Non-Neoplastic Lesions of the Salivary Glands

Clinical Features

Heterotopia of salivary gland is the existence of salivary gland tissue in locations external to the major and minor salivary glands. In contrast, accessory salivary glands are defined as isolated lobules of glands situated along a major salivary duct. Heterotopic or ectopic salivary gland tissue has been reported in a myriad of anatomic locations ( Table 11.1 ) and is usually found incidentally, although it may be discovered due to signs and symptoms associated with inflammation or neoplasia. The more common sites for heterotopic salivary gland are the middle ear, neck, mandible, and pituitary gland. Sites outside the head and neck include the mediastinum, stomach, prostate gland, rectum, and vulva. Removal of these salivary gland tissue deposits may occur for cosmetic reasons, as intervention for a congenital abnormality (oncocytosis), or due to neoplasia. In the case of malignancy, confusion may arise, particularly if the remaining normal gland architecture has been destroyed, as to whether the tumor is primary in heterotopic salivary gland tissue versus a metastatic deposit from a nearby salivary gland.

Oncocytes are characterized by the presence of abundant finely granular, bright eosinophilic cytoplasm surrounding a round nucleus that contains a single nucleolus. The granular cytoplasm is due to an overabundance of mitochondria. The number and distribution of oncocytic cells in salivary gland vary, as does the growth pattern. The occurrence of oncocytic cells in salivary gland can be categorized as oncocytic metaplasia within a duct or isolated aggregate, focal and diffuse oncocytosis, multifocal oncocytic hyperplasia, and oncocytoma. Oncocytic metaplasia involves the abnormal change or transformation (metaplasia) of acinar cells (serous, mucous, and seromucous) and/or striated ducts to oncocytes. Oncocytic metaplasia is uncommon before the age of 50 and increases with advancing age. The metaplasia is usually seen focally within a duct and may be found in conjunction with salivary gland neoplasms (pleomorphic adenoma, mucoepidermoid carcinoma). Oncocytosis is an unencapsulated (mass-forming) collection of oncocytes, which may occur in minor or major salivary glands. This alteration may involve either ducts, predominantly, or acini and may be associated with fatty infiltration and acinar atrophy. The rare condition nodular oncocytic hyperplasia (NOH) is characterized by multiple nodules of oncocytic cells in a lobular distribution within one or both parotid glands (bilateral in 40% of cases) ( Fig. 11.1 ). NOH has been reported associated with oncocytoma and benign or malignant salivary gland neoplasms. These nodules or islands may be large, but they lack the encapsulation of an oncocytoma. The oncocytic islands of NOH may involve the intraparotid lymph nodes, which often contain salivary gland ducts, or the hilum of the lymph node. It is worth highlighting that these oncocytic islands within the lymph nodes can be incorrectly confused with metastatic deposits.

Pathologic Features

Microscopic Findings

Like any salivary gland, histologic sections of heterotopia reveal a variably mixed population of large pale mucous cells with poorly staining mucigen granules and condensed peripheral nuclei and the more basophilic serous cells with strongly staining zymogen granules and central nuclei. Intermixed are the intercalated ducts with a lining of cuboidal secretory cells.

Developmental Lesions, Including Heterotopia and Oncocytosis—Pathologic Features

Gross Findings

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  Oncocytic nodules may measure up to 7 cm, with small, cystic areas

Microscopic Findings

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  Oncocytic cells are characterized by finely granular, eosinophilic cytoplasm

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  There is a single round nucleus with conspicuous nucleolus

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  Architectural growth patterns are usually organoid with variable areas showing cording and prominent capillaries

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  Oncocytes may undergo “clear cell” change

Ancillary Studies

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  PTAH stain accentuates granules

Pathologic Differential Diagnosis

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  When clear cell oncocytes are present, differential includes metastasis from clear cell mucoepidermoid carcinoma, clear cell acinic cell, and renal cell carcinoma

PTAH , Phosphotungstic acid–hematoxylin stain.

Histologic examination of an oncocytic lesion shows the characteristic polygonal cells with abundant finely granular eosinophilic cytoplasm. This oncocytic transformation can involve acinar and ductal cells, and the cytologic distinction can be striking ( Fig. 11.2 ). The nuclei are usually uniformly round with granular chromatin and contain a single nucleolus. Mitotic figures are absent or rare. The presence of a complete or partial fibrous capsule surrounding an oncocytoma will aid in the distinction between an oncocytoma and NOH. Oncocytes may grow as a solid nodule of cells or within ducts. There may be unencapsulated focal cystic areas with papillary proliferations within ducts or as an isolated parenchymal aggregate. The architectural growth pattern of the cells within a solid nodule is often organoid or forming cords in a hepatoid pattern. The individual cells show a variable eosinophilic staining quality ( Fig. 11.3 ) and, on a rare occasion, may contain focal or diffuse clear cells.

Ancillary Studies

Although not necessary for the diagnosis, the following may be useful in demonstrating the presence of mitochondria within oncocytic lesions.

Differential Diagnosis

Distinguishing between nodular hyperplasia, nodular oncocytosis, and oncocytoma may be problematic and sometimes impossible. Some authorities define an oncocytoma as a single nodule, whereas others require the presence of at least a partial capsule . The distinction between oncocytic hyperplasia and neoplasia is still not well defined. Oncocytic metaplasia and a variety of clear cell neoplasms are included in the differential diagnosis with oncocytoma. Areas of oncocytic metaplasia have been reported in pleomorphic adenomas and within mucoepidermoid carcinomas; however, these areas are usually isolated. Furthermore, oncocytomas lack the architectural patterns of these two neoplasms: Focal mucus cell differentiation and squamous metaplasia are exceedingly rare within oncocytomas and help to distinguish oncocytoma from mucoepidermoid carcinoma; and oncocytomas do not have myoepithelial cell proliferation with ductal structures, or myxoid or chondroid differentiation, which is characteristic of pleomorphic adenoma.

Acinic cell carcinoma may be difficult to distinguish from a multi NOH. However, the presence of zymogen granules combined with the microcystic and papillary follicular growth patterns of acinic cell carcinoma is not seen in oncocytic hyperplasia.

Prognosis and Therapy

Oncocytic metaplasia and oncocytosis are usually identified in a gland removed for another reason. No therapy is necessary for these benign reactions. Heterotopias are excised for symptomatic relief in some cases, with an excellent prognosis.

Clinical Features

The most common non-neoplastic lesion of salivary gland tissue is the mucocele. The mucocele is defined as the pooling of mucin in a cystic cavity. Two types of mucoceles are described: (1) the retention type ( Fig. 11.4 ), characterized by mucin pooling confined within a dilated excretory duct ( Figs. 11.5 and 11.6 ), and (2) the extravasation type ( Fig. 11.7 ), showing escape of salivary-secreted mucin from the duct system into connective tissue ( Figs. 11.8 and 11.9 ). The mucus retention cyst is more common in the parotid and submandibular glands, and the peak incidence is in the 7th to 8th decade. The extravasated type is the most common mucocele, and its peak incidence is in the 3rd decade. The lower lip is the most common site, followed by the tongue, floor of mouth, palate, and buccal mucosa. The extravasated type most commonly occurs in the lower lip, often appearing as blue-tinged, dome-shaped swellings. A large mucocele that may arise in the floor of the mouth from the sublingual or minor salivary gland and descend into the soft tissues of the floor of the mouth is called a ranula .

A sialolith is a collection of often laminated concretions that form a stone within the salivary gland excretory duct system. Sialolithiasis most frequently involves the submandibular gland and may cause a chronic sclerosing sialadenitis distal to the stone ( Fig. 11.10 ). The stone will cause distention of the duct system and retention of secreted fluids, resulting in glandular swelling and pain.

Radiographic Features

Sialoliths are always visible on radiographic examination. The Wharton duct of the submandibular gland is the most common site for a sialolith, which can be visualized easily on a radiograph ( Fig. 11.10 ).

Pathologic Features

Histologically, the retention cyst captures the mucus within an epithelium-lined lumen. The cyst shows an attenuated epithelium. There is usually minimal inflammatory infiltrate within the wall ( Fig. 11.5 ) unless there is adjacent rupture. In contrast, the lesions of extravasated mucin (mucocele) show compression of the adjacent connective tissue with a brisk inflammatory reaction circumscribing the mucin pool ( Fig. 11.8 ). Often within the infiltrate of the mucocele wall, there are numerous foamy macrophages containing phagocytized mucin ( Fig. 11.9 ). As the lesion progresses, granulation tissue from the wall becomes more prominent and organizes to obliterate the lumen of the mucocele. In a primarily granulation tissue–laden lesion, a mucicarmine stain will highlight the residual mucin-containing macrophages.

A sialolith will frequently demonstrate a nidus of cellular debris found in the center of the concentric laminated calcium deposits ( Fig. 11.11 ).

Differential Diagnosis

Few entities enter into the differential diagnosis of an extravasated-type mucocele. Certainly, a resolving extravasated mucocele with only remaining granulation tissue may be misinterpreted as a small hematoma or a thrombus. However, the use of mucicarmine would illustrate the presence of mucin-laden macrophages and aid in this distinction. The mucus retention cyst is lined by a thin layer of cuboidal epithelium with little to no inflammatory cell infiltrate. Mucoepidermoid carcinoma could enter the differential diagnosis of a mucus retention cyst. However, mucoepidermoid carcinoma contains three cell types: mucus goblet cells, intermediate cells, and squamous cells. Moreover, within mucus retention cysts, the epithelium is attenuated and it lacks papillary projections that often protrude into the lumen of a mucoepidermoid carcinoma.

Prognosis and Therapy

Surgical excision to include the minor mucoserous gland is suggested, as clinically indicated by the patient's condition. Alginate has been used by some with varying results. Recurrence is seen in patients with inadequate excision. Lithotripsy, sialoendoscopy, and other supportive measures are used for symptomatic sialoliths.

Clinical Features

Necrotizing sialometaplasia is an uncommon destructive reactive inflammatory process of the salivary gland. The clinical and histologic characteristics resemble those of malignant neoplasms and can lead to misdiagnosis and inappropriate therapy. The age range of reported patients with necrotizing sialometaplasia is from 1.5 to 83 years, with the average age of ~46 years. The lesion has a 2 : 1 predominance in men. Its etiology is somewhat speculative, although strong evidence suggests the cause may be vascular compromise leading to ischemic necrosis. The vast majority of these lesions affect the minor salivary glands in the hard palate or at the junction of the hard and soft palate ( Fig. 11.12 ). Lesions are most commonly unilateral; however, occasional bilateral or midline lesions develop. Other common sites for this lesion are oral cavity, lower lip, retromolar trigone, tongue, and buccal mucosa, although the entire upper aerodigestive tract can be affected. Occurrence of this lesion in major salivary glands, primarily the parotid gland, is uncommon, representing 8.5% of necrotizing sialometaplasia cases.

Clinically, the lesion appears in the palate as a deep, sharply defined, up to 3 cm crater-like ulcer that develops rapidly over a few days and fails to heal for an extended period of time. Duration of healing of this lesion can range up to 6 months, although most heal within 1 month. All such lesions that fail to resolve usually undergo a biopsy. Other symptoms associated with this lesion (pain or numbness) may simulate malignancy.