1. Fine needle aspiration (FNA) is the procedure of choice for initial characterization of salivary gland lesions for many reasons (see cytology section that follows).

2. Core needle and incisional biopsies of the parotid gland can damage the facial nerve branches so are rarely performed.

1. Bacterial sialadenitis is rare and is generally a result of obstruction by stones (sialolithiasis). The causative organism is usually Staphylococcus aureus, followed by Streptococcus viridans and gram-negative rods. Surgical specimens from bacterial sialadenitis are almost never seen. However, sialadenitis may lead to an abscess that requires surgical drainage. Gross specimens may show a purulent exudate or a relatively intact gland. Microscopic sections can show abscesses, cystic degeneration, and/or bacterial colonies.

2. Viral sialadenitis is most commonly caused by mumps (paramyxovirus), but can also be associated with Epstein-Barr, coxsackie, influenza A, and parainfluenza viruses. Surgical specimens are rarely encountered. Grossly infected glands are boggy and edematous, and chronic inflammation may be seen microscopically.

3. Autoimmune sialadenitis is relatively common, and usually presents as Sjögren’s syndrome, characterized by facial swelling, dry mouth, and dry eyes (termed Sicca syndrome) with inflammatory arthritis and elevated autoantibodies. On physical examination, bilateral, symmetric enlargement of the salivary and lacrimal glands is seen. Diagnosis may be facilitated by a minor salivary gland biopsy, typically taken from the inner lip.

Grossly, the major glands usually have a discrete, tan nodularity. Microscopically, in early disease, there is a lymphoplasmacytic septal inflammatory infiltrate with little to no abnormality of the parenchyma. The so-called “focus score,” a nodular collection of >50 lymphocytes, is considered diagnostic of autoimmune sialadenitis in the appropriate clinical context. In larger glands or in more severe disease, there is typically an extensive lymphoid infiltrate with germinal centers (e-Fig. 6.4). The acini are often atrophic, and interstitial fibrosis may be present. In late disease, acini may be completely absent leaving only isolated residual ducts, termed “epimyoepithelial islands,” with an associated dense intraepithelial lymphocytosis. In Sjögren’s syndrome, the lymphocytic infiltrate is polyclonal, in contrast to the monoclonal lymphoid proliferation seen in mucosa-associated lymphoid tissue (MALT) lymphoma.

4. Chronic sialadenitis (or chronic sclerosing sialadenitis) is usually unilateral and clinically can mimic a true salivary gland neoplasm. When it occurs in the submandibular gland, it is known as a Kuttner tumor. Chronic sialadenitis most commonly results from sialolithiasis with obstruction, although some cases may be due to radiation therapy or duct strictures. It can have no structural or obvious etiology and recently most of these cases have been shown to be an autoimmune-related IgG4-related sclerosing disease similar to that occurring in the pancreas. Grossly, it is characterized by a very hard, fibrotic gland with lobulation and septation (e-Fig. 6.5). Histologic examination of the gland early in the disease process shows dilated ducts filled with secretions with an associated lymphocyte and plasma cell-rich infiltrate, occasionally with germinal center formation. As the disease progresses, fibrosis surrounds the ducts and results in lobulation of the gland (e-Fig. 6.6) with acinar atrophy and broad fibrous bands. Surgical excision may be required, either to definitively rule out a neoplasm or just for symptom relief.

5. Necrotizing sialometaplasia is a rare inflammatory/destructive lesion that simulates malignancy and is thought to occur because of ischemic injury. Although it can occur anywhere along the UADT, the vast majority of cases occur in the hard palate. Men are slightly more commonly affected, and the average patient age is 46 years. Clinically, the lesion consists of a sharply defined and deep ulcer that develops rapidly (over a few days) and can persist for months. Grossly, the lesion consists of loose tissue with a surface ulcer and no distinguishing mass lesion. Microscopically, the most typical feature is coagulative necrosis of the minor salivary gland lobules with a prominent associated inflammatory response. There is extensive squamous metaplasia of the ducts (an alarming feature), but the lesion retains its overall lobular architecture (e-Fig. 6.7). The surface squamous mucosa may show pseudoepitheliomatous hyperplasia. The lack of peripheral infiltration and the retained lobular architecture are keys to recognizing the lesion as benign. No specific therapy is indicated because the lesion is self-healing.

1. Acquired immune deficiency syndrome (AIDS)-related parotid cysts (ARPCs) are benign lymphoepithelial cysts. Patients present with unilateral or bilateral, painless, slowly enlarging parotid masses. They sometimes have associated cervical lymphadenopathy and/or nasopharyngeal swelling. Grossly, these lesions have multiple cystic spaces usually containing serous fluid. Microscopically, ARPCs consist of cysts that most often have a thin, mature squamous epithelial lining, although the lining is sometimes cuboidal or columnar with goblet cells. Below the epithelium, the cyst wall has dense lymphoid tissue with germinal centers. Occasionally, lesions within the gland can lack cystic change and appear similar to epimyoepithelial islands.

Unlike autoimmune sialadenitis, the vast majority of human immunodeficiency virus (HIV) patients with ARPC have no autoimmune symptoms, no Sicca syndrome from glandular dysfunction, and no serum autoantibodies. The etiology of ARPC is thus unclear. Patients usually have bilateral disease by radiologic examination, even if there are no symptoms and no clinical mass in the contralateral gland. If the diagnosis is established by radiologic imaging and cytology, surgery is not necessary for other than cosmetic reasons.

2. Benign lymphoepithelial cysts are unifocal lesions that occur in patients in their fifth and sixth decades. They most commonly involve the parotid gland, but are occasionally seen in the oral cavity. There is no association with systemic disease. Grossly, they consist of well-circumscribed unilocular cysts with contents ranging from serous to mucoid to caseous; keratinous debris may be present. Microscopically, they consist of a cyst lined by thin, mature squamous epithelium without papillary projections. In rare cases, the lining is cuboidal or columnar with goblet cells. Below the epithelium, the cyst
wall has dense lymphoid tissue with germinal centers (e-Fig. 6.8). Excision is curative, and the lesion does not recur.

3. Mucoceles are the most common non-neoplastic lesion of salivary gland tissue and are defined as pooling of mucin in a cystic cavity. Two types are recognized. In the retention type, the mucin is within a dilated duct. In the extravasation type, the mucin accumulates in the soft tissue. The lower lip is the most common site for mucoceles, followed by the tongue, the floor of the mouth (where the lesion is termed a “ranula”), and the buccal mucosa. The peak incidence of mucoceles is in the third decade. Grossly, a mucocele presents as a cystic cavity in the connective tissue that is filled with glistening fluid. Microscopically, the cyst wall may or may not have an epithelial lining, depending on the type. Those of the retention type have a lining and usually no surrounding inflammation, whereas those of the extravasation type consist of mucin with surrounding inflammatory cells and no lining. Some late lesions consist only of a collection of foamy histiocytes containing mucin (e-Fig. 6.9), which can be confirmed by PAS or mucicarmine stains. Surgical excision is usually curative.

1. Pleomorphic adenoma (PA) is the most common neoplasm of the salivary glands. Ninety percent of PAs occur in the parotid gland and PAs represent 60% of parotid gland neoplasms; the majority of the remaining cases occur in the hard palate or submandibular gland. The tumor occurs over a wide age range, but the peak incidence is in the fourth and fifth decades. The tumor presents as a slow-growing, painless mass that usually is between 2 and 5 cm in diameter. On gross examination, these tumors appear well-circumscribed but are not usually encapsulated. They are never encapsulated when occurring in minor salivary glands. Sectioning reveals a rubbery, myxoid, tanwhite mass (e-Fig. 6.10). The microscopic appearance, as the name suggests, is highly variable, but always shows an intimate admixture of epithelial and mesenchymal elements. The epithelial component consists of ductal structures with an associated myoepithelial layer but also may contain collections of myoepithelial cells that can range from spindled to clear, plasmacytoid, or basaloid. The mesenchymal, or stromal, component is typically myxoid, hyaline, or chondroid (e-Fig. 6.11). Although defined subcategories have no clinical significance, pleomorphic adenomas have been divided into a myxoid type (>80% mesenchymal-type tissue), cellular type (>80% epithelial-type tissue), and mixed or classic type (generally an equal mix of components).

Treatment requires complete excision because PAs are likely to recur if tumor is left behind or transected. Multinodular growth is uncommon in primary tumors but is frequent in recurrent disease, yielding a so-called “buckshot” pattern (e-Fig. 6.12). Therapy for recurrence is consequently more difficult.

2. Warthin tumor (papillary cystadenoma lymphomatosum) is the second most common benign salivary gland tumor and is found exclusively in the parotid gland. It is the most common bilateral or multifocal salivary gland tumor, usually presents in the sixth or seventh decade, and is associated with smoking. Grossly, it presents as a soft, brown or yellow mass that is composed of cysts that are classically filled with viscous brown fluid. Microscopically, the lesion has a characteristic and highly reproducible morphology with papillary projections into cystic spaces which have an epithelial lining composed of two layers of cells with oncocytic features (e-Fig. 6.13). The epithelium overlies a dense, polyclonal, lymphoid component with germinal centers. Warthin tumors may show a giant cell reaction, fibrosis, or squamous metaplasia from trauma and/or cyst rupture. Surgical excision is almost always curative as recurrence is rare. Associated malignancy is also very rare and is usually either squamous cell carcinoma or lymphoma.

3. Basal cell adenomas are benign tumors that are composed of small basaloid cells. They generally occur in adults, and 75% occur in the parotid gland. They usually present as an asymptomatic, slowly growing mass. The membranous subtype (“dermal anlage tumor”) may be multicentric. The occurrence of numerous basal cell adenomas, dermal cylindromas, and trichoepitheliomas is called Brooke-Spiegler Syndrome.

On gross examination, these tumors are usually solid, well-circumscribed, and pink to brown. Some may be cystic. Microscopically, four patterns are recognized: tubular, solid, trabecular, and membranous (Table 6.2). In all patterns, the tumor is composed of two cell types. Small cells with little cytoplasm typically lie at the neoplasm’s edge, frequently show peripheral palisading, and give the tumor its basaloid appearance. Polygonal basaloid cells with slightly more cytoplasm and round to oval nuclei with more open chromatin usually lie in the center of the nests. The trabecular and membranous patterns have a “jigsaw puzzle” appearance with rounded nests of tumor cells shaped like puzzle pieces (e-Fig. 6.14). The membranous pattern additionally shows hyalinized, eosinophilic, linear, or nodular basement membrane-like material around the nests (e-Fig. 6.15). The tubular pattern consists of tubular, gland-like structures (eFig. 6.16). The solid pattern consists of solid nests of cells. The tumor cells express ductal and myoepithelial markers including pan-cytokeratin, S-100, smooth muscle actin, and p63.