TITLE: SALIVARY GLAND
SOURCE: Dept. of Otolaryngology UTMB Grand Rounds
DATE: October 30, 1996
RESIDENT PHYSICIAN: Kyle Kennedy, M. D.
FACULTY PHYSICIAN: Brian Driscoll, M. D.
SERIES EDITOR: Francis B. Quinn, Jr., M.D.
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This presentation will attempt to achieve the following objectives. The first is to provide a useful scheme for classifying these hetergeneous disorders so that they may be approached in a systematic manner. The second is to enumerate the distinguishing features of these entities to aid in their appropriate recognition. Finally, general management principles for the various conditions will be discussed.
Acute inflammation of the salivary glands is usually of viral or bacterial origin. Of the viral illnesses, mumps is the most common. This illness is caused by an RNA virus from the paramyxovirus group and typically involves the parotid glands bilaterally. Children are most often affected with peak incidence at approximately 4 to 6 years of age. Transmission is via infected respiratory droplets. The parotid swelling is accompanied by constitional symptoms such as fever and malaise, and many cases are mild and subclinical in nature. Onset of symptoms usually follows a 2 to 3 week incubation period, and infection may be documented by a rise in convalescent serum titers to viral antigens or to isolation of the virus from the urine for a period from approximately 1 week prior to and 2 weeks after onset of symptoms. Treatment is symptomatic. Serious sequelae are fortunately rare and often stem from involvement of other organ systems such as the CNS, pancreas, and gonads.
Salivary gland involvement may be seen in a wide range of other viral illnesses including those caused by cytomegalovirus, lymphocytic choriomeningitis virus, coxsackievirus A, echovirus, and parainfluenza virus type C among others. Again, treatment is symptomatic.
Acute suppurative sialadenitis is most commonly bacterial in origin and most often involves the parotid, and to a lesser extent, the submandibular glands. The more mucinous saliva produced by the submandibular glands is felt to confer more bacteristatic properties than the serous saliva of the parotids. The causative agent most frequently implicated is Staphylococcus aureus. Other aerobic organisms isolated are Streptococcus pneumoniae, Hemophilus influenzae, and Escherichia coli. Anaerobic bacteria such as Bacteroides have been involved as well. Stasis of saliva, often as a result of dehydration, is thought to be an integral component in the pathogenesis of this condition perhaps secondary to obstruction or decreased production.
Common clinical settings in which this entity may occur include the elderly postoperative patient after cardiothoracic or gastrointestinal surgery and perhaps more frequently the elderly nursing home patient. Onset is typically heralded by unilateral abrupt diffuse swelling of the parotid perhaps with accompanying induration and tenderness. Mucopurulent material may be expressed from the opening of Stensen's duct with massage of the gland, and a sample should be obtained for Gram stain and culture. Fluctuance is often not present due to the multiple fascial investments with the substance of the parotid gland. Therapy is initially conservative with adequate hydration, sialogogues, heat, massage of the affected gland, and the administration of an appropriate intravenous antibiotic, usually a penicillinase-resistant antistaphylococcal antibiotic. Improvement is expected within the first 24 to 48 hours. If this does not occur, operative intervention may be indicated. This usually consists of a standard parotidectomy skin incision and flap followed by creation of several openings within the substance of the gland parallel to the course of the facial nerve. A drain is then placed over the gland and the wound closed. Complications include possible septicemia or deep space neck infection. Mortality has been reported as high as 20% and is likely related to the severity patient's underlying medical condition.
Decreased salivary flow with stasis is a key factor in chronic sialadenitis. Like acute sialadenitis, this condition is more common in the parotid gland. Its development is often associated with a previous episode of acute suppurative inflammation with subsequent glandular destruction. Another possibility is the recurrent parotitis of childhood which has continued into adulthood. With the onset of the chronic inflammatory process, alterations in salivary chemistry and enzyme and immunoglobulin content take place. Sialectasis, ductal ectasia, and acinar atrophy occur, accompanied by a lymphocytic infiltrate. Symptoms include recurrent mildly painful swelling of the parotid which often accompany eating. Approximately 80% of patients experience permanent xerostomia.
Treatment is initially conservative with acute exacerbations treated similarly to acute sialadenitis. A thorough search is made for treatable predisposing factors such as a calculus or stricture. If conservative measures fail, ductal dilatation, ligation of the duct, tympanic neurectomy, irradiation of the gland, or excision of the gland may be performed. Only the last of these has been predictably effective.
Recurrent parotitis of childhood may affect children up to the age of 12 years and is more common in males than females and differs from the adult form in this regard. Symptoms usually include the sudden onset of uni- or bilateral parotid swelling with varying degrees of enlargement. There may be mild discomfort, but the child is usually not visibly ill and xerostomia is not present. Salivary chemistries are altered as in the adult. The condition may resolve at puberty or continue on into adulthood, as mentioned previously.
Tuberculous and non-tuberculous (atypical) mycobacterial involvement of the salivary glands may occur. Primary tuberculous infection of the salivary glands is uncommon and most often consists of unilateral parotid gland involvement. The infection is thought to arise in the teeth or tonsils and may result in acute inflammation or a chronic tumorlike lesion. Secondary tuberculosis more often involves the submandibular or sublingual glands and is accompanied by pulmonary disease. Diagnosis may be made with the application of a PPD skin test and staining for acid-fast bacilli from saliva or fine needle aspiration biopsy.
Atypical mycobacterial infection may be more difficult to diagnose. Therapy consists of administration of the appropriate antituberculous chemotherapeutic agents. Excision may occasionally be required.
Cat scratch disease may involve the parotid gland by direct extension from periparotid lymph nodes. Treatment is symptomatic for this self-limited illness. Actinomycosis may involve the salivary glands directly from direct extension from a focus of infection in the teeth or tonsils. Treatment consists of incision and drainage with long-term administration of an appropriate antibiotic.
Sarcoidosis is a chronic granulomatous disease of unknown etiology and is characterized by the presence of noncaseating granulomas in the involved tissues. There is often multisystem involvement typically with prominent pulmonary and cutaneous findings, as well as involvement of the liver, spleen, and various locations in the head and neck. Constitutional symptoms of fever, weight loss, anorexia, fatigue, and night sweats may be noted with evidence of hilar adenopathy on chest roentgenography. The diagnosis is one of exclusion and is made only when other possible etiologies have been ruled out. Histologically, the noncaseating granulomas are composed of aggregations of epithelioid histiocytes often with the presence of Langhans' or foreign body-type giant cells. Schaumann bodies (laminated concretions of calcium and proteins) and asteroid bodies (stellate intracytoplasmic inclusions) may also be seen microscopically.
Salivary gland involvement may occur as an isolated head and neck finding or as a component of uveoparotid fever (Heerfordt's syndrome). This syndrome consists of uveitis, parotid swelling, and facial nerve paralysis. It usually begins with a prodrome of constitutional symptoms and involvement of the submandibular, sublingual, and lacrimal glands may occur. The swelling may last months to years and usually resolves spontaneously. Treatment is usually symptomatic with steroids being most beneficial when administered in the acute phase of the illness. They are particularly helpful with regard to the facial paralysis, but in most instances, the paralysis is transient even without treatment. Approximately 65 to 70% of patients may achieve remission with little or no evidence of residual sequelae.
Benign lymphoepithelial lesion (BLL) results in the non-neoplastic uni- or bilateral enlargement of the major or minor salivary glands or lacrimal glands and may be associated with an autoimmune disease. The enlargement is usually unilateral and involves the parotid. Unless infection is present, the swelling is asymptomatic. Females are slightly more often affected than males, and Sjogren's syndrome may or may not be present or develop. Histopathologically, a diffuse or nodular lymphocytic infiltrate is present with acinar atrophy and metaplasia of the ductal epithelium. With proliferation of ductal epithelium and infiltration of lymphocytes, ductal lumina are obliterated with creation of epimyoepithelial islands surrounded by a chronic mixed inflammatory cell infiltrate. Treatment is symptomatic with a good prognosis, and spontaneous resolution may occur. Benign lymphoepithelial lesion has been associated with the development of lymphoproliferative disorders such as lymphoma and with lymphoepithelial carcinoma. The latter lesion has shown an increased incidence among individuals of Eskimo extraction.
Sjogren's syndrome is an autoimmune disorder which results in immunologically-mediated destruction and inflammatory enlargement of the lacrimal and salivary glands. Other exocrine glands throughout the body may be involved as well. This leads to the development of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) also known as the sicca syndrome or primary Sjogren's syndrome. When the keratoconjunctivitis sicca and xerostomia are also associated with another autoimmune disorder, most commonly rheumatoid arthritis, the secondary form of Sjogren's syndrome exists. Other possible associated disorders include systemic lupus erythematosus, scleroderma, dermatomyositis, and mixed connective tissue disease. Mickulicz's syndrome is a general term applied to concomitant enlargement of the lacrimal and major salivary glands which may occur as a result of a wide variety of disorders including Sjogren's, sarcoidosis, and lymphoma. This term has sometimes been used synonymously with benign lymphoepithelial lesion. As mentioned previously, Sjogren's syndrome may occur in the presence of BLL. There appears to be no histopathologic difference between BLL occuring alone and that which occurs in association with Sjogren's syndrome.
Approximately 90% of the time, the disorder occurs in adult females aged 40 to 60 years, and patients typically present with complaints of burning oral discomfort and what is described as a "sandy" sensation in the eyes. Uni- or bilateral salivary gland enlargement, usually the parotid, occurs in approximately 80% of primary and 30 to 40% of secondary cases of Sjogren's syndrome.
The lymphocytic infiltrate is predominantly of T cell origin, and serologic evidence exists for the presence of B cell dysfunction and possible loss of immunoregulation. Numerous autoantibodies have been indentified, and the two most important serologic markers for Sjogren's syndrome are anti-ribonucleoprotein antibodies termed anti-SS-A (Ro) and anti-SS-B (La). Of the two, anti-SS-B appears to be more specific for Sjogren's syndrome. Certain genetic differences have also been noted between primary and secondary Sjogren's syndrome, such as associations with different HLA types. Various other autoantibodies which have been identified include those to salivary duct cells, gastric parietal cells, smooth muscle mitochondria, and thyroid antigens. These may account for some of the other findings in this disease. Minor salivary gland involvement forms the basis for labial biopsy in the histopathologic diagnosis of Sjogren's syndrome. The specimens are graded on the basis of lymphocytic infiltrate with focus scores of greater than l focus/4 square mm proposed as diagnostic.
Treatment for Sjogren's syndrome is primarily symptomatic. In those instances in which persistent complications arise or in which marked glandular enlargement results in cosmetic deformity, excision of the involved gland may be necessary. Of important note is the recognition that Sjogren's syndrome has been associated with an increased incidence of lymphoid malignancy, particularly of B cell origin. It has been estimated that this risk is increased perhaps 40-fold, and close observation of these patients is warranted.
Mucoceles and mucous retention cysts most often involve the minor salivary glands of the lower lip, buccal mucosa, and floor of the mouth. Mucoceles lack an epithelial lining and are therefore not true cysts. They are thought to result from ductal obstruction or trauma and represent accumulation and extravasation of mucus into adjacent tissues. Mucous retention
cysts do have a true epithelial lining. The simple ranula is a form of mucous retention cyst
involving the ducts of the sublingual salivary gland and typically presents as an asymptomatic soft, fluid-filled mass in the lateral floor of mouth. Management of these lesions consists of marsupialization or complete excision. The plunging ranula represents a form of mucocele which has extended outside the mucous membranes of the floor of mouth inferiorly into the submental or submandibular triangle via a defect in the mylohyoid muscle. They present as neck masses in these areas and require complete excision in continuity with their salivary gland of origin.
The formation of salivary gland calculi occurs in the submandibular gland approximately 80 to 90% of the time and in the parotid gland the remaining 10 to 20%. The sublingual and minor salivary glands are rarely involved. Stone formation is thought to be more common in the submandibular gland secondary to the higher mucin content of its saliva and the anti-gravity flow of saliva within the duct. Its saliva is also more alkaline and has a higher calcium and phosphorous content. Submandibular stones are usually also larger in size. Serum calcium and phosphorous levels have no known correlation with the formation of calculi. Calculi may be found within the ductal system itself or within salivary gland parenchyma. In most cases of sialolithiasis, a single calculus is involved. Stone formation occurs via the deposition of calcium phosphate and an organic matrix of carbohydrates and amino acids about a nidus of debris or other material. With the occurrence of ductal obstruction, stasis of saliva may occur with varying degrees of surrounding inflammation and possible ascending bacterial infection. Streptococcus viridans is a common offending pathogen.
Stone formation most often occurs in middle-aged males and may result in intermittent salivary gland swelling and discomfort, especially with eating. Calculi have been associated with the existence of chronic sialadenitis and may present as an acute suppurative sialadenitis.
During an episode of obstruction complicated by acute infection, mucopurulent material may be expressed from the duct orifice with massage of the involved gland. Gout is the only systemic illness associated with the formation of calculi, and these are composed of uric acid. Plain radiograpy (e.g. submentovertex or occlusal films) is occasionally useful in the diagnosis and location of calculi. 90% of submandibular calculi are radiopaque while 90% of parotid calculi are radiolucent. Sialography is very accurate in the diagnosis of sialolithiasis but is most often unnecessary. Sialolithiasis may also result in subsequent ductal ectasia and stricture formation. Smaller stones may pass spontaneously with appropriate conservative management including adequate hydration, sialogogues, heat, massage, and appropriate antibiotics for intercurrent infection. Stone removal may be performed transorally for those calculi located distally within the duct. However, adequate removal of those calculi located
near the hilum of the gland often require complete excision of the involved gland.
Stenosis, stricture, or congenital atresia represent much less common causes of salivary ductal obstruction. Kussmaul's disease (sialodochitis fibrinosa) is a condition in which ductal obstruction occurs due to the presence of fibromucinous plugs in the ductal system of certain dehydrated patients.
Salivary gland tissue may arise in various aberrent locations within the head and neck. Probably the most common site is in periparotid lymph nodes. Other sites include the lower neck, sternoclavicular joint, thyroglossal duct, middle ear, tonsils, hypopharynx, and mandible. This aberrant tissue may be located within or on the surface of the mandible. That which is located within the mandible may at times be associated with the development of a malignant neoplasm (most commonly mucoepidermoid carcinoma), while that which is on the surface is usually represents benign salivary gland tissue.
Necrotizing sialometaplasia is a benign, self-healing process of unknown etiology. Ischemia is thought to play some role in its development. It is self-limiting, and no treatment is required. It typically involves the minor salivary glands of the hard palate but may occur in salivary tissue elsewhere. Presentation is usually as an asymptomatic mucosal ulceration or nodular lesion of the hard palate which may be misstaken clinically and histologically for a malignant neoplasm, especially squamous cell carcinoma or mucoepidermoid carcinoma. Histologically, lobular necrosis is present with squamous metaplasia of the remaining acini and ductal elements. This metaplasia is bland in appearance and native lobular architecture is maintained. Pseudoepitheliomatous hyperplasia may also be seen. Biopsy may be required to establish the diagnosis and may present diagnostic difficulties.
Cysts of salivary gland origin may be congenital or acquired. Most true cysts are located within the parotid gland. Congenital cysts like the first arch branchial cleft cysts comprise an uncommon form of branchial cleft anomaly. Type 1 cysts are of ectodermal origin and involve the first arch only. They represent a duplication anomaly of the membranous portion of the external auditory canal. Type 2 cysts are of ectodermal and mesodermal origin and involve both the first and second arches. They represent a duplication anomaly of both the membranous and cartilaginous portions of the external auditory canal. Recurrent infection of these lesions may obscure their boundaries, but all are known to lie in close proximity to the facial nerve and require great care during their excision. Dermoid cysts are another form of congenital cyst consisting of keratinizing squamous epithelium and skin appendages which require complete excision.
Acquired cysts may result from sialadenitis, sialolithiasis, ductal obstruction, trauma, BLL, or neoplasm. These typically require no treatment unless symptomatic or if they occur in association with a neoplastic process.
Salivary gland irradiation either for diagnostic or therapeutic purposes may result in disruption of serous acini which are extremely sensitive to the effects of radiation. Leakage of enzymes into the surrounding salivary tissues results in an acute inflammatory process with subsequent development of a painful, swollen gland. If the irradiation is discontinued, the inflammatory process typically resolves. However, if the radiation is continued, glandular atrophy and xerostomia are the result. Neoplasms have been known to arise in irradiated glands as well.
Penetrating or blunt trauma most commonly involves the parotid gland. The submandibular and sublingual glands are afforded some protection by the mandible.
Penetrating facial trauma may involve the parotid duct and/or facial nerve, and a thorough assessment of facial nerve function should be performed in any case of facial trauma. If the injury occurs posterior to the anterior border of the masseter muscle, parotid duct injury may be suspected, and exploration of the wound should be performed to evaluate this possibility. If ductal injury has occurred, identification of the proximal and distal segments with primary reanastomosis is the ideal therapy. Reanastomosis is performed over a polyurethane catheter which may be removed when adequate healing has occurred. Closure of salivary gland parenchyma may usually be managed conservatively with interrupted sutures for the parenchyma and fascia. A salivary fistula may be a complication, but this usually heals with repeated aspirations and application of a pressure dressing. If this is not the case, gland excision may be necessary.
The wounds of penetrating facial injuries must be assessed for disruptions of the facial nerve. If injury has occurred posterior to a vertical line from the lateral canthus to the mental foramen, an attempt is made to identify proximal and distal nerve segments with subsequent primary reanastomosis. If injury has occurred anterior to this line, recovery will usually take place even in the event that obvious dysfunction is present at the time of injury.
Blunt trauma may result in the formation of a hematoma. This requires adequate drainage to prevent its subsequent organization, fibrosis, and possible cosmetic deformity.
Sialadenosis is the term used to describe the non-neoplastic, non-inflammatory enlargement of the salivary glands, usually the parotid, which occurs in association with many systemic disorders. The involvement is usually bilateral, and the etiology of the often asymptomatic enlargement unclear. Obesity, malnutrition of many causes, and alcoholic cirrhosis are common associations. Any condition affecting nutritional absorption may be involved, as well as hypothyroidism, gonadal atrophy, diabetes mellitus, and other endocrine abnormalities. Salivary gland enlargement usually resolves with treatment of the underlying condition.
Cheilitis glandularis represents hypertrophy of labial salivary glands which may result
in eversion of the lower lip and require vermilionectomy for repair. Pneumoparotitis may arise in instances of large increases in intraoral pressure. A variety of medications may result in salivary gland enlargement including phenothiazines, iodide-containing compounds, and heavy metals, among others. Lastly, infection with the Human Immunodeficiency Virus may result in diffuse, symmetric, bilateral parotid (and possibly submandibular) gland enlargement. Also commonly associated with HIV infection is the development of lymphoepithelial cysts which may become quite large and require frequent aspiration or other intervention.
The heterogeneous nature of the non-neoplastic salivary gland diseases requires a useful classification scheme to assist in the systematic approach to these disorders. The enumeration of their sometimes subtle characteristics serves as an aid in their recognition and subsequent appropriate management. It is also beneficial to always bear in mind that a significant number of these disorders have other important disease associations and that these entities may require careful attention as well.
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