Salivary gland tumors pose a special challenge to clinicians because of their infrequency and remarkable variation in presentation and behavior. The current incidence of malignant salivary tumors in the United States is less than 10 cases per million people. This means that approximately 2,500 new cases are diagnosed each year and that salivary gland neoplasms account for about 7% of all epithelial cancers arising in the upper aerodigestive tract.
In our hospital, 1% of all admissions and 6% to 7% of patients treated on the head and neck service have salivary gland tumors, 70% of which arise in the parotid gland. The submandibular gland is the site of origin in 8% of patients, and the sublingual gland, the most uncommon of the three paired, or major, salivary tumor sites, accounts for only 0.05% of salivary tumors. About 22% of salivary gland tumors originate in the so-called minor salivary glands, the tiny, predominantly mucus-secreting glands that are found everywhere beneath the mucous membranes of the upper aerodigestive tract but are most densely clustered in the palate.[1]
The probability of a malignant diagnosis is less than 25% in patients with parotid gland tumors, about 50% in those with submandibular gland primaries, more than 80% in those with minor salivary lesions, and virtually 100% in those few who present with sublingual gland lesions. It is important to remember that statistics on the distribution of salivary gland tumors and the proportion that are malignant usually derive from the tumor registries of large tertiary care centers, where there is obvious referral bias. In the community hospital setting, virtually all of the salivary gland tumors encountered originate in the parotid and the incidence of malignant tumors is usually lower.
Clinical Presentation
Salivary gland tumors can occur at any age, and incidence does not differ significantly by gender. In our experience, patients with benign lesions tend to be younger than those with carcinomas (median age, 46 vs 54 years). Moreover, low-grade, less aggressive malignant tumors are the rule for younger patients, whereas older patients more often have high-grade or anaplastic tumor types.
Whether these tumors arise in the major salivary glands or the minor glands in the oral cavity or oropharynx, the typical presenting feature is asymptomatic swelling. The fact that swelling may have been present for several years is no assurance of a benign diagnosis. Conversely, pain or rapid growth often, but not invariably, indicates that the tumor is malignant. Patients with a tumor arising in the nasal cavity, paranasal sinuses, hypopharynx, or larynx develop symptoms identical to those described for squamous cell carcinomas occurring in the same sites.
Small, asymptomatic parotid or submandibular gland tumors are clinically indistinguishable from their benign counterparts. Conversely, facial nerve palsy, cervical node enlargement, and skin adherence, in the absence of prior treatment, are virtually certain indicators that a tumor is malignant and usually advanced.
About 10% of parotid tumors arise below the plane of the facial nerve in the so-called deep “lobe.” This is never obvious clinically unless swelling of the palate or tonsil indicates the presence of a retromandibular component. Another unusual source of “parotid” tumors (1%) involves the nubbin of accessory tissue adjacent to Stensen’s duct at the anterior margin of the gland. In our experience, the incidence of malignant salivary tumors at either of these sites is similar to that noted in the rest of the gland.[2,3]
Minor salivary gland tumors typically present as a nodule or mass beneath an intact mucous membrane. As with major salivary gland tumors, small benign minor gland tumors have a similar appearance as their malignant counterparts. When ulceration is present, either related to biopsy, denture irritation, or other trauma, these lesions may be confused with squamous cell carcinomas.
Classification
The histologic classification system now used by most centers is basically a modification of that proposed more than 40 years ago in the classic paper by Foote and Frazell (Table 1).[4] In 1978, Batsakis and Regezi proposed a more detailed classification of epithelial salivary gland tumors that incorporated newer concepts of histogenesis, with emphasis on the role of the myoepithelial cell (Table 2).[5] The second edition of the World Health Organization’s histologic classification of salivary gland tumors, published in 1992, proposed an even more complex histologic breakdown (Table 3).[6]
Although unique subtypes of malignant tumors are better defined in this newest classification, overall it is rather unwieldy. What emerges from all this refinement is the reality that detailed subclassification may be exciting to pathologists but is confusing to clinicians.
In our experience, more than 80% of benign tumors are pleomorphic adenomas. This is the histology most often encountered in the submandibular gland, as well as the parotid gland. In patients with malignant neoplasms, mucoepidermoid carcinoma is the most frequent diagnosis (34%), followed by adenoid cystic carcinoma (22%), adenocarcinoma (18%), and malignant mixed tumor (13%). Less frequently diagnosed malignant salivary neoplasms include acinic cell carcinoma (7%), epidermoid carcinoma (4%), and other anaplastic variants (3%).
There is an interesting correlation between the histologic diagnosis and the site of origin. About 40% of minor salivary gland tumors in our patients involve the palate, by far the most common site; this is also where almost all of the relatively few benign minor salivary tumors in our patients originate. Aside from a few other patients with benign tumors in the lips or nasal cavity, minor salivary tumors arising in other anatomic sites are almost invariably malignant.[7]
With respect to the distribution of malignant salivary tumors, we find that mucoepidermoid carcinoma is the most common diagnosis in the parotid gland, whereas adenoid cystic carcinoma is the malignant tumor most often encountered in submandibular or minor salivary sites.[8] Most adenocarcinomas histologically resemble breast carcinomas of ductal origin, but some have unusual features, characterized as papillary, mucus-secreting, colonic type, clear cell, and so on. More recently, it has been appreciated that some adenocarcinomas arising in the nasal cavity or paranasal sinuses have morphologic features that distinguish them as being of mucus membrane, rather than minor salivary, origin.
Grading
The concept of tumor grading can be traced back to a 1945 report by Stewart et al, in which the term “mucoepidermoid” was first used for a neoplasm that previously had been poorly characterized under a variety of names. For many years thereafter, pathologists argued over whether some of these mucoepidermoid tumors were benign, despite the fact that Stewart et al had divided their patients into “relatively favorable” and “highly unfavorable” groups, with the caveat that the term “benign” was “. . . scarcely ever applicable in the absolute sense.”[9]
The importance of grading salivary gland tumors has become widely accepted. Most centers now categorize mucoepidermoid carcinomas as low, intermediate, or high grade. We have been able to make similar distinctions for many adenocarcinomas despite the bewildering variety of subtypes mentioned above.[10] When we graded acinic cell carcinomas, we designated the uncommon papillocystic carcinoma as a high-grade variant of this tumor type.[11]
Significant differences in tumor behavior are apparent when certain salivary tumor types are subdivided according to histologic grade. Low-grade mucoepidermoid carcinomas, for example, almost never metastasize and typically behave in a relatively benign fashion. Similar, less aggressive growth patterns are evident in patients who have low-grade acinic cell carcinomas or adenocarcinomas.
Experts currently disagree about the value of grading in patients with adenoid cystic carcinoma, an indolent but highly aggressive tumor. Tumors that display a cribriform, rather than a solid, pattern are considered to be less aggressive and more favorable in some centers,[12,13] but our experience indicates that differences in survival based on tumor appearance alone disappear when patients are followed for more than 10 years.[14,15]
Clinicians need to appreciate that not all malignant salivary can be graded. Moreover, different pathologists may disagree about the grade of a given tumor, even when they are using similar criteria. It is important to remember that the classification of salivary gland tumors is an evolving art. In our experience, diagnoses are frequently changed when histologic material is reviewed retrospectively, which confirms that the identification of these tumors can be a formidable challenge even to experienced pathologists.
A 52-year-old man presented with an erythematous lesion in the axilla of unknown duration. Surgical excision was performed. What is your diagnosis?
