INTRODUCTION — Salivary gland tumors include a wide range of tumor types, which can be either benign or malignant (table 1). Approximately 85 percent arise in the parotid; the remainder originate in the submandibular, sublingual, and minor salivary glands, which are located throughout the submucosa of the mouth and upper aerodigestive tract (figure 1) [1]. Approximately 25 percent of parotid tumors are malignant, compared with 40 to 45 percent of submandibular gland tumors, 70 to 90 percent of sublingual gland tumors, and 50 to 75 percent of minor salivary gland tumors.
Treatment recommendations are based upon retrospective reviews of clinical experience, and there are almost no data from randomized trials to guide treatment decisions. The published literature predominately focuses on the parotid gland, reflecting the relative frequency of parotid gland tumors compared with tumors at other sites. The treatment of locoregional disease, which includes stages I through IVB (table 2A-B), will be discussed here.
All malignant tumors of the salivary glands should be staged according to the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) eighth edition cancer staging manual (table 2A and table 2B). Important changes were made to this edition involving the recognition of extranodal extension (ENE) of tumor in lymph nodes [2]. This will now be noted in both clinical and pathological staging. ENE will increase the clinical node (N) characterization to N3b when clear evidence of ENE is determined on clinical exam and supported by radiological studies. Clinical ENE of nodes should only be considered positive when nodes exhibit fixation to surrounding structures, cranial nerve involvement (not facial from the primary tumor), or skin involvement. Pathological ENE should be noted and graded as to whether it is present and >2 mm, or present and ≤2 mm.
Other topics on salivary gland tumors include:
●(See "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging".)
●(See "Malignant salivary gland tumors: Treatment of recurrent and metastatic disease".)
●(See "Pathology of head and neck neoplasms", section on 'Salivary gland tumors'.)
SURGERY — Complete surgical resection is the cornerstone of treatment [3]. Patients with benign tumors and low-grade malignancies are typically treated with surgery alone; patients with high-grade carcinomas and those with positive margins or other high-risk features are usually treated with surgery and adjuvant radiation therapy (RT). Patients with unresectable tumors may be treated with RT alone or RT in combination with chemotherapy. (See 'Definitive radiation therapy' below.)
Preoperative assessment of salivary gland masses guides the surgical approach. Contemporary imaging techniques (magnetic resonance imaging [MRI], computed tomography [CT], positron emission tomography [PET], PET/CT, ultrasound) aid the evaluation of regional lymph node involvement and the extent of tumor invasion, such as facial nerve and skull base involvement with parotid tumors.
Biopsy or fine needle aspiration cytology can usually discriminate benign tumors from malignant lesions and primary salivary gland tumors from metastases or lymphoma, but they are less specific in determining the exact type of tumor, and there may be difficulty differentiating benign from low-grade malignant tumors. (See "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging", section on 'Diagnosis'.)
Parotid gland tumors — Surgical resection of parotid tumors depends upon whether the tumor is benign or malignant, its location within the parotid gland, its size and invasiveness, and its relationship to the facial nerve. The facial nerve divides the parotid gland into a superficial and deep lobe (figure 2).
Parotidectomy is classified as conservative, superficial, or total, based upon the lobes resected and extent of facial nerve dissected:
●A conservative, partial, or limited superficial parotidectomy is any procedure that is less extensive than a superficial parotidectomy and does not fully dissect the facial nerve.
●A superficial parotidectomy involves resection of the entire superficial lobe and dissection along all branches of the facial nerve.
●A total parotidectomy involves dissection and preservation of the facial nerve with removal of parotid tissue in the deep as well as superficial lobes.
These procedures are in contrast to a simple enucleation, or shelling out of tumor, which is rarely indicated for salivary gland tumors.
Adequate resection of tumor with preservation of the facial nerve is the prime objective in management of salivary gland tumors. Unless the facial nerve is directly involved by malignant tumor, every effort is made to protect and preserve its function.
Preservation of the facial nerve may result in a pathologically positive margin; however, this typically does not carry the same negative implications as mucosal disease. In fact, whole organ sectioning suggests that the vast majority of parotid dissections will harbor a pathologic positive margin [4]. The addition of RT for a malignant tumor with a positive margin is discussed below but is not mandated by a pathological positive margin. Benign tumors rarely require additional surgery or radiation for a positive nerve margin. (See 'Definitive radiation therapy' below.)
Benign tumors — Superficial parotidectomy is recommended for most benign tumors confined to the superficial lobe, including pleomorphic adenomas (the most common benign salivary gland tumor) [5,6]. (See 'Pleomorphic adenoma' below.)
However, a conservative parotidectomy has been advocated to remove selected tumors in the inferior portion of the gland, particularly Warthin tumors. For benign tumors lying deep to the plane of the facial nerve, the facial nerve is preserved [5-8].
Malignant tumors — For malignant tumors of the parotid gland, the extent of resection depends upon the histologic degree of differentiation, as well as the location and size of the tumor (table 3).
High-grade tumors are often treated with a total parotidectomy. Lower grade malignant tumors and high-grade tumors located peripherally within the superficial lobe (particularly the inferior aspect) may be treated with a superficial parotidectomy [5,6,9-15]. For deep malignant tumors, a total parotidectomy is typically performed, depending upon the location of the tumor within the gland, with preservation of the facial nerve unless direct invasion is found at operation.
For more invasive, T4 tumors (table 2A-B), obtaining wide surgical margins of normal uninvolved tissue may entail resection of skin of the face and neck, contiguous soft tissue and muscle, and mandible or temporal bone. Tumors that extend to bone may require a lateral or subtotal temporal bone resection, or resection of zygoma or mandibulectomy.
Partial or complete facial nerve paralysis due to tumor is present in as many as 15 to 23 percent of malignant parotid lesions at diagnosis and is associated with a worse prognosis [16-18]. Total parotidectomy with resection of the involved portion of the facial nerve is typically performed for patients who present with facial nerve dysfunction or with clinical suspicion of tumor infiltration at operation. If possible, reconstruction of the nerve with interposition of a nerve graft or static procedures to mitigate facial droop should be done at the same procedure [19].
If the facial nerve is functioning preoperatively, every effort is made to preserve it. Prophylactic resection of the nerve, in the absence of clinical involvement, adds little to surgical margins or tumor control and results in substantial morbidity. (See 'Complications' below.)
Although the use of an electromyography (EMG)-based intraoperative facial nerve monitor has not been conclusively shown to reduce the risk of postoperative facial nerve paralysis, many surgeons consider it a useful surgical adjunct [20-23].
Complications — The risk and the nature of complications following parotidectomy depend upon the extent of surgery, pathology of the tumor, location of the tumor within the gland, and the experience of the surgeon.
●Even when the intent is to preserve the nerve, there remains a risk of facial paralysis, with some reports citing incidence rates ranging as high as 27 to 43 percent for temporary paresis or paralysis and 4 to 22 percent for permanent paralysis [20,21].
●Frey syndrome, also known as auriculotemporal syndrome or gustatory sweating, is characterized by sweating and flushing of the facial skin over the parotid bed and neck during mastication. Frey syndrome is thought to be due to aberrant regeneration of cut parasympathetic fibers between the otic ganglion and salivary tissue, which leads to innervation of sweat glands and subcutaneous vessels [24].
Frey syndrome is reported by approximately 10 percent of patients, although rigorous testing may detect gustatory sweating in as many as 95 percent of patients after parotidectomy. Frey syndrome may occur from two weeks to two years after surgery due to a latency in the regeneration of parasympathetic nerve fibers; the area of involved skin may increase over time [25,26].
The incidence of Frey syndrome is reduced by minimizing the parotid wound bed using reconstructive techniques such as thick skin flaps, and also postoperative RT [24,27]. Intracutaneous injection of botulinum toxin A is an effective, well-tolerated, and long-lasting treatment for symptomatic patients; it may be repeated for recurrent symptoms [24,25]. Some authors recommend the use of a sternocleidomastoid flap to decrease the incidence of symptomatic Frey syndrome; however, the data are inconclusive [27,28].
●Other uncommon complications include:
•Numbness in the distribution of the great auricular nerve including the ear, especially the lobule, and the face and neck is a common occurrence. Over time the majority of this will resolve, but permanent areas of numbness may occur [29].
•Sialocele and salivary fistula are uncommon long-term problems, but may occur in the postoperative period in up to 5 percent of patients.
•Bleeding and hematoma are also potential complications from any neck surgery.
•First bite syndrome is a rare but very problematic complication of deep lobe parotid and parapharyngeal space dissections and is characterized by severe cramping or spasm in the parotid region with the first bite of each meal that diminishes over the next several bites [30]. This is best managed conservatively using analgesics, antidepressants, and gabapentin.
Submandibular gland tumors — Submandibular gland tumors, nearly half of which are malignant, are treated with submandibular sialoadenectomy, a resection of the submandibular gland.
Anatomical considerations of a submandibular sialoadenectomy include the close proximity of the facial artery and vein, the marginal mandibular branch of the facial nerve, the hypoglossal and lingual nerves, and submandibular duct. It is the proximity of these structures that determines the major surgical complications [31,32]. The surgical approach may be transcervical, intraoral, or endoscopic [33-36]. The choice of approach is based upon fine needle aspiration (FNA) cytology, imaging findings, clinical experience of the surgeon, as well as potential associated complications, including aesthetic considerations. Malignancy should be treated with an external approach to adequately address the surrounding tissue and nodes.
Benign tumors are most commonly treated by simple excision of the gland. The marginal mandibular branch of the facial nerve, the hypoglossal nerve, and the lingual nerve should be spared.
Malignant tumors are removed en bloc with the affected gland. This often necessitates resection of the surrounding skin, muscles, and nerves, although effort is made to preserve the marginal mandibular branch of the facial nerve, the lingual nerve, and the hypoglossal nerve, unless they are encased with tumor [37]. (See 'Management of the neck' below.)
Despite the increasing use of fine needle aspiration cytology for diagnosis, some patients with a submandibular gland mass undergo initial surgical enucleation of the gland before a diagnosis of malignancy can be established. In this setting, the necessity of reoperation to obtain adequate margins remains uncertain.
In a single institution review of 87 patients, no statistically significant difference in locoregional disease control or overall survival was found for patients managed with enucleation of the gland alone followed by adjuvant RT compared with patients who underwent enucleation, definitive surgical resection, and adjuvant RT [37]. Based upon these findings, patients without clinical and radiographic evidence of disease after enucleation of a malignant submandibular gland tumor may be adequately treated with adjuvant RT, whereas those with gross residual disease following tumor enucleation should undergo definitive surgical resection prior to adjuvant RT. This does not, however, mean that enucleation should be done for known malignant tumors. (See 'Adjuvant therapy' below.)
Sublingual gland tumors — Sublingual gland tumors are rare but usually malignant. Like salivary gland tumors at other sites, surgery is the mainstay of treatment.
Resection of the floor of the mouth and involved sublingual gland as well as the ipsilateral submandibular gland is suggested even for small tumors [38-40]. Concurrent removal of the submandibular gland along with sublingual gland resection may be necessary since its ducts may be compromised even with a limited resection [40]. For larger tumors, en bloc resection may entail a marginal or segmental mandibulectomy and resection of the lingual nerve. In large resections, reconstruction, often with microvascular free-flaps, is appropriate to improve function with floor of the mouth and mandibular defects. (See "Mandibular and palatal reconstruction in patients with head and neck cancer".)
Despite low rates of nodal involvement, an elective selective neck dissection is commonly performed for sublingual gland tumors, particularly when a free flap is utilized [39,40]. A more comprehensive neck dissection is indicated for the node-positive neck. Generally, elective neck dissection should be considered when the histology is known prior to surgery and is high grade, involves the mandible, significant floor of mouth structures or requires a free flap reconstruction. A relative indication for elective neck dissection of levels I-III is in a high grade tumor where adjuvant RT is to be avoided. Adjuvant RT may be added for patients with high-grade tumors, positive margins, perineural invasion, or advanced-stage disease [38-40]. (See 'Management of the neck' below and 'Adjuvant therapy' below.)
Minor salivary gland tumors — The oral cavity contains 500 to 1000 minor salivary glands, which are most common on the hard palate [41]. Minor salivary glands are also found in the lips, superior poles of the tonsils, nasopharynx, paranasal sinuses, oropharynx, hypopharynx, larynx, and trachea. Minor salivary gland tumors are staged according to the anatomic site in which they arise.
Surgical resection is the mainstay of management. Postoperative adjuvant therapy is prescribed for the same general indications as a comparably staged squamous cell carcinoma. [42,43]. Occasionally, minor salivary gland tumors are treated with RT alone [41,44,45]. Although minor salivary gland cancers may achieve local control with the use of RT (or chemoradiation) alone, surgical resection alone or followed by RT is strongly preferred. (See 'Definitive treatment' below.)
Management of the neck — Selection of therapy for the neck is based upon the presence of nodal metastases, the type of therapy used for the primary tumor, and select tumor features.
Clinically involved nodes — For patients with clinically or radiographically apparent nodal metastases, our approach to management of the neck is as follows:
●For patients whose primary tumor is treated with surgery, we recommend a comprehensive (ie, radical) neck dissection (levels II to III, I, IV, and V when indicated (figure 3)) followed by adjuvant RT rather than RT alone to the neck.
●For patients treated with definitive RT to the primary tumor, we suggest RT alone to the neck rather than comprehensive neck dissection and adjuvant RT [46].
Approximately 20 percent of patients with malignant salivary gland tumors have clinically apparent nodal metastases at presentation. These patients should be treated with a therapeutic neck dissection of the involved nodes and echelons at highest risk (levels II to III, for most parotid cancers, I, IV and V when indicated, (figure 3)) followed by adjuvant RT in most cases [42,47-50]. At this point in time, there are no data on sentinel node mapping in parotid gland tumors.
Patients with clinically involved nodes whose primary tumor is treated with definitive RT also typically receive RT to the neck rather than comprehensive nodal dissection followed by adjuvant RT. We prefer this approach because most patients treated with definitive RT have unresectable disease, and it also avoids the potential toxicities of multimodality therapy. Observational studies suggest that definitive RT (to both the primary tumor and the neck) offers patients similar disease-specific survival but lower locoregional control rates compared with surgery and adjuvant RT [46,51-53].
Clinically negative nodes — For patients with no clinical or radiologic evidence of nodal metastases (N0), management of the neck is primarily based upon data from parotid gland tumors. Similar management is generally also applied to most other salivary gland tumors based upon comparable treatment outcomes and behavior, although there are some exceptions.
●For patients whose primary tumor is treated with surgery and has high-risk features, we suggest elective neck dissection (figure 3) rather than observation. Such high-risk features include tumors with high-grade pathology, locally advanced disease (T3 and T4 tumors), and facial nerve paralysis/weakness.
●Although data are limited, we also suggest elective neck dissection rather than observation for all patients with resected sublingual gland tumors or minor salivary glands arising in the nasopharynx [39,40,54].
●For patients whose primary tumor is treated with RT alone or those with a resected primary tumor and clinical indications for adjuvant RT whose neck has not been addressed surgically, elective RT to the neck is an appropriate alternative to elective neck dissection.
In patients with a clinically negative neck, the rate of occult metastases ranges between 12 to 45 percent, with higher rates among those with large or high-grade tumors [47,50,55,56]. Based on these data, we offer elective neck dissection for patients with features suggestive of high-risk for occult nodal disease such as high-grade tumors, large tumors (T3 and T4), and facial nerve paralysis/weakness [42,47,48].
Elective neck dissection includes the nodes most frequently involved with occult disease, which varies by primary tumor site. For parotid gland tumors, elective neck dissection includes levels II to IV [57]. In contrast, submandibular and sublingual gland tumors are treated with elective supraomohyoid dissection, which includes levels I to III [58]. Minor salivary gland malignancies are treated based upon their location; those located in the oropharynx are treated similarly to parotid gland tumors whereas those located in the oral cavity are treated similarly to submandibular gland tumors.
In patients with a clinically negative neck whose primary tumor was treated with definitive RT, elective RT to the neck is an appropriate alternative to elective neck dissection [52]. Elective RT may also substitute for elective neck dissection in patients with a resected primary tumor and clinical indications for adjuvant RT whose neck has not been addressed surgically. In one observational study, 251 patients with salivary gland tumors and clinical N0 disease were treated with surgery to the primary tumor but not neck dissection. Patients were then subsequently evaluated for postoperative RT based on the presence of high-risk features. In this study, elective neck RT was associated with decreased 10-year nodal failure rates compared with those who did not receive elective neck RT (0 versus 26 percent) [59]. Similar results have been seen in other studies [60].
Adjuvant therapy — Adjuvant (postoperative) RT is suggested after surgical resection for patients at high risk for locoregional recurrence based upon histology, grade, and/or extent of disease. High-risk features include high-grade and advanced-stage (select T3 and all T4) lesions; positive surgical margins; perineural, vascular, or lymphatic invasion; lymph node involvement; extracapsular spread; and most adenoid cystic carcinomas. RT is administered to both the salivary gland surgical bed and appropriate nodal levels.
●Patients with high-risk features – Although there are no randomized clinical trials, observational data indicate that adjuvant RT improves both local control and survival for selected patients [49,60-64]. As an example, a multivariate analysis of outcomes from 2170 patients with high grade or locally advanced malignant major salivary gland tumors identified in the Surveillance, Epidemiology, and End Results (SEER) database found that the addition of RT to surgery was associated with improved overall survival (hazard ratio [HR] for mortality 0.76, 95% CI 0.65-0.89) [63]. Similarly, in a retrospective study of 621 patients with low- or intermediate-grade salivary cancers, the addition of postoperative RT was associated with lower rates of locoregional recurrence at 10 years (HR 0.53, 95% CI 0.29-0.97) [65]. On multivariable analysis, the patients who appeared to benefit from RT were those with positive margins, lymphovascular invasion, lymph node involvement, or clinical stage T3 and T4 tumors.
Patients with salivary gland tumors arising in anatomic sites not amenable to wide resection, such as the nasopharynx, should also receive adjuvant RT given risk of recurrence. Although data are more limited, adjuvant RT may also be considered in submandibular gland tumors, sublingual gland tumors, and minor salivary tumors if there are high-risk features [37,38,40,51,66,67].
●Patients with low-risk tumors – Adjuvant radiation is not recommended for patients with lower-risk tumors. Benign salivary gland tumors and early-stage, low-grade malignancies including low-grade mucoepidermoid carcinomas, acinic cell carcinomas, and low-grade adenocarcinomas are well controlled with complete surgical resection, with control rates reaching 85 percent at 10 years. If margins are negative, adjuvant RT is generally not indicated [68]. RT was not associated with any benefit in patients with early-stage, low-grade salivary gland cancer in a retrospective analysis [65].
The optimal adjuvant radiation dose for a malignant salivary gland tumor depends upon the fractionation scheme utilized, but most use doses of 60 to 66 Gy at 2 Gy per fraction. The radiation treatment volume encompasses the original tumor bed and regional lymph nodes only if involved or thought to be at high risk. For adenoid cystic carcinoma, neural pathways to the skull base are also included.
Retrospective data do not provide evidence that adjuvant chemoradiation is more effective than adjuvant RT alone. An analysis of over 2000 patients from the National Cancer Database failed to demonstrate any improvement in overall survival with the addition of chemotherapy to RT compared with RT alone [69]. Even when controlling for potential confounding factors that may occur due to selection bias, there was a trend towards a worse outcome with the addition of chemotherapy. The role of adjuvant chemoradiation is being investigated in a randomized phase II/III clinical trial (RTOG 1008) comparing RT with chemoradiation using weekly cisplatin in high-risk patients following surgical resection. We await further prospective data from this trial, which has completed accrual.
Although systemic therapy has been used for palliative treatment in patients with metastatic disease, there is no evidence to support its use without RT in an adjuvant setting in patients with salivary gland tumors. (See "Malignant salivary gland tumors: Treatment of recurrent and metastatic disease", section on 'Metastatic disease'.)
DEFINITIVE RADIATION THERAPY
Definitive treatment — Definitive radiation therapy (RT) is reserved for patients who are medically inoperable or who have unresectable disease, either by extent of tumor invasion or location such that resection would result in a significant functional and/or cosmetic deficit [41,44,61,70,71].
Although the behavior and treatment response of salivary gland tumors may differ from squamous head and neck cancers, many of the principles are shared based upon the much larger body of data available for squamous head and neck cancers. The techniques, dosing, and schedule for RT for head and neck tumors are discussed in detail separately. (See "General principles of radiation therapy for head and neck cancer" and "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations".)
Definitive RT may be delivered as conventional radiation with photons and electrons, most often with inverse treatment planning techniques (intensity modulated RT). Proton beam RT offers the opportunity to deliver very high doses to the targeted tumor while maximally sparing adjacent critical tissues, including the brain, spinal cord, contralateral salivary tissues, and the oral cavity [72]. Although heavy particle RT with neutrons and carbon ions has been advocated as potentially providing better disease control, the data supporting these approaches are limited, and these techniques are not widely available [73-75].
We do not routinely offer concurrent chemoradiation with cisplatin outside of a clinical trial, since there are no data to support this approach.
Complications — The complications of RT, either as definitive therapy or as a postoperative adjuvant, vary according to the anatomic location of the tumor and are dose dependent. The complications of RT for head and neck malignancies are discussed separately. (See "Management and prevention of complications during initial treatment of head and neck cancer" and "Management of late complications of head and neck cancer and its treatment".)
PLEOMORPHIC ADENOMA — Pleomorphic adenoma, also known as benign mixed tumor, is the most common salivary gland tumor. The majority of these tumors occur in the superficial lobe of the parotid gland. Pleomorphic adenoma has historically been characterized as having a propensity for local recurrence and a potential for malignant transformation to the so called "carcinoma ex pleomorphic adenoma." (See "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging" and "Pathology of head and neck neoplasms", section on 'Salivary gland tumors'.)
Superficial parotidectomy is the treatment of choice for pleomorphic adenomas arising in the parotid gland. The recurrence rate after simple enucleation is 20 to 45 percent; with superficial parotidectomy, recurrence rates are reduced to less than five percent [76,77]. For most pleomorphic adenomas, a more extensive procedure (total parotidectomy) does not reduce the risk of recurrence further and is associated with higher rates of facial nerve dysfunction and other complications [76,78,79].
Positive margins, capsule rupture, and tumor spillage have been implicated as potential causes for high recurrence rates, and these should be avoided when possible. However, positive margins are common after resection of this tumor; these occur because of an incomplete tumor capsule, a tendency of the tumor to form perforating pseudopodia, and close proximity of the tumor to the facial nerve [4,76,80].
Rarely, pleomorphic adenoma has been reported to metastasize to the lung, bone, and elsewhere. Furthermore, carcinoma ex pleomorphic adenoma, an aggressive malignancy, may arise in a small percentage of pleomorphic adenomas. Evidence suggests that the occurrence of both is related to incomplete or inadequate primary surgery [81]. (See "Pathology of head and neck neoplasms", section on 'Salivary gland tumors'.)
Recurrent pleomorphic adenomas are treated with resection, but the likelihood of control diminishes with each subsequent surgery while the morbidity increases [82-85]. These include facial nerve dysfunction, Frey syndrome, salivary fistula, and necrosis [78,85].
The role of postoperative radiation following resection of recurrences is debated, but improved local control with postoperative radiation therapy (RT), particularly for positive margins and/or multinodular recurrence, has been reported [78,80,82]. Although reresection should be performed, if possible, for positive margins, many experts would consider postoperative RT for patients with recurrent pleomorphic adenoma and positive margins, depending upon factors such as rapidity of recurrence, patient age, and completeness of resection. Unresectable recurrences are also treated with RT. RT doses used for pleomorphic adenomas are generally lower than for carcinomas, 50 to 54 Gy in 1.8 to 2.0 Gy fractions.
PROGNOSTIC FACTORS — Tumors of major gland salivary glands generally have a better prognosis than those of minor salivary glands, while parotid tumors tend to have a better prognosis than submandibular tumors [86,87]. Several factors have been identified as prognostic of both locoregional control and survival for patients with malignant salivary gland tumors.
Negative prognostic factors include [86,88-97]:
●Preoperative facial nerve dysfunction
●Larger primary tumor (T category)
●Positive cervical lymph nodes
●Perineural invasion
●Positive surgical margins
●High tumor histology or grade
●Older age
●Male sex
●Smoking history
POSTTREATMENT SURVEILLANCE — Regular posttreatment follow-up is commonly employed to detect early recurrences and to monitor for complications. Patients should be educated about possible signs and symptoms of tumor recurrence, including hoarseness, pain, dysphagia, bleeding, and enlarged lymph nodes. (See "Posttreatment surveillance of squamous cell carcinoma of the head and neck".)
For patients with malignant salivary gland tumors, the intensity of follow-up is generally greatest in the first two to four years since approximately 80 to 90 percent of all recurrences occur within this timeframe [11]. However, continued follow-up is generally suggested as there is a risk of recurrence even beyond the first five years. Locoregional recurrence rates were higher in patients with malignant submandibular or minor salivary gland primaries. Distant metastases occurred in 17 percent of parotid primary tumors, but they occurred in 37 percent of those with submandibular primary malignancies. In contrast, 7 percent of local recurrences were observed in patients with benign parotid neoplasms, with a median disease-free interval of seven years and 34 percent occurring more than 10 years after the original diagnosis.
For patients with adenoid cystic carcinoma, distant metastases are of particular concern and may occur even 20 to 30 years after successful treatment of the primary tumor. Chest imaging is useful to monitor for metastatic disease in these patients. In a single institution series of 467 patients treated over a 46 year period, 31 percent had distant metastases, with 75 percent of these being predominantly lung lesions [98]. Of those developing distant metastases, 80 percent occurred within the first eight years. Even with known metastatic disease, disease progression can follow an indolent course, with median one-, three-, and five-year survival rates of 75, 47, and 26.5 percent, respectively, often without intervention.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Head and neck cancer".)
SUMMARY AND RECOMMENDATIONS
●Clinical behavior of salivary gland tumors – Salivary gland tumors include a wide array of benign and malignant histologies that can occur in salivary gland tissue throughout the head and neck. The clinical behavior and management of these tumors depend upon both histology and tumor location. (See 'Introduction' above.)
●Management of the primary tumor – Definitive therapy is indicated for patients with locoregional salivary gland tumors.
•Surgery – For patients with resectable tumors, surgical resection is indicated. In general, simple enucleation is considered inadequate for treatment of salivary gland tumors, whether benign or malignant. The extent of surgical resection of salivary gland tumors depends upon the histology and anatomic location of the tumor. (See 'Surgery' above.)
•Definitive radiation therapy – For patients who are medically inoperable or who have unresectable disease, definitive radiation therapy (RT) is an appropriate alternative. We do not routinely offer concurrent chemoradiation with cisplatin outside of a clinical trial. (See 'Definitive radiation therapy' above.)
●Management of the neck – Selection of therapy for the neck is based upon the presence of nodal metastases, the type of therapy used for the primary tumor, and select tumor features. (See 'Management of the neck' above.)
•Clinically involved nodes – For patients with clinically or radiographically apparent nodal metastases whose primary tumor is treated with surgery, we suggest a comprehensive neck dissection (levels II to III, I, IV, and V when indicated (figure 3)) followed by adjuvant RT rather than RT alone to the neck (Grade 2C).
For patients treated with definitive RT to the primary tumor, we suggest RT alone to the neck rather than comprehensive dissection and adjuvant RT (Grade 2C).
•Clinically negative nodes – For patients with no clinical or radiologic evidence of nodal metastases (cN0) whose primary tumor is treated with surgery and has high-risk features, we suggest elective neck dissection rather than observation (Grade 2C). High-risk features include tumors with high-grade pathology, locally advanced disease (T3 and T4 tumors), and facial nerve paralysis/weakness.
For all patients with resected sublingual gland tumors or minor salivary gland malignancies arising in the nasopharynx, we suggest elective neck dissection rather than observation (Grade 2C).
For patients whose primary tumor is treated with RT alone or those with a resected primary tumor and clinical indications for adjuvant RT whose neck has not been addressed surgically, elective RT to the neck is an appropriate alternative to elective neck dissection.
●Indications for adjuvant radiation therapy – For patients treated with surgical resection who are at increased risk of local or regional recurrence, we suggest the addition of adjuvant RT to the salivary gland surgical bed and appropriate nodal levels (Grade 2C) (see 'Adjuvant therapy' above). Such high-risk features include:
•Tumors with high-grade pathology.
•Selected T3 and all T4 tumors.
•Tumors with other high-risk pathologic features, including positive surgical margins; perineural, vascular, or lymphatic invasion; lymph node involvement; and extracapsular spread.
•Adenoid cystic carcinomas.
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