Head & Neck

Salivary Gland Cancer

Includes illustrated staging details

Salivary glands produce saliva to help you swallow, chew and digest food and keep your mouth and throat moist. Saliva contains enzymes that begin the process of breaking down food and antibodies that help prevent mouth and throat infections.

Your head and neck contain major and minor salivary glands, with a set of three major glands on each side of your face. The parotid glands are the largest of the major glands and are located just in front of each ear. The submandibular glands below your mandible (jawbone) are smaller. The sublingual glands under the mouth floor are the smallest. You also have hundreds of microscopic minor salivary glands.

Tumors most often occur in the parotid glands. Tumors in the minor salivary glands are not common; however, they are more likely to be malignant when they occur.

Treatment Options

Your doctor will consider the subtype, stage and grade of your cancer when developing a treatment plan for you. Multiple subtypes have been identified in salivary gland cancer. Some are benign, and others are cancerous.

Treatment for salivary gland tumors is also based on the grade of the cancer. In general, the lower the tumor grade, the better the prognosis (outlook).

Treatment to salivary glands can impact your speech, chewing and swallowing. Talk with your doctor about the benefits and risks as well as the potential side effects and late effects of each type of therapy before making decisions.

One or more of the following options may be part of your treatment plan.

Surgery is the most common treatment for salivary gland cancer to remove the tumor and surrounding tissue. More than one surgery may be needed to treat the cancer and to repair the area. One of the following procedures may be used.

Superficial parotidectomy may be used to remove cancer in the outside part of the parotid gland, also known as the superficial lobe. This involves removing the lobe.

Total parotidectomy to remove the entire parotid gland may be used if the cancer extends to deeper tissues. Removal of the facial nerve may be required, which would affect facial movement.

Other surgical procedures include endoscopic surgery, removal of the submandibular or sublingual glands, and a lymph node dissection (lymphadenectomy) to remove lymph nodes in the neck.

Radiation therapy may be recommended for intermediate or high grade or advanced salivary gland cancers after surgery (adjuvant therapy) to kill remaining cancer cells. If surgery is not an option, radiation may be the main treatment, but radiation treatment may not be effective alone against some salivary gland tumors. It is sometimes used to manage symptoms of pain, bleeding or trouble swallowing and in cases of recurrent or advanced salivary gland cancer. Two main types of radiation may be used.

External-beam radiation therapy (EBRT) uses a machine outside the body to send radiation toward the cancer. Different types of EBRT are available and include intensity-modulated radiation therapy and proton therapy, which uses charged particles called protons.

Internal radiation therapy, also called brachytherapy, uses a radioactive substance sealed in needles, seeds, wires or catheters that are placed directly into or near the cancer.

Radiation therapy may also be combined with chemotherapy, known as chemoradiation.

Drug therapy may be recommended for some cases.

Chemotherapy may be used to treat late-stage salivary gland cancer or to treat symptoms.

Immunotherapy in the form of immune checkpoint inhibitors may be used to treat recurrent or metastatic salivary gland cancer that has stopped responding to chemotherapy. The doctor will test for the tumor’s PD-L1 expression, which may indicate whether the tumor could respond to immunotherapy. If expression is more than 1 percent, the tumor is considered to be PD-L1 positive and immunotherapy alone may be used. If PD-L1 is negative, immunotherapy and traditional chemotherapy are often combined for patients who have recurrent/metastatic cancer.

Targeted therapy may be an option for some subtypes of salivary gland cancer through clinical trials. This type of personalized treatment attacks the source of a tumor’s growth, focusing on certain parts of cells and the signals that cause them to grow unchecked or keep from dying. These signals are often sent by proteins called tyrosine kinases. In salivary gland cancer, some of these drugs also target specific genes or molecular alterations, including neurotrophic tyrosine receptor kinase (NTRK), human epidermal growth factor receptor-2 (HER2) and epidermal growth factor receptor (EGFR).

Staging

Diagnosing your type of salivary gland cancer is an important step in creating the best treatment plan for you. Your doctor will perform a thorough exam, imaging studies, blood tests and a biopsy and use these test results to stage the cancer. Staging determines the extent of your cancer, where it is located and whether it has metastasized (spread) to nearby organs, tissues or lymph nodes, or to other parts of your body.

The TNM staging system, developed by the American Joint Committee on Cancer (AJCC), is typically used to classify and stage major salivary gland cancer. This system classifies the cancer by tumor (T), node (N) and metastasis (M). The T category describes the size and location of the primary tumor. The N category indicates whether the lymph nodes show evidence of cancer cells. The number and location of these lymph nodes are important because they show how far the disease has spread. The M category describes metastasis (spread of cancer to another part of the body), if any.

Staging Criteria

Once the cancer is classified, an overall stage is assigned. Major salivary gland cancer may be Stage 0 through Stage IV. Also known as “in situ,” Stage 0 is a precursor of an invasive cancer. Stages I and II are generally confined to the local area where the cancer is found, and Stage III has spread to the regional lymph nodes in the neck. Stage IV is further divided into Stages IVA, IVB and IVC. Stages IVA and IVB are locally or regionally advanced disease, and Stage IVC has spread to distant sites, such as the liver, lungs or bone.

These basic stages are designed to group patients who have a similar prognosis (outlook). This grouping allows doctors to more accurately predict outcomes for patients depending on the type of treatment they receive. In certain cancers, the stage is also determined by other factors.

Sometimes your doctor may reassess your stage after treatment or if cancer recurs. This is known as restaging. It is rarely done but typically involves the same diagnostic tests used for the original staging. If a new stage is assigned, it’s often preceded by an “r” to denote that it’s been restaged and different from the original stage given at diagnosis.

TNM Classification for Major Salivary Gland Cancer

Classification Definition
Tumor (T)
TX Primary tumor cannot be assessed.
T0 No evidence of primary tumor.
Tis Carcinoma in situ.
T1 Tumor 2 cm or smaller in greatest dimension without extraparenchymal extension (spread to surrounding tissues).
T2 Tumor larger than 2 cm but not larger than 4 cm in greatest dimension without extraparenchymal extension (spread to surrounding tissues).
T3 Tumor larger than 4 cm and/or tumor having extraparenchymal extension (spread to surrounding tissues).
T4 Moderately advanced or very advanced disease.
  T4a Moderately advanced disease.
Tumor invades skin, mandible (lower jaw), ear canal, and/or facial nerve.
  T4b Very advanced local disease.
Tumor invades skull base and/or pterygoid plates and/or encases carotid artery.
Node (N)
NX Regional lymph nodes cannot be assessed.
N0 No regional lymph node metastasis.
N1 Metastasis in a single ipsilateral (on the same side) lymph node, 3 cm or smaller in greatest dimension and ENE*(-).
N2 Metastasis in a single ipsilateral (on the same side) lymph node, 3 cm or smaller in greatest dimension and ENE*(+);
or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-);
or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-);
or in bilateral (on both sides) or contralateral (on the opposite side) lymph node(s), none larger than 6 cm in greatest dimension, ENE(-).
  N2a Metastasis in single ipsilateral (on the same side) node 3 cm or smaller in greatest dimension and ENE*(+);
or a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-).
  N2b Metastases in multiple ipsilateral (on the same side) nodes, none larger than 6 cm in greatest dimension and ENE*(-).
  N2c Metastases in bilateral (on both sides) or contralateral (on the opposite side) lymph node(s), none larger than 6 cm in greatest dimension and ENE*(-).
N3 Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE*(-);
or metastasis in a single ipsilateral (on the same side) node larger than 3 cm in greatest dimension and ENE(+);
or multiple ipsilateral, contralateral (on the opposite side) or bilateral (on both sides) nodes, any with ENE(+);
or a single contralateral node of any size and ENE(+).
  N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-).
  N3b Metastasis in a single ipsilateral (on the same side) node larger than 3 cm in greatest dimension and ENE*(+);
or multiple ipsilateral, contralateral (on the opposite side) or bilateral (on both sides) nodes, any with ENE(+);
or a single contralateral node of any size and ENE(+).
Metastasis (M)
M0 No distant metastasis.
M1 Distant metastasis.

*Extranodal extension (ENE) refers to cancer cells that have spread beyond the lymph node into surrounding tissues.

Staging Major Salivary Gland Cancer

Stage T N M
0 Tis N0 M0
I T1 N0 M0
II T2 N0 M0
III T3
T0, T1, T2, T3
N0
N1
M0
M0
IVA T4a
T0, T1, T2, T3, T4a
N0, N1
N2
M0
M0
IVB Any T
T4b
N3
Any N
M0
M0
IVC Any T Any N M1

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this information is the AJCC Cancer Staging Manual, Eighth Edition (2017) published by Springer Science+Business Media.

Illustrated Stages of Major Salivary Gland Cancer

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