Salivary Glands




Keywords

parotid, salivary, facial nerve, deep lobe, reanimation

 









Salivary glands are divided into major (parotid, submandibular, and sublingual) and minor salivary glands. Major salivary glands are paired structures, and minor glands exist in a submucosal location throughout the upper aerodigestive tract starting from the nasal cavity and lips down to the esophagus and trachea. Embryologically, the salivary glands are tubuloacinar structures arising from invaginations of the somatoderm (ectodermal) and foregut (endodermal). The salivary gland network is composed of secretory elements that produce saliva upon stimulation by mastication or sensory/autonomous nervous system stimuli (i.e., smell, taste, and thought).


The composition of saliva depends on the site of the salivary gland producing it. For example, a larger concentration of serous glands is found in the parotid and mucous glands in the hard palate. Saliva produced by these glands facilitates digestion, provides lubrication and protection of mucous membrane and dentition, and provides clearance of foreign materials. In addition, saliva contains enzymes (e.g., amylases, lipases, other enzymes) that initiate the digestive process, primarily of materials that contain starch. Saliva also plays an essential role in preventing dental caries and infection by direct cleansing of foreign materials and antibacterial activity that is mediated through multiple factors (i.e., immunoglobulin A and leukotrienes).


Neoplasms of the salivary glands are rare and account for approximately 3% to 6% of all tumors of the head and neck region. Cancers of the salivary gland occur with an incidence of approximately 2.5 to 3.0 cases per 100,000 per year in the United States. Factors that predispose to neoplastic processes in the major salivary glands include a history of exposure to low-dose radiation. In addition, chronic exposure to wood dust (especially soft wood) and chemicals used in the leather tanning industry also may increase the risk for minor salivary gland cancers in the sinonasal tract (especially adenocarcinomas). An increased incidence of adenocarcinoma of minor salivary origin of the nasal cavity and ethmoid region is reported from Europe, in contrast to the United States, where squamous cell carcinoma is most common in these sites. Although no known links exist, a higher rate of malignant oncocytomas in Alaskan natives suggests that other unidentified environmental and/or inherited factors also may contribute to salivary carcinogenesis.


The risk for malignancy and the histopathologic distribution of malignant tumors differs between major and minor salivary glands. The incidence of malignancy in the parotid, submandibular, and minor salivary glands is 25%, 50%, and 80%, respectively ( Fig. 13.1 ). Overall, 65% of salivary gland cancers arise in the parotid gland, 8% arise in the submandibular gland, and 27% arise in the minor salivary glands ( Fig. 13.2 ). The mucosa of the hard palate is the most frequent site of origin of minor salivary gland tumors, followed by other sites in the oral cavity and paranasal sinuses ( Fig. 13.3 ). The histologic classification of salivary tumors is shown in Table 13.1 .




Figure 13.1


The incidence of malignant tumors among salivary glands.



Figure 13.2


The distribution of salivary tumors among major and minor salivary glands.



Figure 13.3


The distribution of the anatomic sites of origin for minor salivary gland tumors. FOM, Floor of mouth.


Table 13.1

The World Health Organization Histologic Classification of Salivary Gland Tumors















Nonneoplastic epithelial lesions


  • Sclerosing polycystic adenosis



  • Nodular oncocytic hyperplasia



  • Lymphoepithelial sialadenitis



  • Intercalated duct hyperplasia

Benign tumors


  • Pleomorphic adenoma



  • Myoepithelioma



  • Basal cell adenoma



  • Warthin’s tumor



  • Oncocytoma



  • Lymphadenoma



  • Cystadenoma



  • Sialadenoma papilliferum



  • Ductal papillomas



  • Sebaceous adenoma



  • Canalicular adenoma and other ductal adenomas

Uncertain malignant potential Sialoblastoma
Malignant tumors


  • Acinic cell carcinoma



  • Secretory carcinoma



  • Mucoepidermoid carcinoma



  • Adenoid cystic carcinoma



  • Polymorphous adenocarcinoma



  • Epithelial myoepithelial carcinoma



  • Clear cell carcinoma



  • Basal cell adenocarcinoma



  • Sebaceous adenocarcinoma



  • Intraductal carcinoma



  • Cystadenocarcinoma



  • Adenocarcinoma not otherwise specified (NOS)



  • Salivary duct carcinoma



  • Myoepithelial carcinoma



  • Carcinoma ex pleomorphic adenoma



  • Carcinosarcoma



  • Poorly differentiated carcinoma (undifferentiated carcinoma, large cell neuroendocrine carcinoma, and small cell carcinoma)



  • Lymphoepithelial carcinoma



  • Squamous cell carcinoma



  • Oncocytic carcinoma



The most common benign tumor of salivary gland origin is the pleomorphic adenoma (mixed tumor). The parotid gland is the most common site of origin, followed by the submandibular gland and then by minor salivary glands. These tumors most frequently arise in the fifth to sixth decades of life and have a slight predilection for women. In general, pleomorphic adenomas tend to be asymptomatic and grow slowly; rapid growth raises concern for malignant transformation. Warthin’s tumor is the next most common benign salivary neoplasm, which occurs most frequently in the tail of the parotid gland. An association with tobacco use has been suggested, because smokers have a fivefold to tenfold increased risk for these tumors. These tumors have a predilection for older white men and can be bilateral in up to 10% of cases.


Oncocytomas typically occur in older persons and are relatively rare. These tumors are characterized by a high mitochondrial content, which accounts for fluorodeoxyglucose avidity on positron emission tomography scans, similar to Warthin’s tumors. Lymphoepithelial lesions are relatively rare but can occur in increased frequency in patients with human immunodeficiency virus infection, in whom they are often bilateral. Monomorphic adenoma is a term that was used in the past to describe a less heterogeneous group of tumors than pleomorphic adenoma that includes basal cell adenoma, canalicular adenoma, and myoepithelioma. Of these, basal cell adenoma is the most common and typically occurs in the parotid gland of older persons. Although canalicular adenomas also occur in older persons, they typically originate from the minor salivary gland of the upper lip and buccal mucosa.


The distribution of various types of malignant tumors of the salivary glands is shown in Fig. 13.4 . Mucoepidermoid carcinomas are found most commonly in the parotid gland, whereas adenoid cystic carcinomas are seen most frequently in submandibular and minor salivary glands. Histologic differentiation is crucial in predicting the biological behavior of salivary neoplasms. Low-grade malignant tumors have an indolent course and have an excellent prognosis. On the other hand, high-grade tumors behave aggressively, with increased risk of regional and distant metastasis, and are associated with poor prognosis.




Figure 13.4


The histologic distribution of malignant tumors of the salivary glands.


Mucoepidermoid carcinoma is the most common malignant salivary gland tumor. Based on their histologic features, these tumors are further subdivided into low-grade, intermediate-grade, and high-grade tumors. Although low-grade and intermediate-grade tumors are slow growing, they can be locally aggressive; however, they rarely metastasize. In contrast, high-grade mucoepidermoid carcinomas have an aggressive clinical course with local invasion and increased risk of regional nodal metastasis.


Mucoepidermoid carcinomas can arise not only in minor salivary glands but also in salivary nests within the mandible (i.e., a “central salivary carcinoma”) and in ectopic salivary tissue in the parapharyngeal space.


Adenoid cystic carcinoma is the most common malignant tumor of the submandibular and minor salivary glands. Although grading systems have been proposed for these tumors, tumor grading does not seem to influence the behavior of adenoid cystic carcinomas. These tumors have a high degree of neurotropism, leading to the propensity for perineural spread. Although the overall outcome of adenoid cystic carcinomas is poor, the disease course typically is protracted, with survival measuring in decades, even in the presence of distant metastases . Although regional lymph node metastases are uncommon, pulmonary metastases occur frequently.


Polymorphous adenocarcinomas occur mainly in minor salivary glands and typically have an indolent course. These tumors most commonly arise in the oral cavity, with the hard palate being the principal site of origin. The “adenocarcinoma not otherwise specified (NOS)” category includes a heterogenous group of neoplasms that lacks any of the histologic features that characterize the other defined types of salivary tumors. Among other malignant tumors are acinic cell carcinomas, mammary analog secretory carcinoma, salivary duct carcinoma, myoepithelial carcinoma, and carcinoma ex pleomorphic adenoma. About 10% of malignant neoplasms of salivary origin are acinic cell carcinomas, and they most commonly arise from the parotid gland. These tumors tend to be indolent but have the capacity of high-grade tumors.


Primary squamous cell carcinoma of the parotid gland is extremely rare and needs to be differentiated from squamous cell carcinoma that has metastasized to an intraparotid lymph node from a synchronous or previously treated skin cancer.




Evaluation


Tumors of salivary gland origin usually present as an asymptomatic mass. The majority of parotid tumors arise in the superficial lobe and present as a rubbery nodular mass, generally located anterior to the lobule of the ear in the region of the tail of the parotid gland ( Figs. 13.5 through 13.7 ). Most mixed tumors are asymptomatic. Facial paralysis does not occur with mixed tumors regardless of the size of the tumor. Enlarged ipsilateral cervical lymph nodes or the presence of facial nerve dysfunction or invasion of the overlying skin almost invariably are suggestive of a malignant tumor ( Figs. 13.8 through 13.11 ). Tumors in the deep lobe of the parotid gland usually present with diffuse enlargement and fullness in the retromandibular region.




Figure 13.5


A large benign mixed tumor of the right parotid gland. Note stretched skin over the tumor.



Figure 13.6


The anterior view of a patient with a benign mixed tumor of the left parotid gland.



Figure 13.7


A large parotid tumor of the left parotid gland.



Figure 13.8


Involvement of a periparotid or cervical lymph node by metastasis is almost diagnostic of a malignant parotid tumor.



Figure 13.9


Invasion of the overlying skin is highly suggestive of a malignant tumor.



Figure 13.10


The lateral view of a patient with a carcinoma of the parotid gland.



Figure 13.11


Facial nerve paralysis is diagnostic of a malignant tumor of the parotid gland.


Radiographic studies are essential to accurately delineate the location and extent of the deep lobe tumor. Tumors of the deep lobe of the parotid gland, extending into the parapharyngeal space, may cause medial displacement of the soft palate, tonsil, and/or lateral pharyngeal wall ( Fig. 13.12 ). They may or may not be associated with a palpable parotid mass. Occasionally tumors may arise in accessory parotid tissue along the course of the Stensen duct and present as a mass in the soft tissues of the midportion of the cheek ( Fig. 13.13 ). Metastatic tumors to the parotid gland from primary cutaneous malignant lesions of the scalp and forehead such as squamous cell carcinomas and melanomas also are important differential diagnostic entities. Diffuse enlargement of the entire parotid gland may be seen in patients with lymphoma, Sjogren’s syndrome, and those with extensive eosinophilic infiltrate, as seen in patients with Kim-Kimura’s disease ( Fig. 13.14 ).




Figure 13.12


A deep lobe parotid tumor presenting as a parapharyngeal mass.



Figure 13.13


An accessory parotid tumor.



Figure 13.14


Diffuse enlargement of the entire parotid gland with a firm to hard mass (Kim-Kimura disease).


A painless swelling in the submandibular triangle is the usual presenting symptom for a tumor of the submandibular gland ( Fig. 13.15 ). The presence of pain signifies an obstructive and/or inflammatory phenomenon and may prove to be sialadenitis of the submandibular salivary gland. Bimanual palpation of the mass through the floor of the mouth confirms the location of the tumor in the submandibular gland and differentiates this entity from adjacent enlarged cervical lymph nodes.




Figure 13.15


A mixed tumor of the submandibular salivary gland.


Tumors of minor salivary gland origin usually present as a submucosal mass that may be ulcerated ( Figs. 13.16 and 13.17 ). The majority of tumors of minor salivary gland origin are malignant. Minor salivary tumors of the lip often mimic a mucocele or a mucous cyst ( Fig. 13.18 ). The presence of a soft-to-firm rubbery submucosal mass should raise the index of suspicion regarding the possibility of a minor salivary gland tumor.




Figure 13.16


An adenoid cystic carcinoma of the hard palate.



Figure 13.17


A malignant mixed tumor of the hard palate.



Figure 13.18


An adenocarcinoma of the upper lip.


Radiographic Evaluation


Diagnostic imaging studies are necessary if clinical examination does not provide accurate delineation of the location and extent of the tumor. Thus imaging is essential in the evaluation of a deep-seated or a fixed lesion for which invasion into adjacent anatomic structures is a concern. Plain radiographs, sialography, nuclear scans, and ultrasonography add very little to the desired diagnostic information and are seldom indicated. On the other hand, computerized tomography (CT) and magnetic resonance imaging (MRI) permit better visualization of masses of the salivary glands.


CT and MRI are equally satisfactory in differentiating cystic from solid lesions and allow evaluation of the relationship of the mass to the major salivary gland or adjacent structures, including soft tissues and bones ( Figs. 13.19 through 13.21 ). For minor salivary lesions, CT provides valuable information that assists in treatment planning; in particular, it shows the relationship of the tumor to surrounding structures and demonstrates tumor extension, permitting assessment of the resectability of advanced lesions. CT scans are invaluable in the evaluation of deep lobe parotid tumors and assist in differentiating them from tumors arising in the parapharyngeal space ( Figs. 13.22 through 13.25 ). MRI is equally valuable in the assessment of deep lobe parotid tumors and in differentiating them from tumors of ectopic or minor salivary gland origin ( Fig. 13.26 ). CT scans are particularly of value in the assessment of bone erosion, whereas MRI is of particular value in demonstrating tumor extension along cranial nerves.




Figure 13.19


A computed tomography scan showing bilateral Warthin’s tumors, which are multiloculated on the right-hand side ( arrow ) and uniloculated on the left-hand side.



Figure 13.20


A T1-weighted magnetic resonance imaging scan showing a benign mixed tumor in the superficial lobe of the left parotid gland ( arrow ).



Figure 13.21


A T2-weighted magnetic resonance imaging scan showing a benign mixed tumor in the superficial lobe of the left parotid gland ( arrow ).



Figure 13.22


An axial view of a computed tomography scan showing a deep lobe parotid tumor ( arrow ).



Figure 13.23


A coronal view of the computed tomography scan of the same patient as in Fig. 13.20 showing the deep lobe parotid tumor ( arrow ).



Figure 13.24


An axial view of a magnetic resonance imaging scan of the same patient as in Fig. 13.20 showing the deep lobe parotid tumor ( arrow ).



Figure 13.25


A coronal view of the magnetic resonance imaging scan of the same patient as in Fig. 13.20 showing the deep lobe parotid tumor ( arrow ).



Figure 13.26


An axial view of a contrast-enhanced T2-weighted magnetic resonance imaging scan showing a left parapharyngeal space tumor of ectopic salivary tissue. Note fat separating the tumor from adjacent deep lobe parotid tissue.




Pathology


Histologically, major and minor salivary glands consist of the secretory acinus and related ducts and myoepithelial cells. Acini may be serous, mucous, or mixed serous and mucinous. The cytoplasm of serous cells contains zymogen granules, and their principle secretion is amylase. The cytoplasm of mucinous cells is clear and contains mucin. Secretions from the acini empty into smaller duct systems that lead to branching larger duct systems and eventually into the main excretory duct ( Fig. 13.27 ). Myoepithelial cells surround the acinar and ductal cells.




Figure 13.27


The histologic structure of the normal salivary gland.


In most patients presenting with the clinical features of a discrete parotid tumor, tissue diagnosis is seldom required before surgical exploration. However, if clinical suspicion of a malignant tumor is high, then cytologic diagnosis of a malignant tumor can be established by a fine-needle aspiration biopsy. Aspiration with a 21-gauge needle is usually satisfactory in securing tissue for diagnosis or as a screening tool to triage the patients to different treatment. The rate of correctly establishing the diagnosis as benign or malignant range from 81% to 98%; however, a specific diagnosis can be made in only 60% to 75%. Inadequate sampling appears to be the most frequent cause of false negatives.


Pleomorphic Adenoma (Mixed Tumor)


Pleomorphic adenoma is a benign neoplasm characterized by an admixture of epithelial, myoepithelial, and stromal elements with architectural pleomorphism. This neoplasm represents two-thirds of all tumors of the major salivary glands and less than half of those in the minor salivary glands, with the greatest frequency of occurrence in the superficial lobe of the parotid gland.


Grossly, pleomorphic adenoma is generally white and firm, with a smooth outer and cut surface. The tumor may be vaguely lobulated and nodular, with “podocytes,” which are more commonly noted microscopically. Microscopically, pleomorphic adenomas demonstrate an admixture of epithelial and mesenchymal elements, with ductal and myoepithelial cell types intermingled with myxoid, mucoid, or chondroid stroma ( Figs. 13.28 and 13.29 ). Most pleomorphic adenomas are encapsulated, especially in the major salivary gland, with a variable amount of capsule thickness. Irregular peripheral borders and local extension of fingerlike processes into the capsule might be seen. Pleomorphic adenomas are characterized by a remarkable degree of morphologic diversity between individual tumors or within a single tumor. Therefore a definite diagnosis might not be possible on a representative frozen section or on a small amount of fine-needle aspiration material. Recurrence of pleomorphic adenomas generally represents local regrowth and not necessarily malignancy, and further surgery becomes technically demanding with reference to the safety of the facial nerve. Many recurrent pleomorphic adenomas are multifocal, and some can be so widely distributed that surgical control becomes impossible.




Figure 13.28


Pleomorphic adenoma demonstrating abundant myxochondroid matrix and myoepithelial cells (25× H&E stain).



Figure 13.29


Pleomorphic adenoma demonstrating abundant myxochondroid matrix and myoepithelial cells (50× H&E stain).


Carcinoma ex pleomorphic adenoma is a malignant neoplasm that arises in association with pleomorphic adenoma. Typically, these tumors are high grade and show similar histology to their de novo counterparts. The malignant tumor component is most frequently salivary duct carcinoma, followed by myoepithelial carcinoma. However, any histologic subtype of salivary gland carcinoma can arise in association with pleomorphic adenoma. Carcinoma ex pleomorphic adenoma is classified based on the degree of tumor invasion through the preexistent pleomorphic adenoma capsule into the surrounding tissue as intracapsular, minimally invasive, and invasive. The extent of invasion has been found to correlate with the clinical outcome. A very low rate of local recurrence and regional metastases are noted in patients with intracapsular minimally invasive tumors, while the risk of local recurrence, metastases, and fatal outcome is higher in patients with invasive tumors. At the molecular level, rearrangements of PLAG1 (pleomorphic adenoma gene 1) on 8q12 and HMGA2 on 12q14-15 are the most frequent genetic alterations in both pleomorphic adenoma and carcinoma ex pleomorphic adenoma.


Warthin’s Tumor (Papillary Cystadenoma Lymphomatosum)


Warthin’s tumors are benign salivary gland neoplasia that usually arise in the parotid gland and are composed of eosinophilic glandular epithelium, lined by basaloid cells, with papillary cystic spaces, embedded in dense lymphoid tissue ( Fig. 13.30 ).




Figure 13.30


Warthin’s tumor with adjacent normal parotid gland parenchyma on the right (50× H&E stain).


Oncocytoma


Oncocytoma, also known as oxyphil adenoma or oncocytic adenoma, is a benign salivary gland neoplasm composed of oncocytes that are benign epithelial cells packed with mitochondria, imparting a granular appearance to the cytoplasm ( Fig. 13.31 ).




Figure 13.31


Abundant eosinophilic cells of oncocytoma separated by thin fibrovascular septae (100× H&E stain).


Mucoepidermoid Carcinoma


Mucoepidermoid carcinoma is the most common malignant salivary gland tumor in both adults and children. More than half of these tumors occur in the parotid gland; when they arise in the minor salivary glands, they are most frequently in the palate.


Histologically, this tumor is composed of varying proportions of epidermoid (squamoid), mucous, and intermediate cells, arranged in cystic or glandular structures or in a solid growth pattern. Mucicarmine stain highlights intracytoplasmic mucin. CK5/6 and p63 immunohistochemical stains will stain the epidermoid and intermediate cells. S100 and myoepithelial markers (Calponin and smooth muscle actin) are usually negative in mucoepidermoid carcinoma. Variable histologic parameters such as perineural invasion and vascular invasion have been reported to correlate with the patients’ clinical outcome. However, prognosis seems to be largely dependent on tumor grade. Several grading systems exist for mucoepidermoid carcinomas, but they are graded by most pathologists, using three tiers (based on tumor cytologic and proliferative features and architecture): low, intermediate, and high grade ( Fig. 13.32 and Fig. 13.33 ). At the molecular level, a chromosomal translocation (11,19), resulting in MECT1/MAML2 fusion genes, has been identified in 40% to 80% of mucoepidermoid carcinomas. The translocation has been suggested to be associated with more indolent clinical behavior.




Figure 13.32


Low-grade mucoepidermoid carcinoma with more than 20% of the tumor represented by cystic spaces lined by squamoid epithelial cells (25× H&E stain).



Figure 13.33


High-grade mucoepidermoid carcinoma demonstrating marked nuclear pleomorphism and areas of single-cell necrosis (200× H&E stain).


Adenoid Cystic Carcinoma


Adenoid cystic carcinoma is a slowly growing, insidious salivary gland malignancy, occurring in both minor and major glands, notorious for its tendency for perineural invasion, as well as local invasion and recurrence after surgical resection. These tumors may arise in the major salivary glands and also in the oral cavity, nasopharynx, nasal cavity, paranasal sinuses, lacrimal glands, and lower respiratory tract. Adenoid cystic carcinoma grows as solid, white to gray, scirrhous, infiltrative masses that tend to be hard and fixed and may tether overlying skin.


Histologically, adenoid cystic carcinoma is composed of ductal and myoepithelial cells and shows hyalinized or myxoid matrix ( Fig. 13.34 ). The tumor demonstrates three main growth patterns: cribriform, tubular, and solid ( Fig. 13.35 ). Perineural invasion is commonly seen in adenoid cystic carcinoma ( Fig. 13.36 ).




Figure 13.34


Adenoid cystic carcinoma of the parotid gland demonstrating a predominantly cribriform architectural pattern (50× H&E stain).



Figure 13.35


Area of solid growth in adenoid cystic carcinoma, with rare ductal cells and a predominance of myoepithelial cells (400× H&E stain).



Figure 13.36


Perineural invasion is present centrally within this adenoid cystic carcinoma (400× H&E stain).


Unlike mucoepidermoid carcinoma, grading of adenoid cystic carcinoma does not seem to be significant in the prediction of the behavior of this malignancy. The presence of solid tumor growth seems to correlate with more aggressive behavior and poor survival. It is infrequent to see lymph node metastases; rather, one is more likely to see distant spread to the lungs and solid organs such as the kidney, with as much as a 15-year latency period.


The MYB protooncogene occurs in the majority of adenoid cystic carcinomas, with a translocation (6,9) resulting in fusion of the MYB and NFIB genes being the most common mechanism. The 6,9 translocation has been described in about 65% of adenoid cystic carcinomas of the head and neck and various anatomic sites, including the breast and lung.


Polymorphous Low-Grade Adenocarcinoma


Polymorphous low-grade adenocarcinoma (PLGA), now shortened to polymorphous adenocarcinoma (PAC), occurs mainly in minor salivary glands, with the hard palate being the most common location. It is important to differentiate PAC from adenoid cystic carcinoma since it typically has an indolent course. These tumors show one cell type with cytologic uniformity and various growth patterns. Perineural invasion may be seen. A cribriform variant, which is considered a separate entity by some authors, has been reported to have a greater capacity for regional metastasis. Activation of PRKD1 point mutation has been recently reported in about 73% of PLGA.


Epithelial-Myoepithelial Carcinoma


Epithelial-myoepithelial carcinoma is another typically indolent salivary gland tumor that is characterized by a multinodular pattern and biphasic or bilayered arrangement of inner ductal cells and outer myoepithelial cells, with classically clear cytoplasm.


Acinic Cell Carcinoma


Acinic cell carcinomas account for approximately 10% of all malignant salivary gland carcinomas and arise almost exclusively in the parotid. These tumors are characterized by serous acinar cell differentiation with zymogen-type cytoplasmic granules. They tend to be indolent and low grade but have the capacity to present as high-grade tumors.


Secretory Carcinoma


Mammary analog secretory carcinoma (MASC) is a recently described salivary gland tumor that was likely classified as acinic cell carcinoma in the past. The tumor has striking histologic and molecular similarities to secretory carcinoma of the breast. The official terminology of this entity is now “secretory carcinoma.” At the histologic level, tumor cells have eosinophilic or clear bubbly cytoplasm, and they may grow as tubules or microcysts, papillae, or macrocysts. Secretions are almost always present in the microcysts and/or macrocysts. MASC characteristically harbors a balanced chromosomal translocation (12, 15), resulting in the formation of the ETV6–NTRK3 fusion genes.


Salivary Duct Carcinoma


Salivary duct carcinoma is an aggressive, high-grade carcinoma that resembles high-grade breast ductal carcinoma. Typically the tumor is composed of ductal cells arranging in tubules, as solid and cribriform growth with central necrosis ( Fig. 13.37 ). Androgen receptor (AR) expression by immunohistochemistry is identified in the vast majority of salivary duct carcinoma. In addition to AR, immunohistochemical overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in a good percentage of salivary duct carcinoma with or without amplification of the gene by fluorescence in situ hybridization. Targeted therapeutic modalities, including anti-ERBB2 antibodies and androgen deprivation therapy, are characterized by variable results. Additionally, various genetic alterations have been reported in salivary duct carcinoma, including TP53, PTEN, EGFR, and phosphoinositide 3-kinase (PIK3CA) pathway.




Figure 13.37


Salivary duct carcinoma.


Myoepithelial Carcinoma


Myoepithelial carcinoma is a rare salivary gland tumor that is composed almost exclusively of myoepithelial cells. The tumor seems to be locally aggressive with diverse clinical outcome. Both myoepithelial carcinoma and salivary duct carcinoma may arise de novo or in association with pleomorphic adenoma (carcinoma ex pleomorphic adenoma).




Treatment


The primary goal for treatment of patients with benign or malignant tumors of the salivary glands is gross total removal of the tumor for accurate diagnosis and local control. Because the majority of salivary tumors are benign and occur with the highest frequency in the parotid gland, the goal of therapy is to achieve complete excision of the tumor to reduce the risk of local recurrence. The same principles of treatment apply for benign tumors arising from the submandibular, sublingual, and minor salivary glands.


Preservation of function, particularly of the facial nerve and its branches, is an important goal in surgery for parotid and submandibular gland tumors. Similarly, the goal for treatment of malignant tumors of salivary origin is control of cancer with preservation of function when feasible. Regardless of the histology, if a parotid tumor is confined to the superficial lobe of the parotid gland and the facial nerve is not directly infiltrated by the tumor, a superficial parotidectomy with dissection and preservation of the facial nerve is indicated. Sacrifice of a functioning, uninvolved facial nerve is rarely necessary for resection of malignant tumors of the parotid gland. Deliberate sacrifice of the facial nerve can be justified if an invasive tumor directly extends into the facial nerve or when resection of the facial nerve would facilitate monobloc excision of a malignant tumor. Whenever the facial nerve is resected, rehabilitation of the paralyzed face becomes an important priority. Rehabilitation may be accomplished by primary nerve grafting to reconstruct the excised facial nerve or by secondary means of restoration of function or appearance. For cancers of the submandibular salivary gland, wider resection of adjacent soft tissues in the submandibular triangle, including a limited neck dissection, may be necessary to improve local control. Surgery remains the mainstay of initial therapy for malignant tumors of the salivary glands.


Although generous surgical resection with adequate soft-tissue margins remains the fundamental principle in surgical oncology, it may not be feasible in malignant tumors of the parotid gland, where a functioning facial nerve is contiguous to the tumor. Thus close margins and/or microscopically positive margins in the vicinity of the facial nerve are acceptable, because adjuvant radiation therapy offers respectable local control rates. Radiotherapy as definitive treatment is rarely indicated for salivary tumors other than in a palliative setting. On the other hand, it is of great value as adjuvant treatment after surgery for improvement of local and regional control for advanced malignant tumors of the major and minor salivary glands.


Advanced unresectable tumors generally are treated by radiotherapy with a palliative intent. Although treatment with neutrons is considered preferential, no high-level evidence exists to support its superiority over photons. In addition, its long-term sequelae with extensive fibrosis is a major and significant drawback. Currently, interest is increasing in the use of protons to limit irradiation to adjacent vital structures and to deliver an effective target dose. Data on long-term outcomes and sequelae of proton therapy for salivary tumors are not available at this time. In addition, no chemotherapeutic agents with predictable efficacy are available for routine use in the treatment of salivary gland tumors at present. Thus systemic chemotherapy currently is used only in a palliative setting. The role of targeted agents against EGFR, estrogen receptor, and human epidermal growth factor receptor 2/neu–positive salivary gland tumors remains investigational.


Factors Affecting Choice of Treatment


The factors that affect the choice of initial therapy are related to the tumor and the patient. The size of the primary tumor and its histologic grade are vitally important tumor factors that influence choice of initial therapy. Low-grade, low-stage malignant tumors confined to the superficial lobe of the parotid gland are easily treatable with a superficial parotidectomy. Surgery alone in this clinical setting is adequate treatment. On the other hand, high-grade, high-staged tumors may require a total parotidectomy or even an extended radical parotidectomy with or without sacrifice of the facial nerve and with or without neck dissection.


Advanced tumors occasionally may require excision of the auditory canal, the ascending ramus of the mandible, or even temporal bone resection. Sacrifice of the facial nerve leads to significant functional and aesthetic morbidity in all age groups. Therefore facial nerve grafting should be considered when appropriate. If a facial nerve graft is not feasible, then rehabilitative measures for facial nerve paralysis should be instituted. These measures include a lateral tarsorrhaphy, a lateral canthoplasty, and a gold weight implant in the upper eyelid as well as static or dynamic reconstruction of the oral commissure.


Similar principles can be applied to malignant tumors of the submandibular salivary gland and those of minor salivary origin. Loss of the hypoglossal and lingual nerves and the marginal branch of the facial nerve is not as debilitating as the loss of the entire facial nerve. Therefore special rehabilitative measures are seldom indicated for radical operations for submandibular salivary gland tumors.




Surgical Treatment


Surgical Anatomy


The three paired major salivary glands are associated with cranial nerves V, VII, and XII and the peripheral branches of the cervical plexus ( Fig. 13.38 ). Because of the proximity of these nerves, appreciation of surgical anatomy is crucial in salivary gland surgery.




Figure 13.38


The anatomic relationships of the parotid and submandibular salivary glands to adjacent cranial nerves.


The parotid glands lie in the retromandibular fossae posterior to the ascending ramus of the mandible and in the area anteroinferior to the external auditory canal. The parotid gland is a unilobular structure traversed by the extracranial portion of the facial nerve and its branches. The facial nerve divides the gland into superficial and deep portions. Nearly 80% of the parotid gland is lateral to the facial nerve and is called the “superficial lobe.” The remaining portion of the gland lying medial to the facial nerve consists of approximately 20% of parotid tissue and is considered the “deep lobe.” The parotid gland drains its secretions through the Stensen duct, which lies on the lateral surface of the anterior aspect of the masseter muscle, traverses through the buccinator muscle, and opens into the oral cavity on the cheek mucosa at the occlusal dental line adjacent to the second upper premolar tooth.


Three important nerves are related to the parotid gland: the facial nerve, the greater auricular nerve, and the auriculotemporal nerve. The greater auricular nerve lies on the tail of the parotid gland and divides into anterior and posterior branches. It provides sensations to the skin of the face near the tragus and the earlobe. The auriculotemporal nerve is a branch of the mandibular division of the fifth cranial nerve. It contains the parasympathetic fibers to the parotid gland by the otic ganglia. The facial nerve exits from the stylomastoid foramen lateral to the styloid process and is located cephalad to the posterior belly of the digastric muscle and anteroinferior to the external auditory canal, where it enters the substance of the parotid gland. The anatomic landmarks for the main trunk of the facial nerve, which measures anywhere from 5 to 15 mm, are at a point where the tip of the mastoid process, cartilaginous auditory canal, and superior border of the posterior belly of the digastric muscle meet ( Fig. 13.39 ). The main trunk usually branches into the zygomaticotemporal and cervicofacial divisions. Significant anatomic variations in the intraglandular branching of the facial nerve exist, some examples of which are shown in Figs. 13.40 through 13.55 .




Figure 13.39


Anatomic landmarks for intraoperative identification of the facial nerve.



Figure 13.40


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.41


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.42


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.43


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.44


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.45


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.46


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.47


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.48


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.49


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.50


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.51


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.52


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.53


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.54


Anatomic variation in the intraglandular branching of the extracranial facial nerve.



Figure 13.55


Anatomic variation in the intraglandular branching of the extracranial facial nerve.


The anatomic relationship of the deep portion of the parotid gland to other structures in the parapharyngeal space is shown in Fig. 13.56 . Although tumors arising in the deep lobe of the parotid gland are rare, they are the most common neoplasms encountered in the prestyloid compartment of the parapharyngeal space (masticator space). Tumors of the deep lobe of the parotid gland, by definition, arise in parotid tissue lying medial to the facial nerve. They may present in the retromandibular location or in the parapharyngeal location. From a surgical standpoint, it is important to understand the anatomic relationships of structures in the parapharyngeal space with the deep lobe parotid tissue. Salivary tumors in the parapharyngeal space also arise from ectopic salivary tissue and occasionally from minor salivary glands of the lateral pharyngeal wall.




Figure 13.56


The anatomic relationships of the deep lobe of the parotid gland.


The submandibular glands, also called the submaxillary glands, reside in the submandibular space within the digastric triangle and beneath and anterior to the angle of the mandible. They overlie the mylohyoid muscle and extend around its free border in the floor of the mouth along the course of Wharton’s duct. The gland lies on the hyoglossus muscle and is in direct contact with the stylomandibular ligament posteriorly. Three important nerves are in direct contiguity to the gland: the marginal branch of the facial nerve, the hypoglossal nerve, and the lingual nerve ( Fig. 13.57 ). Submandibular glands drain into the anterior floor of the mouth through Wharton’s duct, the papilla of which opens just lateral to the frenulum of the tongue.




Figure 13.57


The anatomic relationships of the submandibular salivary gland. M, muscle; n, nerve.


The smallest of the major salivary glands are the sublingual glands, which are located just beneath the mucous membrane of the floor of the mouth and rest on the mylohyoid muscle ( Fig. 13.58 ). They are poorly encapsulated and drain by way of several small ducts directly into the oral cavity or into the submandibular duct.




Figure 13.58


The anatomic relationships of the sublingual and submandibular salivary glands to the oral cavity.


Preoperative Preparation


All patients undergoing parotid surgery should be counseled about potential transient or permanent loss of facial nerve function. If facial nerve sacrifice is anticipated, then preoperative counseling regarding rehabilitative measures should be discussed with the patient.


Although parotid gland surgery opens salivary ducts into the surgical field, the operation is essentially clean, and use of perioperative antibiotics usually is not necessary. Preoperative preparation for surgical treatment of a malignant tumor of minor salivary origin is essentially the same as it would be for any epithelial lesion in a similar location of the upper aerodigestive tract.


Excision of the Submandibular Salivary Gland for Infection, Calculus, or Tumor


Chronic inflammatory disease occurs more frequently in the submandibular salivary gland than in the parotid gland. Repeated attacks of the inflammatory process eventually may develop into calculus disease, producing chronic intermittent obstruction with painful enlargement of the gland. If the calculus lodged in Wharton’s duct presents in the oral cavity and is easily palpable, then the stone may be extracted intraorally by a direct mucosal incision over Wharton’s duct. This extraction of the calculus preferably should be performed under general anesthesia in the operating room. If this conservative procedure does not resolve the chronic inflammatory process, then it is advisable to proceed with excision of the entire submandibular gland to alleviate the persistent problem.


The patient shown in Fig. 13.59 has a 4-cm enlargement of the right submandibular salivary gland. The mass is firm, discrete, mobile, and somewhat sensitive, although not very tender. No calculi could be palpated in Wharton’s duct by bimanual palpation of the floor of the mouth. The clinical diagnosis of a chronic sialadenitis was entertained based on the patient’s history of fluctuation in the size of this mass, but the possibility of a primary tumor could not be ruled out. Such uncertainty in clinical diagnosis is common.




Figure 13.59


A patient with enlargement of the right submandibular salivary gland. The surface markings indicate the angle of the mandible and the proposed line of incision.


The patient is placed on the operating table under general endotracheal anesthesia. The patient is in a supine position with the neck turned to the opposite side. The palpable mass is outlined in red. The surface marking of the angle of the mandible and the proposed line of incision also are shown in Fig. 13.59 . The skin incision is made on an upper neck skin crease at least two fingerbreadths below the angle of the mandible to protect the mandibular branch of the facial nerve. The surface marking for the mandibular branch of the facial nerve is at a point two fingerbreadths below the angle of the mandible and two fingerbreadths anterior to the angle of the mandible, where it lies over the surface of the submandibular salivary gland. The skin incision is completed, remaining superficial to the platysma ( Fig. 13.60 ). The upper skin flap is elevated first with an electrocautery, remaining superficial to the platysma ( Fig. 13.61 ).




Figure 13.60


The skin incision is made through subcutaneous tissue up to the platysma.



Figure 13.61


The upper skin flap is elevated superficial to the platysma.


The mandibular branch of the facial nerve is now carefully identified, dissected, and protected in the following manner: The platysma is incised with a scalpel in a small area at a point two fingerbreadths below and two fingerbreadths anterior to the angle of the mandible. The remaining platysma along the length of the incision is then divided after blunt dissection underneath with a hemostat, spreading the hemostat open and protecting the underlying soft tissues over the capsule of the submandibular gland. The mandibular branch of the facial nerve rests on this fascia. If the nerve is not located during division of the platysma, a meticulous search is now undertaken so it can be identified.


The mandibular branch and the cervical branch are shown descending down in the neck in Fig. 13.62 . Note also the posterior facial vein running almost parallel to the cervical branch. Both of these structures are divided to facilitate retraction of the mandibular branch cephalad along with the upper skin flap. It is important to note that the posterior facial vein lies deep to the mandibular branch. Thus dividing the posterior facial vein low and retracting its upper stump cephalad will protect the dissected and mobilized mandibular branch of the facial nerve on the upper skin flap.




Figure 13.62


The mandibular and cervical branches of the facial nerve are seen anterior to the facial vein.


In Fig. 13.63 , the upper skin flap is shown retracted with rake retractors, thus protecting the mandibular branch underneath them. With use of an electrocautery, the soft tissues overlying the submandibular salivary gland are now dissected. The anterior belly of the digastric muscle is identified anteriorly in the submental region. During this dissection, small blood vessels overlying the anterior belly of the digastric and the mylohyoid muscles are divided. This procedure enables mobilization of the submandibular gland, which is retracted caudad as shown in Fig. 13.64 , exposing the anterior belly and the tendon of the digastric muscle further. More traction on the gland in the caudad direction exposes the underlying mylohyoid muscle.




Figure 13.63


The gland is now retracted caudad, exposing the anterior belly of the digastric muscle.



Figure 13.64


Further retraction of the submandibular gland exposes the anterior belly and tendon of the digastric muscle.


The nerve and vessels to the mylohyoid muscle located over its surface are individually clamped, divided, and ligated. The facial artery and vein on the posterior aspect of the gland proceeding toward the body of the mandible are dissected next. They are individually clamped, divided, and ligated. Minor branches of the facial nerve crossing this area are carefully protected. Division of the facial vessels permits caudad retraction of the submandibular gland, fully exposing the underlying mylohyoid muscle ( Fig. 13.65 ). A large loop retractor is now used to retract the mylohyoid muscle toward the chin, exposing the underlying lingual nerve and the secretomotor branches to the submandibular gland. The submandibular ganglion and the secretomotor fibers are clamped, divided, and ligated ( Fig. 13.66 ). The remaining attachments of the submandibular gland are Wharton’s duct and the vessels running along with it and the proximal part of the facial artery and vein.




Figure 13.65


The mylohyoid muscle is dissected up to its lateral border.



Figure 13.66


The submandibular ganglion and the secretomotor fibers are clamped, divided, and ligated.


Wharton’s duct is divided as close to the floor of the mouth as possible ( Fig. 13.67 ). The duct is isolated by dissecting the underlying soft tissues with a hemostat. During this dissection, the hypoglossal nerve is seen in a plane deep to Wharton’s duct. It should be carefully protected. Division of Wharton’s duct close to the floor of the mouth is particularly important in operations for chronic inflammatory disease with calculi either in the gland or in the duct. Further caudad traction on the gland exposes the proximal part of the facial artery deep to the posterior belly of the digastric muscle. It is carefully dissected, clamped, and divided. This artery often is accompanied by its vena comitantes, and if these are present, they also are divided and ligated.




Figure 13.67


Wharton’s duct is divided, and its stump is ligated.


Fig. 13.68 shows the surgical field after removal of the specimen. The hemostat is on the stump of the facial artery, which is to be ligated. The hypoglossal nerve is adjacent to the tendon of the digastric muscle overlying the hyoglossus, and the lingual nerve is just cephalad to it, with the stump of the secretomotor fibers ligated. The wound is now irrigated with Bacitracin solution. A Penrose drain is inserted, and the wound is closed in layers ( Fig. 13.69 ).


Sep 29, 2019 | Posted by in HEAD AND NECK SURGERY | Comments Off on Salivary Glands
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