eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery

Management of the N3 Neck: Workup

Author: Niels Kokot, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, Keck School of Medicine of the University of Southern California
Coauthor(s): Gregory S Weinstein, MD, FACS, Professor and Vice-Chairman, Department of Otorhinolaryngology-Head and Neck Surgery, Director of Division of Head and Neck Surgery, Director of Head and Oncology Fellowship, Director of Otorhinolaryngology-Head and Neck Clinic, Co-director of The Center for Head and Neck Surgery, University of Pennsylvania School of Medicine
Contributor Information and Disclosures

Updated: Apr 8, 2009

Workup

Laboratory Studies

Standard laboratory tests in the work-up of the patient with N3 neck disease include a complete metabolic panel and a complete blood count. Liver function tests, as a part of the metabolic panel, may be used to identify liver metastasis. However, they are nonspecific and are not sensitive. Elevated results of liver function tests may reflect associated alcoholic liver disorders. Electrolyte abnormalities may reflect tumor-induced syndrome of inappropriate antidiuretic hormone (SIADH). Pre-albumin, albumin, and transferrin provide information about the nutritional status of the patient. Patients undergoing surgery should also have coagulation panel, including prothrombin time (PT) and partial thromboplastin time (PTT), as well as a blood type and cross.

Imaging Studies

  • Evaluation of N3 neck disease is as follows:  
    • CT scan with contrast is useful in determining resectability and the extent of the primary tumor and nodal disease.
    • MRI with gadolinium can demonstrate soft tissue changes and reveal perineural spread.
    • Positron emission tomography (PET)–CT fusion study may be helpful in patients who present with N3 nodes with an unknown primary tumor. PET-CT scans were able to reveal an unknown primary tumor in 57% of cases compared with CT scan alone, which identified the unknown primary tumor in 23% of cases. Despite the increased ability of PET-CT scanning to reveal unknown primary sites, 43% of the primary sites were not identified.8
  • Evaluation for lung metastasis is as follows:
    • Patients with N3 neck disease are at increased risk for developing distant metastasis. Garavello et al (2006) found patients with N3 disease developed distant metastases 29.55% of the time and had a 10.7 times increased risk of developing distant metastases.
    • The lung is the most common site of distant metastasis in head and neck cancer, as supported by both clinical and autopsy studies. Chest radiographs had been the standard in the pretreatment evaluation of patient with head and neck cancer; however, its sensitivity is only 50%, while its specificity is 94%.9
    • The incidence of pulmonary malignancy in head and neck cancer is 4.5-14%. Secondary lung malignancy is a high risk if the primary tumor originated from the larynx or pharynx.
    • The lifetime risk in developing secondary malignancy in patients with head and neck cancer can be as high as 20%.
    • CT scan is the single most sensitive imaging study used to reveal lung metastasis and, therefore, should be the modality of choice, at least in high-risk patients (stage 4 disease, T4 tumor, N2 or N3 nodal disease, tumors that arise from the oropharynx, larynx, hypopharynx, or supraglottis).10

Other Tests

  • Evaluation for liver metastasis
    • Liver metastasis usually presents in association with other metastases, especially lung metastasis. Liver metastasis alone is rare. Screening tests used to identify liver metastasis are nonspecific and are not sensitive. Elevated results of liver function tests may reflect associated alcoholic liver disorders.
    • Although ultrasonography, CT scanning, and MRI are sensitive imaging modalities for liver metastasis, if the index of suspicion is high, especially in the presence of lung metastasis, a liver ultrasound or CT scan can be performed to confirm clinical suspicion.11
  • Evaluation for bone metastasis
    • Bone metastasis is invariably associated with lung metastasis; 50% of cases of bone metastasis involve multiple bony sites. The spine is the most common site of metastasis (12.7%), followed by the skull (4.2%), the rib (3.1%), and axial bone (femur, humerus [2.1%]).5
    • Alkaline phosphatase is sensitive for osteoblastic bone metastasis. It is not sensitive for revealing bone metastasis in head and neck squamous cell cancer head because this type of bone metastasis is osteolytic.
    • Bone scan is sensitive in the diagnosis of bone metastasis; however, it is useful only if the patient is clinically symptomatic. Routine bone scan is not necessary.
  • Carotid artery evaluation
    • MR studies have shown that, if the carotid artery is surrounded by tumor in 270° or less, no carotid artery invasion has occurred.12 Yoo et al compared preoperative CT findings with histologic findings in patients who underwent carotid artery resection.13 If the carotid artery was encircled more than 180° by the tumor on CT scan, then the tumor invaded the elastic lamina of the carotid artery and patients had poorer outcomes.
    • In patients who have undergone chemotherapy or radiation treatment, surgical planes between the carotid artery and the tumor are obscured. In these cases, CT scanning or MRI are less accurate in predicting carotid artery invasion.12
    • Planned carotid artery resection or embolization requires preoperative testing to assure adequate collateral blood flow through the contralateral carotid artery and/or vertebral artery system. In addition, the presence or absence of carotid stenosis must be assessed. The following tests may be indicated in these situations:
      1. Baseline neurologic examination
      2. Functional assessment of cerebral blood flow (CBF) under the following conditions:
        1. At rest
        2. Upon cerebral vasodilatory conditions by inducing hypercapnia, administering acetazolamide, or using hand movements (normal value, increase CBF)
        3. CBF/CBF vasodilatory ratio
        4. PET scanning to measure quantitative CBF and metabolic parameters
      3. Balloon occlusion test
      4. Balloon occlusion test with hypotensive challenge, with or without
        single-photon emission computed tomography (SPECT)
      5. Magnetic resonance angiography (MRA)
      6. Carotid Doppler to reveal carotid stenosis and evaluate for concomitant atherosclerotic plaque
      7. Angiography
      8. Xenon CT scan
      9. Carotid stump back pressure

Discussing the different indications and contraindications, complications, and advantages of each test is beyond the scope of this chapter. Invasive tests used to evaluate collaterals of the carotid artery can cause neurologic complications post-procedure. Several studies have conclusively shown that severe hemodynamic impairment is a strong predictor of stroke in patients who undergo carotid artery occlusion. In the St Louis Carotid Occlusion Study, a prospective study that evaluated cerebral hemodynamic and stroke risk, more than half of the symptomatic and asymptomatic patients had a normal oxygen extraction fraction.14

Diagnostic Procedures

  • Biopsy is necessary to confirm the diagnosis. Fine-needle aspiration biopsy (FNAB) of the neck mass is the only required test for the diagnosis. If readily available, a biopsy procedure can be performed on the primary tumor. The use of core biopsy has also been reported.15
  • The use of an open biopsy procedure is necessary only if the diagnosis cannot be attained with FNAB and a lymphoma is suspected.
  • Patients with head and neck carcinoma are at risk for synchronous primary tumors. Panendoscopy, including direct laryngoscopy, bronchoscopy, and esophagoscopy, has classically been performed to assess the both the primary tumor and to identify the presence of synchronous primary tumors. 

Histologic Findings

As mentioned above, squamous cell carcinoma is the most common cause of carcinoma of the aerodigestive tract with cervical metastasis. Histologic diagnosis is based on either FNAB of the neck mass or incisional biopsy of the primary tumor. For patients who undergo surgical treatment of their disease, the histologic features of the primary tumor and neck dissection are important for determining the need for adjuvant therapy.

At the primary site, the surgeon and pathologist alike are interested in the size of the tumor, the presence of positive surgical margins, perineural or lymphovascular invasion, and invasion of surrounding structures. In addition, the pathologist will comment on the grade of differentiation of the tumor, ranging from well differentiated, to moderately differentiated, and poorly differentiated.

However, in squamous cell carcinoma, the grade of the tumor in general does not impact prognosis. On the other hand, the grade of the tumor is important in salivary gland carcinomas. In the neck, features of interest include the size of the tumor, the number and location of involved nodes, and the presence of extracapsular extension of the tumor outside the lymph node.

High-risk features that have long been considered indications for postoperative radiotherapy include advanced T stage, perineural invasion, and multiple positive lymph nodes. Bernier et al (2005), in their meta-analysis studying the benefit of postoperative chemoradiation, found positive surgical margins and extracapsular extension to be the most significant indicators for adjuvant chemoradiation.16

Staging

The reader is referred to the current AJCC (6th edition) and UICC guidelines for T staging of the primary tumor at the individual head and neck sites.  

AJCC and UICC nodal categories (except thyroid and nasopharyngeal carcinoma) are as follows:

  • Nx - Regional lymph nodes that cannot be assessed
  • N0 - No regional node metastasis
  • N1 - Metastasis in a single ipsilateral lymph node, 3 cm or smaller
  • N2 - Metastasis in a single ipsilateral lymph node, larger than 3 cm but not larger than 6 cm in greatest dimension is found; multiple ipsilateral lymph nodes, none larger than 6 cm; bilateral or contralateral lymph nodes, none larger than 6 cm
  • N2a - Metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm
  • N2b - Metastasis in multiple ipsilateral lymph nodes, none larger than 6 cm
  • N2c - Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm
  • N3 - Metastasis in a lymph node larger than 6 cm
Distant metastasis categories are as follows:
  • Mx - Distant metastasis cannot be assessed
  • M0 - No distant metastasis
  • M1 - Distant metastasis
The combination of the primary tumor, nodal status, and presence or absence of distant metastasis is used as a part of the overall staging of the patient’s disease according to AJCC and UICC guidelines, as follows:
 

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Table
Stage IT1N0M0
Stage IIT2N0M0
Stage IIIT3N0M0
 T1N1M0
 T2N1M0
 T3N1M0
Stage IVaT4aN0M0
 T1N1M0
 T2N2M0
 T3N2M0
 T4aN2M0
Stage IVbAny TN3M0
 T4aAny NM0
Stage IVcAny TAny NM1
Stage IT1N0M0
Stage IIT2N0M0
Stage IIIT3N0M0
 T1N1M0
 T2N1M0
 T3N1M0
Stage IVaT4aN0M0
 T1N1M0
 T2N2M0
 T3N2M0
 T4aN2M0
Stage IVbAny TN3M0
 T4aAny NM0
Stage IVcAny TAny NM1


More on Management of the N3 Neck

Overview: Management of the N3 Neck
Workup: Management of the N3 Neck
Treatment: Management of the N3 Neck
Follow-up: Management of the N3 Neck
Multimedia: Management of the N3 Neck
References
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Further Reading

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Keywords

neck disease, advanced neck disease, lymph nodes neck, n3 neck, neck cancer, squamous cell carcinoma, neck treatment, head neck cancer, cancer treatment, cancer management, SCCA, inoperable cancer of the neck, N3 disease of the neck, stage IV disease, tonsil cancer, cancer of the tonsil

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Contributor Information and Disclosures

Author

Niels Kokot, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, Keck School of Medicine of the University of Southern California
Niels Kokot, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society, and Society of University Otolaryngologists-Head and Neck Surgeons
Disclosure: Nothing to disclose.

Coauthor(s)

Gregory S Weinstein, MD, FACS, Professor and Vice-Chairman, Department of Otorhinolaryngology-Head and Neck Surgery, Director of Division of Head and Neck Surgery, Director of Head and Oncology Fellowship, Director of Otorhinolaryngology-Head and Neck Clinic, Co-director of The Center for Head and Neck Surgery, University of Pennsylvania School of Medicine
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 Association, American Laryngological Rhinological and Otological Society, American Medical Association, American Radium Society, American Society for Head and Neck Surgery, Pennsylvania Medical Society, Philadelphia County Medical Society, and Society of University Otolaryngologists-Head and Neck Surgeons
Disclosure: Nothing to disclose.

Medical Editor

William M Lydiatt, MD, Professor and Division Director, Head and Neck Surgical Oncology, Department of Otolaryngology-Head and Neck Surgery, University of Nebraska Medical Center
William M Lydiatt, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, and Nebraska Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Karen Hall Calhoun, MD, Professor, Department of Otolaryngology-Head and Neck Surgery, The Ohio State University
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 Head and Neck Society, American Medical Association, American Rhinologic Society, Association for Research in Otolaryngology, Society of University Otolaryngologists-Head and Neck Surgeons, Southern Medical Association, Texas Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

CME Editor

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.

Chief Editor

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: Covidien Corp Consulting fee Consulting; US Tobacco Corporation unstricted gift unknown; Axis Three Corporation Ownership interest Consulting; Omni Biosciences Ownership interest Consulting; Sentegra Ownership interest Board membership; Syndicom Ownership interest Consulting; Oxlo  Consulting; Medvoy Ownership interest Management position

 
 
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