Inflammatory salivary gland disorders

Clinical findings

• Mucoceles are most common in the first three decades of life; they manifest as dome-shaped, faintly bluish, sessile nodules most commonly located on the lower lip mucosa (70%–90% of cases), ventral tongue, buccal mucosa, and floor of mouth (the last also referred to as ranula); plunging ranula occurs when it extends beneath the mylohyoid appearing as a diffuse swelling of the submental or submandibular region. Mucoceles wax and wan and are usually painless ( Fig. 12.1 A–D); some resolve spontaneously.

  

• Superficial mucoceles are seen in patients with hyposalivation and mucosal disease and are most frequent on the palatal mucosa, especially in patients with chronic graft-versus-host disease and even lichen planus; they are generally painless blisters or vesicles, <5 mm in diameter, often leading to a clinical misdiagnosis of herpes infection, which is almost always painful (see Fig. 12.1 E–F).

Etiopathogenesis and histopathologic features

Mucoceles are pseudocysts that arise from trauma to the excretory salivary duct resulting in loss of duct integrity and spillage of mucin into the surrounding soft tissues. This becomes walled off by granulation tissue which is eventually organized into fibrous tissue. Superficial mucoceles occur because of either salivary gland hypofunction (such as dehydration or chronic graft-versus-host disease) or mucosal disease causing inflammation around the ducts (such as chronic graft-versus-host disease or lichen planus).

• There is a cyst-like cavity filled with mucin with muciphages and variable numbers of neutrophils, surrounded by condensed granulation tissue also containing muciphages, and sometimes neutrophils and lymphocytes, and even multinucleated foreign body–type giant cells. Eosinophilic globular condensations of mucin are sometimes present (referred to as myxoglobulosis) and can be prominent, and they are mucicarmine-positive; a feeder duct exhibiting squamous metaplasia may be seen in the vicinity (see Figs. 12.2–12.4 ). Very infrequently, a sialolith occurs within a mucocele (see Fig. 12.4 D).

  
  
  

• Mucin may be present diffusely in the connective tissue or within glandular parenchyma rather than in a cyst-like space ( Fig. 12.5 ); lesions not removed intact manifest as fragments of granulation tissue with muciphages and sometimes condensed mucin globules, but without obvious mucin pools ( Fig. 12.6 ). Ventral tongue lesions tend not to have a thick wall of granulation tissue ( Fig. 12.7 ).

  
  
  

• Minor salivary glands maintain their lobular architecture and exhibit variable degrees of obstructive changes, namely acinar atrophy, ductal dilatation with inspissated secretions, periductal hyalinization, periductal inflammation, interstitial fibrosis, and an interstitial lymphoplasmacytic infiltrate ( Fig. 12.8 ).

  

• An organizing mucocele may consist of a solid mass of granulation tissue with muciphages, with or without condensed mucin droplets without a mucin pool ( Fig. 12.9 ); muciphages may have clear cytoplasm and should not be mistaken for a clear cell carcinoma ( Fig. 12.10 ).

  
  

• Papillary synovium-like areas are frequently seen and similar to synovium, consist of fibroblasts, macrophages, and blood vessels, but unlike normal synovium, also exhibit muciphages and often neutrophils and lymphocytes ( Fig. 12.11 ).

  

• Superficial mucoceles contain mucin pools that abut the overlying atrophic epithelium and are often surrounded by a collarette of epithelium that forms part of the wall of the mucocele ( Figs. 12.12 and 12.13 ).

  
  

Differential diagnosis

• An organizing mucocele with a predominance of clear cells may resemble a salivary gland neoplasm such as a clear cell mucoepidermoid carcinoma or even clear cell carcinoma, but there is lack of stromal invasion by nests of neoplastic cells and the cells are keratin-negative and CD163+.

• Periductal lymphocytic infiltrates are frequently seen in obstructive or other nonspecific sialadenitis and should not be confused with autoimmune sialadenitis as seen in Sjögren syndrome, in which obstructive changes are minimal and the lymphocytic infiltrate is strikingly periductal, at least in early stages (see later).

Management

• Enucleation or excision of the mucoceles, sometimes with overlying mucosa (especially superficial mucoceles), and removal of damaged salivary glands in the vicinity are curative; recurrence rate is up to 8% after excision because of further damage of salivary glands.

Clinical findings

• This lesion is more common in adults with a median age in the sixth decade and 58% occur in women. The buccal mucosa, lower lip mucosa and maxillary and mandibular sulcus/vestibule (mucobuccal fold) are affected in approximately 50% of cases; upper lip lesions are often associated with sialoliths) ( Fig. 12.14 ); it appears as a bluish, mucosal-colored nodule that may feel hard if a sialolith is present.

  

Etiopathogenesis and histopathologic features

This cyst arises from retention of secretions within a duct from a distal obstruction, such as a sialolith or even viscid secretions, although in some cases the etiology is unclear.

• The cyst is composed of a single cystically dilated excretory salivary duct that may be lined by a double layer of low cuboidal-to-columnar cells or may exhibit squamous, ciliated cell, or oncocytic metaplasia ( Figs. 12.15–12.17 ). Apocrine snouting may be present. There may be surface undulations but true papillae with fibrovascular cores are not usually seen; a sialolith may be present; a variable lymphoplasmacytic infiltrate is present, often just beneath the lining epithelium.

  
  
  

• Multiple cystically dilated ducts exhibiting oncocytic metaplasia may occur in both extralobular and intralobular locations close to the cyst, with the surrounding salivary gland lobules exhibiting other chronic inflammatory changes such as acinar atrophy, and interstitial fibrosis and inflammation ( Figs. 12.18 and 12.19 ).

  
  

Differential diagnosis

• Gingival cyst of the adult that occurs on the attached gingiva is lined by two to three layers of low cuboidal-to-columnar cells with squamous epithelial plaques containing clear cells. Salivary glands are not present in the gingiva.

• Multifocality, lack of encapsulation, or significant adenomatous hyperplasia differentiates multifocal oncocytic ductal metaplasia from cystadenoma.

• True oral papillary cystadenoma lymphomatosum has been reported but is extremely rare and must show true papillary structures and a substantial lymphoid mantle around the cystic structures.

Management

• Enucleation or excision with surrounding glands is curative.

Clinical findings

• Sialolith of the minor salivary glands occurs most commonly in the fifth to seventh decades of life, usually in the upper lip (45% of cases) and buccal mucosa (40% of cases), and occurs as a firm-to-hard nodule, usually asymptomatic, unless ruptured and inflamed.

• Sialolith of the major glands is most common within the Wharton (submandibular) duct (80% of cases), causing pain from pressure from build-up of saliva proximal to the sialolith just before meals (meal symptoms); it may be seen on intraoral occlusal radiographs if it is sufficiently calcified as well as on computed tomography ( Fig. 12.20 ).

  

Etiopathogenesis and histopathologic features

Sialoliths form from precipitation of hydroxyapatite that is codependent on magnesium concentration and saliva pH among other factors and are mostly composed of apatite and whitlockite. This occurs around a central nidus of salivary proteins, cellular debris, and bacteria especially Streptococcus spp., Fusobacterium spp., and Eikenella spp. Development of sialoliths is unassociated with hypercalcemic syndromes although some studies suggest this occurs in populations where the drinking water is high in calcium and magnesium.

• Basophilic concentric lamellar and globular calcifications occur within a cystically dilated duct that exhibits squamous and often mucous cell metaplasia. Suppuration may be seen if there is infection and bacteria may be identified ( Figs. 12.21 and 12.22 ); the associated minor glands exhibit obstructive changes ( Fig. 12.23 ).

  
  
  

Differential diagnosis

• Calcified thrombi occur in the setting of other features of thrombosis within a vein and is not lamellar and globular.

• Phleboliths are usually smaller, do not have a globular component, and are present within venules.

Management

• Excision of the sialolith with surrounding minor salivary glands is curative.

• Submandibular sialoliths are removed by transoral extraction, sialoendoscopy with extraction, or extracorporeal shockwave lithotripsy.