Salivary Gland Tumors, Major, Benign 

Tumors of the salivary glands are uncommon and represent 2-4% of head and neck neoplasms. They may be broadly categorized into benign neoplasms, tumorlike conditions, and malignant neoplasms. The glands are divided into major and minor salivary gland categories. The major salivary glands are the parotid, the submandibular, and the sublingual glands. The minor glands are dispersed throughout the upper aerodigestive submucosa (ie, palate, lip, pharynx, nasopharynx, larynx, parapharyngeal space).

Most (70%) salivary gland tumors (SGTs) originate in the parotid gland. The remaining tumors arise in the submandibular gland (8%) and minor salivary glands (22%). Although 75% of parotid gland tumors are benign, slightly more than 50% of tumors of the submandibular gland and 80% of minor SGTs are found to be malignant. Pleomorphic adenomas (benign mixed tumors) are the most common benign SGTs, comprising 85% of all salivary gland neoplasms.

Note the images below.

The ubiquitous deposition of the minor salivary glands complicates the diagnosis and management of SGTs. The approach for a suspected tumor of the minor salivary glands begins with a thorough history and a physical examination. Radiographic imaging (CT with or without MRI) and a histopathologic diagnosis (obtained based on fine needle aspiration biopsy [FNAB]) often provide useful information prior to definitive surgical therapy.^{[1, 2]}

The anatomy of the parotid gland and the role of the main ducts were described in the mid-17th century. The earliest references to "para-auricular swellings," as the Greeks called them, described the findings associated with calculi and inflammation.

From 1650-1750, salivary gland surgery was limited to the treatment of ranulas and oral calculi. The concept of surgical excision of a parotid tumor has been attributed to Bertrandi in 1802. The initial applications of this surgery included an extensive approach, causing serious disfiguration and disability.

By approximately 1850, the focus shifted toward dissection and the intimate relationship between the facial nerve and the parotid gland. Attempts were made to perform the surgery with nerve preservation. John C. Warren, MD, was the first to use ether inhalation anesthesia during his resection of a parotid tumor in Boston in 1846. In 1892, Codreanu (a Romanian native) performed the first total parotidectomy with facial nerve preservation. Grafting of the facial nerve after resection was attempted in the early 1950s.

Beahrs and Adson (1958) eloquently described the relevant anatomy and surgical technique of current parotid gland surgery.^[3] They stressed surgical landmarks for avoiding injury to the main trunk and branches of the facial nerve and advocated complete removal of the superficial portion of the parotid gland for noninvasive lesions confined to that portion of the gland.^[3]

SGTs usually manifest as an enlargement or growth of the major salivary glands. Depending on the location of the gland, they can be presented with nerve compression symptoms when presented later in the course with larger size tumors.

Investigate and exclude a history of weight loss, underlying infectious processes (eg, chest pain, cough, lymphadenopathy), and clinical indications of lymphoma-type B symptoms (eg, night sweats, fever).

Frequency

SGTs represent 2-3% of head and neck neoplasms. Of the SGTs, 85% are pleomorphic adenomas. SGTs are more common in women than in men, with the peak incidence in the third and fourth decades of life. Pleomorphic adenomas make up 70% of parotid gland tumors and 50% of submandibular gland tumors.

Warthin tumors (adenolymphoma) account for 5-15% of SGTs. Warthin tumors are the second most common neoplasm of the parotid gland. They are more common in men than in women, with peak incidence in the fifth and sixth decades of life. Note the image below.

Of minor SGTs, 50% are malignant. Mucoepidermoid cancer is the most common parotid malignancy. Overall, adenoid cystic carcinoma is the most common malignant tumor of all minor salivary glands and, specifically, the submandibular gland.

Although the etiology of SGTs is unknown, the involvement of environmental or genetic factors has been suggested. Radiation exposure has been linked to the development of the benign Warthin tumor and to the malignant mucoepidermoid carcinoma. Epstein-Barr virus may be a factor in the development of lymphoepithelial tumors of the salivary glands. Genetic alterations, such as allelic loss, monosomy and polysomy, and structural rearrangement, have all been studied as factors in the development of SGTs.

The histogenesis of SGTs is based on the salivary gland unit as seen in the image below.

According to the multicellular theory of SGTs, pleomorphic adenomas originate from the intercalated duct cells and myoepithelial cells; oncocytic tumors originate from the striated duct cells; acinic cell tumors originate from the acinar cells; and mucoepidermoid and squamous cell tumors originate from the excretory duct cells.

The classic presentation of a benign SGT is a painless, slow-growing mass on the face (parotid), angle of the jaw (parotid tail, submandibular), or neck (submandibular) or a swelling at the floor of the mouth (sublingual). A sudden increase in size may be indicative of infection, cystic degeneration, hemorrhage inside the mass, or malignant degeneration. Benign SGTs are almost always freely mobile, and, for masses that arise in the parotid gland, facial nerve function is typically unaffected.^[4]

Because of the multiple and varied sites of minor salivary glands, the presentation of benign tumors in these sites may be less specific. For example, bleeding and airway compromise may be the first signs of minor SGTs of the nasal septum, whereas tumors of the base of tongue may present with dysphagia and a globus sensation. The authors have each observed one patient treated for a pleomorphic adenoma of the nasal septum and the base of the tongue. Benign tumors of the parapharyngeal space may present as trismus. Differentiating a benign, space-occupying lesion from one that is truly invading the masseter and pterygoid musculature is important. Note the image below.

Rule out signs of a malignant lesion, such as new onset of pain, facial nerve weakness, rapid growth, paresthesias, hoarseness, skin involvement, a fixed lesion, and cervical lymphadenopathy.

Tumors of the salivary glands are classified based on their cytological, architectural, and biological characteristics. The World Health Organization classification of 1992 groups both benign and malignant tumors into epithelial and nonepithelial categories. Benign epithelial tumors include pleomorphic adenoma, Warthin tumor, monomorphic adenoma, intraductal papilloma (IDP), oncocytoma, and sebaceous neoplasms. Benign nonepithelial tumors (mesenchymal origin) include hemangioma, angioma, lymphangioma (cystic hygroma), lipoma, and neural sheath tumors.

An additional category of tumor-like lesions includes necrotizing sialometaplasia, benign lymphoepithelial lesions, cystic lymphoid hyperplasia (in persons with AIDS), and salivary gland cysts.

Pleomorphic adenoma

Pleomorphic adenomas (benign mixed tumors) are the most common tumors of the salivary gland and are most often located in the tail of the parotid gland. When found in the minor salivary glands, the hard palate is the site most frequently involved, followed by the upper lip. Note the images below.

These tumors were termed pleomorphic because of the epithelial and connective tissue components that compose them in varying degrees. Their gross appearance is a round, smooth mass with a thin, delicate, incomplete capsule. Of note, pleomorphic adenomas that arise in the minor salivary glands usually lack a capsule. These tumors grow slowly, although they may become larger than other SGTs. The thin, delicate capsule may have projections into the surrounding parotid tissue. This is of particular clinical significance because obtaining clean margins and avoiding spillage are mandatory to minimize recurrence.

Microscopically, benign mixed tumors are characterized by variable, diverse, structural histologic patterns. Frequently, they have growth patterns of sheets, strands, or islands of spindle and stellate cells, with a myxoid configuration occasionally predominating. Treatment of benign neoplasms involves the complete surgical excision of the affected gland. If the parotid gland is involved, superficial parotidectomy with standard facial nerve dissection and preservation is the procedure of choice. Enucleation is contraindicated because of the tendency towards tumor spillage that can lead to tumor recurrence.

Warthin tumor (ie, papillary cystadenoma lymphomatosum, cystic papillary adenoma, adenolymphoma)

Albrecht first recognized this tumor in 1910, and Warthin later described it in 1929. In gross appearance, it is a smooth, soft, parotid mass. It is well encapsulated when located in the parotid gland and contains multiple cysts. Histologically, the Warthin tumor has a heavy lymphoid stroma and aciniform epithelial cells that line the cystic areas with papillary projections. Malignant transformation has not been observed. All patients with this tumor survive, and the recurrence rate is 5%. The Warthin tumor tends to be bilateral (10% of cases) and is usually found in the major glands, as are most other types.

Intraductal papilloma

IDP is a small, tan, fairly smooth lesion that is usually found in the submucosal layer. Microscopically, IDP consists of a cystically dilated duct partially lined with a cuboidal epithelium with complex anastomosing papillary fronds of variable size filling the cystic area. IDP of the minor salivary gland is a rare lesion that has been described only in various case reports.

Histologically, the differential diagnosis of IDP includes papillary cystadenoma, which is commonly but erroneously diagnosed as IDP. In papillary cystadenoma, intraductal hyperplasia occurs and the dilated duct contains some papillary folds and projections. However, this occurs much less frequently than in IDP.

Oxyphil adenoma (oncocytoma)

Duplay first described the oncocytic tumor in 1875. Oncocytomas of the salivary glands are very uncommon. Such neoplasms occur more often in women than in men, with a female-to-male ratio of 2:1. Patients are older than 50 years, and the superficial lobe of the parotid gland is the most commonly reported location. Oncocytomas rarely, if ever, occur in the minor salivary glands. Oncocytomas manifest as small (< 5 cm in diameter), firm, slow-growing, spherical masses. Bilateral oncocytomas of the parotid glands have been described. Histologically, they are large and spherical and have a distinct capsule. Uniform cells are arranged in solid sheets. These tumors recur if excision is incomplete.^[5]

Hemangiomas

Hemangiomas are the most common SGTs in children and usually involve the parotid gland. Less often, they may involve the submandibular gland. These vascular tumors may be distinguished from vascular malformations by their presence early in life, rapid growth phase in children aged approximately 1-6 months, and gradual involution over 1-12 years. The typical presentation is an asymptomatic, unilateral, compressible mass. Gross examination reveals a dark red, lobulated, unencapsulated mass. Microscopically, hemangiomas are composed of solid masses of cells and multiple anastomosing capillaries that replace the acinar structure of the gland. Because they lack a capsule, they tend to infiltrate neighboring structures.

Treatment should initially consist of steroids administered 2-4 mg/kg/d. Although the response may be immediate, only 40-60% of hemangiomas exhibit a response to steroids. Despite the tendency toward spontaneous involution, specific conditions may warrant surgical excision.

Lymphangioma (cystic hygroma)

Lymphangiomas are most commonly located in the head and neck region of infants and children. They are believed to be due to lymphatic sequestration of primitive embryonic lymph ducts that undergo irregular growth and canalization. They are spongy, multiloculated masses with a yellowish or bluish surface and are formed by endothelial-lined spaces. More than 50% manifest at birth, and 80% manifest by age 2 years. Usually, they manifest as painless masses that may involve parotid glands, submandibular glands, or both. Diagnosis is made based on clinical findings. Surgical excision with preservation of the vital structures is the treatment of choice. Lymphangiomas rarely cause symptoms of airway obstruction, and excision is usually for cosmetic reasons.

Lipoma

Lipoma tumors are relatively uncommon in a major salivary gland. They derive from fat cells and appear grossly as smooth, well-demarcated, bright-yellow masses. Histologically, the tumor consists of mature adipose cells with uniform nuclei.

These tumors manifest as soft, mobile, painful masses and peak in the fifth and sixth decades of life, with a male-to-female ratio of 10:1. They are slow-growing tumors with an average diameter of 3 cm. Treatment is surgical excision.

Necrotizing sialometaplasia

Necrotizing sialometaplasia may easily be mistaken for a malignant tumor because it presents as a single, unilateral, painless or slightly painful lesion on the hard palate. However, it is a benign, self-healing lesion of the minor salivary glands that is seen in adults older than 40 years and is 2-3 times more common in men than in women. Although the etiology is unknown, it may represent a reparative process in response to ischemic necrosis of salivary tissue. A biopsy helps to rule out a malignant process; otherwise, no treatment is indicated.

Lymphoepithelial hyperplasia (Mikulicz disease, sicca complex, chronic punctate sialadenitis)

This disorder can manifest as a diffuse enlargement of all or part of the parotid gland, or it may manifest as a discrete mass.

Histologically, the lesion is composed of a diffused, well-organized lymphoid tissue and lymphocytic interstitial infiltrate with obliteration of the acinar pattern.

Lymphoepithelial hyperplasia is more frequent in females than in males, and its peak incidence is in the fourth and fifth decades of life. Occasionally, both parotid glands are involved. The growth of this tumor is slowly progressive, and it gives rise to pain around the ear or the retromandibular area.

Metastatic disease of the parotid gland

Of these metastatic tumors, 46% are melanoma, 37% are squamous cell carcinoma, and 17% are various other tumors. This diagnosis carries a poor prognosis.^[6]

Indications include a mass of the face, neck, and floor of the mouth and the presence of clinical signs of malignancy. Such clinical signs of malignancy include a rapid growth on a slow growing tumor, bleeding, airway compromise due to larger size tumors, and nerve dysfunction (eg, paresthesia).

As a rule, excise all SGTs. Eneroth et al and others have advocated fine-needle aspiration (FNA) application and reported accuracy rates of 74-90%.^[7] FNA is mainly useful in nonneoplastic masses, metastatic tumors to the parotid gland, and nonsurgical lymphomas.

Almost all neoplasms should be removed surgically because only positive diagnostic results from FNA are significant.

The parotid gland is situated in the musculoskeletal recess formed by portions of the temporal bone, atlas and mandible, and their related muscles. The gland has a superficial and deep lobe, between which runs the extratemporal portion of the facial nerve. The deep lobe is in contact with the parapharyngeal space. The deep cervical fascia surrounds the parotid gland. This fascia has an anteroinferior portion that becomes the stylomandibular ligament, separating the parotid gland from the submandibular gland.

The facial nerve exits the stylomastoid foramen just posterior to the base of the styloid, gives off small branches to the postauricular and posterior belly of the digastric muscles, and then turns anterolaterally. The main trunk then becomes embedded in parotid tissue and divides into temporofacial and cervicofacial branches just superficial to the retromandibular vein and external carotid artery. Beyond this point, the nerve anatomy varies some; however, 5 general peripheral nerve branches exist: frontal, zygomatic, buccal, marginal mandibular, and cervical. Surgical landmarks for the main trunk of the facial nerve include the tragal pointer and the tympanomastoid suture line. Note the images below.

The submandibular gland encompasses most of the submandibular or digastric triangle. Similar to the parotid gland, the submandibular gland can be divided into a superficial and deep lobe based on the relationship to the mylohyoid muscle. The marginal mandibular branch of the facial nerve courses between the deep surface of the platysma and the superficial aspect of the fascia that lies over the submandibular gland. The facial artery and vein are located just deep to this nerve, and ligation and superior traction of these vascular structures can prevent nerve injury. Along the posterior border of the mylohyoid are located the lingual nerve and submandibular duct (Wharton duct). The hypoglossal nerve courses deep to the tendon of the digastric and then lies medial to the deep cervical fascia.

The sublingual gland occupies the same anatomical space as the submandibular gland, located between the mylohyoid and hyoglossus muscles. The gland can often be palpated in the floor of mouth, as it is rather superficial, covered by only a thin layer of oral mucosa.

The minor salivary glands are widely dispersed throughout the upper respiratory tract, including the palate, lip, pharynx, nasopharynx, larynx, and parapharyngeal space. The greatest densities of glands are located in the hard (250 glands) and soft (150 glands) palates.

Experienced clinicians agree that surgical excision is indicated for all patients in whom a parotid or salivary gland enlargement develops, unless associated medical problems preclude general anesthesia.

Surgical excision aids in establishing the diagnosis and in determining the treatment plan.