Version May 2024
INTRODUCTION — This topic discusses the clinical presentation, diagnosis, initial evaluation, and staging of salivary gland tumors.
Other important topics related to salivary gland tumors include the following:
●(See "Salivary gland tumors: Treatment of locoregional disease".)
●(See "Malignant salivary gland tumors: Treatment of recurrent and metastatic disease".)
●(See "Pathology of head and neck neoplasms", section on 'Salivary gland tumors'.)
SPECTRUM OF SALIVARY GLAND TUMORS — Salivary gland tumors constitute an uncommon, heterogeneous group of neoplasms that vary considerably in their anatomic site of origin, histology, and biologic behavior (figure 1). Both benign and malignant salivary gland tumors are classified according to the 2017 World Health Organization (WHO) system (table 1) [1]. (See "Pathology of head and neck neoplasms", section on 'Salivary gland tumors'.)
Anatomically, the parotid gland is the most frequent site of salivary gland tumors, accounting for approximately 80 to 85 percent of these tumors [1,2]. Approximately three-fourths of parotid lesions are benign, and approximately 25 percent are malignant [3].
Less frequently, salivary gland tumors originate in the submandibular, sublingual, and minor salivary glands, which are located throughout the submucosa of the mouth and upper aerodigestive tract [2]. In contrast to tumors arising in the parotid, 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 are malignant.
Histologically, the most common type of benign salivary gland tumor is pleomorphic adenoma, which comprises approximately half of all salivary tumors. Other rarer benign salivary gland tumors include Warthin tumor, basal cell adenoma, and canalicular adenoma. (See "Pathology of head and neck neoplasms", section on 'Salivary gland tumors'.)
The most common malignant salivary gland tumors are mucoepidermoid carcinoma and adenoid cystic carcinoma, which together comprise approximately one-half of all malignant salivary gland tumors [4-6].
Salivary gland cancers vary in their aggressiveness and their propensity to recur and metastasize. A histologic grading system has been proposed in which salivary gland malignancies are classified as high grade or low to intermediate grade based on clinical behavior and outcomes (table 2) [1,2]. A higher tumor grade appears to correlate with more aggressive behavior in mucoepidermoid carcinoma and adenocarcinoma not otherwise specified, but there are conflicting data on the importance of grading according to histological pattern in adenoid cystic carcinoma. (See "Pathology of head and neck neoplasms", section on 'Salivary gland tumors'.)
Other rare but aggressive salivary gland tumors include primary small cell carcinomas, which account for approximately 1 to 2 percent of all salivary gland tumors and often have distant disease at presentation, and salivary ductal carcinoma, a cancer of older men [7]. (See "Extrapulmonary small cell cancer", section on 'Salivary gland ESCC'.)
In addition to primary tumors arising the salivary glands, other malignancies that arise in the head and neck region (eg, lymphoma, cutaneous squamous cell carcinoma, melanoma) can present as major salivary gland masses due to lymph node metastases [1,8]. These may account for up to 10 percent of major salivary gland masses. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis" and "Classification of hematopoietic neoplasms", section on 'Lymphoid neoplasms'.)
EPIDEMIOLOGY AND RISK FACTORS — Salivary gland tumors are rare, representing only 6 to 8 percent of head and neck tumors; in the United States, there are approximately 2000 to 2500 cases per year [1,2]. There are substantial geographic variations in the incidence of salivary gland tumors and in the types of tumors in a given area.
Although there is no one predominant factor known to be associated with the development of salivary gland tumors, a number of factors have been implicated as potential causes:
●Radiation – Radiation exposure has been associated with the development of both benign and malignant salivary gland tumors. This relationship was initially based on data from atomic bomb survivors in Japan [9]. There also appears to be an increased risk in long-term cancer survivors who received radiation therapy as part of their treatment for Hodgkin lymphoma [10,11] and in individuals who received radiation to the head and neck region for childhood cancers or benign conditions [12,13]. Those with a prior history of Hodgkin lymphoma may be at risk of onset of a salivary cancer at a younger-than-typical age for this malignancy [11].
●Smoking – Warthin tumor has a strong association with smoking, in contrast to other salivary gland tumors for which there is no clear relationship. Although this benign tumor has been historically associated with older men, the incidence in women has increased and parallels the increased smoking rates of women [1,14,15].
●Viral infections – Viral infections may be associated with an increased risk of salivary gland cancers.
•Epstein Barr virus (EBV) – Lymphoepithelial carcinoma is an undifferentiated carcinoma that accounts for less than 1 percent of salivary gland tumors; lymphoepithelial carcinoma has been strongly associated with EBV in areas where EBV is endemic [1].
•Human immunodeficiency virus (HIV) – Epidemiologic studies have reported an increased incidence of these tumors in individuals infected with HIV [16,17].
•Human papillomavirus (HPV) – While high-risk serotypes [18,19] of HPV have occasionally been detected in mucoepidermoid carcinoma [20,21], others have not confirmed this observation [22], and it has only rarely been detected in other salivary cancers [23-25]. There are no conclusive data that support a causative role for HPV in the etiology of salivary gland cancers.
●Environmental factors and industrial exposure to factors such as rubber manufacturing, hair dressers, beauty shops, and nickel compounds have been reported to be associated with the development of salivary gland tumors [2,26,27].
CLINICAL PRESENTATION — The clinical presentation of a salivary gland neoplasm depends on its specific site of origin and the extent of involvement of adjacent organs.
●Patients with a tumor of a major salivary gland typically present with a painless mass or swelling of the parotid, submandibular, or sublingual gland. The presence of a parotid mass in combination with signs or symptoms indicative of facial nerve involvement (eg, facial nerve paralysis) is generally indicative of a malignant rather than a benign tumor.
●Minor salivary gland tumors arising within the oral cavity may present with a painless submucosal mass or mucosal ulceration in the palate, lips, or buccal mucosa, with an appearance similar to sialometaplasia (squamous metaplasia of salivary glands) or squamous cell carcinoma. Symptoms due to more advanced minor salivary gland tumors are a function of the location of the tumor and can include nasal obstruction, congestion, vision changes, or trismus when present in the nasal cavity or maxillary sinus. Minor salivary gland tumors involving the nasopharynx usually present at an advanced stage; invasion of the skull base, intracranial extension, or involvement of cranial nerves is common [28].
Tumors with a high malignant potential are more likely to spread to regional lymph nodes and result in a palpable mass (table 2) [4]. Lymphatic drainage varies according to the location of the salivary gland. For parotid malignancies, which constitute the majority of salivary gland tumors, the first site of lymphatic spread is the intraparotid lymph nodes, followed by level I and level II cervical nodes (figure 2). Submandibular gland tumors spread to adjacent perivascular nodes and then to the cervical region. The sublingual gland drains to the submental and submandibular nodes, and the minor salivary glands within the oropharynx drain to the retropharyngeal nodes. (See "Evaluation of a neck mass in adults", section on 'Physical examination'.)
Distant metastases most frequently localize to lung, followed by bone and liver [18]. Adenoid cystic carcinoma is associated with a high risk of distant metastases, which can occur as late as 10 to 20 years after diagnosis and treatment [5].
DIFFERENTIAL DIAGNOSIS — A wide range of pathologic processes can cause a salivary gland mass or enlargement. In addition to benign and malignant tumors, the differential diagnosis of patients includes salivary cysts, cysts of the first branchial cleft, salivary gland stones, sarcoid, Sjögren disease, metastases from other tumors, lymphoepithelial cysts (particularly in an immunocompromised host), chronic sclerosing sialadenitis (Küttner tumor), and regional lymphadenopathy from infectious, inflammatory, or malignant diseases. Distinguishing among these possibilities may require a tissue diagnosis. (See "Differential diagnosis of a neck mass".)
In patients presenting with facial nerve palsy, a high suspicion of malignant involvement of the parotid gland must be entertained in those with a history of skin cancer or melanoma of the scalp or face, as well as in those with a history of removal of a skin lesion that was not sent for pathologic examination.
A malignant parotid tumor must be distinguished from Bell's palsy. Patients with apparent Bell's palsy require further evaluation if there are other neurologic abnormalities, there are features on physical examination that suggest a parotid tumor, or there is no evidence of improvement within a reasonable time frame [29]. (See "Bell's palsy: Pathogenesis, clinical features, and diagnosis in adults", section on 'Imaging studies'.)
Other rare causes of facial nerve paralysis that must be distinguished from a parotid tumor include sarcoid infiltration of the parotid gland (known as Heerfordt syndrome) and intraparotid facial nerve schwannoma [19]. (See "Clinical manifestations and diagnosis of sarcoidosis".)
INITIAL ASSESSMENT
History and physical examination — The initial history should evaluate the duration the mass has been present, the rapidity of its growth, and the presence of pain, numbness, or any subtle asymmetry of facial motion. In addition, the patient should be questioned for a history of previous skin cancers, such as squamous cell carcinoma or melanoma of the scalp or facial region. (See "Evaluation of a neck mass in adults".)
Physical examination should document the size of the mass, its mobility, fixation to overlying skin or to deep structures, any limitation in jaw opening, pharyngeal asymmetry or buccal involvement, pain with palpation, skin or scalp lesions suggestive of primary malignancy, and a detailed facial nerve examination that details specific branch involvement if present. Examination of the neck should include assessment for cervical lymphadenopathy.
Imaging studies — The role of imaging studies in addition to physical examination in the evaluation of salivary gland tumors is to differentiate neoplastic from benign disease, define intra- versus extraglandular location, assess local extension and invasion, and detect nodal and systemic metastases.
The initial imaging evaluation varies in part based on the location of the enlarged gland:
●Both computed tomography (CT) and magnetic resonance imaging (MRI) may be necessary to assess the extent of a salivary gland tumor, which may be greater than can be appreciated on physical examination. Such imaging is also useful to evaluate local, bony, and perineural invasion and lymph node metastases, as well as to assess the parapharyngeal space for involvement from lesions in the parotid [30,31]. MRI is suggested in the evaluation of all sublingual gland tumors given the high risk for malignant disease. Temporal bone or mandibular destruction is best identified by CT, while MRI permits more detailed evaluation of soft tissue infiltration, perineural invasion, and intracranial extension [32]. In addition, CT or MRI can provide anatomic details that are useful for surgical planning.
●Depending on the location and size of a mass, ultrasound may also provide high-quality resolution and tissue characterization while being timely and cost effective for imaging the parotid, submandibular, and sublingual glands [33,34]. These glands are superficial structures and are readily amenable to high-resolution ultrasound examination. In addition, ultrasound can facilitate fine needle aspiration (FNA) and core needle biopsy [35,36]. Ultrasound is not as useful as other modalities for planning surgical treatment.
●When a Warthin tumor is diagnosed, both parotid glands should be imaged since these tumors have a tendency for multifocality and bilaterality [37,38]. Synchronous bilateral malignancy in the parotid glands is rare in other histologic tumor types [39].
DIAGNOSIS — A tissue diagnosis is required to make the diagnosis of a salivary gland tumor and to determine whether such a tumor is benign or malignant.
The tissue diagnosis should be obtained prior to definitive treatment whenever possible to avoid major surgery for a benign tumor or a lymphoma [2]. Options include fine needle aspiration (FNA) or ultrasound-guided core needle biopsy [40-42]. Both techniques are safe, simple procedures that can help direct subsequent evaluation and/or treatment. (See "Salivary gland tumors: Treatment of locoregional disease".)
STAGING — Cancers of the major glands are staged according to the eighth edition (2017) of the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) tumor, node, metastasis (TNM) system (table 3 and table 4) [43]. Tumors arising in minor salivary glands are staged similar to squamous cell carcinoma, according to their anatomic site of origin.
Imaging studies (CT, MRI) that are obtained prior to diagnosis can provide important information for staging in those patients who are ultimately found to have a malignant tumor. Although not routine in the evaluation of all malignant salivary gland tumors, fludeoxyglucose (FDG) positron emission tomography (PET) has good diagnostic accuracy in the assessment of regional lymph nodes and distant metastases in patients with salivary gland malignancies [44-46]. Integrated PET/CT may be more accurate than PET alone [47]. However, PET is not able to distinguish benign from malignant parotid tumors. CT may also be useful to examine the chest to rule out lung metastases.
SUMMARY
●Spectrum of salivary gland tumors – Salivary gland tumors comprise a rare, diverse group of benign and malignant histologies. (See 'Spectrum of salivary gland tumors' above.)
•Parotid gland tumors – Most salivary gland tumors are benign and occur in the parotid gland (figure 1). Pleomorphic adenoma is the most common of these benign lesions.
•Other salivary gland tumors – Tumors of the submandibular, sublingual, and minor salivary glands are more likely than parotid tumors to be malignant.
●Clinical presentation – Most patients with salivary gland tumors present with a painless mass or swelling. Neurologic signs or symptoms, such as facial nerve paralysis, indicative of facial nerve involvement, are almost always indicative of a malignant tumor. (See 'Clinical presentation' above.)
●Differential diagnosis – The differential diagnosis of a salivary gland mass includes a wide range of cystic and inflammatory disorders as well as benign and malignant tumors (table 1).
●Initial evaluation – The initial evaluation of a salivary gland tumor includes (see 'Initial assessment' above):
•History and physical examination – The history should evaluate for the duration the mass has been present, rate of growth, the presence of pain, numbness, or any subtle asymmetry of facial motion, and history of previous skin cancers. Physical exam should include evaluation of the primary mass and surrounding structures, the neck for cervical lymphadenopathy, and a detailed facial nerve examination. (See 'History and physical examination' above.)
•Imaging studies – Both CT and MRI may be necessary to assess extent of local invasion or dissemination of the tumor. (See 'Imaging studies' above.)
Ultrasound may be useful for imaging the parotid, submandibular, and sublingual glands and can facilitate fine needle aspiration (FNA) and core needle biopsy.
●Diagnosis – A tissue diagnosis is required to establish a definitive diagnosis of a salivary gland tumor and to plan therapy. If anatomically feasible, a preoperative biopsy (either fine needle aspiration [FNA] cytology or ultrasound-guided core needle) can be performed to avoid operating on a nonsurgically managed disease process and to aid in surgical planning. However, a preoperative histologic diagnosis is not always possible. (See 'Diagnosis' above.)
●Staging – Malignancies of the parotid, submandibular, and sublingual glands are staged according to the American Joint Committee on Cancer (AJCC) and Union for International Cancer Control (UICC) tumor, node, metastasis (TNM) system (table 3 and table 4). (See 'Staging' above.)
•Tumors arising in minor salivary glands are staged according to their anatomic site of origin.
•Imaging studies using CT and MRI (often obtained prior to diagnosis), and in some cases positron emission tomography (PET) may provide important information about the extent of local invasion or dissemination.
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