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9 Salivary Glands

There are three paired major salivary glands ( ▶ Fig. 9.1):

1. 
   

   Parotid gland.

   
   
2. 
   

   Submandibular gland.

   
   
3. 
   

   Sublingual gland.

In addition, there are 700 to 1,000 separate minor salivary glands, occurring mainly in the oral and pharyngeal mucosa ( ▶ Fig. 9.2).

9.1 Embryology, Structure, and Congenital Anomalies

The major salivary glands arise from solid aggregations of ectodermal cells in the foregut between the fourth and eighth weeks of embryonic development. Thickening of the surrounding mesenchyme encapsulates the developing gland and also includes lymph-node primordia. The ducts become patent in the 22nd week. ▶ Fig. 9.3 shows the cellular architecture of the secretory apparatus and drainage system of the salivary glands.

Aplasia of one or more glands may occur, but complete absence of all the major glands is extremely rare.

Diverticula and ectasia of the parotid duct system may predispose to parotitis.

Aberrant salivary gland tissue may be found in the cervical lymph nodes, the middle ear, and the mandible.

Accessory glands are appendages of the major glands, most commonly the parotid; they possess efferent ducts and have functional capabilities.

The theory that the parotid gland consists of two lobes located lateral and medial to the facial nerve, connected by an isthmus, has been rejected as incorrect, although the terms “superficial parotidectomy” and “total parotidectomy” are still used (see also ▶ Fig. 9.28).

9.2 Anatomy and Physiology of the Major and Minor Salivary Glands

9.2.1 Parotid Gland

The largest of the salivary glands lies in the retromandibular fossa, in a subcutaneous pocket surrounded by a capsule of compressed connective tissue. This pseudocapsule is very thick, especially laterally, and is the cause of tension pain in parotid swelling. Inferiorly, there are defects in this connective-tissue mantle through which infections and tumors can penetrate into the pterygopalatine fossa or parapharyngeal space.

Borders: The superior part of the parotid glands is limited anteriorly by the anterior border of the ascending ramus of the mandible, posteriorly by the external acoustic meatus, and above by the zygomatic arch. The inferior portion of the gland is the cervical portion, which lies between the angle of the jaw and mastoid process. The gland is bounded inferiorly by the anterior margin of the sternocleidomastoid muscle and the posterior belly of the digastric muscle.

Clinical significance: Pleomorphic adenomas arising in the cervical part of the gland may form a dumbbell tumor extending into the oropharynx, with only a relatively small external tumor.

The parotid duct (Stensen duct) is ≈6 cm long. It leaves the anterior border of the gland, crosses the masseter muscle, and perforates the buccinator muscle and the buccal mucosa. The edges of its orifice are slightly elevated and are red and swollen in inflammation. The orifice lies opposite the second upper molar tooth.

The facial nerve leaves the base of the skull through the stylomastoid foramen and enters the gland parenchyma as a short trunk 0.7 to 1.5 cm long. It divides into two or three main branches (pes anserinus or goose foot) and then divides again peripherally into 5 branches: the terminal temporal, frontal, zygomatic and buccal, and cervical branches. The zygomatic and buccal branches have numerous anastomoses with each other. The forehead branch and the marginal mandibular branch for the lower lip usually have no anastomoses with neighboring branches (see ▶ Fig. 1.123).

The facial nerve supplies all of the mimetic muscles and the platysma. The branches of the external carotid artery—the transverse facial, maxillary, and retroauricular arteries—lie medial to the nerve and supply the parotid gland. Venous drainage is via the internal jugular vein.

Lymph drainage: There are several intraglandular and periglandular lymph nodes from which the lymph drains via the submandibular nodes or directly into the upper deep cervical nodes. The first regional lymph-node station for the parotid lies inside the gland—a fact that has major clinical significance in oncology patients.

Autonomic control of salivary secretion: The preganglionic fibers originate in the inferior salivatory nucleus. They follow the glossopharyngeal nerve to the jugular foramen, leave that nerve at the inferior ganglion, and then join the tympanic nerve to form the tympanic plexus of the middle ear, from which the lesser superficial petrosal nerve arises. The fibers finally reach the otic ganglion, in which they synapse.

The postganglionic parasympathetic fibers run from the otic ganglion with the auriculotemporal nerve to the parotid gland.

The sympathetic fibers arise from the carotid plexus and regulate the circulation of the gland by vasoconstriction. They have less effect on salivary production.

9.2.2 Submandibular Gland

The submandibular gland is embedded in the submandibular triangle. It is bordered anteriorly by the digastric muscle, posteriorly by the stylomandibular ligament, and superiorly by the mandible.

The main part of the gland lies inferior to the mylohyoid muscle and is covered by the external cervical fascia.

The submandibular duct (Wharton duct) is ≈5 cm long, runs forward beneath the mucosa of the floor of the mouth, and opens close to the frenulum in the sublingual caruncle in the floor of the mouth.

Clinical significance: Infection can spread along the U-shaped body of the gland into the posterior part of the floor of the mouth, causing a phlegmon or abscess in the floor of the mouth.

The duct crosses posterolaterally over the lingual nerve. If the duct is slit over a probe (e.g., for acute obstruction due to a sialolith), the nerve is not in danger. The very thin marginal mandibular branch of the facial nerve running between the upper pole of the gland and the mandible is vulnerable during surgery on the submandibular gland. Injury to the lingual or hypoglossal nerves during removal of the gland for sialolithiasis or benign tumors is avoided by exposing the nerves.

Autonomic supply: The gland receives its autonomic supply from the lingual nerve through preganglionic para-sympathetic fibers that reach it via the chorda tympani and synapse in the submandibular ganglion to give off postganglionic fibers.

Sympathetic fibers from the superior cervical ganglion control the blood supply.

9.2.3 Sublingual Gland

The smallest of the major salivary glands lies beneath the mucosa of the oral floor, its posterior part touching the anterior end of the submandibular gland. Its duct system usually unites with that of the submandibular gland, and its innervation is the same as that of the submandibular gland.

Clinical significance: A ranula is a retention cyst caused by obliteration of one of the smaller openings of the sublingual gland; the principal opening is unaffected. Depending on its size, a ranula can cause difficulty in swallowing and speaking, due to interference with the mobility of the tongue. Treatment consists of surgical removal or epithelial drainage by marsupialization of the ranula.

9.2.4 Minor Salivary Glands

These glands are scattered throughout the oropharyngeal, nasal, sinus, laryngeal, and tracheal mucosa. There are also collections on the inner surface of the lip, in the buccal mucosa, and in the palate. The minor salivary glands produce only 5% to 8% of the entire volume of saliva, but despite that they ensure satisfactory moistening of the mucosa if one or more of the major salivary glands fails to function. Severe xerostomia may occur if their secretory function is suppressed due to radiotherapy or other causes.

Clinical significance: Tumors of the minor salivary glands are often malignant (adenoid cystic carcinoma, acinar cell tumor). Benign tumors (e.g., pleomorphic adenoma) occur less frequently.

9.3 Formation and Function of Saliva

Physical, chemical, and mental factors stimulate the production of saliva. The amount produced in a day ranges from 1,000 to 1,500 mL, and 99.5% of it is water. The rest consists of inorganic, organic, and cellular material. The individual salivary glands make a variable contribution to the quantity and quality of the total output ( ▶ Table 9.1 ).

The secretion is formed in two steps: The primary secretion is formed in the acini and is then partially resorbed and modified during passage through the duct system, in a manner somewhat analogous to urine production by the kidneys.

9.3.1 Physiologic Functions of the Saliva

• 
  

  Saliva has a protective effect on the mucosa of the mouth and upper respiratory tract, through mechanical cleansing and an immunologic mechanism based on proteins, lysozymes, and immunoglobulins, especially immunoglobulin A (IgA).

  
  
• 
  

  Saliva has a digestive function; it lubricates the food and initiates the cleavage of starch by amylase.

  
  
• 
  

  Saliva aids in the excretion of autogenous and foreign material, particularly iodine and coagulating factors, alkaloids, viruses including Epstein-Barr virus, poliomyelitis, rubella, coxsackievirus, cytomegalovirus (CMV), and hepatitis virus. The excretion of blood group substances in the saliva may be important in forensic medicine.

  
  
• 
  

  Saliva aids in protection of the teeth. The organic and inorganic (e.g., fluoride) content of the saliva is important in the formation and maintenance of the dental enamel. It helps prevent bacterial deposition.

  
  
• 
  

  Saliva helps mediate the sense of taste by lavage of the taste buds.

Composition: The composition of the saliva depends on its flow rate, the circadian rhythm, the season of the year, sex, and nutrition. The wide variability of this parameter needs to be taken into account during analysis, although it should be emphasized that saliva analysis has not become clinically important.

Disturbances of secretion: Xerostomia is extremely distressing. It may be caused centrally by lesions of the autonomic nervous supply to the salivary glands, by diseases of the salivary glands, by dehydration due to diarrhea or vomiting, by radiotherapy, or by systemic diseases such as Sjögren syndrome.

Sialorrhea means excessive saliva flow. Predisposing factors are diseases of the oral and lingual mucosa and teeth, as well as psychogenic factors.

Ptyalism is abnormal dribbling of saliva from the mouth in neurologic disease, as may occur in Parkinson disease, epilepsy, and paralysis of the muscles of deglutition.

Saliva production is also influenced by generalized diseases and drugs.

9.4 Methods of Investigation

The diagnosis of salivary gland diseases is a difficult and specialized field in otolaryngology, as the findings can be caused either by diseases of the salivary glands themselves or by a systemic disease.

Salivary gland diseases can often be diagnosed on the basis of the patient’s medical history, their age, and the clinical findings ( ▶ Table 9.2 ). The latter includes swelling, consistency, mobility, rapidity of enlargement, pain, and facial nerve function.

9.4.1 Examples of Salivary Gland Dysfunction

• 
  

  Recurrent attacks of severe pain indicate sialolithiasis or recurrent parotitis.

  
  
• 
  

  Bilateral disease indicates sialadenosis or mumps.

  
  
• 
  

  Sex: myoepithelial sialadenitis, Sjögren disease, occurs almost exclusively in women.

  
  
• 
  

  Malignancy is indicated by pain, facial paralysis, regional lymph-node metastases, and ulceration.

9.4.2 Age-Dependent Conditions

• 
  

  Congenital hemangiomas and lymphangiomas occur in neonates.

  
  
• 
  

  Mumps and chronic recurrent parotitis occur in school-age children.

  
  
• 
  

  Adenomas and sialadenosis occur in middle age.

  
  
• 
  

  The proportion of malignancy increases with age.

Normally, only the flat contour of the submandibular gland can be recognized by its soft overlying skin in the submandibular triangle. The parotid gland is not visible unless it is enlarged. Specific findings can be detected by palpation, which should be performed bimanually to allow both sides to be compared and may include both intraoral and extraoral palpation ( ▶ Fig. 9.4a, b).

The size of the gland in centimeters, its consistency, superficial profile, mobility, tenderness, and reddening of the overlying skin should be noted. Redness and swelling of the ducts and their orifices should also be looked for, and the appearance of the expressed saliva (clear, flocculent, purulent, or bloodstained) should be assessed. Stones in the ducts, particularly the submandibular duct, are often palpable.

9.4.3 Diagnostic Imaging

There is wide range of salivary gland imaging available and practice will vary according to local facilities and experience. However, an excellent guidance document has been published for reference by The Royal College of Radiologists in the UK (iRefer Guidelines: making the best use of clinical radiology. 8th edition. Royal College of Radiologists; 2017).

9.4.3.1 Sonography/Ultrasound

This is the first imaging study after palpation. Its accuracy depends on the examiner’s degree of experience ( ▶ Fig. 9.5a–h). In view of its ease of use, low cost, and good diagnostic yield, sonography is the diagnostic method of choice for salivary gland diseases. Ultrasound is helpful for calculus and inflammatory disease, and is recommended for all salivary tumors, when it should be combined with fine needle aspiration cytology (FNAC) and review by an expert histopathologist. It has the advantage of facilitating valuable information on cervical lymphadenopathy but has limitations with regard to tumors with deep extension.

9.4.3.2 Computed Tomography

Contrast administration is helpful (80–150 mL of nonionic-iodinated medium). Computed tomography (CT) of the parotid gland, especially when combined with sialography, provides information about the size and extent of parotid tumors, especially lesions involving the deep lobe. CT makes it possible to distinguish tumors arising from the gland itself from tumors that have invaded the gland from other structures, such as metastatic and parapharyngeal tumors. The findings may be equivocal for the diagnosis of small or malignant tumors. Patients with malignant salivary tumors will often undergo an MRI scan of the head as well as a CT of the chest, abdomen, and pelvis to exclude metastatic disease.

9.4.3.3 Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) provides high-resolution images of soft tissue structures using T 1-weighted and T 2-weighted spin-echo sequences. Fluids have a high signal intensity, while solid structures appear hypointense. Contrast medium (gadolinium) is useful for tumor diagnosis and also provides helpful information on any cervical lymph-node disease.

Magnetic resonance sialography is an alternative imaging technique for patients with inflammatory salivary gland disease, and requires cannulation and injection of the salivary duct prior to scanning.

9.4.3.4 Sialography

Sialography is contrast visualization of the salivary drainage system and portions of the glandular parenchyma.

Although sialography is not often used today, it is a method that can broaden the practitioner’s understanding of salivary gland pathologies. The technique necessitates cannulation of the parotid or submandibular salivary duct that requires expertise of the radiologist and may not always be possible.

Technique of sialography: A plastic catheter and a cannula are introduced into the duct of the parotid gland or submandibular gland. Contrast medium is injected slowly in small amounts. Radiographs are taken in two planes or with an image intensifier.

In chronic recurrent sialadenitis, sialographic images show a typical “tree-in-leaf” pattern, caused by ectasia of the acini and terminal and excretory ducts. Benign tumors frequently appear as a round mass displacing the contrast-filled ducts. Malignant tumors may cause duct tears, sudden changes in duct width, and contrast extravasation. The findings in Sjögren syndrome vary: initially, the picture is that of a “ripe tree” with delicate branching of the ductal system and an indistinct gland periphery. Later cases show a “bare tree” pattern, marked by rarefaction of the ducts and parenchymal atrophy ( ▶ Fig. 9.6a–g).

9.4.3.5 Positron Emission Tomography

Positron emission tomography (PET) may be useful in special cases such as recurrent tumor or carcinoma with unknown primary (CUP) syndrome. The PET-CT scan is of value in postoperative assessment about 3 months following resection of a malignant tumor but it does not distinguish between localized inflammation and recurrence.

9.4.3.6 Plain Radiographs

Plain radiographs of the oral floor with lateral and tangential views of the submandibular and parotid glands are helpful only if the stone has a high calcium content. Radiolucent stones can often be detected with sialography, which shows a circular filling defect.

9.4.4 Function Studies

Loss of function (Galen functio laesa) is another clinical manifestation of inflammatory disease, especially in parenchymatous organs. It is therefore important to obtain information about the functional status of the gland.

9.4.4.1 Methods

Sialometry: A small catheter is introduced into the papillae of both glands (parotid or submandibular). Saliva is collected for 10 minutes in a small test tube. It is important to note any difference between the sides and to classify secretory function as normal, increased, or decreased.

Scintigraphy: This can be used to conduct a functional study of the secretory activity of the gland ( ▶ Fig. 9.7).

9.4.5 Biopsy

Histological diagnosis is the key to all salivary gland disease. It is the basis on which the decision is made on whether to operate or treat the patient medically, as in patients with sialadenosis or Sjögren disease.

Fine needle aspiration biopsy is only beneficial if the findings are positive; if it is inconclusive, the biopsy may need to be repeated. Smaller lesions may need ultrasound guidance during biopsy. The biopsy specimens should be interpreted by an experienced cytologist.

A core needle biopsy, if necessary, should be taken in more than one direction. This is a more useful test, but is difficult in cystic tumors. Care needs to be taken to avoid injury to the facial nerve. It is conceivable that tumor cells might be seeded along the needle track, but this has never been documented. Biopsy of an ulcerated lesion is easy. If the skin is intact, the best site for a parotid gland biopsy is the part of the parotid in the retromandibular fossa, to protect the facial nerve.

If the clinical findings indicate a salivary tumor, superficial parotidectomy or excision of the submandibular gland will provide a large biopsy and is also the correct treatment for a benign tumor. Intraoperative frozen-section biopsy enables the surgeon to decide between carrying out a partial or total parotidectomy, or a more extensive procedure. However, experience has shown that intraoperative diagnosis of a salivary gland tumor is often difficult. Diagnosis is easier with a fixed specimen.

9.5 Clinical Aspects

9.5.1 Inflammatory Diseases

See ▶ Table 9.3 .

9.5.1.1 Acute Bacterial Infections

Clinical features: The gland suddenly becomes swollen and tender. Infection of the parotid gland causes a protrusion of the auricle, which is most easily seen from behind the patient.

The overlying skin may be red ( ▶ Fig. 9.8), and fluctuation may be felt if suppuration is present. An infection may rupture spontaneously to the outside or through the Santorini cleft (fissures in the external auditory canal cartilage) into the external auditory meatus. The duct orifice appears red and swollen. Pus drains spontaneously, or after external massage. Trismus is also present.

Pathogenesis: Reducing salivary flow is an important prerequisite when there is ascending bacterial infection in the duct. Postoperative parotitis, which used to be common particularly after abdominal surgery, has now become much less frequent due to the use of antibiotics, fluid and electrolyte replacement, and postoperative oral hygiene. However, acute purulent infections still occur occasionally in patients with uncontrolled diabetes or renal failure with electrolyte disturbances and dehydration, or in the presence of carious teeth or poor oral hygiene. Nursing-home residents are predisposed to developing acute parotitis.

Diagnosis: The history shows a previous disease or operation. Clinical findings are noted (external appearance, palpable findings, gross characteristics of secretions), and saliva samples can be obtained for microbiological analysis.

Differential diagnosis: The differential diagnosis includes lymphadenitis due to a meatal furuncle, dentogenic abscess of the cheek, unerupted teeth, infected sebaceous cyst, and zygomatic abscess of mastoiditis in children.

Treatment: High-dose parenteral antibiotics are given, particularly agents that are active against gram-negative organisms. The drug can be changed later if necessary, depending on the results of culture and sensitivity tests. Adequate hydration is provided, the fluid and electrolyte balance is corrected, and sialogogues are given. Fan-shaped external incisions are made for an abscess, with care being taken to avoid the facial nerve (see ▶ Fig. 1.123).

Antibiotics: Broad-spectrum antimicrobial therapy is indicated to cover all possible aerobic and anaerobic pathogens, including coverage for Staphylococcus aureus, hemolytic streptococci, and β-lactamase-producing anaerobic gram-negative bacilli. A penicillinase-resistant penicillin or first-generation cephalosporin is generally satisfactory. Methicillin-resistant staphylococci may make it necessary to use vancomycin. Clindamycin, cefoxitin, imipenem, a combination of metronidazole and a macrolide, or a penicillin plus a β-lactamase inhibitor will provide adequate coverage for anaerobic as well as aerobic bacteria.

The same treatment is prescribed for purulent infections of the submandibular gland. The most common cause in this case is obstruction by a stone or dental disease.

9.5.1.2 Viral Infections

Mumps

Clinical features: Clinical features include swelling of the affected gland, redness and slight swelling of the ductal orifice, and displacement of the auricle. The secretions are not purulent, and 30% of patients are nonfebrile. Both glands are involved in 75% of cases. Swelling on one side may precede swelling on the other by up to 5 days. The submandibular and sublingual glands may also be involved, but they are rarely affected alone without parotid involvement.

An irreversible lesion of the eighth cranial nerve may be caused by this neurotropic virus, leading to unilateral or bilateral complete deafness. The pancreas, testes, ovaries, and central nervous system may also be affected, or any one of these organs may be involved in a synchronous or metachronous fashion.

Pathogenesis: The virus belongs to the Paramyxoviridae family. Local epidemics are known to occur in kindergartens and schools. The incubation period is 20 ± 10 days. An infection usually confers permanent immunity.

Diagnosis: Direct demonstration of the virus is possible only during the early phase of the disease, ranging from a few hours to several days.

The virus can be isolated from saliva, cerebrospinal fluid (CSF), or urine. It is demonstrated by culture in the kidneys of apes or the cells of hens or guinea pigs.

Serologic tests consist of complement-binding reaction or hemagglutination inhibition tests. The initial value is assessed and another reading is taken 2 to 3 weeks later. A fourfold rise in the antibody titer is evidence of a mumps infection. Increased amylase excretion in the blood and urine reaches its maximum on the third or fourth day of the illness.

Note: Unilateral deafness in children often goes unnoticed by the child and by the parents. Audiologic tests during the course of the illness are therefore important.

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