From: Cancer: Principles & Practice of Oncology, 6th Editions
Vincent T. DeVita, Jr., MD, Samuel Hellman, MD, Steven A. Rosenberg, MD, PhD
January 2001
Chapter 30.4: Tumors of the Salivary Glands and Paragangliomas
Roy B. Sessions, Louis B. Harrison, Arlene A. Forastiere
Major Salivary Gland Tumors
Section on: Natural History, Behavior Staging, and Treatment Principles

Natural History, Behavior Staging, and Treatment Principles
Malignant tumors of major salivary gland origin are a heterogeneous group of diseases; three primary sites and at least eight different histologic patterns have been identified for this relatively uncommon group of cancers. Studies reporting treatment results have, therefore, often grouped primary sites and histologic types. This method is flawed, however, and because the problem often has been compounded by analyzing short-term results in diseases that often have a long natural history, many questions remain unanswered.

Most patients with benign tumors, whether in minor or major salivary glands, present with asymptomatic swelling of the lip or the parotid, submandibular, or sublingual glands (floor of the mouth). Neurologic signs, such as mucosal or tongue numbness, associated with a floor of mouth mass usually indicate a malignancy. In the presence of a lip mass, a numb lower lip can result from tumor involvement of the submental nerve. Facial nerve weakness that is associated with a parotid or submandibular tumor is an ominous finding. Even in huge tumors of the parotid gland that are benign, the facial nerve usually is not affected. Essentially, any compromise in nerve function greatly heightens concern for malignancy. Overall, malignant parotid gland tumors are associated with facial nerve paralysis in 10% to 20% of patients.40 Although benign tumors occasionally cause facial discomfort, persistent facial pain is strongly suggestive of malignancy in a salivary gland tumor; in fact, approximately 10% to 15% of patients with malignant parotid neoplasms present with pain.29 Furthermore, those malignancies that are characterized by pain seem to have a worse prognosis.

The majority of parotid tumors, whether benign or malignant, present with an asymptomatic mass in the gland; in fact, this is the case even in the majority of malignant tumors.

The most common benign tumor, the pleomorphic adenoma, can be problematic. Usually a pseudocapsule is found around this lesion, and, importantly, finger-like projections of tumor penetrate into the surrounding glandular parenchyma, whether it is parotid or submandibular. Enucleation of these lesions tends to leave behind foci of tumor that result in frequent local recurrence. It should be remembered that benign mixed tumor, although not classified as malignant, can ultimately cause great hardship for a patient. Multiple recurrences, skull base involvement, facial nerve paralysis, malignant transformation and, ultimately, incurable disease can all result from a casual initial approach to this neoplasm. This tumor should be regarded as locally dangerous, and any operation should provide a wide margin of normal tissue.

Special problems exist with tumors of the parotid deep lobe, because they are frequently surrounded by little or no glandular parenchyma; thus, even the best of operations consists largely of tumor enucleation. In this circumstance, the probability is high for leaving behind histologic disease, and postoperative radiation therapy must be considered.

Malignant tumors of the parotid can be locally aggressive, demonstrating invasiveness that leads to involvement of the facial nerve, skin, bone, and surrounding soft tissue. Prognosis is related to tumor size and stage and is affected by histologic grade. Decreasing survival occurs for many years, especially in patients with adenoid cystic carcinoma and malignant mixed tumor, and in those lesions, distant metastasis may not always represent a terminal event. The treatment of primary disease, therefore, is not necessarily precluded by lung metastasis, especially in adenoid cystic carcinoma.

Overall, the prognosis for parotid gland cancer is better than it is for the submandibular gland lesions: 50% to 81% 5-year survival is reported for the former and 30% to 50% for the latter29,41; the 10-year survival rate declines in both sites. The lower survival rate for the submandibular gland group probably relates to the larger proportion of adenoid cystic carcinomas in that group. Spiro and colleagues42 reported survival results in 474 patients with major salivary gland tumors treated at the Memorial Sloan-Kettering Cancer Center from 1944 to 1986. The 5-, 10-, and 15-year survival rates were 54%, 43%, and 34%, respectively, with determinate survivals of 63%, 47%, and 42%, respectively. Multivariate analysis showed that advanced stage, higher histologic grade, and submandibular location were prognostic for a poorer outcome. In addition, treatment after 1966 was found to be an important prognostic factor and was thought to relate to an increased use of postoperative radiation therapy beginning during this latter period.

Differences in histologic features affect natural history. The prognosis for acinic cell carcinoma is the most favorable for the major salivary cancers; more than 75% 5-year and more than 65% 10-year survivals are reported in various series.26,37 Low-grade mucoepidermoid carcinomas show 76% to 95% 5-year survival rates, whereas only 30% to 50% of those with high-grade tumors are alive at 5 years.26,32 The survival rates for intermediate-grade mucoepidermoids are between those of the low and high grades. Adenoid cystic carcinoma, on the other hand, must be analyzed with the realization that 5-year survival rates are always better than 10-year figures, which in turn are better than those at 15 years, and so on. Most series show 50% to 90% 5-year survival rates, 30% to 67% 10-year survival rates, and 25% 15-year survival rates for treated adenoid cystic carcinoma.38,39,41,43 Patients with adenocarcinomas of major salivary glands show gradual deterioration of survival statistics with the passage of time; 76% to 85% survival at 5 years and 34% to 71% at 10 years.31 Patients with malignant mixed tumors do not do well; only 31% to 65% survive 5 years and 23% to 30% survive 10 years.6,41

Distant metastasis is predictive of a poor prognosis, and it occurs in approximately 20% of parotid malignancies.44 Distant metastasis is a significant concern in most higher-grade salivary gland malignancies. At least 40% of patients with adenoid cystic carcinoma and 26% to 32% with malignant mixed tumors demonstrate this feature.38 Even with lower-grade tumors, such as acinic cell carcinoma, a measurable incidence of distant metastasis is found.9,26 In all of these lesions, the site of distant metastasis is most often the lung(s). Overall, the likelihood of metastasis from the submandibular gland is almost twice that from the parotid gland.22

Regional lymphatic metastasis is a subject of considerable importance in relation to malignant salivary gland tumors. In the extensive series reported from Memorial Sloan-Kettering Cancer Center, 14% of patients presented with palpable nodal metastases. Thirty-four percent of the patients with high-grade tumors demonstrated this finding, compared to only 2% of patients with low-grade lesions. Additionally, in the group of patients who had clinically negative necks but underwent elective neck dissections, 49% of the high-grade and 7% of the low-grade tumors turned out to have histologically positive necks.45,46 These statistically significant figures suggest that the rates of occult and clinically positive node disease are increased with high-grade malignant salivary gland tumors.

With submandibular gland malignancies, as with parotid tumors, prognosis is dependent on a number of factors, the most significant of which seem to be clinical stage and perineural invasion.47,48

Spiro and associates believed that the most important prognosticator for survival is tumor stage. Accordingly, in 1975, they proposed a staging system that was later incorporated into the current American Joint Committee on Cancer staging system.29,49 This system addresses the size of the primary lesion and the presence or absence of fixation or facial nerve dysfunction. It was first applied only to parotid sites but seems to serve all salivary sites. Table 30.4-4 describes the American Joint Committee on Cancer staging system. According to Spiro,22 cumulative survival exceeds 90% at 10 years for patients with stage I or II disease, whereas only 22% of stage III or IV patients are alive after 10 years.

Table 30.4-4: Staging System for Major Salivary Gland Malignancies

(Adapted from American Joint Committee on Cancer. Cancer staging manual, 5th ed. Philadelphia: Lippincott–Raven, 1997, with permission.)

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