Approach to salivary gland swelling

INTRODUCTION — 

Salivary gland swelling is frequently encountered by clinicians and has a variety of causes. This topic will address the evaluation and diagnostic approach to salivary gland swelling in adults, focusing mainly on the parotid and submandibular glands.

Common causes of salivary gland swelling include sialosis (sialadenosis), sialoliths (salivary stones), bacterial infections, Sjögren's disease, and tumors. The diagnosis and management of these specific conditions is reviewed in detail separately:

●(See "Salivary gland stones".)

●(See "Suppurative parotitis in adults".)

●(See "Treatment of Sjögren's disease: Constitutional and non-sicca organ-based manifestations", section on 'Salivary gland enlargement'.)

●(See "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging".)

●(See "Salivary gland tumors: Treatment of locoregional disease".)

●(See "Malignant salivary gland tumors: Treatment of recurrent and metastatic disease".)

DEFINITIONS AND TERMINOLOGY

●Sialadenitis is inflammation of a salivary gland.

●Sialosis (or sialadenosis) is a multifocal (usually bilateral), noninflammatory, nonneoplastic enlargement of the salivary glands (typically the parotid glands) that is often associated with systemic metabolic conditions. (See 'Metabolic sialosis' below.)

●Unifocal symptoms refer to symptoms that affect a single salivary gland, whereas multifocal symptoms refer to involvement of multiple glands.

●"Acute" salivary gland swelling refers to symptoms that have been present for days to several weeks, and "chronic" salivary gland swelling refers to symptoms that have been present for weeks to months. These terms are descriptive, but there are no established guidelines defining them specifically for salivary gland disorders. Acute sialadenitis is characterized by sudden enlargement and pain of the affected gland, whereas chronic sialadenitis is less likely to be painful and is often characterized by an abnormally firm gland that may be enlarged, normal, or even atrophic in size.

ANATOMY AND PATHOGENESIS — 

The major salivary glands include the paired parotid, submandibular, and sublingual glands; these are collectively responsible for the production of over 95 percent of saliva (figure 1). In addition, there are approximately 1000 minor salivary glands dispersed through the submucosa of the oral cavity, with each measuring from 1 to 2 mm in size. Salivary gland swelling can occur due to swelling within the gland itself (eg, as seen in viral infections such as mumps), or due to obstruction of the salivary ducts (eg, strictures, stones, or tumors) leading to accumulation of saliva in the gland with associated pain and swelling. In addition, perceived salivary swelling may result from enlargement of nonsalivary structures adjacent to or within the salivary glands, including enlarged lymph nodes, masseter hypertrophy, tumors, and vascular malformations [1]. (See 'Processes that mimic salivary gland enlargement' below.)

ETIOLOGIES — 

Common etiologies of salivary gland swelling are briefly summarized below. They can be categorized based on chronicity of symptoms and number of glands affected (table 1).

Acute symptoms — Salivary gland swelling can be considered acute if the duration is less than several weeks. We place conditions that typically cause intermittent, recurring salivary gland swelling within this category. The most common causes of acute salivary gland swelling include sialoliths (salivary stones), infections (bacterial or viral), and duct strictures.

Sialoliths (salivary stones) — Sialoliths are among the most common causes of salivary gland swelling [2]. They usually present with pain and swelling of the involved gland (up to 90 percent occur in the submandibular glands), which worsens with eating or anticipation of eating [3]. The mechanical obstruction of salivary flow within the duct causes swelling of the gland as saliva is produced but is unable to drain normally. Swelling and discomfort can be episodic or persistent, and secondary bacterial infection is possible. In the case of long-term duct obstruction (with or without recurrent episodes of acute swelling), the affected gland may ultimately become atrophic (figure 2). The clinical presentation, evaluation, and treatment of salivary stones are described in detail elsewhere. (See "Salivary gland stones".)

Infections — Bacterial infections usually cause unifocal swelling (ie, single gland affected), whereas viral infections often cause multifocal (ie, multiple glands affected) symptoms.

●Bacterial infection – Bacterial sialadenitis most commonly involves the parotid or submandibular glands. It is characterized by the sudden onset of pain and swelling of a single salivary gland, with an indurated, tender, and swollen gland on physical examination. Patients may report a foul taste. Massage of the gland may produce purulent material at the duct orifice (picture 1 and movie 1). The risk factors, microbiology, diagnosis, and treatment of bacterial sialadenitis is discussed in detail elsewhere. (See "Suppurative parotitis in adults".)

●Viral infection – Viral infections typically cause acute, multifocal salivary gland swelling. Salivary gland swelling is usually accompanied by systemic symptoms, such as fever, headache, malaise, or myalgias. Laboratory evaluation can help confirm the diagnosis.

•Mumps – Mumps is a contagious viral illness caused by the mumps virus, and is characterized by fever, headache, myalgia, and fatigue, followed by the development of salivary gland (typically parotid) swelling within 48 hours of symptom onset. Although often unilateral at onset, parotid gland swelling and inflammation becomes bilateral in over 90 percent of cases within a few days [4]. Diagnosis of mumps is confirmed by laboratory testing. (See "Mumps".)

•Other viral causes (mumps-like) – Other viral infections are associated with clinical parotitis and may mimic mumps infection (See "Mumps", section on 'Differential diagnosis'.).

Examples of viruses that may be associated with similar parotitis include [5-8]:

-Epstein-Barr virus (EBV)

-Parainfluenza virus

-Cytomegalovirus (CMV)

-Hepatitis C virus (HCV)

-Influenza virus

-SARS-CoV2 (COVID-19)

Although salivary gland swelling has been reported in association with COVID-19 infection [8-10], but it may reflect enlarged intraparotid lymph nodes rather than true parotitis [11].

HIV (human immunodeficiency virus) may also be associated with acute salivary gland swelling, but it more commonly causes chronic swelling from benign lymphoepithelial cysts. (See 'Tumors or other masses' below.)

●Other infectious causes – Other less common causes of infectious sialadenitis include actinomycosis [12,13] and mycobacteria [14-19]. These typically cause acute, unifocal symptoms. While mycobacterial infections of the lymph nodes (tuberculous lymphadenitis) typically involve the cervical lymph nodes, in rare cases the salivary gland itself may become involved. (See "Actinomycosis: Microbiology, epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations' and "Tuberculous lymphadenitis", section on 'Cervical lymphadenopathy'.)

Duct strictures — Salivary ductal stricture is a narrowing in the salivary duct lumen that impairs normal salivary flow. Strictures may be characterized as either single or multiple, and discrete or diffuse. Ductal stricture often presents similarly to sialolithiasis, although the overall course may typically be more of relapsing and remitting symptoms. Imaging is helpful to evaluate for most ductal strictures. Alternatively, distal strictures (at the end of the duct as it enters the oral cavity) may be identified by inspection or probing for patency. Proximal (closer to the gland than the mouth) duct dilation on ultrasound suggests a diagnosis of ductal stricture, but ultrasound may not be sufficiently sensitive to fully evaluate the extent and number of strictures. Sialography is the optimal test to evaluate for strictures, and when done through the cannulation and infusion approach, is often also therapeutic [20-22]. (See 'Sialography' below.)

Common causes of duct strictures include irradiation, prior infection, and autoimmune processes; however, in many cases, the cause of stricture remains unknown.

Exposures — Exposures to drugs, radioiodine treatment, intravenous contrast, and external beam radiation can all cause salivary gland swelling. In most cases, symptoms develop acutely, and the temporal association between exposure and the development of symptoms helps identify the cause. However, with radioiodine sialadenitis, swelling and pain associated with progressive ductal obstruction often does not manifest until 6 to 12 months after exposure.

●Drug-induced sialadenitis – Drug-induced parotitis is a rare, adverse drug reaction that has been associated with l-asparaginase, clozapine, and phenylbutazone [23]. The mechanism of action for drug-induced salivary swelling is largely unknown but may include spasm of smooth muscle within the gland, altered autonomic effect with interference in sympathetic vasoconstrictor effect, and anticholinergic effect [24].

●Radioiodine treatment (131-I) – 131-I (used therapeutically in the treatment of differentiated thyroid carcinomas as well as hyperthyroidism), can cause inflammation of the salivary glands. Symptoms of salivary gland inflammation typically begin within hours of receiving 131-I therapy and generally resolve within several days. In some cases, 131-I therapy can induce ductal stricture months to years after treatment [25]. Although the salivary gland may atrophy in response to therapy, the ductal stricture may be symptomatic if the narrowing becomes tighter as the gland continues salivary production (image 1). Prevention and treatment of radioiodine-induced sialadenitis is discussed elsewhere. (See "Differentiated thyroid cancer: Radioiodine treatment", section on 'Sialadenitis'.)

●Contrast-induced sialadenitis – Rapid, painless enlargement of the salivary glands ("iodide mumps") may rarely occur shortly after infusion of iodinated contrast dye [26]. The risk of developing contrast-induced sialadenitis is associated with high serum iodide levels (>10 mg/100 mL) and is more likely to occur with impaired kidney function due to reduced elimination of contrast material [27]. It has been reported that the high concentration of iodine dye in salivary glands results in local inflammation and edema, leading to blockage of the salivary duct [28]. Symptoms usually resolve rapidly, within hours to a few days, with general supportive measures (see 'Supportive measures' below). For patients with severe symptoms that do not resolve quickly with supportive measures, systemic glucocorticoids may be used [26,28]. Treatment with dialysis is another management option for patients with severe and persistent symptoms.

●Postradiation sialadenitis – Acute, unifocal salivary gland swelling may develop from external beam radiation, which is most often administered as part of cancer treatment. If multiple salivary glands are included in the radiation field, then multifocal salivary gland swelling may develop. The swelling is usually due to damage to the gland parenchyma; less frequently, it may occur from ductal obstruction associated with duct narrowing. Swelling and pain usually resolve over a period of months [29]. Following the initial radiation-induced sialadenitis, chronic destructive changes to the glands can result in gland atrophy associated with symptomatic xerostomia. Prevention and treatment of long-term radiation-related salivary gland damage and xerostomia is discussed elsewhere. (See "Management of late complications of head and neck cancer and its treatment", section on 'Salivary gland damage and xerostomia'.)

Other (rare causes) — Additional obstructive and nonobstructive causes can uncommonly cause salivary gland swelling.

●Obstructive causes – Additional obstructive causes of acute salivary gland swelling include:

•Ductal foreign body – Rarely, a foreign body (eg, fish bones, grass blades, hair, toothbrush bristles) may enter the salivary ducts in a retrograde fashion from the oral cavity and cause obstruction [30]. Foreign bodies within the ducts may additionally serve as a nidus for the development of a sialolith [31]. Foreign bodies can usually be identified on ultrasound or computed tomography (CT) scan; they can be removed via sialendoscopy.

•Pneumoparotitis – Sialadenitis may result when air is forced into the duct and gland (termed "pneumoparotitis" when it affects the parotid gland). It has been described in association with the use of positive pressure ventilation [32,33] and activities that cause increased intraoral pressure, including wind instrument playing [34], glass blowing, exercising, and behaviors associated with psychiatric abnormalities [35]. Pneumoparotitis is typically an acute process, lasting only as long as the precipitating event. If chronic or recurrent, however, it may lead to ductal changes, causing chronic or recurrent obstruction and possibly chronic infection and inflammation [36].

Pneumoparotitis can also occur as a result of oronasal continuous positive airway pressure (CPAP). The obstruction is caused by the air in the duct and should resolve within a few hours after discontinuation of the positive airway pressure ventilation or conversion from oronasal CPAP to nasal CPAP [33,37]. However, air may remain within the gland longer and the resulting sialadenitis may take several days (or longer, depending on the severity of the inflammation) to resolve.

Pneumoparotitis is suspected in patients with the above risk factors, although some patients with self-induced disease may fail to report the precipitating events. On physical examination, expressed saliva from the affected duct may appear "bubbly"; on ultrasound, air is identified within the ducts and gland.

•External compression of the duct – Less common causes of obstruction to salivary flow may occur from other processes, including pressure from denture flanges impacting the submandibular duct orifice [38], from an enlarged mandible, or from a hypertrophied masseter, causing kinking of the parotid duct [39-41].

●Nonobstructive causes – Additional nonobstructive causes of acute salivary gland swelling include:

•Acute sialadenosis of bulimia nervosa – Chronic parotid gland enlargement is widely described in patients with bulimia nervosa [42-45]. In addition, cessation of purging (ie, vomiting) may result in acute sialadenosis, characterized by painful, bilateral parotid gland swelling [46]. Symptoms are typically managed with supportive measures as needed until the discomfort resolves.

•Juvenile recurrent parotitis (JRP) – JRP is a recurrent, acute parotitis of unknown etiology characterized by intermittent painful swelling of one or both glands and redness of the overlying skin, often accompanied by fever [47]. Episodes of swelling typically last from 24 to 48 hours but may last for several weeks [48]. JRP most often occurs in boys between the ages of four months and 15 years and is generally self limited with spontaneous remission of episodes at puberty [48]. The majority of patients are free of symptoms by age 22. Prior to the decrease in incidence of mumps, among children, JRP had been the second most common salivary gland disorder after mumps; however, it may now be the most common [47].

The diagnosis of JRP is made based on the patient's history, with laboratory tests used to exclude other conditions such as mumps, Sjögren's disease, and sarcoidosis. Recommended laboratory testing includes antinuclear antibodies (anti-Ro/SSA and anti-La/SSB) and measurement of angiotensin-converting enzyme (ACE) level (these are normal in JRP) [49]. Ultrasound helps to support the diagnosis, demonstrating heterogeneous glandular tissue with nodular hypoechoic areas, and is the preferred initial imaging test. Other imaging modalities (CT, magnetic resonance imaging [MRI], sialography, and sialendoscopy) may be useful if additional evaluation is necessary [48,49]. There is not, however, a widely accepted set of guidelines required to establish the diagnosis.

Chronic symptoms — Salivary gland swelling is considered chronic when it has been present for at least several weeks (without interim improvement). Chronic unifocal symptoms are suggestive of a mass or tumor, whereas chronic multifocal symptoms usually indicate an underlying systemic disorder.

Tumors or other masses — Tumors are a common etiology of chronic, unifocal salivary gland swelling.

●Tumors – Primary tumors of the salivary glands may be benign or malignant. They most commonly present as a painless mass, although tumors of different histologic subtypes may present with additional symptoms including pain, paresthesia, and facial nerve paralysis. Accelerated enlargement of a previously stable growth may represent malignant transformation of a benign tumor. Patients with a suspected tumor should have imaging; diagnosis is based on biopsy of the affected gland. Primary tumors of the salivary glands are discussed elsewhere. (See "Salivary gland tumors: Epidemiology, diagnosis, evaluation, and staging" and "Pathology of head and neck neoplasms", section on 'Salivary gland tumors'.)

In addition to primary tumors, metastases to the parotid gland can occur from cutaneous malignancies in the head and neck area, including melanoma and squamous cell carcinoma [50,51]. (See "Surgical management of primary cutaneous melanoma or melanoma at other unusual sites", section on 'Head and neck' and "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy".)

Lymphomas may develop within the salivary gland parenchyma (picture 2) but may also develop within lymph nodes embedded in a salivary gland. (See 'Processes that mimic salivary gland enlargement' below.)

●Polycystic parotid disease – Sclerosing polycystic adenosis (SPA), or polycystic dysgenic disease, is a rare pseudoneoplastic condition of unknown etiology resulting in cystic changes, fibrosis, and epithelial proliferation within the salivary glands [52]. SPA typically occurs within the parotid gland, but may be also seen in the submandibular gland, and develops as a slow-growing mass. Patients often experience a mild pain or a tingling sensation, and the affected gland may be mildly tender on examination, with multiple firm, rubbery nodules ranging from a few millimeters to as large as 7 cm [53]. As with other salivary gland masses of uncertain etiology, a biopsy is needed for diagnosis. The recommended treatment for polycystic parotid disease is complete excision via superficial parotidectomy [54].

●Benign lymphoepithelial cysts (associated with HIV) – Salivary gland swelling is frequently seen among patients with HIV infection and most commonly results from benign lymphoepithelial cysts (BLEC) [55]. Individuals with HIV infection and BLEC usually develop chronic, painless bilateral parotid swelling not typically accompanied by xerostomia. Ultrasound patterns of parotid enlargement in patients with HIV infection include lymphocytic aggregations, lymphoepithelial cysts, and lymphadenopathy [56]. When identified, cystic enlargement of the parotid gland warrants investigation for possible HIV infection. For those with HIV infection, treatment with antiretroviral therapy (ART) often successfully decreases the size of the cysts [57]. For large cysts that persist despite ART, ultrasound-guided fine-needle aspiration may be done to rule out the coexistence of a malignancy as well as to decrease the size of the cyst. Management options for those patients with significant cosmetic deformity that persists despite ART include repeated cyst aspirations, sclerosing therapy, radiation therapy [58,59], and surgical excision of the affected gland(s).

Systemic disorders — Chronic multifocal salivary gland swelling is often indicative of an underlying systemic disorder, most commonly metabolic sialosis or Sjogren's syndrome.

Metabolic sialosis — Sialosis, also known as sialadenosis, is defined as chronic enlargement of the salivary parenchyma with gradually progressive swelling that does not fluctuate and is not associated with the stimulus of eating [60]. Although it typically presents as painless bilateral parotid enlargement, it may occasionally affect the submandibular glands and be associated with mild discomfort [61].

Approximately half of all cases are associated with one of the recognized risk factors, including diabetes, metabolic syndrome, alcohol use, bulimia, malnutrition, and liver disease [62-65]. With the rising prevalence of obesity and diabetes, sialosis is seen with increasing frequency and may now be the most common cause of salivary gland swelling in the United States [60,66,67]. In a study of 200 patients with diabetes or prediabetes, 24 percent had parotid gland enlargement due to sialosis, although most were not aware of the enlargement [68].

Sialosis due to alcohol and diabetes may have a similar clinical presentation, but histologically alcohol-related sialosis is associated with enlarged acini and minimal parenchymal fat content, while diabetic sialosis is associated with smaller acini and greater fatty infiltration [69-71]. The buildup of secretory granules seen in the acinar cells may be responsible for enlargement of the gland parenchyma. As the process matures, acinar enlargement may give way to fatty infiltration of the gland [72,73]. When discomfort does occur in association with sialosis, it may be due to the pressure and necrosis of the enlarged acini.

Sialosis should be suspected based upon the patient's clinical history (ie, the presence of risk factors) and physical examination. Ultrasound, which will show diffuse enlargement of the major salivary glands with a greater than normal hyperechoic and homogeneous echotexture [74] can be done to help support the diagnosis. If the clinical history, examination and ultrasound are consistent with sialosis, then no further evaluation is needed. The primary management of sialosis involves addressing the underlying disorder, although complete resolution of gland enlargement does not always occur.

Sjögren's disease — Sjögren's disease is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands, with resultant dry eyes, dry mouth, salivary gland swelling, and, less commonly, extraglandular abnormalities [75]. Almost all patients with salivary gland swelling due to Sjögren's disease will also describe dry eyes and dry mouth. Salivary gland involvement with Sjögren's disease may also include painful swelling associated with ductal obstruction from scarring, mucus plugs, and a higher propensity for stone formation.

It is important to note that patients with Sjögren's disease have an elevated risk of non-Hodgkin lymphoma, with >60 percent arising within the parotid gland [76,77]. Clinicians should be aware of this increased risk and consider lymphoma, as the cause of new salivary gland enlargement in a patient with known Sjögren's disease.

The diagnosis of Sjögren's disease and management of salivary gland swelling in Sjögren's disease is discussed elsewhere. (See "Diagnosis and classification of Sjögren's disease" and "Overview of the management and prognosis of Sjögren's disease" and "Treatment of Sjögren's disease: Constitutional and non-sicca organ-based manifestations", section on 'Salivary gland enlargement'.)

Other systemic causes (uncommon)

●Immune-mediated

•IgG4-related disease (IgG4-RD) – IgG4-RD is an immune-mediated fibro-inflammatory process most frequently involving the pancreas and salivary glands, but often involving other exocrine glands, lymph nodes, and multiple other organs [78]. Patients with IgG4-related sialadenitis (IgG4-RS) present with persistent parotid and/or submandibular gland swelling, which is usually bilateral (picture 3) [79]. There may be associated lacrimal gland swelling, and approximately 15 percent of patients have evidence of concurrent autoimmune pancreatitis [80]. The diagnosis is suspected based on clinical features and laboratory testing and imaging, but biopsy of the affected gland is required to confirm the diagnosis. Compared with Sjögren's disease, IgG4-related disease is more likely to affect males, and patients are more likely to have elevated IgG4 and IgE levels (table 2). The clinical manifestations, diagnosis, and treatment of IgG4-related disease is discussed elsewhere. (See "Clinical manifestations and diagnosis of IgG4-related disease", section on 'Salivary gland involvement' and "Treatment and prognosis of IgG4-related disease".)

•Eosinophilic sialodochitis (also known as Kussmaul disease) – Eosinophilic sialodochitis disease is characterized by painful swelling of the parotid and/or submandibular glands, resulting from obstruction of the salivary ducts by mucofibrinous plugs [81]. This disorder has been determined to be more common than previously considered and has had multiple terms associated with it, including "sialodochitis fibrinosa" and "allergic parotitis" [82,83]. The disorder is characterized by:

-Recurring episodes of major salivary gland swelling

-Discharge of mucofibrinous plugs with a high content of eosinophils from salivary ducts

-Elevated levels of serum IgE and/or eosinophilia

-Presence of concomitant asthma or allergic rhinitis

-Irregular dilation of the main salivary ducts on imaging (sialography or MRI)

-Periductal lymphocytic infiltrates and abundant eosinophils on salivary gland biopsy

Kussmaul disease is believed to be an allergic process; it is treated with antihistamines, systemic glucocorticoids, leukotriene receptor antagonists, immunomodulators [84], and possibly duct dilation with steroid insufflation [85]. Dupilumab has also been used to treat a refractory case [86].

●Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides – Patients with ANCA-associated vasculitides, including granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA), may occasionally develop salivary gland involvement with clinically apparent swelling of the affected glands.

•GPA – Salivary gland swelling, occasionally painful, has been reported in 1 to 4 percent of patients with GPA, with one or multiple glands affected [87,88]. In addition, GPA may infrequently present with isolated salivary gland enlargement before the appearance of systemic symptoms or kidney involvement [89-91]. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis", section on 'Other manifestations'.)

•EGPA – Salivary gland involvement in EGPA is uncommon and, when present, usually occurs in the presence of other symptoms. In rare cases, however, multifocal swelling of all four major salivary glands may be a prominent presenting complaint [92]. (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA)" and "Eosinophilic granulomatosis with polyangiitis: Treatment and prognosis", section on 'Systemic glucocorticoids (for all patients)'.)

●Infiltrative causes – Infiltrative causes of salivary gland swelling include sarcoidosis and amyloidosis.

•Sarcoidosis – Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that can involve the parotid and other salivary glands. Salivary gland swelling is typically painless and can be unifocal or multifocal [93]. The combination of anterior uveitis, parotid gland enlargement, facial nerve palsy (due to compression of the nerve by the enlarged parotid gland), and fever (referred to as Heerfordt syndrome) is a pathognomonic presentation of sarcoidosis. (See "Overview of extrapulmonary manifestations of sarcoidosis", section on 'Parotid and salivary glands'.)

•Amyloidosis – Localized major salivary gland involvement with amyloidosis is rare, with reports of amyloidomas (tumor-like accumulations of amyloid) of the parotid and submandibular glands [94-96]. Treatment may involve excision of the affected gland (if appropriate), and systemic therapy aimed at the underlying cause of the amyloidosis. (See "Overview of amyloidosis".)

●Idiopathic causes – The idiopathic causes of chronic, multifocal salivary gland swelling are rare and include inflammatory myofibroblastic tumor, Kimura disease, and Rosai-Dorfman disease.

•Inflammatory myofibroblastic tumor – Inflammatory myofibroblastic tumor (inflammatory pseudotumor, plasma cell granuloma, fibrous histiocytoma) is a rare benign neoplasm that most frequently occurs in the lungs and orbit but also may develop in the neck, skull base, thyroid, liver, parotid gland, or other organs [97,98]. Inflammatory myofibroblastic tumor of the parotid presents as a slow-growing mass, and ultrasound will demonstrate a hypoechoic mass. Biopsy is essential to the diagnosis; spindle cells, plasma cells, and lymphocytes are key histologic findings [99]. Complete surgical resection is usually the treatment of choice. (See "Inflammatory myofibroblastic tumor (plasma cell granuloma) of the lung".)

•Kimura disease – Kimura disease is a rare, chronic inflammatory disease of unknown etiology that is characterized by painless subcutaneous nodular lesions in the head and neck accompanied by enlarged cervical lymph nodes. The orbits, nasal sinuses, oral cavity, and parotid glands may be involved. Biopsy is required for diagnosis. Kimura disease is discussed in detail elsewhere. (See "Angiolymphoid hyperplasia with eosinophilia and Kimura disease", section on 'Kimura disease'.)

•Rosai-Dorfman disease – Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is a rare non-Langerhans cell histiocytosis characterized by painless lymphadenopathy (typically cervical), with frequent involvement of extranodal sites including the salivary glands [100-104].

Histologically, in Rosai-Dorfman disease, a mixed inflammatory background with plasma cells and lymphocytes with varying degrees of stromal fibrosis is seen, along with the hallmark "Rosai-Dorman cells" [105]. These are large, polygonal S-100 protein-positive histiocytes with emperipolesis (also known as lymphophagocytosis), a phenomenon characterized by the presence of lymphocytes or other inflammatory cells seen within the cytoplasm.

Although complete and spontaneous remission may occur, in a few cases the disease follows an aggressive course and may be fatal [106]. There are international consensus guidelines for the evaluation and management of Rosai-Dorfman disease [107].

INITIAL EVALUATION

Key elements of history — The clinical history is essential in assessing salivary gland swelling; key elements are useful to guide further diagnostic testing (table 3).

Chronicity of symptoms — Acute symptoms (duration less than several weeks) are most likely due to salivary stones, infections, duct strictures, or exposures (eg, iodinated contrast). Among those with acute symptoms, further clarifying the onset can be helpful. Swelling due to salivary stones can develop in minutes and may last for days, while infectious sialadenitis develops over hours to days. Chronic symptoms raise concern for a mass if a single gland is affected, or a systemic condition (eg, Sjögren's disease) if multiple glands are affected.

Number of glands affected — Patients who have a single gland affected commonly have either a bacterial infection, salivary stone, or duct stricture as the cause of their symptoms. Tumors or other masses are considerations in those with chronic swelling of a single gland. In contrast, if multiple glands are affected, common etiologies include viral infections (eg, mumps) if symptoms are acute, or an underlying systemic disorder if symptoms are chronic. (See 'Systemic disorders' above.)

Systemic symptoms — The presence or absence of systemic symptoms can help suggest an underlying etiology:

●For those with acute salivary gland swelling, associated fevers or chills suggest an infectious etiology. Viral infections often have additional systemic symptoms, such as headache, myalgias, respiratory symptoms, or gastrointestinal symptoms. Lack of systemic symptoms suggests stone, stricture, or exposure as the cause of swelling.

●For those with chronic salivary gland swelling, unexplained fevers or weight loss raise suspicion for an underlying immune-mediated or vasculitic etiology. Sicca symptoms (dry eyes and mouth) suggest Sjögren's disease, whereas associated arthritis or chronic rhinosinusitis can indicate an ANCA-associated vasculitis (see 'Systemic disorders' above). Lack of systemic symptoms suggests sialosis from metabolic conditions (if multiple glands are affected), or a mass (if single gland affected).

Predisposing factors — We ask about underlying factors that may cause swelling, including medical conditions and potential exposures.

●Underlying conditions – Common underlying conditions that can lead to salivary gland swelling including metabolic disorders (eg, diabetes mellitus, alcohol use, malnutrition), immune-mediated disease (commonly Sjögren's disease), infiltrative disease (amyloidosis or sarcoidosis), and vasculitic processes. (See 'Systemic disorders' above.)

●Possible exposures – We ask about recent radioiodine treatment, receipt of intravenous contrast, external beam radiation, or drugs that can cause salivary gland swelling (eg, cloazapine). Each of these causes acute swelling, which usually starts within the first few days after exposure; there are usually no systemic symptoms. (See 'Exposures' above.)

In addition, activities associated with an increase in intraoral pressure can cause "pneumoparotitis" (air forced into the duct and gland). This is commonly seen with CPAP use and has also been described with wind blowing instruments and glass blowing.

Physical examination — Key elements of the physical examination include:

●Confirmation of salivary gland swelling – Many processes can mimic salivary gland swelling; a careful physical examination can help distinguish these possibilities. If there is diagnostic uncertainty, imaging is appropriate. (See 'Processes that mimic salivary gland enlargement' below.)

●Gland characteristics – We inspect and palpate bilateral parotid and submandibular glands to confirm whether the swelling is affecting a single or multiple glands. We also palpate for gland size (enlarged, normal, atrophic) and gland texture (smooth, soft/firm, nodular, or discrete mass). Bimanual palpation is done with one finger inside the oral cavity. Atrophic gland typically indicates long-term duct obstruction. Experienced specialists may be able to appreciate additional differences that can be helpful in determining etiology.

●Tenderness or overlying erythema – Gland tenderness or erythema over the overlying skin indicate possible bacterial infection.

●Expression of salivary discharge with massage of gland – We massage the gland and attempt to express saliva (movie 2 and movie 3). Possible types of salivary discharge include:

•Normal – thin and watery.

•Purulent – indicates bacterial infection.

•Bubbly – indicates pneumoparotitis (air in the duct or gland, as can be seen with CPAP use and other activities that increase intraoral pressure). (See 'Other (rare causes)' above.)

•Reduced or mucoid – may indicate obstruction or chronic inflammation.

•Absent – may indicate obstruction of gland, although could be due to other variables (eg, degree of hydration or recent emptying of the gland).

In addition, a focused cranial nerve (CN) examination should be performed to evaluate CN V (the trigeminal nerve) and CN VII (the facial nerve). With parotid gland swelling, all branches of the facial nerve may be affected (figure 3). However, if swelling affects only the submandibular gland, involvement is generally limited to the marginal mandibular branch.

Imaging for most patients — We obtain imaging in most patients with salivary gland swelling. Imaging helps determine whether swelling is from the salivary gland itself or from another structure (eg, an embedded or nearby lymph node). It may also help identify common etiologies, including stones or stricture, and can provide useful information about the characteristics of swelling (eg, cystic versus diffuse enlargement).

Patient selection — We obtain imaging during initial evaluation for patients with severe, recurrent (two or more lifestyle episodes), or chronic symptoms. We also obtain imaging in patients who have an uncertain diagnosis after clinical evaluation, and in those who have signs or symptoms of a bacterial infection.

There are limited exceptions. Patients who do not require imaging include those who meet all of the following criteria:

●First episode of salivary gland swelling

●Mild symptoms

●Clear etiology of swelling based on history and physical examination

●Low suspicion for bacterial infection

●Resolution with supportive measures within four to six weeks

Examples of patients who do not require imaging are those who had a clear exposure (external beam radiation, contrast, or drugs) or have a viral syndrome (eg, mumps). Imaging should be obtained if they do not improve with supportive measures within the expected timeframe (usually several weeks).

Initial modality — We prefer ultrasound for initial imaging; CT scan with contrast is an appropriate first-line alternative. MRI is reserved for patients in whom a neoplasm or vascular lesion of the salivary gland is suspected.

●Ultrasound preferred – We typically perform initial imaging with ultrasound, as it is able to give helpful information in most cases and is widely available. If available, ultrasound with elastography may be performed to assess tissue characteristics and help diagnose certain pathologies (eg, diseased parenchyma or tumor) [108]. It is important to note that the quality of salivary gland ultrasound is highly dependent on operative technique, and it is best done in a facility with experience and expertise in salivary gland ultrasound.

•Possible findings – In some cases, ultrasound may be diagnostic (eg, detection of stone or foreign body). Specific patterns on ultrasound can suggest possible diagnoses:

-Proximal duct dilation can be seen with ductal stenosis or other obstructive condition (eg, stone). If no cause of obstruction is detected on ultrasound, CT scan is helpful to evaluate for stones.

-Diffuse enlargement of the major salivary gland with a greater than normal hyperechoic and homogenous echotexture is a common finding seen in sialosis [74]. (See 'Metabolic sialosis' above.)

-Air within the ducts and glands indicates pneumoparotitis. (See 'Other (rare causes)' above.)

-Heterogenous glandular tissue with nodular hypoechoic areas is consistent with autoimmune sialadenitis, such as occurs with Sjögren's disease and juvenile recurrent parotitis. (See 'Other (rare causes)' above.)

-Cystic enlargement of the parotid gland can be due to benign lymphoepithelial cysts; this finding should prompt evaluation for possible HIV infection. (See 'Tumors or other masses' above.)

●CT with contrast if ultrasound not available or not diagnostic – If salivary gland ultrasound is not available, alternative first-line imaging is CT with contrast [109]. If a patient is unable to receive intravenous contrast, a CT without contrast is acceptable. Some prefer CT without contrast to avoid mistaking contrast-enhanced vascular structures for stones, but we prefer the additional soft tissue definition provided with the use of contrast.

CT with contrast is also appropriate follow-up imaging in patients who have an initial ultrasound that is normal or indeterminant. For example, we perform CT scan with contrast if there is a high clinical suspicion for a stone but with normal ultrasound (or if ultrasound shows proximal duct dilation). CT scan has a greater sensitivity for detecting stones or strictures [110]. The contrast does not help in detecting stones but does assist in identifying associated findings such as lymphadenopathy and sialadenitis.

●MRI if there is suspicion for a neoplasm or vascular lesion – If a neoplasm or vascular lesion of the salivary gland is suspected (based on history, physical examination, and/or initial imaging), we obtain MRI. Ultrasound and CT generally provide sufficient detail of the ductal system and gland, but MRI is the most sensitive imaging modality for evaluation of most neoplasms and vascular lesions of the salivary glands [111].

Laboratory testing for selected patients — Laboratory evaluation is usually not necessary in the evaluation of salivary gland swelling but is helpful when there is a clinical suspicion for an immune-mediated, vasculitic, infiltrative, or other systemic conditions. Blood work, including autoantibodies, specific immunoglobulin levels, and angiotensin-converting enzyme (ACE) levels, can help support a diagnosis. (See 'Systemic disorders' above.)

If blood tests are not diagnostic, biopsy of the clinically affected gland can be performed.

WHEN TO REFER — 

A single minor (transient and without significant pain) episode of salivary gland swelling is sufficiently common that imaging and a referral to an otolaryngologist are usually not required.

We suggest referral to an otolaryngologist in the following situations [1]:

●Single episode characterized by significant pain

●Chronic salivary gland swelling (generally a period of weeks to months), unless initial clinical evaluation and imaging are consistent with sialosis

●Recurrent salivary gland swelling (two or more lifetime episodes)

These patients typically warrant advanced visualization (sialendoscopy or sialography) and may require advanced treatment options (eg, steroid insufflation, botulinium toxin injection, ductal dilation). (See 'Possible options for refractory symptoms' below.)

If the clinical history, examination, and ultrasound are consistent with sialosis, then no further evaluation is needed. However, if there is associated pain, fluctuation in salivary gland size, progressive gland enlargement, or involvement of the minor salivary glands, referral is indicated for further evaluation.

PROCESSES THAT MIMIC SALIVARY GLAND ENLARGEMENT — 

Due to the proximity of the salivary glands to various anatomical structures, enlargement or changes in other local sites may mimic salivary gland swelling. These abnormalities are often identified as part of the evaluation for apparent salivary gland enlargement. Ultrasound will typically distinguish between true salivary gland enlargement and other abnormalities, but CT or MRI are often performed if further detail is needed. (See 'Imaging for most patients' above.)

●Masseter hypertrophy – Masseter muscle enlargement may be bilateral or unilateral and, if unilateral, may present with facial asymmetry and be confused with parotid enlargement (figure 4). Masseter enlargement has been attributed to bruxism, temporomandibular joint dysfunction, and malocclusion [112,113]. Muscle enlargement from other causes should be considered, including neoplastic, inflammatory, myopathies, and vascular malformations [114-116]. In many cases, however, the etiology of masseter enlargement remains unknown. Treatment of masseter hypertrophy is discussed elsewhere. (See "Botulinum toxin for cosmetic indications: Treatment of specific sites", section on 'Masseteric hypertrophy'.)

●Vascular malformations – Vascular malformations may present as salivary gland swelling, and the malformations may be present within or adjacent to a gland. The swelling may fluctuate, can be positional (ie, increasing in size with head down), and pain may or may not be present [117]. Initial evaluation with ultrasound is appropriate and may be diagnostic. However, further detailed examination with CT or MRI is typically needed (figure 5). If treatment is indicated for patient discomfort or cosmesis, options include surgical removal, injection of sclerosing agents, or laser therapy [118,119].

●Branchial cleft cyst – First arch branchial cleft cysts (specifically Type I) are uncommon but may present clinically as parotid swelling due to passage of the cyst through the gland (figure 6 and image 2) [120]. Patients may develop recurrent swelling, occasionally associated with drainage from a fistula tract. When present, cysts are more likely to become symptomatic in childhood [121,122]. Treatment is surgical excision [123]. (See "Differential diagnosis of a neck mass", section on 'Branchial cleft cyst'.)

●Salivary gland lymphadenopathy – Due to embryologic timing of lymphocyte migration and lymph node formation, there are multiple intra-parotid lymph nodes, but none within the capsule of the submandibular gland. However, there are multiple lymph nodes adjacent to the submandibular gland that, when enlarged, are often mistaken for enlargement of the gland itself. Similarly, enlargement of the periparotid lymph nodes may mimic parotid gland swelling [124]. Ultrasound can distinguish lymph node involvement from gland enlargement as the cause of apparent salivary gland swelling.

Salivary gland lymphadenopathy may have various causes, including tumors (eg, lymphoma and metastatic carcinoma) and infections such as cat scratch disease, toxoplasmosis, and tuberculosis. (See "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease", section on 'Lymphadenopathy' and "Toxoplasmosis: Acute systemic disease", section on 'Lymphadenopathy' and "Tuberculous lymphadenitis", section on 'Cervical lymphadenopathy'.)

●Angioedema – Angioedema is a cause of intermittent and recurrent facial swelling and may therefore mimic salivary gland swelling. However, angioedema of the face is rarely confined to or centered around the salivary glands. If there is uncertainty, ultrasound imaging can help confirm that salivary glands are normal. (See "An overview of angioedema: Clinical features, diagnosis, and management".)

●Melkersson-Rosenthal syndrome – This rare disorder is characterized by a fissured tongue, swollen lip(s), recurrent episodes of orofacial edema, and unilateral facial paralysis (picture 4) [125]. Although Melkersson-Rosenthal syndrome does not directly affect the major salivary glands, the facial swelling may mimic parotid enlargement [126].

The etiology remains uncertain; infectious agents, genetic factors, allergic reactions, and benign lymphogranulomatosis have all been implicated [127]. Connection to autoimmune disorders with overlapping features with systemic lupus erythematosus, scleroderma, and polymyositis has led some to consider it an early manifestation of mixed connective tissue disease [128]. Biopsy of edematous tissue reveals noncaseating granulomas grouped around blood vessels [129]. (See "Hereditary angioedema (due to C1 inhibitor deficiency): Pathogenesis and diagnosis", section on 'Cutaneous and/or upper airway swelling'.)

Treatment includes topical or intralesional steroids for persistent mucosal symptoms. (See "Cheilitis", section on 'Treatment'.)

SPECIALIZED TESTING FOR SELECTED PATIENTS — 

For patients in whom the diagnosis is still uncertain after initial evaluation (including clinical evaluation and initial imaging), specialized diagnostic testing may be necessary. Diagnostic options include sialography and sialendoscopy, both of which are typically performed by otolaryngologists, as well as gland biopsy when needed.

Sialography — During sialography, the salivary ductal orifice is cannulated and a small amount a radio-opaque contrast material is injected into the ductal system. This allows for evaluation of duct anatomy and the identification of strictures. When this is done under fluoroscopy, dynamic changes can be visualized [130].

Sialography is more sensitive than ultrasound for identifying duct stenosis and characterizing the extent and the number of stenoses present [131]. In our experience, contemporary dynamic fluoroscopic sialography with duct cannulation and radiocontrast insufflation offers the highest-quality assessment of duct anatomy and may additionally be therapeutic in the course of performing a hydrodilation with 'flushing out' [22]. Recent reports identify the capacity to substitute gadolinium as an adequate contrast agent for patients unable to tolerate iodinated contrast [132].

However, sialography is not as widely used as other methods due to the technical nature of the procedure, which requires expertise and special equipment.

Sialendoscopy — Sialendoscopy is a procedure in which a semirigid microendoscope (diameter between 0.8 to 1.6 mm) is placed within the salivary ducts, allowing direct visualization of the ducts. Microinstruments can be deployed to remove debris, stones, or foreign bodies. The procedure can be used for duct dilation in the case of strictures. In the United States, this is most commonly performed under general anesthesia, although can be done under local anesthesia in some cases.

Gland biopsy — Biopsy of the affected gland may be necessary if tumor is suspected (based on clinical evaluation and/or initial imaging). This is usually done as an ultrasound-guided fine needle aspiration, although core needle biopsy may be necessary in some cases. In addition, biopsy can be useful in diagnosing some conditions that cause chronic multifocal swelling (eg, IgG4-related disease, Kussmaul disease), if the diagnosis remains uncertain after initial evaluation. (See 'Systemic disorders' above.)

GENERAL MANAGEMENT PRINCIPLES

Supportive measures — We advise the following supportive care for all patients with salivary gland swelling. These strategies are variably helpful depending on the underlying etiology of the swelling. They are most helpful with sialadenitis due to obstruction from any cause (eg, stone), and are also helpful in cases of ductal stricture.

●Sialagogues (salivary stimulants such as sour candy)

●Local heat (warm compresses)

●Oral hydration

●Massage of the involved gland (movie 2 and movie 3)

●Nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen if needed

In the majority of patients with new-onset, acute swelling, improvement in symptoms will typically happen quickly (within one to five days). However, if there is complete obstruction of the duct, these treatments may increase pain if salivary drainage is not restored. (See "Salivary gland stones", section on 'Primary care management'.)

Treatment of underlying cause — The primary treatment is aimed at the underlying etiology:

●Sialoliths (salivary stones) – For patients who do not improve with conservative therapy, sialoendoscopy is generally used for extracting stones; other minimally invasive and surgical interventions are sometimes necessary. (See "Salivary gland stones".)

●Bacterial infection – Treatment is with antibiotics, including coverage for Staphylococcus aureus. It is important to note that patients with obstructive sialadenitis from other causes (eg, stone or stricture) can develop secondary bacterial infection. (See "Suppurative parotitis in adults".)

●Duct stricture – Strictures in the main or secondary ducts may respond to dilation (image 3). This is usually done under general anesthesia with sialendoscopy, with or without concurrent steroid insufflation. For persistent symptoms, botulinum toxin injection can be used. Rarely, ductal reconstruction or sialadenectomy are necessary.

●Salivary gland tumors – Treatment depends on the type and extend of the tumor. This is discussed in detail elsewhere. (See "Salivary gland tumors: Treatment of locoregional disease" and "Malignant salivary gland tumors: Treatment of recurrent and metastatic disease".)

●Sialosis – Treatment of the underlying conditions (eg, diabetes, metabolic syndrome, alcohol use, etc) may help improve symptoms, although complete resolution of the gland enlargement does not always occur, and patients may require additional treatment. (See 'Possible options for refractory symptoms' below.)

●Rheumatologic conditions – For those with an underlying rheumatologic disorder (eg, Sjogren's disease, sarcoidosis, or an ANCA-associated vasculitis), treatment with systemic glucocorticoids in consultation with the treating rheumatologist may be considered for patients whose symptoms do not respond to conservative therapy.

Possible options for refractory symptoms — Treatment of refractory symptoms is typically guided by an otolaryngologist and depends on the underlying condition. Steroid insufflation can be done via sialendoscopy and may be helpful even if there are no underlying strictures. It has been used to address salivary gland swelling due to Sjögren's disease and radioiodine sialadenitis [133,134]. Botulinum toxin injection into glands is a well-established treatment option for chronic sialadenitis and can be used in concert with or as an alternative to sialendoscopy, steroid infusion, and gland removal [135-137].

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: IgG4-related disease" and "Society guideline links: Sjögren's disease".)

SUMMARY AND RECOMMENDATIONS

●Acute versus chronic – We use "acute" salivary gland swelling to refer to symptoms that started within a few weeks to months (including recurrent symptoms), and "chronic" to refer to persistent symptoms of longer duration. However, there are no established guidelines defining the transition from "acute" to "chronic" salivary gland swelling. (See 'Definitions and terminology' above.)

●Differential diagnosis – Causes of salivary gland swelling can be categorized based on chronicity of symptoms and number of glands affected (table 1).

•Acute symptoms – Acute symptoms are most commonly due to sialoliths (salivary stones), infections (viral or bacterial), duct strictures, and following exposures (eg, certain drugs, intravenous contrast, or external beam radiation) (See 'Acute symptoms' above.)

•Chronic symptoms – Chronic symptoms may occur due to obstruction from tumors or other masses, or due to systemic disorders such as metabolic sialosis or Sjögren's disease. Less common systemic causes include other immune-mediated conditions (eg, IgG4-related disease), ANCA-associated vasculitides, and infiltrative causes (eg, amyloidosis or sarcoidosis). (See 'Chronic symptoms' above.)

●Initial clinical evaluation – The initial clinical evaluation involves determining the chronicity of symptoms and the number of glands affected to help narrow the differential diagnosis (table 3). Systemic symptoms (eg, fevers) and predisposing factors (eg, known medical conditions or exposures) can further help determine the etiology. Physical examination includes confirming salivary gland swelling, evaluating for gland tenderness or overlying erythema (both of which can indicate bacterial infection), and expressing salivary discharge with massage of the gland. (See 'Initial evaluation' above.)

●Imaging for most patients – We obtain imaging in most patients with salivary gland swelling, including those with severe, recurrent, chronic, or unexplained symptoms. Imaging helps determine whether swelling is from the salivary gland itself or from another structure (eg, an embedded or nearby lymph node) and also helps identify common etiologies, including stones or strictures. Patients who have a single episode of mild symptoms with a clear etiology and resolution within the expected timeframe do not require imaging. When imaging is necessary, we prefer ultrasound as the initial modality; CT with contrast is an alternative if salivary gland ultrasound is not available. (See 'Imaging for most patients' above.)

●When to refer – We refer patients to an otolaryngologist if they have significant pain associated with acute swelling, or if they have chronic or recurrent swelling (two or more lifetime episodes). A single minor (transient and without significant pain) episode of salivary gland swelling is sufficiently common that a referral to an otolaryngology is usually not required. (See 'When to refer' above.)

●Specialized testing for selected patients – For patients in whom the diagnosis is still uncertain after initial evaluation (including clinical evaluation and initial imaging), specialized diagnostic testing such as sialography or sialendoscopy may be necessary. Gland biopsy is warranted if tumor is suspected and may also be diagnostic in some cases of chronic multiglandular swelling. (See 'Specialized testing for selected patients' above.)

●Generalized management principles – General supportive measures include sialagogues (eg, sour candy), warm compresses, oral hydration, gland massage (movie 2), and analgesia with NSAIDs or acetaminophen are often helpful in patients with sialadenitis due to obstruction from any cause and are reasonable interventions pending a firm diagnosis. (See "Salivary gland stones" and 'Supportive measures' above.)

Additional treatment is directed at the underlying cause of symptoms. (See 'Treatment of underlying cause' above.)