Management of the Clinically Negative Neck
The current consensus involves treatment of the neck for selected patients with tumors that display poor prognostic features for metastasis, although some do advocate elective treatment of the neck for all salivary gland malignancies. Reported rates of occult metastasis in the literature range from 12% to 48%, likely due to varying proportions of the diverse histologic types of salivary malignancy with differing propensities for nodal spread. A study by Stennert et al. found a high incidence of occult cervical lymph node metastasis in major salivary gland malignancies, regardless of tumor stage or type. All patients had ipsilateral neck dissection, and of the 139 that were clinically node-negative, 45% had occult metastases. Frequent occult metastases were found for patients even with lower risk histologic types and smaller tumors. Other studies have shown that elective neck treatment should be reserved for patients with tumors prone to occult metastases only. Armstrong et al. reviewed 407 salivary cancer cases with clinically node-negative necks, of whom 90 underwent elective neck dissection. Occult metastases were found in 38% of these cases, who tended to have higher grade and more advanced tumors. Submandibular gland cancers had the highest rate of occult nodal involvement at 21%, whereas parotid tumors had a nodal involvement rate of only 9%. These results agree with those of Spiro and Yu and Ma, which showed that submandibular and sublingual sites tend to metastasize more frequently than parotid and minor salivary gland malignancies.
Primary tumor size and extraglandular extension have also been shown to correlate with risk of metastasis. Frankenthaler et al. found that one of the most predictive variables for occult metastasis in parotid tumors was extraparotid extension, and other studies concur that advanced T stage is associated with a higher risk of metastasis. Armstrong et al. showed that primary tumor size >4 cm had a 20% risk of metastasis, while smaller tumors had only a 4% risk. In addition, primary tumor grade and histologic type have also been shown to correlate with risk of occult metastasis. The histologic types considered high risk for occult nodal metastasis include: undifferentiated carcinoma, squamous cell carcinoma, high-grade mucoepidermoid carcinoma (MEC), adenocarcinoma, carcinoma ex-pleomorphic adenoma, salivary duct carcinoma, and tumors with high-grade transformation. Lower risk types include: typical acinic cell carcinoma, grade 1 or 2 adenoid cystic carcinoma and low-grade MEC, although periparotid nodes may be involved. Armstrong et al. showed that high-grade tumors had occult metastasis in 49% of their cases, while intermediate or low-risk tumors only had a 7% risk. Bhattacharyya and Fried found that high-grade tumors had a 1.99 odds ratio of having occult nodal metastasis. It is worth noting that often only a minority of prognostic factors are available prior to surgery.
In patients with clinically node-negative necks, a selective neck dissection is preferred when an elective neck dissection is performed. The site of the primary tumor determines the included neck levels. In parotid malignancies, Armstrong et al. reported that dissection of levels I through IV detected all occult metastases, with level I positive in only 10% of cases. Ali et al. found occult metastases only present at levels I and V in 6.7% of cases. Many authors suggest SND involving levels IB-IV or II-IV due to the lower risk for occult nodal disease in levels I and V. For submandibular and sublingual malignancies, SND of levels IA-III is recommended. In minor salivary gland malignancy, elective neck dissection is usually not necessary due to the low risk of cervical metastases, except with high-grade MEC or other high-grade malignancies. Similarly, major salivary malignancies with low risk histology and no poor prognostic factors may also not require elective neck dissection.
Management of the Clinically Positive Neck
Treatment of the clinically node-positive neck in the setting of salivary gland malignancy is generally more established, although some differences in management do exist based on tumor site. Staging in the 8th edition of the American Joint Commission on Cancer guidelines follows that for upper aerodigestive tract malignancies with clinically evident extranodal invasion being defined as N3b. An ipsilateral neck dissection should always be performed in patients with cervical lymph nodes that are palpable, radiographically enlarged and suspicious by CT scan or have increased uptake on 18F-FDG PET scan. The contralateral clinically negative side can be spared due to the low probability of nodal involvement. In parotid malignancies, Ali et al. reported a relatively equal distribution of involved neck levels during therapeutic neck dissection. Levels II, III, and IV had a high percentage of involvement (77%, 73%, and 53%, respectively) as expected, but levels I and V also were involved (51.6% and 40%, respectively). Klussmann et al. reported a probability of cervical lymph node involvement in clinically positive necks at levels I of 9%, while that for levels II (25%), III (22%), IV (19%), and V (19%) were similar. While the most frequently involved levels are II, III, and IV, generally a comprehensive neck dissection including levels IA-VB or SND of levels IA-VB is performed for patients with primary parotid malignancies.
For non-parotid salivary malignancies with node-positive necks, several management strategies exist. Yoo et al. found that nodal metastatic incidence in submandibular, sublingual and minor salivary glands was 74.2% for level I, 64.5% for level II, 51.6% for level III, 29% for level IV, and 22.6% for level V. Due to the possibility that metastatic salivary gland malignancies can involve any of the neck levels and can skip levels, it is recommended by some to perform a comprehensive modified radical neck dissection including levels IA-VB in node-positive necks regardless of primary site. However, others advocate supra-omohyoid neck dissection (levels IA-III) for submandibular, sublingual and minor salivary gland malignancies in the setting of clinically positive neck disease.
Adjuvant treatment with radiotherapy, chemotherapy, and immunotherapy is individually based on factors such as staging, tumor grade, nodal involvement including extranodal extension, perineural invasion, margin status, and facial nerve involvement, as well as molecular testing such as for HER2/neu overexpression in salivary duct carcinomas.
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