Updated: Aug 20, 2007
The treatment of patients with N0 squamous cell carcinoma (SCCA) of the head and neck remains controversial. The negative impact of regional lymph node metastases on the survival in patients with SCCA of the upper aerodigestive tract has been well established. The presence of lymph node metastases is the most important prognostic factor for survival in head and neck SCCA. Histologically proven lymph node metastasis increases the stage to 3 and may decrease survival by 50%.
Watchful waiting until a patient with an N0 neck develops detectable neck disease has been shown to significantly decrease survival. Elective or prophylactic neck dissection improves regional control, and the results of salvage surgery for N0 neck, which were observed and have progressed to N+ neck, are poor. Therefore, the challenge of caring for patients with an N0 neck lies in identifying which patients are at risk for developing lymph node metastases in order to treat those patients prophylactically and to decrease the risk of neck failure in the neck.
The basic rule for prophylactic treatment of the N0 neck is to treat any patient whose risk of occult lymph node metastases is greater than 15%. The risk of regional lymph node metastases varies according to primary site and stage. Areas such as the glottis carry a relatively low risk (< 4% for a T1 lesion), whereas the risk in a site such as the tongue base is as high as 55%. The prevalence of occult neck metastases by site is as follows:
The following are the lymphatic drainage nodes and the corresponding tumor locations from which they receive drainage:
Obtain patient's history and perform a complete head and neck physical examination. Although detailing a proper history taking for a head and neck examination is beyond the scope of this chapter, the following signs and symptoms should increase the index of suspicion for possible malignancy:
The indication for treating the N0 neck with surgery or radiation is a risk of occult metastases in excess of 15-20%.
Surgery (elective neck dissection) is indicated if the patient is undergoing surgery for the primary lesions. This approach allows accurate staging because it is supported by histologic studies.
Radiation is indicated in the following situations:
During physical examination or during neck dissection, anatomical boundaries are used to identify the lymph nodal levels. The radiologic boundaries are used as reference points during the reading of radiologic images and identification lymph node nodal levels.
The anatomical and radiologic nodal boundaries are as follows:
| Modality | Sensitivity | Specificity |
| Ultrasound | 50-58% | 75-82% |
| CT | 40-68% | 78-92% |
| MRI | 55-93% | 82-95% |
| PET* | 87-90% | 80-93% |
| CT-PET | 96% | 98.5% |
Histology is important in determining the best treatment for patients with oral cavity cancer and an N0 neck. Tumors with an invasion depth of more than 3 mm have been shown to have a significantly higher rate of occult lymph node metastasis (>20%) and require prophylactic treatment of the neck. Although tumor thickness has been studied in other head and neck sites, including the larynx, this finding has proved to be significant only in the oral cavity cancer.
A study by Lim et al regarding predictive markers for late cervical metastasis in stage 1 and 2 invasive SCCA of the oral tongue showed that, in a univariate analysis, tumor thickness, Broder grade, nest shape, mode of invasion, Anne Roth score, Byrne score, and E-cadherin expression correlated with late cervical metastasis.1 Multivariate analysis in the same study also revealed that tumor thickness, mode of invasion, grade 3 or 4, and low E-cadherin expression were independent factors for cervical metastasis. Other variables for occult metastasis include age of over 65 years with advance T stage, vascular invasion, and perineural invasion.
Treatment is planned after preoperative evaluation confirms the N0 status of the patient. If the likelihood of metastasis is low ( <15%), watchful waiting is appropriate. However, if the primary tumor contains aggressive characteristics such as perineural invasion, deep penetration (more than 3mm in the oral cavity), or angiolymphatic invasion, prophylactic treatment is necessary.
Radiation has been shown to control regional recurrences in 95% of cases in which the primary site remains free of disease. Radiation has the advantage of decreased operative time, lacks the morbidity of neck dissection (shoulder discomfort), and is usually necessary to treat the primary site. Disadvantages include neck stiffness, skin changes, loss of hair in the treatment field, xerostomia, and increased morbidity and mortality if surgery in the irradiated area becomes necessary.
Surgery for the N0 neck has changed significantly and morbidity has greatly decreased. The first description of the radical neck dissection by George Crile in 1906 explains the importance of the fascial envelops that contains the lymph nodes that drain specific head and neck sites. These principles still apply today as the philosophy behind functional neck dissection.
Selective neck dissection is the mostly commonly used surgical therapy today in treating the N0 neck. The main advantages of selective neck dissection include pathologic identification of metastases (more accurate staging) and removal of occult disease. In selective neck dissection, nodal tissue is removed from the zones specifically related to the drainage patterns of a particular site. The internal jugular vein, sternocleidomastoid muscle (SCM), and spinal accessory nerve are preserved.
The oral cavity lymphatics drain into levels 1, 2, and 3, while the oropharynx, hypopharynx, and larynx drain into levels 2, 3, and 4.
Supraomohyoid neck dissection includes levels 1, 2, and 3 and is used to treat cancer of the oral cavity, some oropharyngeal cancers, and other cancers that drain to this nodal basin.
Lateral neck dissection includes levels 2, 3, and 4 and is used in patients with cancer of the hypopharynx, larynx, and other cancers that drain to this nodal basin. Level 2 dissection requires dissection of the fibrofatty tissue around the jugular, digastric, and spinal accessory nerve.
Modified radical neck dissection involves dissection of nodal basins 1-5 with preservation of the internal jugular vein, SCM, and the spinal accessory nerve. Because the incidence of nodal metastasis that involves level 5 in a clinically and radiologically negative neck or N0 neck is low (4%), the modified radical neck dissection is seldom used.
Retropharyngeal lymph node dissection is controversial for the N0 neck. The frequency of positive retropharyngeal node involvement in pyriform sinus with oropharyngeal invasion, postcricoid tumors, and tumors of the posterior wall are as follows:
In a study by Yoshimoto and Kawabata, patients with positive retropharyngeal nodes tend to have poor control rates; retropharyngeal node dissection did not improve survival.2 A study on the prognostic influence of retropharyngeal adenopathy by Dirix noted more local recurrence (45%), and disease-free survival was significantly lower in the patients with retropharyngeal nodes. McLaughlin et al also noted that retropharyngeal adenopathy is a strong predictor of poor prognosis.3 However, other studies by Shimizu et al and Gross et al revealed that no significant difference between survival rates and local recurrences can be found in patients with and without retropharyngeal lymph node metastasis.4
Another area of controversy is level 2B node dissection. A study by Elsheikh on level 2B nodes after supraomohyoid neck dissection for oral SCCA revealed that 31% were positive by histopathological analysis.5 However, when molecular analysis was used, level 2B positivity increased to 45%. No instance of isolated metastasis to level 2B lymph nodes without involvement of other nodes was found.
Level 2B node dissection should be considered in histologically positive nodes in the N0 neck, histologically positive nodes in level 2 or 3, primary tumors in the pharynx, extracapsular spread in the lymph node, tongue cancers, tonsillar cancer, skin cancer that drains to level 2, and parotid cancers.
Level 2B involvement in laryngeal cancer in an N0 neck is rare. The prevalence of level 2B metastasis is 1% in the N0 neck. Therefore, level 2B dissection can be avoided in the clinically N0 neck, which in turn prevents postoperative shoulder dysfunction. However, studies have shown that the prevalence of level 2B metastasis in a clinically positive neck is 37%.
Cancer of the head and neck metastasizes in an orderly manner; however, skip metastasis or discontinuous metastasis can occur. The incidence of skip metastasis to level 2 and 3 in oral cancer is 10%. The incidence of metastasis to level 4 lymph nodes in tongue cancer is 15.8%. Skip metastasis in cancer of the larynx, glossoepiglottic area, and parotid is uncommon.
The treatment options are as follows
The regional recurrence of a pathologic N0 neck is 1.9% even after neck dissection.
Radiation is indicated following selective neck dissection if 3 or more nodes contain metastases, if extracapsular spread is present, or if a nodal metastasis is found in 2 noncontiguous zones (ie, skip metastases). In patients who meet these criteria, radiation is recommended because it has been shown to significantly decrease the risk of recurrence.
Based on the American Head and Neck Society Practice guidelines, the suggested follow-up schedule is as follows:
Because the local recurrence occurs within 2 years, standard follow-up of patients with head and neck cancer should be based on the individual patient characteristics.
Life-long follow-up is recommended because of the 20% lifetime risk of developing a second primary tumor.
Studies regarding follow-up have implied that most are aware of significant changes and seek early intervention, making strict routines unnecessary. However, head and neck surgeons (otolaryngologist and general surgeons) currently monitor their patient routinely, regardless of whether the patient has any new reports.
Complications of prophylactic neck dissection include the following:
Complications of radiation therapy include the following:
The overall prognosis of patients with an N0 neck is quite good. Surgery and radiation offer control rates in excess of 95%. However, the prognosis changes if the N0 neck is not truly an N0 neck. Lymph nodes metastases identified with prophylactic neck dissection upstage the patient, and patient survival may decrease by 50%. The primary site and prognostic histologic characteristics affect the survival and should be taken into consideration.
Several investigational but promising new methods of early cancer detection are as follows:
The clinician should bear in mind that the most effective treatment of cancer is to treat the cancer in its earliest stage (when its tumor burden is lowest and when the lymphatic spread is least).
Lim SC, Zhang S, Ishii G, et al. Predictive markers for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral tongue. Clin Cancer Res. Jan 1 2004;10(1 Pt 1):166-72. [Medline].
Yoshimoto S, Kawabata K. Retropharyngeal node dissection during total pharyngolaryngectomy for hypopharyngeal cancer. Auris Nasus Larynx. Jun 2005;32(2):163-7. [Medline].
McLaughlin MP, Mendenhall WM, Mancuso AA, Parsons JT, McCarty PJ, Cassisi NJ. Retropharyngeal adenopathy as a predictor of outcome in squamous cell carcinoma of the head and neck. Head Neck. May-Jun 1995;17(3):190-8. [Medline].
Shimizu K, Inoue H, Saitoh M, Ohtsuki N, Ishida H, Makino K. Distribution and impact of lymph node metastases in oropharyngeal cancer. Acta Otolaryngol. Aug 2006;126(8):872-7. [Medline].
Elsheikh MN, Mahfouz ME, Elsheikh E. Level IIb lymph nodes metastasis in elective supraomohyoid neck dissection for oral cavity squamous cell carcinoma: a molecular-based study. Laryngoscope. Sep 2005;115(9):1636-40. [Medline].
Alvi A, Myers EN, Johhnson JT. Cancer of the oral cavity. In: Cancer of the Head and Neck. WB Saunders Co;1996:321-60.
Andersen P. Cervical metastases. In: Essentials of Head and Neck Oncology. 1998;256-265.
Anzai Y, Brunberg JA, Lufkin RB. Imaging of nodal metastases in the head and neck. J Magn Reson Imaging. Sep-Oct 1997;7(5):774-83. [Medline].
Byers RM, Weber RS, Andrews T, et al. Frequency and therapeutic implications of "skip metastases" in the neck from squamous carcinoma of the oral tongue. Head Neck. Jan 1997;19(1):14-9. [Medline].
Chone CT, Crespo AN, Rezende AS, et al. Neck lymph node metastases to the posterior triangle apex: evaluation of clinical and histopathological risk factors. Head Neck. Sep 2000;22(6):564-71. [Medline].
Chong VF, Fan YF. Radiology of the retropharyngeal space. Clin Radiol. Oct 2000;55(10):740-8. [Medline].
Civantos FJ, Goodwin WF Jr. Cancer of the oropharynx. In: Cancer of the Head and Neck. WB Saunders Co;1996:361-80.
Clayman DL, Weber RS. Cancer of the hypopharynx and cervical esophagus. In: Cancer of the Head and Neck. WB Saunders Co;1996:423-38.
Corlette TH, Cole IE, Albsoul N, et al. Neck dissection of level IIb: is it really necessary?. Laryngoscope. Sep 2005;115(9):1624-6. [Medline].
Coskun HH, Erisen L, Basut O. Selective neck dissection for clinically N0 neck in laryngeal cancer: is dissection of level IIb necessary?. Otolaryngol Head Neck Surg. Nov 2004;131(5):655-9. [Medline].
Dirix P, Nuyts S, Bussels B, Hermans R, Van den Bogaert W. Prognostic influence of retropharyngeal lymph node metastasis in squamous cell carcinoma of the oropharynx. Int J Radiat Oncol Biol Phys. Jul 1 2006;65(3):739-44. [Medline].
Ferlito A, Shaha AR, Rinaldo A, et al. "Skip metastases" from head and neck cancers. Acta Otolaryngol. Oct 2002;122(7):788-91. [Medline].
Gavilian J, Herranz-Gonzalez J, Eric J, Lentsch. Cancer of the neck. In: Cancer of the head and neck. 4th edition. Saunders Co;2003:407-430.
Johnson JT, Barnes EL, Myers EN, et al. The extracapsular spread of tumors in cervical node metastasis. Arch Otolaryngol. Dec 1981;107(12):725-9. [Medline].
Keski-Santti H, Atula T, Tornwall J, et al. Elective neck treatment versus observation in patients with T1/T2 N0 squamous cell carcinoma of oral tongue. Oral Oncol. Jan 2006;42(1):96-101. [Medline].
Layland MK, Sessions DG, Lenox J. The influence of lymph node metastasis in the treatment of squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx: N0 versus N+. Laryngoscope. Apr 2005;115(4):629-39. [Medline].
Li XM, Lu XY, Di B. [Role of clonality analysis by X-chromosome inactivation in the diagnosis of cervical lymph node occult micrometastasis from squamous carcinoma of the head and neck]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. Nov 2005;40(11):862-5. [Medline].
Liao CT, Tung-Chieh Chang J, Wang HM, et al. Telomerase as an independent prognostic factor in head and neck squamous cell carcinoma. Head Neck. Jun 2004;26(6):504-12. [Medline].
Lim YC, Lee JS, Koo BS, Choi EC. Level IIb lymph node metastasis in laryngeal squamous cell carcinoma. Laryngoscope. Feb 2006;116(2):268-72. [Medline].
Magnano M, Bongioannini G, Lerda W. Lymphnode metastasis in head and neck squamous cells carcinoma: multivariate analysis of prognostic variables. J Exp Clin Cancer Res. Mar 1999;18(1):79-83. [Medline].
Menda Y, Graham MM. Update on 18F-fluorodeoxyglucose/positron emission tomography and positron emission tomography/computed tomography imaging of squamous head and neck cancers. Semin Nucl Med. Oct 2005;35(4):214-9. [Medline].
Nason RW, Torchia MG, Morales CM, et al. Dynamic MR lymphangiography and carbon dye for sentinel lymph node detection: a solution for sentinel lymph node biopsy in mucosal head and neck cancer. Head Neck. Apr 2005;27(4):333-8. [Medline].
Paleri V, Rees G, Arullendran P, et al. Sentinel node biopsy in squamous cell cancer of the oral cavity and oral pharynx: a diagnostic meta-analysis. Head Neck. Sep 2005;27(9):739-47. [Medline].
Pitman KT, Johnson JT, Edington H, et al. Lymphatic mapping with isosulfan blue dye in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. Jul 1998;124(7):790-3. [Medline].
Po Wing Yuen A, Lam KY, Lam LK, et al. Prognostic factors of clinically stage I and II oral tongue carcinoma-A comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martinez-Gimeno score, and pathologic features. Head Neck. Jun 2002;24(6):513-20. [Medline].
Rodrigo JP, Ferlito A, Suarez C, et al. New molecular diagnostic methods in head and neck cancer. Head Neck. Nov 2005;27(11):995-1003. [Medline].
Rufener JB, Cohen JI. Metachronous spread of parathyroid carcinoma to a retropharyngeal lymph node. Head Neck. Nov 2003;25(11):968-71. [Medline].
Schoder H, Yeung HW, Gonen M, et al. Head and neck cancer: clinical usefulness and accuracy of PET/CT image fusion. Radiology. Apr 2004;231(1):65-72. [Medline].
Schwartz DL, Ford E, Rajendran J, et al. FDG-PET/CT imaging for preradiotherapy staging of head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. Jan 1 2005;61(1):129-36. [Medline].
Screaton NJ, Berman LH, Grant JW. Head and neck lymphadenopathy: evaluation with US-guided cutting-needle biopsy. Radiology. Jul 2002;224(1):75-81. [Medline].
Shah JP. Cervical lymph node metastases--diagnostic, therapeutic, and prognostic implications. Oncology (Huntingt). Oct 1990;4(10):61-9; discussion 72, 76. [Medline].
Shasha D, Harrison LB. Elective irradiation of the N0 neck in squamous cell carcinoma of the upper aerodigestive tract. Otolaryngol Clin North Am. Oct 1998;31(5):803-13. [Medline].
Silverman DA, El-Hajj M, Strome S, Esclamado RM. Prevalence of nodal metastases in the submuscular recess (level IIb) during selective neck dissection. Arch Otolaryngol Head Neck Surg. Jul 2003;129(7):724-8. [Medline].
Sinard RJ, Netterville JL, Garrett CG. Cancer of the larynx. In: Cancer of the Head and Neck. WB Saunders Co;1996:381-422.
Spiro RH, Huvos AG, Wong GY, et al. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth. Am J Surg. Oct 1986;152(4):345-50. [Medline].
Sticht C, Hofele C, Flechtenmacher C, et al. Amplification of Cyclin L1 is associated with lymph node metastases in head and neck squamous cell carcinoma (HNSCC). Br J Cancer. Feb 28 2005;92(4):770-4. [Medline].
Stoeckli SJ, Pfaltz M, Ross GL, et al. The second international conference on sentinel node biopsy in mucosal head and neck cancer. Ann Surg Oncol. Nov 2005;12(11):919-24. [Medline].
Umeda M, Minamikawa T, Komatsubara H, et al. En bloc resection of the primary tumour and cervical lymph nodes through the parapharyngeal space in patients with squamous cell carcinoma of the maxilla: a preliminary study. Br J Oral Maxillofac Surg. Feb 2005;43(1):17-22. [Medline].
Vartanian JG, Pontes E, Agra IM, et al. Distribution of metastatic lymph nodes in oropharyngeal carcinoma and its implications for the elective treatment of the neck. Arch Otolaryngol Head Neck Surg. Jul 2003;129(7):729-32. [Medline].
management of the n0 neck, neck cancer, cancer of the head and neck, squamous cell carcinoma, SCC, lymph node metastases, oral cavity cancer
Ray G F Blanco, MD, Fellow, Head and Neck Surgical Oncology and Microvascular Surgery, Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Medical Center
Ray G F Blanco, MD is a member of the following medical societies: American Medical Association and Philippine Medical Association
Disclosure: Nothing to disclose.
Lisa T Galati, MD, Assistant Professor, Division of Otolaryngology, Albany Medical Center
Lisa T Galati, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery and Phi Beta Kappa
Disclosure: Nothing to disclose.
Gregory S Weinstein, MD, FACS, Professor and Vice-Chairman, Codirector for the Center for Head and Neck Cancer, Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Hospital
Gregory S Weinstein, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Laryngological Rhinological and Otological Society, and American Medical Association
Disclosure: Nothing to disclose.
Daniel J Kelley, MD, Consulting Staff, Eastern Shore ENT & Allergy Associates
Daniel J Kelley, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, American Laryngological Rhinological and Otological Society, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.
Karen Hall Calhoun, MD, Chair, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Missouri
Karen Hall Calhoun, MD is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Medical Association, American Rhinologic Society, Society of University Otolaryngologists-Head and Neck Surgeons, and Texas Medical Association
Disclosure: Nothing to disclose.
Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.
Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
Disclosure: UST Grant/research funds Consulting
© 1994-
by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)