Eugene N. Myers, MD Johannes J. Fagan, Mbchb, Fcs(Sa)
In the Department of Otolaryngology at the University of Pittsburgh
School of Medicine, cancer of the larynx is usually treated surgically.
Radiation therapy is used as adjuvant treatment in certain patients
who have cancer that has adverse histologic features such as perineural,
vascular, and/or cartilage invasion. With this approach, patients
rarely develop local recurrence.
Patient outcome is therefore unlikely to be improved by changing
the management of the primary tumor. Patient outcome may, however,
be further improved by reducing the incidence of recurrence, in the
neck as well as distant. Hence, we have adopted an aggressive surgical
approach both to the cN+ as well as the N0 neck. The theoretical
basis for this aggressive surgical approach to the neck will be considered
under the following headings: staging, regional control, distant
metastasis, survival, choice of neck dissection, and the pathologically
positive elective neck dissection.
It is reasonable to assume that occult nodal metastasis will become
clinically apparent if left untreated, as the incidence of histologically
positive nodes in electively treated necks corresponds with the nodal
conversion rate of untreated N0 necks.(1) Understaging, and consequent
undertreatment, of the occult positive neck is therefore likely to
adversely affect regional control and survival. The central issue
pertaining to the various staging modalities is the sensitivity,
or false-negative rate, in the N0 neck. Specificity only assumes
importance when the treatment of the false-positive neck has significant
associated morbidity. Because approximately 12% of tumor-positive
neck dissections contain only micrometastases, current preoperative
staging modalities are unable to exceed a sensitivity of 88%.(2)
The sensitivity of preoperative staging is further reduced by an
estimated false-negative rate of 7.5% for pathological staging of
elective neck dissection specimens.(3)
Computed tomography (CT) scanning, magnetic resonance imaging (MRI),
and ultrasound use nodal size as a criterion for malignancy. There
is, however, a trade-off between sensitivity and specificity when
nodal diameter is used to stage the N0 neck. The smaller the minimum
nodal diameter used as a criterion for malignancy, the greater the
sensitivity, but the lower the specificity, and vice versa. Most
authorities recommend a minimum nodal size criterion for malignancy
of 10 mm (4). Yet the great majority of lymph node metastases in
the N0 neck are smaller than 10 mm in diameter(4); nonmalignant nodes
may vary in size between 2 mm and 2 cm.(5) Although 74% of lymph
node metastases have central necrosis, this percentage is much reduced
in smaller nodes found in the N0 neck.(4)
Ultrasound- guided fine needle aspiration cytology (USGFNAC) has
overcome the problems relating to specificity associated with CT,
MRI, and ultrasound alone. Using a cutoff diameter of 3 mm, USGFNAC
has a sensitivity of 76%, a specificity of 100%, and an accuracy
of 89% in the N0 neck.(6) Even when these results are adjusted for
pathological Understaging, USGFNAC is currently the most accurate
preoperative staging modality. Whether these results are, however,
reproducible outside a center of excellence is open to question.
Extracapsular spread (ECS) is an important prognostic indicator
of regional and distant failure and survival.(7-10) It is important
to identify patients with ECS, as, they appear to benefit from adjuvant
radiation and chemotherapy. (1,11-15) Extracapsular spread occurs
in 23% of metastatic nodes <10 mm in diameter.(8) Should reliance
be placed on imaging alone to stage the N0 neck, then a significant
number of patients with ECS would remain untreated until cervical
metastasis becomes clinically apparent.
Because of the limitations of imaging, and because USGFNAC is labor-intensive,
time-consuming, and expensive, we do not rely on imaging, but use
elective neck dissection in combination with intraoperative and pathological
evaluation to stage and plan the treatment of the N0 neck.
Intraoperative diagnosis of occult metastasis in the clinically
N0 neck has a sensitivity of 44% and a specificity of 63% when reliance
is placed on the surgeon's ability to evaluate lymph nodes by inspection
and palpation only. Frozen section diagnosis of malignancy has a
sensitivity and specificity of 100% per suspicious node. In N0 necks
judged by the surgeon to harbor occult metastasis, frozen section
has a sensitivity of 71 %, a specificity of 100%, and an accuracy
of 92.3 % per neck. (16) It has been our practice to sample suspicious
nodes discovered at the time of elective neck dissection, and to
submit the nodes for frozen section. If metastasis is diagnosed by
frozen section, then the staging neck dissection is converted to
a therapeutic neck dissection, usually modified neck dissection type
1.
A philosophy of aggressive surgical staging therefore has a number
of benefits. The risk of understaging the N0 neck is minimized. Patients
with ECS who are at high risk for recurrent cancer, and that often
benefit from adjuvant radiation and chemotherapy, can be identified.
The use of radiation therapy is reserved for the ECS group, and is
therefore used sparingly, appropriately, and effectively.
There are a number of reports of significant improvement in regional
control if the N0 neck is treated by elective neck dissection with
or without adjuvant radiation, as opposed to watchful waiting.(17-21)
It has been proposed that elective neck dissection be performed only
if the risk of occult metastasis exceeds 15% to 30%.(1,5,21-23) Corrected
for pathological understaging,(3) 22% to 37% of patients treated
by watchful waiting might ultimately fail in the neck if such a management
policy was to be followed. Only 11% to 56% of patients managed by
watchful waiting and that subsequently fail in the neck are successfully
salvaged.(23-26) We therefore consider the above-mentioned thresholds
for elective neck dissection to be unacceptably high.
Extracapsular spread is associated with increased risk of regional
failure.(8,27) The incidence of ECS correlates with nodal size, and
occurs with 23% of nodes <1 cm, 44% of nodes 1 to 2 cm, 53 % of
nodes 2 to 3 cm, and 74% of nodes >3 cm.(8) Small metastatic nodes
without ECS, if left untreated, will increase in size and may subsequently
manifest ECS. By intervening early in the course of the disease,
elective neck dissection may theoretically prevent this progression
to ECS. Adjuvant radiation therapy, and possibly chemotherapy, improves
regional control in patients with ECS. (1, 11,13-15) Elective neck
dissection permits earlier detection of patients with ECS who may
benefit from adjuvant therapy.
Said somewhat differently, while watchful waiting will detect many
patients who are operable, some will present with inoperable neck
disease.(28) Many of the operable group will be incurable because
of extensive ECS at presentation. Not doing elective neck dissections
therefore deprives some of these patients of the opportunity to be
cured.
The incidence of distant metastasis is related to tumorburden in
the neck, (1,7,29,30) the duration of nodal metastasis,(31) the number
(7) and level (2,7.29) of nodal metastases, and the presence of ECS.(7.32)
Metastasis to lymph nodes generally first involves the primary and
secondary echelons, and then spreads down the neck, toward the superior
mediastinum.(2) Elective neck dissection should reduce the risk of
distant metastasis by minimizing tumor burden, restricting the duration
of metastasis, and reducing the number of nodes, and has been shown
to reduce the likelihood of involvement of the lower levels of the
neck. (19) We recently reported the use of chemoradiation in patients
with ECS. Despite the nonrandomized nature of the study, it would
appear that chemoradiation did improve patient outcome. (15) Elective
neck dissection permits the early identification of patients with
ECS who may benefit from chemoradiation.
From the preceding discussion, it is reasonable to assume that an
aggressive surgical approach to the N0 neck should not only increase
disease-free interval, but also improve survival. The survival benefit
of elective neck dissection, as opposed to watchful waiting for head
and neck squamous carcinoma is, however, unproven. Two prospective
randomized studies of elective neck dissection versus watchful waiting
in N0 squamous carcinoma of the head and neck reported no significant
difference in survival.(33,34) Neither study, however, had adequate
power to detect a significant difference in outcome.(31,35) In the
study by Vandenbrouck et al,(34) 45% of deaths were unrelated to
regional failure. The study by Fakih et al (33) did not control for
ECS, tumor margins, or contralateral regional failure, and median
follow-up was only 20 months.
The decision to perform elective or comprehensive neck dissection,
and whether to perform ipsilateral or bilateral neck dissection,
is determined principally by tumor site, extent, and intraoperative
staging. Laryngeal carcinoma rarely metastasizes to level I (12,36-39)
or V.(36,39-41) Elective neck dissection, with sparing of levels
I and V, is therefore an appropriate staging and therapeutic measure
if performed electively when occult metastasis, if at all present,
is likely to be confined to the first-echelon nodes. Should there
be evidence of nodal metastasis at the time of elective neck dissection,
then there is an increased likelihood of involvement of levels I
(39,42) and V, (36,39,40,42) and a comprehensive neck dissection
should be performed.
 Table
1 (12,14,21,32,36.39,43-48) summarizes the reported incidence of
occult ipsilateral lymph node metastasis in accordance with the location
of the laryngeal tumor. On the basis of this data, we recommend elective
ipsilateral neck dissection (levels II through IV) with supraglottic,
transglottic, and advanced glottic carcinoma. Level VI (including
thyroid lobectomy) is routinely dissected with glottic and subglottic
carcinoma. The subglottis drains principally to the paratracheal,
pretracheal, and prelaryngeal lymphatic s.(47,49) Carcinoma of the
subglottis has a 65% incidence of occult paratracheal nodal metastasis,(47)
and may involve the thyroid gland by direct extension and/or by lymphatic
spread.(49) Inadequate treatment of the paratracheal lymphatics and
the thyroid gland are the principal reasons for the association of
subglottic carcinoma with peristomal recurrence.(50-52) it has therefore
been proposed that management of carcinoma of the subglottis should
include dissection of level VI, a total thyroidectomy, and adjuvant
radiation therapy to the lower neck and superior mediastinum.(49,50,52)
Elective dissection of the contralateral neck is governed by tumor
site,as shown in table 2 (18.25,46,53,54). Carcinoma of the glottis
(25,53) uncommonly metastasizes to the contralateral neck, and does
not require contralateral neck dissection.  An
exception to this policy is tumor extension through the paraglottic
space to involve the medial wall of the pyriform fossa, as tumors
involving the medial wall of the pyriform fossa have a propensity
for bilateral lymphatic metastasis.(18) Tumors involving the supraglottis
similarly require bilateral elective neck dissection s (25,54) (levels
II-IV; Table 3).
When nodal metastasis is detected on routine pathological examination
of an elective neck dissection specimen, the surgeon has the following
therapeutic options: 1) completion neck dissection, 2) adjuvant radiation
and/or chemotherapy, and 3) watchful waiting. The success of salvage
neck dissection depends on the mobility of the nodal recurrences.
Surgical salvage is therefore rarely successful with regional failure
following radical neck dissection. (8,55) Good salvage rates can,
however, be expected following elective neck dissection for recurrences
within levels not previously dissected.(55)
Factors that may influence the indications for and choice of additional
therapy include the number and distribution of nodal metastases,
ECS, and the need for adjuvant therapy to the primary tumor bed.
We have previously reported that the presence or absence of nodal
metastasis, in the absence of ECS, does not affect outcome of patients
treated with neck dissection.(9,27) We generally would not give adjuvant
therapy to patients who have occult metastasis in an elective neck
dissection specimen, unless there is extensive nodal metastasis approaching
the perimeter of the dissection, or ECS, or if the patient requires
adjuvant radiation therapy for the laryngeal primary tumor.
An aggressive surgical approach to the neck in laryngeal carcinoma
has a number of potential benefits. It ensures accurate staging and
improves regional control. By improving regional control and by permitting
early identification of patients who may benefit from adjuvant therapy,
the incidence of distant metastasis should be reduced, and survival
improved.
1. Snow GB, Patel P, Leemans CR, Tiwari R. Management of cervical
lymph nodes in patients with head and neck cancer. Eur Arch Otorhinolaryngol
1992;249:197-94.
2. van den Brekel MWM, Snow GB. Assessment of lymph node metastases in the
neck. Eur J Cancer B Oral Oncol 1994; 30B:98-92.
3. De Santo LW, Hold JJ, Beahrs OH, O'Fallon WM. Neck dissection: is it worthwhile?
Laryngoscope 1982;92:502-9.
4. van den Bickel MWM, Casielijns JA, Snow GB. Detection of lymph node metastases
in the neck: radiologic criteria. Radiology 1994;192:617-8.
5. Ali S, Tiwari RM, Snow GB. False positive and false negative neck nodes.
Head Neck Surg 1985;8:78-82.
6. van den Brekel MWM, Stell HV, Castelijns JA, Croll GA. Snow GB. Lymph node
staging in patients with clinically negative neck examinations by ultrasound
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7. Leenians CR, Tiwari R, Natita JJP, van der Waal 1, Snow GB. Regional lymph
node involvement and its significance in the development of distant metastases
in head and neck carcinoma. Cancer 1993, 71:452-6.
8. Snow GB, Annyas AA, Van Slooten EA, Bartelink H. Hart AA. Prognostic factors
of neck node metastasis. Clin Otolaiyngol 1982~7:185-92.
9. JohnsonJT. Myers EN, Bedelli CD, Barnes EL, Schramm Vl_ Thearle PB, Cervical
lymph node metastases: incidence and implications of extracapsular carcinoma.
Arch Otolaryngol 1985; 111:534-7.
10. Hirayabashi H, Koshii K, Uno K, et al. Extracapsular spread of squarnous
carcinoma in neck lymph nodes: prognostic factor of laryngeal cancer. Laryngoscope
1991;101:502-6.
11. Annyas AA, Snow GB, van Slooten EA, et al. Prognostic factors in neck node
metastasis: their impact on planning a treatment regime. Read before the American
Society of Head and Neck Surgeons, Los Angeles, Calif, April 6, 1979.
12. Byers RM. Modified neck dissection. A study of 967 cases from 1970-1980.
Am I Surg 1985; 150:414-21.
13. Byers RM, Wolf PF, Ballantyne AJ. Rationale for elective modified neck
dissection. Head Neck 1988; 10: 160-7.
14. Snyderman NL. Johnson JT, Schramm VL, Myers EN, Bedetti CD, Thearle P.
Extracapsular spread of carcinoma in cervical lymph nodes: impact upon survival
in patients with carcinoma of the supraglottic larynx. Cancer 1985:56:1597-9.
15. Johnson IT, Wagner RL, Myers EN. A long-term assessment of adjuvant chemotherapy
on outcome of patients with extracapsular spread of cervical metastases from
squamous carcinoma of the head and neck, Cancer 1996;77:181-5.
16. Rassekh CH, Johnson IT, Myers EN. Accuracy of intraoperative staging of
the N0 neck in squamous cell carcinoma. Laryngoscope 1995; 105:1334-6.
17. Cachin Y. Management of cervical nodes in head and neck cancer. In: Rhys
Evans PH, Robin PE, Fielding JWL, eds. Head and neck cancer. London. England:
Castle House Pub] ications Ltd, 1983:168-77.
18. Johnson IT, Bacon GW, Myers EN, Wagner RL. Medial vs lateral wall pyriform
sinus carcinoma. Head Neck 1994; 16: 401-5.
19. Hughes CJ, Gallo 0, Spiro RH, Shah JP. Management of occult metastases
in oral cavity squamous cell carcinoma. Am I Surg 1993;166:380-3.
20. Weber PC, Johnson IT, Myers EN. The impact of bilateral neck dissection
on pattern of recurrence and survival in supraglottic carcinoma. Arch Otolaryngol
Head Neck Surg 1994; 120:703-6.
21. Ogura JH, Biller HF, Wette R. Elective neck dissection for pharyngeal and
laryngeal cancers. An evaluation. Ann Otol Rhino Laryngol 1971~80:646-53.
22. Bocca E, Pignataro 0, Oldini C. Cappa MD. Functional neck dissection: an
evaluation and review of 843 cases. Laryngoscope 1984;94:942-5.
23. Weiss MH, Harrison LB, Isaacs RS. Use of decision analysis in planning
a management strategy for the stage N0 neck. Arch Otolaryngol Head Neck Surg
1994; 120:699-702.
24. Ho CM, Lam KH, Wei WI, Lau SK, Lain LK. Occult lymph node metastasis in
small oral tongue cancers. Head Neck 1992;14:359-63.
25. Biller HF, Davis WH, Ogura JH. Delayed contralateral cervical metastasis
with laryngeal and hypopharyngeal cancers. Laryngoscope 1971;81:1499-502.
26. Yuen AP, Ho CM, Wei WI, Lam LK. Prognosis of recurrent laryngeal carcinoma
after laryngectomy. Head Neck 1995;17:526-30.
27 ' Johnson IT, Barnes EL, Myers EN, Schramm VL, Borochovitz D, Sigler BA.
The extracapsular spread of tumors in cervical node metastases. Arch Otolaryngol
1981:107:725-9.
28. Yuen AP, Wei WL No CM. Results of surgical salvage for radiation failures
oflaryngeal carcinoma. Otolaryngol Head Neck Surg 1995; 112:405-9.
29. Grandi C, Alloisio E, Moglia D, et al. Prognoqticsignificance of lymphatic
spread in head and neck carcinoma: thei apeutic implications. Head Neck Surg
1985;9:67-73.
30 * Ellis ER, Mendenhall WM, Rao PV. ParsonsJT, Spangler AE. Million RR. Does
node location affect the incidence of distant metastases in head and neck carcinoma?
Int J Radiat Oncol Biol Phys 1989; 17:293-7.
31. Steiner W, Hommerich CP. Diagnosis and treatment of the N0 neck of carcinomas
of the upper aerodigestive tract. Report of an International Symposium, Gottingen,
Germany, 1992. Ear Arch Otodiinolaryngol 1993;250:450-6.
32. Johnson JT, Myers EN, Hao S-P, Wagner RL. Outcome ofopen surgical therapy
for glottic carcinoma. Ann Otol Rhinol Laryngol 1993; 102:752-5.
33. Fakifi AR, Rao RS, Borges AM, Patel AR. Elective vs therapeutic neck dissection
in early carcinoma of the oral tongue. Am J Surg 1989; 158:309-13.
34. VandenbrouckC, Sancho-GamierH, ChassagneD, Saravane D, Cachin Y, Micheau
C. Elective versus therapeutic radical neck dissection in epidernmid carcinoma
of the oral cavity. Cancer 1980;46:386-90.
35. Davidson J, Bient J, Detsky A. The clinically negative neck in patients
with early oral cavity carcinoma: a decisionanalysis approach to management.
J Otolaryngol 1995:24:323-9.
36. Candela FC, Shah J, Jaques DP, Shah JP. Patterns of cervical node metastases
from squamous carcinoma of the larynx. Arch Otolaryngol Head Neck Sing 1990;
116:432-5.
37. Feldman DE, Applebaum EL. The submandibular triangle in radical neck dissection.
Arch Otolaryngol 1977; 103:705-6.
38. Lindberg R. Distribution of cervical nodal metastases from squamous cell
carcinoma of the upper respiratory and digestive tracts. Cancer 1972;229:1446-9.
39. Shah JP. Patterns of cervical lymph node metastasis from squamous carcinoma
of the upper aerodigestive tract. Am J Surg 1990;160:405-9.
40. Davidson BJ, Kulkamy V. Delacure MD, Shah JP. Posterior triangle metastases
of squamous cell carcinoma of the upper aerodigestive tract. Am J Surg 1993;
166:395-8.
41. Skolnik EM, Yee KF, Friedman M, Goldman TAL The posterior triangle in radical
neck surgery. Arch Otolaryngol 1976; 102:1-4.
42. Kowalski LP, Franco EL, de Andrade Sobrinho J. Factors influencing regional
lymph node metastasis from laryngeal carcinoma. Ann Otol Rhinol Laryngol 1995;104:442-7.
43. Hao S, Myers EN, Johnson JT. T3 glottic carcinoma revisited - transglottic
vs pure glottic carcinoma. Arch Otolaryngol Head Neck Surg 1995121:166-70.
44. Mittal B, Marks JE, Ogura JH. Transglottic carcinoma. Cancer 1984;53:151-61.
45. Ramadan HH, Allen GC. The influence of elective neck dissection on neck
relapse in N0 supraglottic carcinoma. Am J Otolaryngol 1993; 14:278-81.
46. Levendag P, Vikram B. The problem of neck relapse in early stage supraglottic
cancer: results of different treatment modalities for the clinically negative
neck. Int Radiat Oncol Biol Phys 1987;46:1621-4.
47. Harrison DFN. The pathology and management of subglottic cancer. Ann Otol
Rhino] Laryngol 197 1;90:6-12.
48. Jones AS, Stell PM. Is laterality important in neck node metastases in
head and neck cancer? Clin Otolaryngol 199 1; 16: 261-5.
49. Fagan JJ, Kaye PV. Management of the thyroid gland with laryngectomy for
cT3 glottic carcinoma. Clin Otolaryngol (in press).
50. Fagan JJ, Loock JW. Tracheostomy and peristomal recurrence. Clin Otolaryngol
(in press).
51. Rubin J, Johnson JT, Myers EN. Stoma] recurrence after laryngectomy: interrelated
risk factor study. Otolaryngol Head Neck Surg 1990; 103:805 -12.
52. Harrison DFN. The thyroid gland in the management of laryngopharyngeal
cancer. Arch Otolaryngol 1973;97:301-2.
53. Till JE, Bruce WR, Elwan A,et al. A preliminary analysis of the end results
for cancer of the larynx. Laryngoscope 1975; 85:259-75.
54. Lutz CK, Johnson JT, Wagner RL, Myers EN. Supraglottic carcinoma: patterns
of recurrence. Ann Otol Rhinol Laryngol 1990;99:12-7.
55. Grandi C, Mingardo M, Guzzo M, Licitra L, Podrecca S. Molinari R. Prognostic
significance of lymphatic spread in head and neck carcinoma: therapeutic implications.
Head Neck Surg 1985;8:67-73
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