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Current Otolaryngology > V. Salivary Glands > Chapter 18. Malignant Diseases of the Salivary Glands >
| General Considerations Malignant salivary gland neoplasms represent 34% of head and neck malignancies and < 0.5% of all cancers diagnosed yearly in the United States, with an incidence of only 12 per 100,000 individuals. Unlike the more common mucosal head and neck cancers, which, in general, are attributed to excessive tobacco and alcohol use, specific carcinogenic factors for malignant salivary gland growths have not been as clearly identified. Viral infections, radiation, environmental exposure, and genetic factors have been hypothesized as causes. Malignant salivary gland tumors are classified by the World Health Organization as carcinomas, nonepithelial tumors, lymphomas, metastatic or secondary tumors, and unclassified tumors (Table 181). | Table 181. World Health Organization Classification of Salivary Gland Malignant Neoplasms.
| | | Carcinomas | | Mucoepidermoid carcinoma | | Adenoid cystic carcinoma | | Acinic cell carcinoma | | Malignant mixed tumor | | Carcinoma in pleomorphic adenoma | | Carcinosarcoma | | Polymorphous low-grade adenocarcinoma (terminal duct adenocarcinoma) | | Epithelial-myoepithelial carcinoma | | Salivary duct carcinoma | | Basal cell carcinoma | | Mucinous adenocarcinoma | | Papillary cystadenocarcinoma | | Adenocarcinoma, not otherwise specified (NOS) | | Clear cell carcinoma | | Sebaceous carcinoma and lymphadenocarcinoma | | Oncocytic carcinoma | | Malignant myoepithelioma (myoepithelial carcinoma) | | Squamous cell carcinoma | | Adenosquamous carcinoma | | Lymphoepithelial carcinoma | | Small cell carcinoma | | Undifferentiated carcinoma | | Other carcinomas | | Tumors | | Sarcoma | | Malignant Lymphomas | | Secondary Tumors | | Melanoma | | Squamous cell carcinoma | | Renal cell carcinoma | | Thyroid carcinoma | | Unclassified Tumors | |
Modified, with permission, from Seifert G, Sobin LH: Histological typing of salivary gland tumours. In: World Health Organization International Histological Classification of Tumours, 2nd ed. New York, Berlin, Heidelberg: Springer-Verlag, 1991. | Only 2025% of parotid gland neoplasms are malignant; approximately 4550% of submandibular gland neoplasms, and > 70% of sublingual and minor salivary gland neoplasms are malignant. However, because 7580% of salivary gland neoplasms are located in the parotid gland, this gland is still the most common salivary gland to be affected with a malignant neoplasm; a ratio of 40:10:1 is cited for malignant tumors of the parotid, submandibular, and sublingual glands, respectively. Table 182 shows the histologic types of malignant salivary gland disease in order of frequency. The disease site also is important for predicting the histology. Mucoepidermoid carcinoma is most common in the parotid gland. Approximately half of malignant submandibular gland neoplasms are adenoid cystic carcinomas. Minor salivary gland malignant neoplasms are most often adenoid cystic carcinomas and adenocarcinomas. Prognosis varies according to histologic type, stage, and primary site. | Table 182. Frequency of Salivary Gland Malignant Neoplasm by Histologic Type.
| | | Histologic Type | Frequency of Occurrence | | Mucoepidermoid carcinoma | 34% | | Adenoid cystic carcinoma | 22% | | Adenocarcinoma | 18% | | Malignant mixed tumor | 13% | | Acinic cell carcinoma | 7% | | Squamous cell carcinoma | 4% | | Other | < 3% | |
Modified, with permission, from Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients . Head Neck Surg 1986;8:177. | | | Anatomy The salivary gland unit is depicted in Figure 181. The acinus is located at the distal end of a salivary unit. It consists of pyramidal saliva-forming cells arranged around a central lumen, with myoepithelial cells interposed between the basal side of these cells and the basement membrane . Acinar cells may be serous, mucinous, or seromucinous, which explains the different chemical compositions of the saliva of each gland. Serous cells predominate in the parotid glands. The submandibular glands have mixed populations of serous and mucinous acinar cells. The sublingual glands have mixed populations of mucinous and seromucinous cells. The minor salivary glands have mostly seromucinous cells. The acinus empties into an intercalated duct, composed of cuboidal cells similarly lined by myoepithelial cells between the basal side and the basal lamina. Intercalated ducts empty into striated ducts composed of columnar cells with fine striations. Lastly, the striated ducts empty into excretory ducts, which are composed of two layers of epithelial cells ranging in shape from cuboidal to squamous. Undifferentiated reserve cells associated with the intercalated ducts differentiate into acinar cells, intercalated duct cells, striated duct cells, and myoepithelial cells. Reserve cells associated with the excretory ducts give rise to excretory duct columnar and squamous cells. Histologically, the salivary glands are arranged into lobules separated by connective tissue septa and encased in a connective tissue capsule ; the salivary unit ducts converge in a treelike fashion into a central draining duct. Salivary gland lobules are made up of the acini, intercalated ducts, and small striated ducts. Larger striated ducts and excretory ducts are located within the connective tissue septa. The major salivary glands are the paired parotid, submandibular, and sublingual glands. In addition, 6001000 minor salivary glands are distributed throughout the rest of the upper aerodigestive tract . The parotid gland is located anteroinferior to the ear, overlying the mandibular ramus and masseter muscle, extending medially between the mandibular ramus and the temporal bone to occupy the parapharyngeal space. The facial nerve travels through the substance of the parotid gland, dividing the gland into superficial and deep lobes , though this distinction is a convenience of surgical dissection and does not reflect an embryologic fusion plane or separate fascial layer. Malignant involvement of the facial nerve can result in facial weakness or paralysis and can provide an avenue for the intracranial extension of tumor. In addition, the facial nerve is at risk for injury during parotid surgery. The lymphatic drainage of the parotid gland is to both intraparotid and periparotid lymph nodes, and locally and regionally to the submandibular and deep jugular chain of nodes (levels I and II). The submandibular glands are located in the submandibular triangle along with lymph nodes and branches of the facial artery and facial vein. The lingual, hypoglossal, and marginal mandibular nerves are all intimately associated with the submandibular gland. As with malignant disorders of the facial nerve and parotid gland, these nerves can be invaded by the cancer, resulting in paresis, paralysis, or numbness, as well as the intracranial extension of tumor. These nerves also are at risk for injury at the time of surgery. Submandibular gland lymphatics drain to the submandibular and deep jugular chain of nodes. The sublingual glands are located deep in the anterior floor of mouth mucosa, adjacent to the submandibular glands. The sublingual gland lymphatics also drain to the submandibular and to the jugular chain of nodes. Most of the minor salivary glands are located in the oral cavity and oropharynx, but minor salivary glands are distributed throughout the upper aerodigestive tract. The lymphatic drainage of the minor salivary glands is according to the lymphatic drainage of the anatomic location. | | Pathogenesis The Reserve Cell Theory (currently favored) of salivary gland neoplasia states that salivary neoplasms arise from reserve (or stem) cells of the salivary duct system. The type of neoplasm depends on the stage of differentiation of the reserve cell at the time at which the neoplastic transformation occurs; it also depends on the type of reserve cell. The intercalated duct reserve cells give rise to adenoid cystic and acinic cell carcinoma. The excretory duct reserve cells give rise to mucoepidermoid, squamous cell, and salivary duct carcinoma. The Multicellular Theory of salivary gland neoplasia states that salivary neoplasms arise from differentiated cells along the salivary gland unit. For example, squamous cell carcinoma arises from the excretory duct epithelium and acinic cell carcinoma arises from the acinar cells. Batsakis JG, Regezi JA, Luna MA et al. Histogenesis of salivary gland neoplasms: a postulate with prognostic implications . J Laryngol Otol. 1989;103:939. (Classic article proposing the Reserve (Stem) Cell Theory of salivary gland histogenesis.) [PMID: 2685148]
| Saku T, Hayashi Y, Takahara O et al. Salivary gland tumors among atomic bomb survivors, 19501987. Cancer. 1997;79(8):1465. (A look at Hiroshima and Nagasaki atomic bomb survivors and salivary gland neoplasms, supporting a role for ionizing radiation in salivary gland tumorigenesis.) [PMID: 9118025]
| | | Staging Table 183 lists the American Joint Committee on Cancer (AJCC) 2002 TNM (tumor, node, metastasis) Staging System used for malignant disorders of the major salivary glands. Malignant diseases of the minor salivary glands are staged according to the staging system for the primary site (oral cavity, pharynx, larynx, nasal cavity, and paranasal sinuses). For the first time, T4 tumors are divided into resectable (T4a) and unresectable (T4b) tumors, and, accordingly , Stage IV is now divided into IVA, IVB, and IVC ( distant metastases present). | Table 183. American Joint Committee on Cancer: T (Tumor), N (Nodes), M (Metastases) Staging for Major Salivary Gland (Parotid, Submandibular, Sublingual) Malignant Neoplasms, 2002 Revision.
| | | Stage | T | N | M | | I | T 1
| N
| M
| | II | T 2
| N
| M
| | III | T 3
| N
| M
| | | T 13
| N 1
| M
| | IVA | T 13
| N 2
| M
| | | T 4a
| N 02
| M
| | IVB | T 4b
| Any N | M
| | | Any T | N 3
| M
| | IVC | Any T | Any N | M 1
| T X
| Primary tumor cannot be assessed | T
| No evidence of primary tumor | T 1
| Tumor  2 cm, no extraparenchymal extension | T 2
| Tumor > 2 cm, 4 cm, no extraparenchymal extension | T 3
| Tumor > 4 cm or extraparenchymal extension (or both) | T 4a
| Tumor invades skin, mandible, ear canal, facial nerve, or any of these structures | T 4b
| Tumor invades skull base or pterygoid plates, or encases carotid artery | | | | N X
| Regional lymph node cannot be assessed | N
| No cervical lymph node metastasis | N 1
| Single ipsilateral lymph node < 3 cm | N 2a
| Single ipsilateral lymph node metastases > 3 cm 6 cm | N 2b
| Multiple ipsilateral lymph node metastases, each 6 cm | N 2c
| Bilateral or contralateral lymph node metastases, each 6 cm | N 3
| Single or multiple lymph node metastases > 6 cm | | | | M X
| Distant metastasis cannot be assessed | M
| No distant metastasis | M 1
| Distant metastasis present | |
Modified, with permission, from Greene FL, Page DL, Fleming ID et al (eds.): American Joint Committee on Cancer: AJCC Cancer Staging Manual, 6th ed. New York, Berlin, Heidelberg: Springer-Verlag, 2002. | American Joint Committee on Cancer. Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, eds. AJCC Cancer Staging Manual, 6th ed. New York, Berlin, Heidelberg: Springer-Verlag, 2002. (The definitive reference for the currently used American Joint Committee on Cancer staging system.)
| | | Clinical Findings Symptoms and Signs Patients with malignant disease of the salivary glands most often present with an incidentally noted mass. Pain, facial nerve palsy (although lingual and hypoglossal nerves can be affected by submandibular and sublingual tumors), and cervical adenopathy portend locally advanced disease and a poor prognosis. In the parotid gland, the superficial lobe refers to the parotid tissue lateral to the facial nerve and encompasses about two thirds of the gland parenchyma; the deep lobe refers to that which is medial, although there is no embryologic fascial plane between these two locations. Parotid gland tumors involving the deep lobe can have parapharyngeal space extension and present as a symptomatic or asymptomatic (usual) oropharyngeal mass with no palpable external abnormality. In the submandibular triangle, it can be difficult to distinguish between a mass in the submandibular gland itself and an enlarged submandibular lymph node. Malignant disease of the minor salivary glands is often submucosal and can be located anywhere throughout the upper aerodigestive tract. Laboratory Findings Fine-needle aspiration (FNA) biopsy of major salivary gland and neck masses is easily performed in the office. For malignant salivary gland neoplasms, FNA is 8090% sensitive. Because the usual recommendation is for surgical removal of a salivary gland with any neoplasm, the cost-effectiveness of routinely performing FNA for salivary neoplasms is a matter of current debate. Imaging Studies Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are both effective modalities for imaging the size and the local and regional extension of malignant salivary gland growths, as well as highlighting potentially malignant cervical nodes. CT and MRI give more detailed information and are therefore preferred to ultrasound , which is also useful in identifying salivary gland masses as well as in distinguishing between solid and cystic masses. Positron emission tomography (PET) scanning is of use in evaluating metastatic or unknown primary site disease. Other nuclear medicine imaging that has been used for the salivary glands includes technetium radioisotope scanning, although this is more useful for benign Warthin tumors. Batsakis JG, Sneige N, El-Naggar AK. Fine-needle aspiration of salivary glands: its utility and tissue effects. Ann Otol Rhinol Laryngol. 1992;101:185. (A look at the use of FNA biopsy in salivary gland neoplasms.) [PMID: 1739267]
| | | Histologic Types The classification of malignant salivary gland neoplasms and the relative incidence by histologic type has been listed in Tables 181 and 182. Malignant salivary gland disorders are further divided into low-grade, intermediate-grade, and high-grade histology based on clinical behavior and prognosis (Table 184). Below are descriptions of the more common histologic types. | Table 184. Grade Classification of Salivary Gland Malignant Neoplasms.
| | | Low Grade | | Low-grade mucoepidermoid carcinoma | | Low-grade adenocarcinoma | | Low-grade squamous cell carcinoma | | Acinic cell carcinoma | | Polymorphous low-grade adenocarcinoma | | Basal cell carcinoma | | Intermediate Grade | | Intermediate-grade mucoepidermoid carcinoma | | Intermediate-grade adenocarcinoma | | Intermediate-grade squamous cell carcinoma | | Adenoid cystic carcinoma | | Epithelial-myoepithelial carcinoma | | Oncocytic carcinoma | | Myoepithelial carcinoma | | Carcinoma in pleomorphic adenoma | | Salivary duct carcinoma | | High Grade | | High-grade mucoepidermoid carcinoma | | High-grade adenocarcinoma | | High-grade squamous cell carcinoma | | Carcinosarcoma | | Undifferentiated carcinoma | |
Reprinted, with permission, from Therkildsen MH, Christensen M, Andersen LJ et al. Salivary gland carcinomas prognostic factors. Acta Oncol 1998;37:701. | Mucoepidermoid Carcinoma Mucoepidermoid carcinoma is the most common type of malignant salivary gland disorder . Eighty to ninety percent of mucoepidermoid carcinoma occurs in the parotid gland. Its prevalence is highest in the fifth decade of life, with a female preponderance as high as 4:1. Histologically, mucoepidermoid carcinomas are characterized by a mixed population of cells: mucin-producing cells, epithelial cells, and intermediate cells (Figure 182). The intermediate cells are believed to be the progenitor of the other two types of cells. No myoepithelial cells are present. Mucoepidermoid carcinomas are classified as low, intermediate, and high grade based on clinical behavior and tumor differentiation. Clinical aggressiveness, local invasion, and lymph node metastases are all greater, and the prognosis is worst for high-grade tumors. Histologically, low-grade mucoepidermoid carcinomas are well circumscribed, with pushing margins and dilated cystic areas containing mucinous material. The cystic structures are lined by mucin-producing, intermediate, or epidermoid cells. As the grade escalates, the tumors become more infiltrative and poorly circumscribed. Cystic formations seen in low-grade tumors are lost. Nests of tumor become more solid and irregular with intermediate or epidermoid cells dominating. High-grade mucoepidermoid carcinomas are characterized by the invasion of adjacent normal structures, atypical mitoses, perineural invasion, and lymph node metastases. High-grade mucoepidermoid carcinoma is distinguished from squamous cell carcinoma by the presence of intracellular mucin. The 5-year survival rate for low-grade mucoepidermoid carcinomas is 70%, whereas for high grade it is only 47%. The 15-year disease-free survival rate is approximately 50% for low-grade mucoepidermoid carcinoma and 25% for intermediate- and high-grade tumors. Adenoid Cystic Carcinoma Ten percent of salivary gland neoplasms are adenoid cystic carcinoma. More than two thirds of them arise from the minor salivary glands. Adenoid cystic carcinoma is the most common type of malignant disorder to arise in the submandibular, the sublingual, and the minor salivary glands. It occurs with equal frequency in men and women and most often presents as an otherwise asymptomatic mass. Adenoid cystic carcinoma is usually partially or nonencapsulated and infiltrates the surrounding normal tissue. There is basaloid epithelium clustered in nests in a hyaline stroma. The most common histologic subtype (44%) is the cribriform type, characterized by a "Swiss cheese" pattern of vacuolated areas (Figure 183A). The prognosis for the cribriform subtype is intermediate. The tubular subtype (35%) carries the best prognosis and is characterized by cords and nests of malignant cells (Figure 183B). The solid subtype (21%) has the worst prognosis and is characterized by solid sheets of adenoid malignant cells (Figure 183C). Adenoid cystic carcinomas are unique among salivary gland tumors because of their indolent and protracted clinical course. Perineural spread, including "skip lesions" or discontinuous areas of spread along a nerve, occurs commonly (up to 80% of cases). For this reason, adjuvant radiation that includes the anatomic course of the regional named nerves is often recommended. Lymphatic spread is uncommon, and consequently neck dissection or wide-field radiation to regional lymphatics is rarely recommended. Distant metastases can occur up to 20 years after the initial diagnosis; disease-specific survival continues to decline for more than 20 years after the initial treatment. Prognostic factors for adenoid cystic carcinoma include site of origin, TNM staging, local spread, nodal status, distant metastasis, and recurrence . The survival rate among patients with adenoid cystic carcinomas arising from the parotid gland is higher than that for patients with similar tumors arising from the minor salivary glands. Acinic Cell Carcinoma Acinic cell carcinoma represents 15% of malignant parotid gland neoplasms. Eighty to ninety percent occur in the parotid gland, and most of the remaining occur in the submandibular gland. Acinic cell carcinoma occurs most often in the fifth decade of life and in women more often than in men. Acinic cell carcinomas are typically encased in a fibrous capsule. Histologically, there are two cell types: (1) serous acinar cells (explaining the predilection for the parotid gland) and (2) cells with clear cytoplasm (Figure 184). There are four histologic patterns: solid, microcystic, papillary, and follicular. Acinic cell carcinomas are low-grade malignancies. The overall survival rate at 5, 10, and 15 years is 78%, 63%, and 44%, respectively. Malignant Mixed Tumors Malignant mixed tumors represent 312% of malignant salivary gland disorders. They arise in benign mixed tumors (pleomorphic adenomas). Microscopically, there may be one small malignant growth within a benign mixed tumor, or the benign tumor may be essentially replaced by the malignant lesion with destructive infiltrative growth. Carcinoma ex-pleomorphic adenoma is the most common malignant mixed tumor variant (Figure 185A); 75% occur in the parotid gland. Histologically, there is a mixture of epithelial and mesenchymal cells, but the distinguishing feature is that the malignant component is purely epithelial. The malignant part may have features of an adenocarcinoma, a squamous cell carcinoma, an undifferentiated carcinoma, or some other form of a malignant epithelial disorder. Carcinoma ex-pleomorphic adenomas are nodular or cystic with minimal encapsulation. Unlike pleomorphic adenomas, they typically have areas of necrosis and hemorrhage. A true malignant mixed tumor, also called carcinosarcoma, is very rare (Figure 185B). It has epithelial and mesenchymal malignant elements in both the primary site and in nodal metastases. Malignant mixed tumors are classified as high grade. If treated before they become invasive, the prognosis is good. However, invasion and locoregional and distant metastases are common. Surgery with adjuvant radiation is the preferred treatment. Nonetheless, the 5-year survival rate is < 10%. Adenocarcinoma Adenocarcinomas of the major salivary glands originate from excretory or striated ducts. In its most differentiated form, the glandular cytoarchitecture is maintained . The growth pattern can be solid or cystic, papillary or nonpapillary, with or without mucin production, and can range from low grade to high grade in histology and clinical course. With newer refinements in special staining and classification systems, many malignant disorders formerly categorized as adenocarcinomas have defined their own categories, including polymorphous low-grade adenocarcinoma, epithelial-myoepithelial carcinoma, and salivary duct carcinoma. Adenocarcinomas of the salivary glands not fitting into one of the more specific classifications are called adenocarcinoma NOS (not otherwise specified). Clinically, poor prognostic indicators for adenocarcinomas include advanced stage, infiltrative growth pattern, and abnormal DNA content. Polymorphous Low-Grade Adenocarcinoma Polymorphous low-grade adenocarcinoma is also termed terminal duct carcinoma or lobular carcinoma and is the second most common malignant disorder of the minor salivary glands. Fifty percent of polymorphous low-grade adenocarcinomas occur in the palate. Women are affected more often than men, typically in the sixth decade. Polymorphous low-grade adenocarcinoma most often presents as a painless, submucosal mass. There is cytologic uniformity of myoepithelial or luminal ductal cells within one tumor, but histologic diversity of the cells between tumors (Figure 186). Patterns of growth include tubular, papillary, glandular, and solid. Despite infiltrative growth and perineural invasion, the clinical course is typically indolent, with < 10% having lymph node metastases. Epithelial-Myoepithelial Cell Carcinoma Epithelial-myoepithelial cell carcinoma represents only 1% of salivary gland neoplasms. Most occur in the parotid gland. Histologically, there are malignant epithelial (ductal) cells and also malignant myoepithelial cells (Figure 187). Cribriform, tubular, or solid patterns can be formed . Forty percent of patients experience local recurrence, 20% experience cervical metastases, and 40% die of disease. Salivary Duct Adenocarcinoma Salivary duct adenocarcinoma is named for its histologic resemblance to intraductal carcinoma of the breast (Figure 188). Unlike intraductal carcinoma of the breast , this disease occurs in men three times more frequently than in women. This malignant disorder arises from the excretory duct reserve cells and is a high-grade malignant disease process with a dismal prognosis. Thirty-five percent of patients have local recurrence; 62% develop distant metastases; 77% die of disease, with a mean survival of 3 years. Clear Cell Carcinoma Clear cell carcinomas arise in the minor salivary glands, usually in the oral cavity. Histopathologically, trabeculae, cords, and nests of monomorphic clear cells are seen. They are glycogen-rich, but mucin-negative. This is a low-grade tumor. Squamous Cell Carcinoma Squamous cell carcinoma (SCC) of the salivary gland is rare (Figure 189). Debate exists as to whether or not true primary SCC of the salivary glands exists. High-grade mucoepidermoid carcinoma must be excluded. The distinction is made with special immunohistochemical staining for mucin, which is positive in mucoepidermoid carcinoma but not in SCC. Metastases to the parotid gland or the direct extension of SCC from the overlying skin must also be considered . Most SCCs of the salivary glands present in advanced stage and > 50% of the time have nodal metastases at diagnosis. Lymphoma Salivary gland lymphoma arises from intraglandular lymph nodes or from extranodal lymphoid tissue within the salivary glands. Patients are typically in their sixth or seventh decade. Ninety percent occur in the parotid gland. Five percent of extranodal lymphomas affect the salivary glands. The majority of salivary gland lymphomas are of B-cell lineage. Upon the diagnosis of a salivary gland lymphoma, a full-body evaluation for other involved sites is performed, as with a new diagnosis of lymphoma anywhere else in the body. There is an association between Sjgren's disease and salivary gland lymphoma, with the risk of developing a salivary gland lymphoma being 44 times higher in patients with Sjgren's disease than in the general population. The prognosis for a lymphoma associated with Sjgren's disease is worse than for salivary gland lymphoma not associated with this disease. Some salivary gland lymphomas are immunohistochemically indistinguishable from low-grade lymphomas of the mucosa-associated lymphoid tissue (MALT) and are therefore termed salivary gland MALT lymphomas. Like the gastrointestinal tract MALT lymphomas, salivary gland MALT lymphoma is an indolent disease and affected patients have a long survival. Metastases to the Salivary Glands Less than 10% of malignant salivary gland disorders are metastases from other sites. Most are lymphatic metastases to the parotid gland from skin cancers of the face, ear, or scalp. These are evenly divided between SCC and melanoma; the likelihood of metastasis depends on the stage/depth of the primary lesion. Hematogenous metastases to the salivary glands are rare, but have been reported from lung, kidney, breast, and thyroid cancers. The contiguous extension of cutaneous malignant disorders, as well as those of sarcomas arising from the facial soft tissues, is another mechanism for secondary malignant involvement of the salivary glands. Malignant Salivary Gland Neoplasms in Children Mucoepidermoid carcinoma is the most common malignant salivary gland neoplasm in children, followed by acinic cell carcinoma. Eighty-five percent of malignant salivary gland disorders in children occur in the parotid gland. Khafif A et al. Adenoid cystic carcinoma of the salivary glands: a 20-year review with long- term follow-up. Ear Nose Throat J. 2005;84(10):662,664. (Review of an institution's experience and analysis of prognostic indicators in patients with adenoid cystic carcinoma.) [PMID: 16382750]
| Seifert G, Sobin LH. Histological typing of salivary gland tumours. In: The World Health Organization Histological Classification of Tumours. 2nd ed. New York, Berlin, Heidelberg: Springer-Verlag, 1991. (The WHO classification of salivary gland neoplasms.)
| Westra WH. The surgical pathology of salivary gland neoplasms. Otolaryngol Clin North Am. 1999;32(5):919. (Review of the cellular and morphologic features of the most common salivary gland neoplasms.) [PMID: 10477796]
| | | Treatment Surgical Measures Surgery with the complete removal of the tumor, including a cuff of histologically normal tissue for adequate margins, is the mainstay of treatment for both major and minor salivary gland malignancies. Surgery for Major Salivary Gland Malignant Neoplasms For malignant parotid gland tumors, a total parotidectomy (or an extended parotidectomy if the tumor extends into surrounding structures) is recommended. The facial nerve is sacrificed if it is directly involved with the tumor (ie, encased in the tumor, unable to be dissected from tumor, paretic, or paralyzed preoperatively). In patients whose facial nerve is intact but the margins of resection are close to the nerve, postoperative adjuvant radiation should be considered because it has been shown to significantly improve local control. The typical surgical approach is through a Blair or modified Blair-type incision. For malignant disorders of the parotid gland with parapharyngeal space extension, surgery must include parapharyngeal space (or infratemporal fossa) dissection, sometimes requiring a submandibular or even a mandibulotomy-mandibulectomy approach. A lateral temporal bone resection may be required as well if the ear canal is involved. For malignant disease of the submandibular and sublingual glands, formal supraomohyoid neck dissection is preferred over a simple gland excision . As with the facial nerve in parotidectomy, the lingual, hypoglossal, and marginal mandibular nerves are preserved unless there is evidence either preoperatively or intraoperatively of their direct involvement by the tumor. Surgery for Minor Salivary Gland Malignant Neoplasms For malignant growths of the minor salivary glands, wide local excision is recommended. This approach may be extensive, even including a skull base resection, depending on the location, size, and extension of the tumor. Tumors involving the maxillary sinus and nasal cavity may require partial or total maxillectomy. If the ethmoid is involved with extra-sinus extension, craniofacial resection, orbital exenteration, or both may be required for more extensive tumors. A transoral or combined transoral-transcervical approach is used for malignant neoplasms of the minor salivary glands that affect the oral cavity and oropharynx. A partial or total laryngectomy or even tracheal resection is required for minor salivary gland tumors involving the larynx or trachea. Neck Dissection Neck dissection is the recommended treatment of the neck for malignant salivary gland tumors (1) with clinically apparent cervical adenopathy (14% of cases); (2) for tumors > 4 cm (in which the risk of occult metastases is > 20%); or (3) for a high-grade histology (in which the risk of occult metastases is > 40%) (Table 185). Elective neck dissection for adenoid cystic carcinoma generally is not recommended, because the risk of occult nodal metastasis is low. | Table 185. Incidence of Occult Lymph Node Involvement for Salivary Gland Malignant Neoplasms.
| | | Salivary Gland Neoplasm | Incidence | | Squamous cell carcinoma | 40% | | Adenocarcinoma | 18% | | Mucoepidermoid carcinoma | 14% | | Acinic cell carcinoma | 4% | | Adenoid cystic carcinoma | 4% | | Tumor < 4 cm | 4% | | Tumor > 4 cm | > 20% | |
| Nonsurgical Measures Radiation Therapy Both conventional and neutron-beam radiation therapy have been advocated as single-modality treatments for T1 and T2 malignant salivary gland neoplasms. This approach is controversial , but may be considered if there are real contraindications to surgery. Adjuvant radiation to the tumor resection bed improves local control for (1) T3 and T4 tumors; (2) tumors of high-grade histology (see Table 184); (3) positive nodes or perilymphatic invasion; (4) facial or other perineural involvement; (5) a close or positive surgical margin; (6) bone, cartilage, or muscle invasion; or (7) recurrent disease. The standard radiation therapy used is a unilateral mixed electron and photon technique. Postoperative radiation to the neck is recommended, as above, for major and certain minor salivary gland primary sites when there are positive neck nodes. Radiation is an acceptable alternative for a node-negative (ie, N0) neck with aggressive features (see indications for neck dissection). For minor salivary gland tumors, elective radiation of the N0 neck is advocated only for primary tumors of the tongue, floor of mouth, pharynx, and larynx. Conventional radiation has been shown to have prohibitively poor local control rates for inoperable disease. Neutron-beam radiation has been shown to be more effective than conventional radiation against malignant salivary gland disorders; it results in a higher degree of tumor destruction with fewer toxic effects to surrounding normal tissues. In particular, neutron-beam radiation protocols have been more successful than conventional radiation in treating adenoid cystic carcinoma. Neutron-beam therapy can achieve excellent locoregional control, higher than mixed beam and photons in advanced, recurrent, as well as incompletely resected salivary neoplasms. It is also the preferred treatment for inoperable disease. Fast neutron therapy is not widely available. Chemotherapy The role for chemotherapy in the treatment of malignant salivary gland disorders is limited to the palliative setting, such as in advanced-stage or metastatic disease not amenable to local therapies including surgery and/or radiation. Partial or complete responses have been achieved in up to 50% of patients, which typically last 58 months and may include significant pain control. Most of these patients have adenoid cystic carcinoma, mucoepidermoid carcinoma, or high-grade adenocarcinoma. Currently, paclitaxel is the agent used most frequently. Although chemotherapy alone does not improve survival rates, the integration of radiation and chemotherapy has been shown to increase local control and represents an improvement in the management of salivary gland malignancies. Treatment of Recurrence Recurrent, malignant salivary gland tumors are treated with the same guidelines as for primary disease. Neutron-beam radiation can, in selected cases, be used when previous external beam radiation has already been administered. Complications of Treatment The complications of the treatment of salivary gland tumors include complications of surgery and those of radiation therapy. Complications Related to Surgery Facial nerve (or other nerve) paralysis, hematoma, salivary fistula or sialocele, Frey syndrome, and cosmetic deformity are among the surgical complications. Complications Related to Radiation Therapy Complications of radiation include acute mucositis, trismus and fibrosis, osteoradionecrosis, and impairment of vision. Since most radiation protocols for malignant salivary gland neoplasms involve unilateral treatment, xerostomia occurs less often than in the treatment of other upper aerodigestive tract tumors. Cortesina G, Airoldi M, Palonta F. Current role of chemotherapy in exclusive and integrated treatment of malignant tumours of salivary glands. Acta Otorhinolaryngol Ital. 2005;25(3):179. (A look at the role of chemotherapy in the treatment of salivary gland malignancies.) [PMID: 16450774]
| Douglas JG et al. Treatment of salivary gland neoplasms with fast neutron radiotherapy. Arch Otolaryngol Head Neck Surg. 2003;129 (9):944. (The University of Washington experience with and their evaluation of the efficacy of neutron-beam radiotherapy for adenoid cystic carcinoma.) [PMID: 12975266]
| Huber PE et al. Radiotherapy for advanced adenoid cystic carcinoma: neutrons, photons or mixed beam? Radiother Oncol. 2001;59(2):161. (Comparison of the different radiotherapeutic treatments of advanced adenoid cystic carcinomas.) [PMID: 11325445]
| Laurie SA, Licitra L. Systemic therapy in the palliative management of advanced salivary gland cancers. J Clin Oncol. 2006;24 (17):2673. (Review of the role of chemotherapy in advanced salivary gland malignancy of different histologies.) [PMID: 16763282]
| Prott FJ, Micke O, Haverkamp U et al. Results of fast neutron therapy of adenoid cystic carcinoma of the salivary glands. Anticancer Res. 2000;20(5C):3743. (The University of Munster experience with neutron-beam radiotherapy and adenoid cystic carcinoma.) [PMID: 11268448]
| Spiro JD, Spiro RH. Cancer of the parotid gland: role of 7th nerve preservation. World J Surg. 2003; 27(7):863. (A look at the management of the facial nerve in surgeries for parotid malignancies.) [PMID: 14509520]
| Spiro RH. Management of malignant tumors of the salivary glands. Oncol. 1998;12(5):671. (Review of treatment guidelines for malignant neoplasms of the salivary glands.) [PMID: 9597678]
| | | Prognosis The indicators of a poor prognosis for malignant salivary gland tumors include pain, facial or other nerve involvement, high-grade histology, the invasion of skin and other surrounding tissues, the presence of cervical or distant metastases, and recurrent disease. For major salivary gland tumors, distant metastases occur most often in adenoid cystic carcinoma and undifferentiated carcinoma. The lungs, liver, bone, and brain are the most common sites. Survival varies greatly with both histologic type and the initial stage. For example, malignant mixed tumors with distant metastases portend a very poor patient survival; whereas survival of more than 10 years has been reported for adenoid cystic carcinoma with distant metastases. For this reason, treatment of the primary adenoid cystic tumor and its metastatic sites is warranted. Figure 1810 shows survival curves, subdivided by histologic type, for major and minor salivary gland tumors. Carinci F, Farina A, Pelucchi S et al. Parotid gland carcinoma: 1987 and 1997 UICC T classifications compared for prognostic accuracy at 5 years. Eur Arch Otorhinolaryngol. 2001;258(3):150. (The 1997 T-staging found to be of greater prognostic value than the earlier 1987 T-staging system for malignant parotid lesions.) [PMID: 11374257]
| Regis de Brito Santos I, Kowalski LP, Cavalcante de Araujo V et al. Multivariate analysis of risk factors for neck metastases in surgically treated parotid carcinomas. Arch Otolaryngol Head Neck Surg. 2001;127(1):56. (Identified risk factors for neck metastasis in parotid carcinoma include histologic type and T stage.) [PMID: 11177015]
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