Salivary gland cancer: Treatment - Health Professional Information [NCI PDQ]

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Salivary Gland Cancer Treatment (PDQ®)

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of salivary gland cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.

Information about the following is included in this summary:

  • Prognostic factors.
  • Histology.
  • Clinical presentation and prognosis.
  • Cellular classification.
  • Staging.
  • Treatment options by cancer stage.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

General Information

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Salivary gland tumors are a morphologically and clinically diverse group of neoplasms, which may present significant diagnostic and management challenges. These tumors are rare, with an overall incidence in the Western world of approximately 2.5 cases to 3.0 cases per 100,000 per year.[1] Malignant salivary gland neoplasms account for more than 0.5% of all malignancies and approximately 3% to 5% of all head and neck cancers.[1,2] Most patients with malignant salivary gland tumors are in the sixth or seventh decade of life.[3,4] Although exposure to ionizing radiation has been implicated as a cause of salivary gland cancer, the etiology of most salivary gland cancers cannot be determined.[2,3,5,6] Occupations associated with an increased risk for salivary gland cancers include rubber products manufacturing, asbestos mining, plumbing, and some types of woodworking.[3]

Tumors of the salivary glands comprise those in the major glands (e.g., parotid, submandibular, and sublingual) and the minor glands (e.g., oral mucosa, palate, uvula, floor of mouth, posterior tongue, retromolar area and peritonsillar area, pharynx, larynx, and paranasal sinuses).[2,7] (Refer to the PDQ summaries on Laryngeal Cancer Treatment, Lip and Oral Cavity Cancer Treatment, Nasopharyngeal Cancer Treatment, Hypopharyngeal Cancer Treatment, and Paranasal Sinus and Nasal Cavity Cancer Treatment for more information.) Minor salivary gland lesions are most frequently seen in the oral cavity.[2]

Of salivary gland neoplasms, more than 50% are benign, and approximately 70% to 80% of all salivary gland neoplasms originate in the parotid gland.[1,2,8] The palate is the most common site of minor salivary gland tumors. The frequency of malignant lesions varies by site. Approximately 20% to 25% of parotid tumors, 35% to 40% of submandibular tumors, 50% of palate tumors, and more than 90% of sublingual gland tumors are malignant.[1,9]

Histologically, salivary gland tumors represent the most heterogenous group of tumors of any tissue in the body.[10] Although almost 40 histologic types of epithelial tumors of the salivary glands exist, some are exceedingly rare and may be the subject of only a few case reports.[1,11] The most common benign major and minor salivary gland tumor is the pleomorphic adenoma, which comprises about 50% of all salivary gland tumors and 65% of parotid gland tumors.[1] The most common malignant major and minor salivary gland tumor is the mucoepidermoid carcinoma, which comprises about 10% of all salivary gland neoplasms and approximately 35% of malignant salivary gland neoplasms.[1] [12] This neoplasm occurs most often in the parotid gland.[2,12,13] This type and other histologic types of salivary gland neoplasms are reviewed in detail in the Cellular Classification section.

Most patients with benign tumors of the major or minor salivary glands present with painless swelling of the parotid, submandibular, or the sublingual glands. Neurological signs, such as numbness or weakness caused by nerve involvement, typically indicate a malignancy.[2] Facial nerve weakness that is associated with a parotid or submandibular tumor is an ominous sign. Persistent facial pain is highly suggestive of malignancy; approximately 10% to 15% of malignant parotid neoplasms present with pain.[8,14] The majority of parotid tumors, both benign and malignant, however, present as an asymptomatic mass in the gland.[2,8]

Early stage low-grade malignant salivary gland tumors are usually curable by adequate surgical resection alone. The prognosis is more favorable when the tumor is in a major salivary gland; the parotid gland is most favorable, then the submandibular gland; the least favorable primary sites are the sublingual and minor salivary glands. Large bulky tumors or high-grade tumors carry a poorer prognosis and may best be treated by surgical resection combined with postoperative radiation therapy.[15] The prognosis also depends on the following:[16,17]

  • Gland in which they arise.
  • Histology.
  • Grade (i.e., degree of malignancy).
  • Extent of primary tumor (i.e., the stage).
  • Whether the tumor involves the facial nerve, has fixation to the skin or deep structures, or has spread to lymph nodes or distant sites.

Overall, clinical stage, particularly tumor size, may be the crucial factor to determine the outcome of salivary gland cancer and may be more important than histologic grade.[18]

Perineural invasion can also occur, particularly in high-grade adenoid cystic carcinoma, and should be specifically identified and treated.[19] Radiation therapy may increase the chance of local control and increase the survival of patients when adequate margins cannot be achieved.[20][Level of evidence: 3iiiDi] Unresectable or recurrent tumors may respond to chemotherapy.[21,22,23] Fast neutron-beam radiation therapy or accelerated hyperfractionated photon-beam schedules have been shown to be effective in the treatment of inoperable, unresectable, and recurrent tumors.[24,25,26]

Complications of surgical treatment for parotid neoplasms include facial nerve dysfunction and Frey syndrome also known as gustatory flushing and sweating and the auriculotemporal syndrome.[8] Frey syndrome has been successfully treated with injections of botulinum toxin A.[27,28,29]

References:

  1. Speight PM, Barrett AW: Salivary gland tumours. Oral Dis 8 (5): 229-40, 2002.
  2. Mendenhall WM, Riggs CE Jr, Cassisi NJ: Treatment of head and neck cancers. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 662-732.
  3. Ellis GL, Auclair PL: Tumors of the Salivary Glands. Washington, DC : Armed Forces Institute of Pathology, 1996. Atlas of Tumor Pathology, 3.
  4. Wahlberg P, Anderson H, Biörklund A, et al.: Carcinoma of the parotid and submandibular glands--a study of survival in 2465 patients. Oral Oncol 38 (7): 706-13, 2002.
  5. Scanlon EF, Sener SF: Head and neck neoplasia following irradiation for benign conditions. Head Neck Surg 4 (2): 139-45, 1981 Nov-Dec.
  6. van der Laan BF, Baris G, Gregor RT, et al.: Radiation-induced tumours of the head and neck. J Laryngol Otol 109 (4): 346-9, 1995.
  7. Spiro RH, Thaler HT, Hicks WF, et al.: The importance of clinical staging of minor salivary gland carcinoma. Am J Surg 162 (4): 330-6, 1991.
  8. Gooden E, Witterick IJ, Hacker D, et al.: Parotid gland tumours in 255 consecutive patients: Mount Sinai Hospital's quality assurance review. J Otolaryngol 31 (6): 351-4, 2002.
  9. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986.
  10. Brandwein MS, Ferlito A, Bradley PJ, et al.: Diagnosis and classification of salivary neoplasms: pathologic challenges and relevance to clinical outcomes. Acta Otolaryngol 122 (7): 758-64, 2002.
  11. Seifert G, Sobin LH: Histological Typing of Salivary Gland Tumours. 2nd ed. Berlin, Germany: Springer-Verlag, 1991.
  12. Guzzo M, Andreola S, Sirizzotti G, et al.: Mucoepidermoid carcinoma of the salivary glands: clinicopathologic review of 108 patients treated at the National Cancer Institute of Milan. Ann Surg Oncol 9 (7): 688-95, 2002.
  13. Goode RK, Auclair PL, Ellis GL: Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria. Cancer 82 (7): 1217-24, 1998.
  14. Spiro RH, Huvos AG, Strong EW: Cancer of the parotid gland. A clinicopathologic study of 288 primary cases. Am J Surg 130 (4): 452-9, 1975.
  15. Parsons JT, Mendenhall WM, Stringer SP, et al.: Management of minor salivary gland carcinomas. Int J Radiat Oncol Biol Phys 35 (3): 443-54, 1996.
  16. Vander Poorten VL, Balm AJ, Hilgers FJ, et al.: The development of a prognostic score for patients with parotid carcinoma. Cancer 85 (9): 2057-67, 1999.
  17. Terhaard CH, Lubsen H, Van der Tweel I, et al.: Salivary gland carcinoma: independent prognostic factors for locoregional control, distant metastases, and overall survival: results of the Dutch head and neck oncology cooperative group. Head Neck 26 (8): 681-92; discussion 692-3, 2004.
  18. Spiro RH: Factors affecting survival in salivary gland cancers. In: McGurk M, Renehan AG, eds.: Controversies in the Management of Salivary Gland Disease. Oxford, UK: Oxford University Press, 2001, pp 143-50.
  19. Gormley WB, Sekhar LN, Wright DC, et al.: Management and long-term outcome of adenoid cystic carcinoma with intracranial extension: a neurosurgical perspective. Neurosurgery 38 (6): 1105-12; discussion 1112-3, 1996.
  20. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999.
  21. Borthne A, Kjellevold K, Kaalhus O, et al.: Salivary gland malignant neoplasms: treatment and prognosis. Int J Radiat Oncol Biol Phys 12 (5): 747-54, 1986.
  22. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb.
  23. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996.
  24. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991.
  25. Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992.
  26. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996.
  27. Naumann M, Zellner M, Toyka KV, et al.: Treatment of gustatory sweating with botulinum toxin. Ann Neurol 42 (6): 973-5, 1997.
  28. Arad-Cohen A, Blitzer A: Botulinum toxin treatment for symptomatic Frey's syndrome. Otolaryngol Head Neck Surg 122 (2): 237-40, 2000.
  29. von Lindern JJ, Niederhagen B, Bergé S, et al.: Frey syndrome: treatment with type A botulinum toxin. Cancer 89 (8): 1659-63, 2000.

Cellular Classification

Salivary gland neoplasms are remarkable for their histologic diversity. These neoplasms include benign and malignant tumors of epithelial, mesenchymal, and lymphoid origin. Salivary gland tumors pose a particular challenge to the surgical pathologist primarily because of the complexity of the classification and the rarity of several entities, which may exhibit a broad spectrum of morphologic diversity in individual lesions, thus making differentiating benign from malignant tumors difficult.[1] In some cases, hybrid lesions may be seen.[2] The key guiding principle to establish the malignant nature of a salivary gland tumor is the demonstration of an infiltrative margin.[1]

The following cellular classification scheme draws heavily from a scheme published by the Armed Forces Institute of Pathology (AFIP).[3] Malignant nonepithelial neoplasms are included because these neoplasms comprise a significant proportion of salivary gland neoplasms seen in the clinic. For completeness, malignant secondary tumors are also included.

Where AFIP statistics regarding the incidence, or relative frequency, of particular histopathologies are cited, some bias may exist because of the AFIP methods of case accrual as a pathology reference service. When possible, other sources are cited for incidence data. Notwithstanding the AFIP data, the incidence of a particular histopathology has been found to vary considerably depending upon the study cited. This variability in reporting may be partially caused by the rare incidence of many salivary gland neoplasms.

Epithelial Neoplasms

The clinician should be aware that several benign epithelial salivary gland neoplasms have malignant counterparts, which are shown below:[3]

  • Pleomorphic adenoma (i.e., mixed tumor) (see carcinoma ex pleomorphic adenoma).
  • Warthin tumor, also known as papillary cystadenoma lymphomatosum.
  • Monomorphic adenomas:
    • Basal cell adenoma (see basal cell adenocarcinoma).
    • Canalicular adenoma.
    • Oncocytoma (see oncocytic carcinoma).
    • Sebaceous adenoma.
    • Sebaceous lymphadenoma (see sebaceous lymphadenocarcinoma).
  • Myoepithelioma (see myoepithelial carcinoma).
  • Cystadenoma (see cystadenocarcinoma).
  • Ductal papillomas.
  • Sialoblastoma.

Histologic grading of salivary gland carcinomas is important to determine the proper treatment approach, though it is not an independent indicator of the clinical course and must be considered in the context of the clinical stage. Clinical stage, particularly tumor size, may be the critical factor to determine the outcome of salivary gland cancer and may be more important than histologic grade.[1] For example, stage I intermediate- or high-grade mucoepidermoid carcinomas can be successfully treated, whereas low-grade mucoepidermoid carcinomas that present as stage III disease may have a very aggressive clinical course.[4]

Grading is used primarily for mucoepidermoid carcinomas, adenocarcinomas, not otherwise specified (NOS), adenoid cystic carcinomas, and squamous cell carcinomas.[1,3] Various other salivary gland carcinomas can also be categorized according to histologic grade as follows:[3,5,6,7,8]

LOW GRADE

  • Acinic cell carcinoma.
  • Basal cell adenocarcinoma.
  • Clear cell carcinoma.
  • Cystadenocarcinoma.
  • Epithelial-myoepithelial carcinoma.
  • Mucinous adenocarcinoma.
  • Polymorphous low-grade adenocarcinoma (PLGA).

LOW GRADE, INTERMEDIATE GRADE, AND HIGH GRADE

  • Adenocarcinoma, NOS.
  • Mucoepidermoid carcinoma*.
  • Squamous cell carcinoma.

INTERMEDIATE GRADE AND HIGH GRADE

  • Myoepithelial carcinoma.

HIGH GRADE

  • Anaplastic small cell carcinoma.
  • Carcinosarcoma.
  • Large cell undifferentiated carcinoma.
  • Small cell undifferentiated carcinoma.
  • Salivary duct carcinoma.

*Some investigators consider mucoepidermoid carcinoma to be of only two grades: low grade and high grade.[5]

Salivary gland carcinomas and mixed tumors

  1. Mucoepidermoid carcinoma.
  2. Adenoid cystic carcinoma.
  3. Adenocarcinomas.
    1. Acinic cell carcinoma.
    2. PLGA.
    3. Adenocarcinoma, NOS.
    4. Rare adenocarcinomas.
      1. Basal cell adenocarcinoma.
      2. Clear cell carcinoma.
      3. Cystadenocarcinoma.
      4. Sebaceous adenocarcinoma.
      5. Sebaceous lymphadenocarcinoma.
      6. Oncocytic carcinoma.
      7. Salivary duct carcinoma.
      8. Mucinous adenocarcinoma.
  4. Malignant mixed tumors.
    1. Carcinoma ex pleomorphic adenoma.
    2. Carcinosarcoma.
    3. Metastasizing mixed tumor.
  5. Rare carcinomas.
    1. Primary squamous cell carcinoma.
    2. Epithelial-myoepithelial carcinoma.
    3. Anaplastic small cell carcinoma.
    4. Undifferentiated carcinomas.
      1. Small cell undifferentiated carcinoma.
      2. Large cell undifferentiated carcinoma.
      3. Lymphoepithelial carcinoma.
    5. Myoepithelial carcinoma.
    6. Adenosquamous carcinoma.

Mucoepidermoid carcinoma

Mucoepidermoid carcinoma is a malignant epithelial tumor that is composed of various proportions of mucous, epidermoid (e.g., squamous), intermediate, columnar, and clear cells and often demonstrates prominent cystic growth. It is the most common malignant neoplasm observed in the major and minor salivary glands.[1,9] Mucoepidermoid carcinoma represents 29% to 34% of malignant tumors originating in both major and minor salivary glands.[3,5,10,11] In 2 large retrospective series, 84% to 93% of cases originated in the parotid gland.[12,13] With regard to malignant tumors of the minor salivary glands, mucoepidermoid carcinoma shows a strong predilection for the lower lip.[3,14] In an AFIP review of civilian cases, the mean age of patients was 47 years, with an age range of 8 years to 92 years.[3] Prior exposure to ionizing radiation appears to substantially increase the risk of developing malignant neoplasms of the major salivary glands, particularly mucoepidermoid carcinoma.[3,13]

Most patients are asymptomatic and present with solitary, painless masses. Symptoms include pain, drainage from the ipsilateral ear, dysphagia, trismus, and facial paralysis.[3]

Microscopic grading of mucoepidermoid carcinoma is important to determine the prognosis.[1,12,15] Mucoepidermoid carcinomas are graded as low grade, intermediate grade, and high grade. Grading parameters with point values include the following:

  • Intracystic component (+2).
  • Neural invasion present (+2).
  • Necrosis present (+3).
  • Mitosis (=4 per 10 high-power field [+3]).
  • Anaplasia present (+4).

Total point scores are 0 to 4 for low grade, 5 to 6 for intermediate grade, and 7 to 14 for high grade.

In a retrospective review of 243 cases of mucoepidermoid carcinoma of the major salivary glands, a statistically significant correlation was shown between this point-based grading system and outcome for parotid tumors but not for submandibular tumors.[12] Another retrospective study that used this histologic grading system indicated that tumor grade correlated well with prognosis for mucoepidermoid carcinoma of the major salivary glands, excluding submandibular tumors, and minor salivary glands.[13] A modification of this grading system placed more emphasis on features of tumor invasion.[16] Nonetheless, though tumor grade may be useful, stage appears to be a better indicator of prognosis.[3,16]

Cytogenetically, mucoepidermoid carcinoma is characterized by a t(11;19)(q14–21;p12–13) translocation, which is occasionally the sole cytogenetic alteration.[17,18,19] This translocation creates a novel fusion product, MECT1-MAML2, which disrupts a Notch signaling pathway.[20] Notch signaling plays a key role in the normal development of many tissues and cell types, through diverse effects on cellular differentiation, survival, and/or proliferation, and may be involved in a wide variety of human neoplasms.[21]

Rarely, mucoepidermoid carcinoma may originate within the jaws. This tumor type is known as central mucoepidermoid carcinoma.[3] The mandibular to maxillary predilection is approximately 3:1.[22]

Adenoid cystic carcinoma

Adenoid cystic carcinoma, formerly known as cylindroma, is a slow-growing but aggressive neoplasm with a remarkable capacity for recurrence.[23] Morphologically, three growth patterns have been described: cribriform, or classic pattern; tubular; and solid, or basaloid pattern. The tumors are categorized according to the predominant pattern.[3,23,24,25] The cribriform pattern shows epithelial cell nests that form cylindrical patterns. The lumina of these spaces contain periodic acid-Schiff (PAS)-positive mucopolysaccharide secretions. The tubular pattern reveals tubular structures that are lined by stratified cuboidal epithelium. The solid pattern shows solid groups of cuboidal cells. The cribriform pattern is the most common, and the solid pattern is the least common.[26] Solid adenoid cystic carcinoma is a high-grade lesion with reported recurrence rates of as much as 100% compared with 50% to 80% for the tubular and cribriform variants.[25]

In a review of its case files, the AFIP found adenoid cystic carcinoma to be the fifth most common malignant epithelial tumor of the salivary glands after mucoepidermoid carcinomas; adenocarcinomas, NOS; acinic cell carcinomas; and PLGA.[3] Other series, however, report adenoid cystic carcinoma to be the second most common malignant tumor with an incidence or relative frequency of approximately 20%.[1] In the AFIP data, this neoplasm constitutes approximately 7.5% of all epithelial malignancies and 4% of all benign and malignant epithelial salivary gland tumors. The peak incidence for this tumor is reported to be in the fourth through sixth decades of life.[3]

This neoplasm typically develops as a slow growing swelling in the preauricular or submandibular region. Pain and facial paralysis develop frequently during the course of the disease and are likely related to the associated high incidence of nerve invasion.[3] Regardless of histologic grade, adenoid cystic carcinomas, with their unusually slow biologic growth, tend to have a protracted course and ultimately a poor outcome, with a 10-year survival reported to be less than 50% for all grades.[1,27] These carcinomas typically show frequent recurrences and late distant metastases.[1,28] Clinical stage may be a better prognostic indicator than histologic grade.[28,29] In a retrospective review of 92 cases, a tumor size larger than 4 cm was associated with an unfavorable clinical course in all cases.[30]

Adenocarcinomas

Acinic cell carcinoma

Acinic cell carcinoma, also known as acinic cell adenocarcinoma, is a malignant epithelial neoplasm in which the neoplastic cells express acinar differentiation. By conventional use, the term acinic cell carcinoma is defined by cytologic differentiation towards serous acinar cells, as opposed to mucous acinar cells, whose characteristic feature is cytoplasmic PAS-positive zymogen-type secretory granules.[3] In AFIP data of salivary gland neoplasms, acinic cell carcinoma is the third most common salivary gland epithelial neoplasm after mucoepidermoid carcinoma and adenocarcinoma, NOS.[3] In these data, acinic cell carcinoma comprised 17% of primary malignant salivary gland tumors or about 6% of all salivary gland neoplasms; more than 80% occur in the parotid gland; women were affected more than men; and the mean age was 44 years. Other studies have reported a relative frequency of acinic cell carcinoma from 0% to 19% of malignant salivary gland neoplasms.[3]

Clinically, patients typically present with a slowly enlarging mass in the parotid region. Pain is a symptom in more than 33% of patients. For acinic cell carcinoma, staging is likely a better predictor of outcome than histologic grading.[3] In a retrospective review of 90 cases, poor prognostic features included pain or fixation; gross invasion; and microscopic features of desmoplasia, atypia, or increased mitotic activity. Neither morphologic pattern nor cell composition was a predictive feature.[31]

PLGA

PLGA is a malignant epithelial tumor that is essentially limited to occurrence in minor salivary gland sites and is characterized by bland, uniform nuclear features; diverse but characteristic architecture; infiltrative growth; and perineural infiltration.[3] In a series of 426 minor salivary gland tumors, PLGA represented 11% of all tumors and 26% of those that were malignant.[32] In minor gland sites, PLGA is twice as frequent as adenoid cystic carcinoma, and among all benign and malignant salivary gland neoplasms, only pleomorphic adenoma and mucoepidermoid carcinoma are more common.[3] In the AFIP case files, more than 60% of tumors occurred in the mucosa of either the soft or hard palates, approximately 16% occurred in the buccal mucosa, and 12% occurred in the upper lip. The average age of patients is reported to be 59 years, with 70% of patients between the ages of 50 and 79 years.[3] The female to male ratio is about 2:1, a proportion greater than for malignant salivary gland tumors in general.[3,33]

PLGA typically presents as a firm, nontender swelling involving the mucosa of the hard and soft palates (is often found at their junction), the cheek, or the upper lip. Discomfort, bleeding, telangiectasia, or ulceration of the overlying mucosa may occasionally occur.[3] This salivary gland neoplasm typically runs a moderately indolent course. In a study of 40 cases with long-term follow-up, overall survival was 80% at 25 years.[34] Because of the unpredictable behavior of the tumor, some investigators consider the qualifying term, low grade, to be misleading and instead prefer the term, polymorphous adenocarcinoma.[1]

Adenocarcinoma, not otherwise specified

Adenocarcinoma, NOS, is a salivary gland carcinoma that shows glandular or ductal differentiation but lacks the prominence of any of the morphologic features that characterize the other, more specific carcinoma types. The diagnosis of adenocarcinoma, NOS, is essentially one of exclusion. In an AFIP review of cases, adenocarcinoma, NOS, was second only to mucoepidermoid carcinoma in frequency among malignant salivary gland neoplasms.[3] Other series have reported an incidence of 4% to 10%.[1] In AFIP files, the mean patient age was 58 years.[3] Approximately 40% and 60% of tumors occurred in the major and minor salivary glands, respectively. Among the major salivary gland tumors, 90% occurred in the parotid gland. This tumor is graded in a similar way to extrasalivary lesions according to the degree of differentiation.[1] Tumor grades include low-grade, intermediate-grade, and high-grade categories.[3]

Patients with tumors in the major salivary glands typically present with solitary, painless masses.[35] Two retrospective studies indicate that survival is better for patients with tumors of the oral cavity than for those with tumors of the parotid and submandibular glands.[35] [36] These studies differ regarding the prognostic significance of tumor grade.

Rare adenocarcinomas

BASAL CELL ADENOCARCINOMA, also known as basaloid salivary carcinoma, carcinoma ex monomorphic adenoma, malignant basal cell adenoma, malignant basal cell tumor, and basal cell carcinoma, is an epithelial neoplasm that is cytologically similar to basal cell adenoma but is infiltrative and has a small potential for metastasis.[3] In AFIP case files spanning almost 11 years, basal cell carcinoma comprised 1.6% of all salivary gland neoplasms and 2.9% of salivary gland malignancies.[3] Nearly 90% of tumors occurred in the parotid gland.[3,37] The average age of patients is reported to be 60 years.[3]

Similar to most salivary gland neoplasms, swelling is typically the only sign or symptom experienced.[37] A sudden increase in size may occur in a few patients.[38] Basal cell carcinomas are low-grade carcinomas that are infiltrative, locally destructive, and tend to recur. The carcinomas occasionally metastasize. In a retrospective series that included 29 patients, there were recurrences in 7 patients and metastases in 3 patients.[37] In another retrospective review that included 72 patients, 37% of the patients experienced local recurrences.[38] The overall prognosis for patients with this tumor is good.[37,38]

CLEAR CELL CARCINOMA, also known as clear cell adenocarcinoma, is a very rare malignant epithelial neoplasm composed of a monomorphous population of cells that have optically clear cytoplasm with standard hematoxylin and eosin stains and lack features of other specific neoplasms. Because of inconsistencies in the methods of reporting salivary gland neoplasms, meaningful incidence rates for this tumor are difficult to derive from the literature.[3] Most cases involve the minor salivary glands.[1,3,39,40,41] In the AFIP case files, the mean age of patients is approximately 58 years.[3]

In most patients, swelling is the only symptom. Clear cell adenocarcinoma is a low-grade neoplasm. As of 1996, the AFIP reported that no patient is known to have died as a result of this tumor.[3]

CYSTADENOCARCINOMA—also known as malignant papillary cystadenoma, mucus-producing adenopapillary, or nonepidermoid, carcinoma; low-grade papillary adenocarcinoma of the palate; and papillary adenocarcinoma—is a rare malignant epithelial tumor characterized histologically by prominent cystic and, frequently, papillary growth but lacking features that characterize cystic variants of several more common salivary gland neoplasms. Cystadenocarcinoma is the malignant counterpart of cystadenoma.[3]

In a review that included 57 patients, the AFIP found that men and women are affected equally; the average patient age was approximately 59 years; and approximately 65% of the tumors occurred in the major salivary glands, and primarily in the parotid.[3] Most patients present with a slowly growing asymptomatic mass. Clinically, this neoplasm is rarely associated with pain or facial paralysis. Cystadenocarcinoma is considered to be a low-grade neoplasm.[