43

DISEASES OF THE
SALIVARY GLANDS
William R. Carroll, MD
C. Elliott Morgan, DMD, MD

The spectrum of diseases involving the salivary glands

includes infections, localized and systemic inflammatory
processes, and benign and malignant tumors.
The parotid gland is located in the space between the
ramus of the mandible and the external auditory canal and
mastoid tip. The anterior portion of the gland overlies the
masseter muscle, and the posterior portion overlies the ster-
nocleidomastoid muscle. The deep, medial portion of the
gland is adjacent to the parapharyngeal space. The parotid
gland is covered by the parotid fascia. This layer is an exten-
sion of the superficial layer of the deep cervical fascia that
splits to envelop the gland. The parotid duct (Stensen’s duct)
exits anteriorly, reaches the anterior aspect of the masseter
muscle to pierce the buccinator muscle, and enters the oral
cavity opposite the second upper molar tooth.
The position of the facial nerve is the dominant consider-
ation in surgery of the parotid gland. As the nerve exits the
stylomastoid foramen, it enters the posterior and medial por-
tion of the gland, usually as a single trunk. Its primary bifur-
cation occurs at the pes anserinus with subsequent secondary
division into five facial and cervical branches. The nerve lies
within the substance of the gland. In our opinion, the most
reliable way to find the main trunk of the facial nerve is by
507
508 Otorhinolaryngology

identification of the tympanomastoid suture. Looking at a

skull, the tympanomastoid suture extends medially along the
skull base until it ends at the stylomastoid foramen. The sty-
lomastoid foramen is almost always within the suture line.
The submandibular gland is located within the sub-
mandibular triangle of the neck. Like the parotid gland, it is
covered with a fascial capsule, which originates from the
superficial layer of the deep cervical fascia. The marginal
mandibular branch of the facial nerve often overlies the lat-
eral aspect of the submandibular gland. It is positioned in a
plane deep to the platysma muscle but superficial to the sub-
mandibular gland fascia.
The anterior border of the submandibular gland is folded
over the posterior border of the mylohyoid muscle, creating
portions of the gland both superficial and deep to the mylo-
hyoid muscle. The lingual nerve is located just medial and
superior to the gland within the sublingual space. The
hypoglossal nerve courses between the medial portion of the
submandibular gland and the hypoglossus muscle deep to the
digastric muscle. The submandibular gland duct (Wharton’s
duct) arises from the medial aspect of the gland and proceeds
submucosally in the floor of the mouth medial to the sublin-
gual gland to reach its papilla at the side of the frenulum of
the tongue.
The sublingual glands are located submucosally in the
floor of the mouth. They are paired structures and nearly meet
in the anterior part of the floor of the mouth. Typically, there
is no single duct draining the submandibular glands. Rather,
there are 10 to 12 smaller ducts that pass directly into the
mucosa of the floor of the mouth.
There are hundreds of small, unnamed minor salivary
glands distributed throughout the upper aerodigestive tract.
These glands are both mucus and serous producing, and each
has its own small duct draining directly to the mucous mem-
brane. The minor salivary glands are most prominent in the
 Diseases of the Salivary Glands 509

oral cavity and are located in the hard and soft palate, lips,
buccal mucosa, floor of the mouth, and tongue.

INFLAMMATORY DISEASES OF
THE SALIVARY GLANDS
Viral Infections (Mumps)
Mumps (epidemic parotitis) is a disease of viral origin that
most commonly occurs in the pediatric age group. Viral
parotitis is usually caused by a paramyxovirus (specifically
the Rubulavirus), but many viral pathogens may cause acute
infections within salivary glands. Typical symptoms include
fever, malaise, and headaches, followed by tenderness and
enlargement of the parotid glands. The most common com-
plication from paramyxovirus parotitis is orchitis, occur-
ring in 20 to 30% of males. Oophoritis occurs in 5% of
females. Involvement of the germinal tissues does not usu-
ally cause sterility. Aseptic meningitis is a complication in
about 10% of patients with viral parotitis. Pancreatitis
occurs in 5%. Treatment of viral salivary gland infection
is supportive. Live attenuated mumps vaccine as part of
mumps, measles, rubella (MMR) immunization is given to
children after 12 months of age.

Sjögren’s Syndrome
Sjögren’s syndrome is a chronic autoimmune disorder of the
exocrine glands, which affects predominantly, but not exclu-
sively, the salivary glands. It is the second most common
autoimmune disease, trailing only rheumatoid arthritis. Women
in the fourth to fifth decade of life constitute 90% of cases.
The most common symptom of Sjögren’s syndrome is
xerostomia (dry mouth). The decreased salivation causes dif-
ficulty with swallowing, altered taste, and speech difficulties.
Long-term xerostomia causes an increase in dental caries.
Ocular involvement in Sjögren’s syndrome is characterized as
510 Otorhinolaryngology

keratoconjunctivitis sicca. Sjögren’s syndrome may progress

to multisystem involvement. The systemic symptoms are
linked to connective tissue disease. Rheumatoid arthritis
occurs in 50% of patients with Sjögren’s syndrome.
Asymmetric enlargement of the parotid that persists or is
rapid in onset should raise suspicion of lymphoma. Patients
have 44 times greater risk of developing lymphoma after
developing Sjögren’s syndrome. Parotid enlargement in the
presence of splenomegaly, lymphadenopathy, immunosup-
pression, or previous radiation should raise suspicion for
lymphoma.
Salivary tissue biopsy is the most commonly employed
method for diagnosing Sjögren’s syndrome. Histologic diag-
nosis is based on the presence of more than one cluster of
greater than 50 lymphocytes per 4 mm2. Lip biopsy has the
highest specificity (95%), sensitivity (58 to 100%), positive
predictive value, and negative predictive value of all tests for
Sjögren’s syndrome.

Human Immunodeficiency Virus

Patients infected with the human immunodeficiency virus
(HIV) may develop a spectrum of salivary gland disorders,
including diffuse infiltrative lymphocytosis, benign lym-
phoepithelial lesions, lymphoepithelial cysts, and malignant
salivary gland tumors, including lymphoma, Kaposi’s sar-
coma, and adenoid cystic carcinoma.
Lymphoepithelial cysts may occur unilaterally or bilater-
ally in the parotid glands. Multiple lymphoepithelial cysts
are so characteristic of HIV infection as to be considered
almost pathognomonic. The pathogenesis of the cysts is
unknown, and they can occur at any stage of the disease.

Sarcoidosis
The salivary glands are involved in 6 to 10% of patients with
sarcoidosis. The parotid gland is involved most commonly.
 Diseases of the Salivary Glands 511

Heerfordt’s syndrome (uveoparotid fever) results from sar-

coidosis and includes uveitis, lacrimal and salivary gland
inflammation, and facial paralysis. The diagnosis is one of
exclusion because the noncaseating granulomas are not
pathognomonic for the disease. Anemia, thrombocytopenia,
leukopenia, eosinophilia, decreased albumin, and hyperglob-
ulinemia support the diagnosis. Elevated angiotensin con-
verting enzyme levels, sedimentation rates, and calcium
levels may also be present. Hilar adenopathy may be present
on a chest radiograph. Corticosteroids are used to treat
patients with more advanced forms of sarcoidosis.

Wegener’s Granulomatosis
Wegener’s granulomatosis is a systemic disorder often
involving the respiratory tract from the nose to the lungs, as
well as the kidneys. Wegener’s granulomatosis affects both
sexes equally, occurs in all ages, and is usually seen in
Caucasians. Histologically, Wegener’s granulomatosis is
characterized by vasculitis of medium and small vessels.
More than 70% of the features associated with Wegener’s
granulomatosis are related to the ears, nose, and throat.
Symptoms develop insidiously, with sinusitis being the most
frequent presentation. Salivary gland enlargement may
accompany the nasal and sinus symptoms, with the parotid or
submandibular glands, or both, being affected. Subglottic
stenosis commonly occurs. In the lower airway, pulmonary
infiltrates or cavitary nodules are also noted. Renal involve-
ment indicates systemic Wegener’s granulomatosis and is the
most frequent cause of death.
Intranasal biopsies should be taken with a generous sec-
tion of viable nasal mucosa. These can be taken from the
turbinate, septum, or lateral nasal wall. The specimen should
be examined for fungal microorganisms as well. Wegener’s
granulomatosis must be differentiated from other granulo-
matous diseases including polymorphic reticulosis, Churg-
512 Otorhinolaryngology

Strauss syndrome, lymphoma, sarcoidosis, scleroma, tuber-

culosis, relapsing polychondritis, and fungal disease.
The “gold standard” for treatment of Wegener’s granulo-
matosis is cyclophosphamide and glucocortoids. Metho-
trexate has been used with corticosteroids in milder forms
of Wegener’s granulomatosis. Upper airway involvement
responds well to trimethoprim and sulfamethoxazole used
in combination with cyclophosphamide and glucocorticoids.

Acute and Chronic Bacterial Infections

of the Salivary Glands
Acute bacterial sialadenitis may involve any salivary gland,
although the parotid gland is affected most frequently.
Suppurative infection of the salivary glands may be an iso-
lated, acute event or a chronic event with recurrent acute
exacerbations.
Acute bacterial infection of the salivary glands may occur
either by retrograde transmission of bacteria from the oral
cavity or by stasis of salivary flow. Saliva contains lysozyme
and immunoglobulin A, which protect the salivary glands
from infection. Stone formation (sialolithiasis) may cause
mechanical obstruction of the salivary duct, causing stasis of
flow with resultant bacterial infection. Elderly patients are at
high risk for salivary gland infection owing to medications
that decrease salivary flow. These medications include diuret-
ics, antidepressants, beta blockers, anticholinergics, and anti-
histamines. Patients with chronic, debilitating conditions,
patients with compromised immune function, HIV-positive
patients, anorexic and bulimic patients, and depressed
patients are at an increased risk for acute bacterial salivary
gland infection. Xerostomia of any cause increases the risk
for bacterial parotitis.
Staphylococcus aureus is the most common microorgan-
ism causing acute bacterial parotitis. Other microorganisms
include beta-hemolytic streptococcus, Haemophilus influen-
 Diseases of the Salivary Glands 513

zae, Streptococcus pneumoniae, and, less frequently, gram-

negative microorganisms.
Symptoms of acute bacterial sialadenitis include rapid
onset of pain, swelling, induration, and fever. The symptoms
may worsen during eating. Examination reveals induration,
erythema, edema and tenderness over the gland, and puru-
lence at the ductal orifice. Bacterial sialadenitis may progress
to abscess formation. Treatment of acute sialadenitis is
directed at improving salivary flow. Antibiotic therapy should
be directed toward the gram-positive and anaerobic microor-
ganisms commonly involved.

Chronic Sialadenitis
Patients with chronic sialadenitis experience recurrent, low-
grade inflammation and edema of the gland, minor pain, and
sialorrhea that may be slightly purulent. Streptococcus viri-
dans is the usual infecting microorganism. Measures to
increase salivary flow should be instituted and appropriate
antibiotics given. Attempts to identify stones or duct stric-
tures should be made.

SALIVARY GLAND NEOPLASMS

Benign Salivary Gland Neoplasms
Pleomorphic Adenoma
Pleomorphic adenoma or benign mixed tumor is the most
common salivary tumor, accounting for up to two-thirds of
all salivary gland neoplasms. Approximately 85% of all
pleomorphic adenomas are located in the parotid glands,
10% in the minor salivary glands, and 5% in the sub-
mandibular glands. Pleomorphic adenomas contain both
mesenchymal and epithelial cells. Abnormalities are found in
chromosome 8q12. This region is the site of the pleomor-
phic adenoma gene PLAG1. Grossly, the tumors appear
encapsulated but, on close inspection, have pseudopod
514 Otorhinolaryngology

extensions into the surrounding tissues. This growth pattern

is thought to be responsible for the high rate of local recur-
rence (approximately 30%) when these tumors are enucle-
ated. Adequate surgical therapy involves nerve identification
and protection with removal of the tumor and an adequate
cuff of surrounding parotid gland parenchyma.

Warthin’s Tumor
Warthin’s tumor or papillary cystadenoma lymphomatosum
is the second most common benign neoplasm of the salivary
glands. Interestingly, Warthin’s tumor occurs almost exclu-
sively in the parotid glands. It typically involves the lower
pole of the parotid gland and may be bilateral in up to 10%
of cases. The most popular etiologic theory suggests that
Warthin’s tumor arises in salivary ducts that are trapped
within intraparotid lymph nodes. The recommended treat-
ment for Warthin’s tumor is complete surgical excision sim-
ilar to that described for pleomorphic adenoma.

Monomorphic Adenomas
Monomorphic adenomas include basal cell adenoma, clear
cell adenoma, and glycogen-rich adenoma among other less
common tumors. The most common monomorphic adenoma
is the basal cell adenoma, which comprises 1 to 3% of sali-
vary gland neoplasms. Treatment of monomorphic adenomas
includes wide surgical excision with an adequate cuff of nor-
mal surrounding tissue.

Oncocytomas
Oncocytomas comprise less than 1% of all salivary gland neo-
plasms. Oncocytomas are grossly encapsulated, single lesions.
Histologically, the tumors are composed of large cells with
round nuclei. Treatment of oncocytoma involves wide local
excision with a cuff of surrounding gland parenchyma. Rarely,
malignant oncocytomas are detected. Cytologic differentia-
 Diseases of the Salivary Glands 515

tion from benign oncocytoma can be difficult, and malignancy

is usually defined by invasive clinical and histologic features.

Hemangiomas
Hemangiomas are the most common tumor arising in the
salivary gland from the connective tissue elements. They are
the most common salivary gland tumor of any type in chil-
dren and are often detected within the first year of life.
Hemangiomas often occur over the angle of the mandible,
and the overlying skin may contain a bluish discoloration.
Engorgement of the lesion with crying or straining is often
also seen. Most hemangiomas in the salivary glands undergo
spontaneous resolution.

Malignant Tumors of the Salivary Glands

Salivary gland malignancies make up a relatively small per-
centage of all cancer occurring in the head and neck region.
Spiro and colleagues analyzed over 7,000 reported salivary
gland neoplasms. Seventy-eight percent of the parotid neo-
plasms, 54% of the submandibular neoplasms, and 35% of
the minor salivary gland neoplasms were benign. Radiation
exposure is one known risk factor, and there seems to be a
dose-response relationship for the development of malignant
tumors. Pain is present in 10 to 29% of patients with cancer
in the parotid gland, and facial paralysis is detected in 10 to
15% of parotid gland malignancies. Of malignant neoplasms,
35% were mucoepidermoid carcinomas, 23% were adenoid
cystic carcinoma, 18% were adenocarcinoma, 13% were
malignant mixed tumor, and 7% were acinic cell carcinoma.

Mucoepidermoid Carcinoma
Mucoepidermoid carcinoma is the most common malignant
salivary gland tumor. Approximately one-half of all mucoepi-
dermoid carcinomas occur in the parotid gland, with the
majority of the remainder occurring in minor salivary glands.
516 Otorhinolaryngology

As the name implies, mucoepidermoid carcinomas are com-

posed of both mucus and epidermoid cells. Histologic grading
of mucoepidermoid carcinoma has correlated with prognosis.
High-grade tumors recur locally nearly 60% of the time,
develop lymph node metastases 40 to 70% and distant metas-
tases 30% of the time, and have 5-year survival rates of 30 to
50%. In contrast, low-grade mucoepidermoid carcinomas
have 5-year survival rates in the 80 to 95% range. They are
much less likely to develop nodal or distant metastasis.
For low-grade mucoepidermoid carcinoma, treatment
usually involves wide surgical excision. Neck dissection or
adjuvant irradiation is used only when clinically evident
metastases are detected or when there is evidence of bone,
nerve, or extraglandular invasion. In contrast, high-grade
mucoepidermoid carcinomas are treated more like squa-
mous cell carcinomas. Wide surgical excision combined
with regional lymph node dissection and adjuvant radiation
therapy is commonplace.

Adenoid Cystic Carcinoma

Adenoid cystic carcinoma is the second most common malig-
nancy of the salivary glands. It is the most common malig-
nancy in the submandibular glands and minor salivary glands.
The most common clinical presentation for adenoid cystic
carcinoma is a painless, slowly enlarging mass. However,
paresthesias and paralysis are more common with adenoid
cystic carcinoma than other salivary malignancies. Indeed,
perineural invasion and spread are hallmarks of adenoid cys-
tic carcinoma. The prognosis of adenoid cystic carcinoma
may be related to histologic grade. Those patients with low-
grade tumors have slow disease progression and infrequent
distant metastasis. Patients with high-grade malignancies
experience much more rapid growth, with higher frequency
of distant metastasis and decreased survival. The early trend
 Diseases of the Salivary Glands 517

toward better survival with low-grade lesions disappears as

the patient follow-up exceeds 10 years. In other words, dis-
ease progression was slower and less fulminant but relent-
less and equally deadly. Fifteen- to 20-year survival rates are
in the 30% range regardless of histologic grade.
Treatment of adenoid cystic carcinoma includes wide
local excision of primary disease and therapeutic lymph node
dissection. Elective node dissections are not typically rec-
ommended. Radiation therapy is usually recommended post-
operatively. Fast neutron radiotherapy has proven effective
for recurrent or unresectable adenocystic carcinoma. In the
University of Washington series, when patients were able to
undergo surgical resection (even if microscopic margins were
not clear) and there was no direct skull base involvement,
5-year regional control rates of 80% were achieved.

Polymorphous Low-Grade Adenocarcinoma

Polymorphous low-grade adenocarcinoma (PLGA) typically
arises from the minor salivary glands and is frequently seen
in the oral cavity. The palate is the most common location
for PLGA. It may be confused with pleomorphic adenoma on
the benign side and with adenoid cystic carcinoma on the
more malignant side. Proper treatment of PLGA is surgical.

Acinic Cell Carcinoma

Acinic cell carcinoma is reasonably rare and comprises
roughly 1 to 3% of all salivary gland tumors. Most acinic cell
carcinomas are found in the parotid gland, where they com-
pose 12 to 17% of parotid malignancies. Bilateral parotid
gland involvement has been reported in up to 3% of cases.
The biologic behavior may range from slow indolent local
growth to a more aggressive form with rapid growth and the
potential for distant metastasis. Treatment of acinic cell car-
cinoma is wide surgical excision.
518 Otorhinolaryngology

Malignant Mixed Tumors

This somewhat confusing group of tumors contains at least
three distinct tumor types: carcinoma ex pleomorphic ade-
noma, malignant mixed tumor (carcinosarcoma), and benign
metastasizing pleomorphic adenoma. Carcinoma ex pleo-
morphic adenoma is the most common of these three. This
tumor represents malignant transformation of the epithelial
component of a pleomorphic adenoma. The risk of malig-
nant transformation increases from 1.5 to approximately
9.5% over the 5 to 15 years’ duration of the pleomorphic
adenoma. The biologic behavior of carcinoma ex pleomor-
phic adenoma is generally more aggressive than other sali-
vary gland malignancies. Treatment is wide local excision
with consideration of lymph node dissection and postopera-
tive radiation therapy. Five- and 10-year survival rates are
40 and 24%, respectively.
Malignant mixed tumor is less common and contains
malignant epithelial and mesenchymal components. This is a
true carcinosarcoma, and both components of the malignancy
are evident in metastatic sites. The sarcomatous component is
often differentiated as a chondrosarcoma, but other types of
sarcoma are also described. Treatment is wide surgical exci-
sion and radiation. Distant metastases are common, and the
prognosis is poor.
Metastasizing pleomorphic adenoma represents an
unusual lesion in which benign-appearing pleomorphic ade-
noma appears in regional lymph nodes. A 22% mortality rate
is associated with this development. There is a suggestion
that the risk of developing metastasizing pleomorphic ade-
noma increases with the longevity of the original tumor and
with local recurrence.

Squamous Cell Carcinoma

Primary squamous cell carcinoma of the salivary glands is
rare. Squamous cell carcinoma is much more commonly
 Diseases of the Salivary Glands 519

metastatic to the parotid gland parenchyma or intraparotid

lymph nodes. The diagnosis of squamous cell carcinoma
within the salivary gland should always trigger an intensive
search for a primary lesion.