– 657–669.
2 Snow GB: Evaluation and staging of the patient 558. 22 Van den Brekel MW, Castelijns JA, Snow GB:
with head and neck cancer; in Myers EN, Suen 13 Van den Brekel MW, Leemans CR, Snow GB: Diagnostic evaluation of the neck. Otolaryngol
JY (eds): Cancer of the Head and Neck, ed 2. Assessment and management of lymph node Clin North Am 1998;31:601–620.
New York, Churchill Livingstone, 1989, pp metastases in the neck in head and neck cancer 23 Van den Brekel MW, Castelijns JA, Snow GB:
435–438. patients. Crit Rev Oncol Hematol 1996;22: The size of lymph nodes in the neck on sono-
3 Robbins KT: Classification of neck dissection: 175–182. grams as a radiologic criterion for metastasis:
Current concepts and future considerations. 14 Kowalski LP, Franco EL, de Andrade Sobrinho How reliable is it? Am J Neuroradiol 1998;19:
Otolaryngol Clin North Am 1998;31:639–655. J: Factors influencing regional lymph node me- 695–700.
4 Banerjee AR, Alun-Jones T: Neck dissection. tastasis from laryngeal carcinoma. Ann Otol 24 Tschammler A, Ott G, Schang T, Seelbach-
Clin Otolaryngol 1995;20:286–290. Rhinol Laryngol 1995;104:442–447. Goebel B, Schwager K, Hahn D: Lymphadeno-
5 Spiro RH, Strong EW, Shah JP: Classification 15 Shah JP, Andersen PE: The impact of patterns pathy: Differentiation of benign from malig-
of neck dissection: Variations on a new theme. of nodal metastasis on modifications of neck nant disease – color Doppler US assessment of
Am J Surg 1994;168:415–418. dissection. Ann Surg Oncol 1994;1:521–532. intranodal angioarchitecture. Radiology 1998;
6 Shah JP: Editorial: dissection: Which and 16 Eicher SA, Weber RS: Surgical management of 208:117–123.
when? Aust NZ J Surg 1994;64:225. cervical lymph node metastases. Curr Opin 25 Feinmesser R, Freeman JL, Feinmesser M,
7 Robbins KT, Medina JE, Wolfe GT, Levine Oncol 1996;8:215–220. Noyek A, Mullen JB: Role of modern imaging
PA, Sessions RB, Pruet CW: Standardizing 17 Shah JP, Medina JE, Shaha AR, Schantz SP, in decision-making for elective neck dissection.
neck dissection terminology. Official report of Marti JR: Cervical lymph node metastasis. Head Neck 1992;14:173–176.
the Academy’s Committee for Head and Neck Curr Probl Surg 1993;30:273–344. 26 Righi PD, Kopecky KK, Caldemyer KS, Ball
Surgery and Oncology. Arch Otolaryngol Head 18 Jones AS, Phillips DE, Helliwell TR, Roland VA, Weisberger EC, Radpour S: Comparison
Neck Surg 1991;117:601–605. NJ: Occult node metastases in head and neck of ultrasound-fine needle aspiration and com-
8 Byers RM: Neck dissection: Concepts, contro- squamous carcinoma. Eur Arch Otorhinolaryn- puted tomography in patients undergoing elec-
versies, and technique. Semin Surg Oncol gol 1993;250:446–449. tive neck dissection. Head Neck 1997;19:604–
1991;7:9–13. 19 Robbins KT: Classification of neck dissection: 610.
9 Medina JE: A rational classification of neck Current concepts and future considerations. 27 Anzai Y, Brunberg JA, Lufkin RB: Imaging of
dissections. Otolaryngol Head Neck Surg 1989; Otolaryngol Clin North Am 1998;31:639–655. nodal metastases in the head and neck. J Magn
100:169–176. 20 Traynor SJ, Cohen JI, Gray J, Andersen PE, Reson Imaging 1997;7:774–783.
10 Sizeland AM, Millar HS: Lymph node dissec- Everts EC: Selective neck dissection and the 28 Merritt RM, Williams MF, James TH, Porub-
tion for head and neck cancer. Aust NZ J Surg management of the node-positive neck. Am J sky ES: Detection of cervical metastasis. A
1987;57:161–167. Surg 1996;172:654–657. meta-analysis comparing computed tomogra-
11 Pitman KT, Johnson JT, Myers EN: Effective- phy with physical examination. Arch Otolaryn-
ness of selective neck dissection for manage- gol Head Neck Surg 1997;123:149–152.
ment of the clinically negative neck. Arch Oto-
laryngol Head Neck Surg 1997;123:917–922.
© 2000 S. Karger AG, Basel Alfio Ferlito, MD, Professor and Chairman
ABC 0301–1569/00/0624–0212$17.50/0 Department of Otolaryngology-Head and Neck Surgery
Fax + 41 61 306 12 34 University of Udine, Policlinico Città di Udine
E-Mail karger@karger.ch Accessible online at: Viale Venezia 410, I–33100 Udine (Italy)
www.karger.com www.karger.com/journals/orl Tel. +39 0432 239302, Fax +39 0432 532179, E-Mail clorl@dsc.uniud.it
Today there are a variety of different types of neck dis- Table 1. The Academy’s classification of the
section that are considered oncologically, functionally neck dissections [from 17]
and cosmetically effective in the therapeutic or prophylac-
Comprehensive neck dissection
tic treatment of the neck in patients with head and neck Radical neck dissection
cancers. These less radical surgical procedures are often Modified radical neck dissection
performed bilaterally and may be followed by postopera- Type I
tive radiotherapy. In properly selected patients, the inci- Type II
Type III
dence of neck recurrences observed with these neck dis-
sections is the same as that obtained with radical or modi- Selective neck dissection
fied radical neck dissections [6, 12–14]. Supraomohyoid neck dissection
Posterolateral neck dissection
Lateral neck dissection
Anterior neck dissection
Neck Dissection Terminology and
Extended neck dissection
Classification
Comprehensive
Radical I, II, III, IV, V None
Modified radical
Type 1 I, II, III, IV, V SAN
Type 2 I, II, III, IV, V SAN, IJV
Type 3 I, II, III, IV, V SAN, IJV, SCM
Selective
Suprahyoid I, II SAN, IJV, SCM
Supraomohyoid I, II, III SAN, IJV, SCM
Extended supraomohyoid I, II, III, IV SAN, IJV, SCM
Posterolateral II, III, IV, V, SAN, IJV, SCM
suboccipital and retroauricolar nodes
Lateral II, III, IV SAN, IJV, SCM
Anterior VI SAN, IJV, SCM
Anterolateral II, III, IV, VI SAN, IJV, SCM
SAN = Spinal accessory nerve; IJV = internal jugular vein; SCM = sternocleidomastoid muscle.
middle and lower jugular nodes (levels II, III and IV) are groups and/or nonlymphatic structures not encompassed
removed. In the anterior neck dissection, the lymph nodes by the radical neck dissection are removed. Examples are
(level VI) surrounding the visceral structures of the anteri- the lymph nodes of the anterior compartment of the neck,
or compartment of the neck are removed (this procedure the carotid artery, and the hypoglossal or vagus nerve.
may be extended to include level VII nodes). Finally, the Table 2 summarizes the different types of neck dissec-
anterolateral neck dissection groups these two previous tions and shows the lymph node levels removed and the
surgical procedures together so that levels II, III, IV and structures preserved [18].
VI are removed. It is important to emphasize the fact that In 1994, Spiro et al. [21] from the Memorial Sloan-
the posterior border of dissection in all these selective pro- Kettering Cancer Center, New York, pointed out that the
cedures, except for the anterior dissection, is the cuta- classification of neck dissections according to Robbins et
neous branches of the cervical plexus [18]; otherwise the al. [17] does not cover all possible operations and suggest-
risk of neck recurrences can be high [19, 20]. Another ed a new classification. They defined a neck dissection as
aspect to be taken into consideration is the fact that radical when four or five lymph node levels are excised
although the spinal accessory nerve, the internal jugular (this includes patients who have an otherwise classical
vein, and the sternocleidomastoid muscle are preserved in neck dissection for supraglottic or hypopharyngeal cancer
the majority of these types of dissections, there is no rea- sparing level I nodes). A selective neck dissection was
son why at least one of these three nonlymphatic struc- defined as any lymphadenectomy that encompassed no
tures cannot be sacrified [14]. In such cases, it is necessary more than three nodal levels, usually the supraomohyoid
to modify the actual classification of selective neck dissec- (levels I, II and III), or jugular (levels II, III and IV) nodes.
tions, specifying the specific nonlymphatic structures re- A limited neck dissection is any lymphadenectomy that
moved. removes no more than two nodal levels. Table 3 summa-
The extended neck dissection is the most aggressive of rizes their proposed neck dissection classification [21].
these surgical techniques because additional lymph node
References
11 Bocca E: Surgical management of supraglottic 20 Clayman GL, Frank DK: Selective neck dissec-
1 Beahrs OH: Surgical anatomy and technique of cancer and its lymph node metastases in a con- tion of anatomically appropriate levels is as
radical neck dissection. Surg Clin North Am servative perspective. Ann Otol Rhinol Laryn- efficacious as modified radical neck dissection
1977;57:663–700. gol 1991;100:261–267. for elective treatment of the clinically negative
2 Crile G: Excision of cancer of the head and 12 Houck JR, Medina JE: Management of cervical neck in patients with squamous cell carcinoma
neck with special reference to the plan of dis- lymph nodes in squamous carcinomas of the of the upper respiratory and digestive tracts.
section based upon one hundred thirty-two head and neck. Semin Surg Oncol 1995;11: Arch Otolaryngol Head Neck Surg 1998;124:
operations. JAMA 1906;47:1780–1786. 228–239. 348–352.
3 Martin H, Del Valle B, Ehrlich H, Cahan WB: 13 Traynor SJ, Cohen JI, Gary J, Andersen PE, 21 Spiro RH, Strong EW, Shah JP: Classification
Neck dissection. Cancer 1951;4:441–499. Everts EC: Selective neck dissection and the of neck dissection: Variations on a new theme.
4 Ogura JH, Bello JA: Laryngectomy and radical management of the node-positive neck. Am J Am J Surg 1994;168:415–418.
neck dissection for carcinoma of the larynx. Surg 1996;172:654–657. 22 Conley JJ, Von Frankel PH: Historical aspects
Laryngoscope 1952;62:1–52. 14 Pellitteri PK, Robbins KT, Neuman T: Ex- of head and neck surgery. Ann Otol 1956;65:
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CE, Ferlito A (eds): Surgery for Cancer of the tion of neck dissection nomenclature. Head 24 Turkula LD, Woods JE: Limited or selective
Larynx and Related Structures. Philadelphia, Neck Surg 1987;10:75–77. nodal dissection for malignant melanoma of
Saunders, 1996, pp 299–324. 16 Medina JE Editorial: A rational classification the head and the neck. Am J Surg 1984;148:
7 Suarez O: El problema de las metastasis linfáti- of neck dissections. Otolaryngol Head Neck 446–448.
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ringe. Rev Otorrinolaringol 1963;23:83–99. 17 Robbins KT, Medina JE, Wolfe GT, Levine ing-based classification for the cervical nodes
8 Bocca E, Pignataro O: A conservation tech- PA, Sessions RB, Pruet CW: Standardizing designed as an adjunct to recent clinically
nique in radical neck dissection. Ann Otol neck dissection terminology. Official report of based nodal classifications. Arch Otolaryngol
1967;76:975–987. the Academy’s Committee for head and neck Head Neck Surg 1999;125:388–396.
9 Calearo CV, Teatini G: Functional neck dissec- surgery and oncology. Arch Otolaryngol Head 26 Robbins KT: Classification of neck dissection.
tion. Anatomical grounds, surgical technique, Neck Surg 1991;117:601–605. Current concepts and future considerations.
clinical observations. Ann Otol Rhinol Laryn- 18 Ferlito A, Rinaldo A: Selective lateral neck dis- Otolaryngol Clin North Am 1998;31:639–655.
gol 1983;92:215–222. section for laryngeal cancer in the clinically 27 Shah JP, Strong E, Spiro RH, Vikram B: Neck
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Functional neck dissection: An evaluation and 1998;112:921–924. ties. Clin Bull 1981;11:25–33.
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942–945. node dissection in patients with squamous car-
cinoma of the larynx or pharynx. Am J Surg
1993;166:399–402.
© 2000 S. Karger AG, Basel Alfio Ferlito, MD, Professor and Chairman
ABC 0301–1569/00/0624–0217$17.50/0 Department of Otolaryngology-Head and Neck Surgery
Fax + 41 61 306 12 34 University of Udine, Policlinico Città di Udine
E-Mail karger@karger.ch Accessible online at: Viale Venezia 410, I–33100 Udine (Italy)
www.karger.com www.karger.com/journals/orl Tel. +39 0432 239302, Fax +39 0432 532179, E-Mail clorl@dsc.uniud.it
sents a source of potential failure that exceeds the risk of disconcerting to note that approximately 20–30% of no-
failure at the primary site. Our concepts of appropriate dal metastases may be unrecognized by pathologists on
management of the neck in laryngeal and other head and routine final histological examination [8]. Reintgen and
neck cancers have also evolved extensively during the Shivers [9], in a recent editorial published in Cancer,
same period, with development of an armamentarium of emphasize the fact that such examination may fail to
surgical procedures of various extent as well as the use of detect low volume micrometastatic disease.
irradiation for definitive or adjuvant therapy. Decisions It has become conventional to describe any neck that
regarding management of the neck in laryngeal cancer appears clinically negative as N0. However, the classifica-
must be considered for the patient with no clinical evi- tion of N0 necks suggested by Ferlito and Rinaldo [10]
dence of neck disease (elective treatment of the neck), as may be more useful. The N0 neck may be either clinically,
well as for the patient with clinically evident cervical radiologically or pathologically negative. The pathologi-
metastases (therapeutic treatment of the neck). cally negative neck may further be defined by convention-
al histological examination (pN0, hematoxylin and eosin),
immunohistochemistry (pN0, immunohistochemistry),
Elective Treatment of the Neck or molecular analysis (pN0, molecular analysis). In fact, a
neck that is N0 on conventional pathologic evaluation
Staging the Clinically Negative Neck may be positive by either immunohistochemical or mo-
Detection and staging of cervical lymph node disease, lecular analysis. The reported incidence of micrometas-
particularly when not clinically evident, continues to tases may vary according to the method used for detection
present a major challenge to the head and neck oncologist. (e.g. semiserial sections and/or histochemistry for cyto-
The status of the cervical lymph nodes, important for its keratins and molecular analysis) [7, 11–13]. While such
prognostic and therapeutic implications, is difficult to reporting obviously has staging implications, the clinical
evaluate in the absence of palpable or radiologically impact of such information is unclear, as the staging sys-
obvious metastases. The reported false negative rate in tems and treatment reports have previously been based
assessing the presence or absence of cervical lymph node upon standard hematoxylin and eosin staining.
metastasis by palpation is 20–51% [1]. Factors affecting
this large variance include not only the experience of the Treatment of the Clinically Negative Neck
examiner and the patient’s body habitus, but also pre- The surgeon should be aware of the relatively high inci-
vious treatment such as surgery or radiotherapy. There is dence of micrometastases in patients with laryngeal can-
extensive evidence that even the most sensitive and tech- cer to establish optimal treatment approaches. Therapeu-
nologically advanced procedures (computed tomography, tic decisions regarding the neck must also be undertaken
magnetic resonance imaging, ultrasound, ultrasound- in context with the size, site, phenotype and treatment
guided fine needle aspiration biopsy, single photon emis- plan for the primary cancer. Elective neck dissection or
sion computed tomography, positron emission tomogra- elective neck irradiation, using a dose of 5,000 rad, are
phy, lymphangiography, radioimmunoscintigraphy, and indicated in reducing the incidence of recurrence in the
radionuclide scanning) may be unable to reveal microme- clinically negative neck, and these treatments may reduce
tastases preoperatively [2–4]. the risk of distant metastases. The choice of surgery or
Clinical and pathologic assessment of lymphatic me- irradiation for elective treatment of the clinically negative
tastases may also be difficult to assess. Evidence of meta- neck often depends on the treatment chosen for the pri-
static infiltration in neck nodes may be minimal, showing mary cancer: neck dissection if surgery has been used to
no change in size, macroscopic morphology, or consisten- treat the primary cancer, or irradiation if that modality
cy [5]. The surgeon often cannot distinguish whether a has been employed for the primary tumor.
node is positive for cancer by palpating and closely exam- The role of elective treatment of the neck in laryngeal
ining it intraoperatively. Frozen section biopsy is a valu- cancer continues to be controversial, and variations in
able tool for intraoperative evaluation of suspect nodes type and extent of surgical dissection have evolved. Op-
[6], although even neck nodes reported as pathologically tions for elective treatment include neck dissection, irra-
disease-free following light microscopic study may not diation, observation with subsequent salvage neck dissec-
truly be free of occult metastases. This may be due to dis- tion if clinical evidence of metastases emerges (the ‘wait-
ease located at another level in the lymph node or, rarely, and-see’ policy), or intraoperative examination of the sen-
to having been overlooked by the microscopist [7]. It is tinel lymph node (sentinel lymphadenectomy) with im-
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657–669. 1294–1315. Tjho Heslinga RE, de Jong JM: T3 laryngeal
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