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Management of Malignant Tumors of the Salivary Glands

Management of Malignant Tumors of the Salivary Glands

ABSTRACT: Results of treatment for patients with salivary gland carcinoma have improved in recent years, most likely due to earlier diagnosis and the use of more effective locoregional therapy. Salivary gland tumors are treated surgically, often in conjunction with postoperative radiation therapy when the tumor is malignant. Good results rest strongly on the performance of an adequate, en bloc initial resection. Radical neck dissection is indicated in patients with obvious cervical metastasis, and limited neck dissection may be appropriate in patients with clinically negative nodes in whom occult nodal involvement is likely. Postoperative radiation therapy should be administered when the tumor is high stage or high grade, the adequacy of the resection is in question, or the tumor has ominous pathologic features. Neutron beam therapy shows promise in controlling locoregional disease but requires further study. No single chemotherapeutic agent or combination regimen has produced consistent results. At present, chemotherapy is clearly indicated only for palliation in symptomatic patients with recurrent and/or unresectable cancers. Patients with salivary gland carcinomas must be followed for long periods, as recurrence may occur a decade or more following therapy. Distant metastasis appears to occur in approximately 20% of patients.[ONCOLOGY 12 (5): 671-683, 1998]

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.


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
).[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

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.


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.


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