Management of the N3 Neck Workup
- Author: Niels Kokot, MD; Chief Editor: Arlen D Meyers, MD, MBA more...
Laboratory studies should include the following:
Basic metabolic panel
Liver function tests
Prealbumin and albumin
Blood type and cross-match
P16 testing on biopsy specimen of oropharyngeal primary (surrogate test for human papillomavirus)
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).
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. 
Evaluation for lung metastasis and second lung primary 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 radiography has poor sensitivity in detecting lung metastasis (sensitivity of 50%, specificity is 94%.  )
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). 
Yearly chest radiography is suggested to evaluate for second primary lung tumors or distant metastasis.
See the list below:
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.
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%]).
- 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. Yoo et al compared preoperative CT findings with histologic findings in patients who underwent carotid artery resection. 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.
- 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.
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.
See the list below:
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.
As mentioned above, squamous cell carcinoma is the most common cause of carcinoma of the aerodigestive tract with cervical metastasis. 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.
Patients who benefit from the addition of chemotherapy to postoperative radiotherapy are those with positive margins and those with extracapsular spread.[18, 9]
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
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:
Table 1. Staging (Open Table in a new window)
|Stage IVb||Any T||N3||M0|
|Stage IVc||Any T||Any N||M1|
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|Stage IVb||Any T||N3||M0|
|Stage IVc||Any T||Any N||M1|
|Type of Neck Dissection||Nodes Removed||Structures Sacrificed|
|Radical||level I-V||Cranial nerve XI, internal jugular, sternocleidomastoid|
|Modified radical||level I-V||Cranial nerve XI, internal jugular, sternocleidomastoid(preserve at least one)|
|Selective neck||Preservation of nodal levels||None|
|Extended radical||level I-V +/- mediastinal, retropharyngeal, perifacial, level VI||Cranial nerve XI, internal jugular, sternocleidomastoid +/- carotid, skin, cranial nerve XII, cranial nerve X, paraspinal muscle|