Malignant Neoplasms of the Salivary Glands

Physical Examination

The clinical presentation of malignant salivary gland neoplasms can range from that of indolent asymptomatic masses to rapidly growing painful masses with progressive facial nerve paralysis. In Spiro's review of 2807 salivary gland tumors, pain was a symptom in only 10% of malignant cases but was more frequently seen with malignant neoplasms than with benign ones. In general, episodic swelling and pain most often indicates salivary gland obstruction and inflammation, whereas constant pain is more worrisome for malignancy. However, sialadenitis can be secondary to obstruction by a salivary gland neoplasm; thus neoplasm must be considered in the evaluation of any salivary gland swelling with pain. Approximately 10% of parotid gland malignancies are seen initially with associated facial paralysis (sometimes mistaken for Bell palsy), and this portends a poor prognosis.

Radiologic Studies

Magnetic resonance imaging (MRI) is the radiologic modality most often recommended to assess salivary gland neoplasms, if no contraindications to its use are present. Benign and malignant neoplasms of the parotid gland are well visualized on T1-weighted imaging (T1WI), because they are easily distinguished from the fatty parenchyma of the gland, which appears hyperintense. In general, benign epithelial neoplasms, such as pleomorphic adenomas, and low-grade malignancies have low T1- and high T2-weighted signal intensities ( Fig. 85.1A and B ). High-grade carcinomas tend to have low to intermediate signal intensities on both T1WI and T2-weighted imaging (T2WI); this will be discussed later in the chapter. The use of contrast material, such as gadolinium, and fat saturation of T1WI can provide additional information regarding the extent of a salivary gland malignancy (see Fig. 85.1C and D ). This is particularly useful in terms of assessing bone involvement and perineural spread. Bone marrow and cortex appear hypointense on fat-saturated images, and infiltrating tumor tissue appears hyperintense when enhanced with gadolinium. Enlarged foramina at the skull base and the presence of hyperintense enhanced tumor tissue are suggestive of perineural spread.

Some have proposed that T2WI is helpful in distinguishing benign from malignant salivary gland neoplasms. Som and Biller examined 35 parotid tumors by MRI and observed that benign tumors and low-grade malignancies had low T1WI and high T2WI signal intensities and clearly defined margins. High-grade malignancies, on the other hand, had low T1- and T2-weighted signal intensities and poorly defined margins. Freling and colleagues, however, did not make the same observations. They examined 116 patients with parotid masses, 30 of which were malignant tumors, and found no correlation between malignancy and signal intensity, heterogeneity, or radiographic margins on MRI. Malignant lesions could be discriminated from benign ones only when infiltration into adjacent structures was apparent. Among the malignant lesions, no correlation was found between tumor grade and MRI features; thus, MRI provides useful information about the extent of the primary, but histopathologic diagnosis is still required to distinguish benign from malignant processes.

Computed tomography (CT) with intravenous contrast is also widely used to evaluate salivary gland masses, primarily because of the speed with which images are acquired. CT is particularly useful for evaluating cortical bone erosion from adjacent tumors. CT is much better than MRI in visualizing small salivary duct calculi, and as such it is particularly helpful in assessing salivary gland masses, if sialolithiasis is considered to be a component of the etiology. Highly cellular tumors can be visualized in the parotid gland because the normal parotid tissue has a high fat content, which results in a lower radiodensity on CT imaging compared with neoplasms. However, in general, MRI is superior to CT for providing soft tissue detail and delineating the extent of salivary gland masses.

Positron emission CT (PET-CT) is increasingly used in pretreatment planning of cytologically confirmed high-grade salivary neoplasms. It is highly effective for the evaluation of distant metastatic disease. Its role is limited in the evaluation of the primary neoplasms because of the background activity from physiologic excretion of ¹⁸ F-fluorodeoxyglucose (FDG) by the salivary glands. Despite this interference, a recent meta-analysis demonstrated that the prevalence of incidental focal uptake in the parotid is 1% among PET scans, and most revealed benign neoplasms without a correlation between SUV and malignant histology.

Biopsy

Pretreatment diagnosis of salivary gland neoplasms has been made possible by the use of fine-needle aspiration (FNA) biopsies. This diagnostic tool was established in the mid- to late 1960s and has become a mainstay in the workup of salivary gland neoplasms. It is an extremely safe procedure that is well tolerated by patients and is considered to have no significant risk of tumor seeding to the surrounding tissue.

Although FNA biopsies of salivary neoplasms have proven to be extremely useful for preoperative planning, the interpretation of these biopsies can be difficult and can result in diagnostic ambiguity and inaccuracy. A few entities have classic, pathognomonic features on FNA biopsy. However, the variety of different tumor types and their widely overlapping histology usually necessitate the acquisition of biopsy or resection tissue for definitive diagnosis. Also, and most importantly, many malignant salivary gland tumors can only be diagnosed as such when the growth pattern (infiltration beyond the capsule into soft tissue, perineural invasion) is taken into consideration. In these cases, tumors can only be definitively diagnosed as malignant on surgical specimens that adequately demonstrate the tumor architecture and the tumor's relationship to peripheral tissue. This is particularly true for low-grade malignant neoplasms, such as polymorphous low-grade adenocarcinoma (PLGA), myoepithelial carcinoma, and basal cell adenocarcinoma, which usually have bland-looking tumor cells and lack necrosis or abundant mitoses. Among tumors of the head and neck, FNA biopsies of major salivary gland tumors are considered to have the highest rate of error. By most reports, the sensitivity of FNA biopsies to diagnose a malignant neoplasm is much lower than the specificity. In other words, it is more common to misdiagnose a malignant tumor as benign than the reverse. A 5-year review of data from 6249 participant responses from the College of American Pathologists Interlaboratory Comparison Program in nongynecologic cytology revealed that FNA biopsies had a 68% sensitivity for diagnosing a salivary gland neoplasm as malignant, corresponding to a false-negative rate of 32%. The greatest number of false-negative diagnoses occurred in cases of lymphoma (57%), followed by ACC (49%), low-grade mucoepidermoid carcinoma (43%), and AdCC (33%). In cases of benign neoplasms from the same study, the specificity of FNA biopsies was 91%, corresponding to a false-positive rate of 8%. The greatest false-positive rates were in cases of basal cell adenoma (53%), which were most often diagnosed as AdCC. When diagnosed as malignant, pleomorphic adenomas were most often misinterpreted as AdCC, and Warthin tumors were misdiagnosed as lymphoma. Recent studies have demonstrated improved sensitivity (73%) and specificity (87%) for the diagnosis of salivary malignancy using ultrasound-guided FNA, with 6% false-negative and 10% false-positive rates. To improve FNA diagnosis for salivary gland lesions (and based on the success of the Bethesda criteria for thyroid FNA), a new classification system has been developed termed the “Milan system”. This will become more commonly used across clinical practices and may become standard for salivary gland tumor FNA specimens.

Ultrasound-guided core tissue biopsy has the best diagnostic performance and should be considered as second line to a non-diagnostic FNA. However, there is the risk of facial nerve injury and, further, there have been reports of tumor seeding decades after core biopsy, which makes this option controversial.

Although the utility and ease of FNA biopsies have resulted in a decline in the use of intraoperative frozen sections, several indications for frozen section studies still exist, as reviewed by Seethala and colleagues and by Westra. These include assessment of the extent of tumor spread to local/regional tissues, such as the nerves and lymph nodes, assessment of surgical resection margins, and confirmation or establishment of the diagnosis in cases where the preoperative FNA biopsy was not diagnostic or was equivocal. In more recent years, many surgeons have used frozen sections to clarify tumor typing after somewhat nonspecific diagnoses on FNA and, furthermore, to make an intraoperative assessment of the extent of resection needed for the primary lesion and for information about the need for neck dissection.

Staging

Clinical staging of salivary gland carcinomas is important for prognosis and treatment decisions. The tumor/node/metastasis (TNM) staging classification for major salivary gland carcinomas established by the American Joint Committee on Cancer (AJCC) is the classification most commonly used in the United States. Recent AJCC 8th edition updates that became standard in 2018 ( Tables 85.3 and 85.4 ) now formally include gross extraparenchymal extension from primary tumors, which has to be established on clinical and macroscopic grounds (histologic extraparenchymal extension alone is not sufficient evidence). The updates also now formally utilize extranodal extension (ENE) in cervical nodal metastases because of its profound effect on prognosis in head and neck carcinomas, including those primary to the salivary glands. The presence of ENE increases the nodal stage by one compared to the prior 2010 TNM classification. ENE can be defined clinically by invasion into skin and/or muscle, fixation to adjacent structures, or weakness/paralysis of surrounding nerves. Radiographic evidence alone is not sufficient for diagnosis of ENE. The pathologic definition of ENE includes the presence of tumor invading through the capsule into surrounding connective tissue, regardless of stromal reaction. Extent of ENE may be important but is not defined well enough to be differentially utilized in staging. Minor salivary gland carcinomas are staged according to the anatomic site of origin (e.g., oral cavity, sinonasal tract, larynx).

Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. The majority of cases occur in the major salivary glands, but MEC can also arise from minor salivary glands in the oral cavity, particularly in the hard palate, and from buccal mucosa, lip, and retromolar trigone. Rarely, they can also arise intraosseously in the mandible and maxilla, but MECs of this location are considered odontogenic in origin and have a less aggressive clinical behavior. Clinically, MECs are slightly more common in women and have a mean age of occurrence at approximately 45 years. They can also occur in children. In fact, they are the most common pediatric salivary gland carcinoma. Patients usually come to medical attention with a painless, slow-growing mass.

Generally, MECs are not distinct. They usually have both solid and cystic components, often with mucinous material within the cysts. This is what sometimes imparts a bluish color to them, which can mimic the appearance of a mucocele in the oral cavity. Microscopically, their hallmark is the presence of three cell types: mucous, squamoid (or epidermoid), and intermediate ( Fig. 85.3A ). The architecture is usually a mixture of cystic (see Fig. 85.3B ) and solid elements, the latter with sheets (see Fig. 85.3C ), nests, or duct-like structures. The mucous cells have abundant, light blue mucin in their cytoplasm, and nuclei are displaced to the periphery. The mucin is usually obvious, but in cases where it is scant, special stains such as PAS, mucicarmine, or Alcian blue can be used to highlight it. The squamoid cells are large with abundant pink cytoplasm, and although they look somewhat squamoid in appearance, they are not truly squamous. True keratinization in MEC is rare, and if present, it should prompt consideration of the tumor as adenosquamous carcinoma. Intermediate cells typically have more modest amounts of pink or clear cytoplasm. The proportion of cell types varies quite a bit among tumors: intermediate cells usually predominate, and mucous cells usually line cystic spaces. Cytologic atypia varies from minimal to quite prominent. Immunohistochemistry (IHC) is of limited utility in the diagnosis.

FNA yields a mixture of cell types. At a minimum, both glandular and squamoid components must be present to make the diagnosis. The mucous cells have abundant vacuolated cytoplasm, intermediate cells are relatively round and small with little cytoplasm and nuclei with open chromatin, and squamoid cells have moderate amounts of dense, homogeneous cytoplasm. These typically appear orange on Papanicolaou staining.

The differential diagnosis, particularly in tumors that arise along mucosal sites, includes necrotizing sialometaplasia, an uncommon nonneoplastic lesion of the hard palate with reactive changes in minor salivary glands and, more importantly, adenosquamous carcinoma—an aggressive variant of SCC. Adenosquamous carcinomas are high-grade, have definitive squamous differentiation, usually with keratinization (unlike MEC), and often have surface mucosal squamous dysplasia, a feature that MEC lacks.

Grading of MEC is important and correlates strongly with clinical behavior, although reproducibility and consistency are major issues and no particular system has been universally accepted. Clinical staging is as important as histologic grade, so the two should be considered in tandem. In general, low-grade lesions have a prominent cystic component and abundant well-differentiated mucous cells with little cytologic atypia and low mitotic activity. High-grade lesions are more solid with squamoid and intermediate cells predominating. They also have cytologic atypia, mitotic activity, necrosis, and infiltrative growth. A number of different grading schemes (well-reviewed by Luna and also by Seethala ) have been reported over the years. The most used grading system, originally designed by Auclair and colleagues, uses a three-tiered score based on a number of histologic features ( Table 85.6 ). The original grading system was initially criticized for a tendency to “undergrade” the tumors, when others demonstrated that a significant number of low-grade MECs developed progressive disease. The later modification by Brandwein and colleagues (see Table 85.6 ) refined the grading system such that none of the tumors that were classified as low-grade in their study went on to progressive disease. Low-grade MEC, as strictly defined by their criteria, rarely ever metastasizes or results in death of the patient. Intermediate-grade MEC is the most challenging for the clinician, because it has the least agreement among pathologists and also has a variable clinical behavior, which may depend greatly on the grading system used. Therapeutic decisions in such tumors often rely on other clinicopathologic features.

In addition to grade, location of the primary tumor is potentially important in predicting clinical behavior. Several studies have shown that low-grade MECs of the submandibular gland recur and metastasize more frequently than those of the parotid or minor salivary glands. Whether this represents truly different biology, it merits the aggressive and thorough resection of any submandibular gland primary malignancy, especially for known MEC. Other prognostic markers are certainly needed. The consistent finding of translocation t(11;19)(q21;p13) seen in greater than half MECs, which results in a fusion of the CRTC1 and MAML2 genes, can be used for confirmation of the diagnosis. This is useful primarily in low- or intermediate-grade tumors since most high-grade MEC are negative. This translocation is associated with a better prognosis but not clearly independent of tumor grade.

Adenoid Cystic Carcinoma

AdCC is one of the more common and certainly more recognizable salivary gland tumors, notorious for its infiltrative growth and a slow, progressive behavior with recurrences and spread over a protracted course of many years. These tumors essentially occur with an even distribution across all salivary gland sites, although the total number of minor salivary gland cases outnumber those of major salivary glands, when all sites are considered together. These malignancies occur with an equal incidence in men and women over a wide age range with the peak incidence between 50 and 60 years of age.

Generally speaking, AdCCs are solid, light tan, firm, and well-circumscribed but unencapsulated tumors. Microscopically, three growth patterns have been described: tubular, cribriform, and solid. The tubular pattern consists of small tubules sitting in a pink, hyalinized, and hypocellular stroma ( Fig. 85.4A ). The solid pattern has only rounded lobules of tumor cells with few, or no, gland-like structures and without a defined architecture (see Fig. 85.4B ). The classic and most easily recognized pattern is cribriform, similar to Swiss cheese. Nests of cells are arranged around gland-like spaces that consist of PAS-positive blue or pink material (see Fig. 85.4C ). The central spaces look like glandular lumina but are actually an extracellular matrix that contains reduplicated basement membrane (or ground substance) material produced by the tumor cells, rather than true epithelial mucin. The cells in AdCC are markedly basaloid in appearance, with little cytoplasm and round-to-oval nuclei that are dark and hyperchromatic without nucleoli (see Fig. 85.4A ). They are quite uniform in size and show little mitotic activity, except for the solid type, in which mitotic activity can range from scant to extremely prominent. A rim of inconspicuous myoepithelial cells with clear cytoplasm is also usually present, particularly in the tubular pattern. Scattered, inconspicuous true ducts are present as well.

FNA frequently yields characteristic results in AdCC. Aspirates have tumor cells with scant cytoplasm and round, regular nuclei in sheets and clusters. These features by themselves are not characteristic and actually are so bland that they might suggest a benign lesion. However, the finding of well-defined, round “cylinders” and/or spheres of acellular stroma accompanying these cells is typical, but not 100% specific, for AdCC. The cells often “cling” to these rounded structures (see Fig. 85.4D ).

Histologic grading has yielded conflicting results in the literature for predicting prognosis. Clinical stage, on the other hand, holds a great deal of prognostic information and, as such, should be considered as much or more than grade in clinical management. Also, as with MEC, AdCC of the submandibular gland has a much more aggressive clinical course than AdCC of other sites. The most accurate prognostic information has been garnered when tumors are not only graded by the predominant pattern—tubular, cribriform, or solid—but are more specifically categorized as Grade I, tubular with or without some cribriform areas and without any solid areas; Grade II, cribriform with minimal tubular areas and with less than 30% solid areas; and Grade III, any mixture of patterns but with greater than 30% solid areas. A frequent histologic feature of AdCC is perineural invasion, which is identified in approximately 70% to 75% of cases. Although somewhat inconsistent in the literature, many have correlated this finding with a worse prognosis, particularly when it involves a major nerve trunk. It is also well accepted that this perineural invasive tumor is probably the source of recurrent tumor, even after seemingly complete surgical resection of the primary tumors.

Another distinguishing feature of AdCC is that metastases tend to be distant and most often to the lungs. Although the exact incidence is somewhat controversial, AdCC only uncommonly metastasizes to regional lymph nodes and these are mostly with solid (Grade III) tumors. Distant metastases of AdCC can remain indolent for many years and, as such, should not necessarily preclude surgical resection of the primary tumor. It is important to assess the pace of the disease progression. Distant metastasis to bone, however, is often associated with a particularly poor outcome, with a 5-year survival of about 30%.

The diagnosis of AdCC is generally straightforward, from routine hematoxylin-eosin examination. However, it can be difficult on small biopsies, because the pathologist may not be able to fully appreciate the architecture and infiltrative growth. The differential diagnosis includes other salivary gland neoplasms, such as polymorphous adenocarcinoma (PAC), epithelial myoepithelial carcinoma, basaloid SCC, or high-grade neuroendocrine carcinoma. Although beyond the scope of this text, IHC is not usually necessary but can occasionally be helpful in differentiating among these tumor types. AdCC has been found to have a relatively consistent molecular translocation, t(6;9), which involves the MYB and NFIB genes. The literature suggests that this rearrangement is present in as many as two-thirds of cases. Although not prognostic or useful for routine clinical practice, it is occasionally useful diagnostically and may have treatment or management significance in the future.

Polymorphous Adenocarcinoma

PAC, formerly known as PLGA, is a unique, almost exclusively low-grade neoplasm first recognized as a distinct entity in the mid-1980s. PACs arise, with only rare exceptions, from the minor salivary glands. In most series, they are the second most common minor salivary gland carcinoma. The most common site is the palate, particularly at the junction of the hard and soft palates. Other sites include the upper lip, buccal mucosa, and base of tongue. Some recent reports suggest these extrapalatal sites to be higher risk for recurrence. PAC arising in major salivary glands is exceedingly rare. PAC is twice as common in women and tends to appear in the fourth to sixth decades as a slow-growing mass that may have been present for years. Such masses are often asymptomatic. On gross examination, they are circumscribed, unencapsulated, pale yellow or tan masses that range from 1 to 3 cm. Microscopically, the architectural features are quite variable, as the name would suggest. They are well-circumscribed but unencapsulated and may appear as solid nests in lobules, cribriform gland-like structures, or duct-like arrangements. A common appearance within the tumor is concentric whorling of the nests around each other in a single-file arrangement. This has been termed the “eye of the storm” pattern ( Fig. 85.5A ). Stromal hyalinization with a slate-gray coloration is also characteristic. Tumor cells are quite regular with moderate eosinophilic cytoplasm and characteristic round to oval, extremely regular nuclei with open chromatin (see Fig. 85.5B ). Little mitotic activity is apparent, and no necrosis is present. The periphery of the tumor shows infiltrative growth, and most cases show perineural invasion (see Fig. 85.5C ).

The differential diagnosis includes pleomorphic adenoma and AdCC. The myxochondroid areas of pleomorphic adenoma are not seen in PAC, and although minor salivary gland pleomorphic adenomas are unencapsulated, they will not show the infiltrative growth pattern of PAC and will not have perineural invasion. One particular immunostain that may be useful in difficult cases is worth mentioning here. Curiously, it has been recognized that almost all pleomorphic adenomas will be positive for glial fibrillary acidic protein, whereas almost all PAC are negative. AdCC is important to differentiate from PAC. This is done primarily by cytologic features, because AdCCs have basaloid cells with dark chromatin and little cytoplasm, whereas PAC cells have moderate eosinophilic cytoplasm and nuclei with open chromatin. Dual p40 and p63 positivity in AdCC versus p40-negative, p63-positive status in PAC has also been reported to be diagnostically useful.

PAC is a very low-grade malignancy, and histologic grading is not applicable. Conservative resection is the treatment of choice. Tumor recurs locally in 10% to 15% of patients. Because lymph node metastases are distinctly uncommon (literature rates of ∼10% or less), neck dissection is only recommended with significant clinical adenopathy or needle-proven metastasis. Distant metastases are equally as uncommon, and patients have an excellent long-term prognosis. In fact, few patients have been documented to die of this tumor and only after prolonged periods. As with all salivary gland carcinomas, rare high-grade transformation can occur with the development of an extremely high-grade carcinoma in a background of otherwise typical PAC. These patients have poor prognosis.

Acinic Cell Carcinoma

ACC, as the name implies, is a tumor with cells that show differentiation toward cells of the normal salivary gland acini (see Fig. 85.2 ). ACC is uncommon and comprises 1% to 3% of all tumors and approximately 10% of all malignant tumors. More than 90% occur in the parotid and the rest are scattered among minor salivary gland sites and, rarely, the submandibular gland. Occurring over a wide age range, from children to the elderly, tumors are relatively evenly distributed in the second through seventh decades with a peak in the third decade. Of note, these tumors are the second most common childhood salivary gland malignancy. They come to medical attention as a slowly growing mass, which is only occasionally painful and is rarely associated with facial palsy.

In general, ACC is found as a single, usually circumscribed, rubbery, solid mass; up to one-third show cystic degeneration. Microscopically, tumors are highly variable, a feature that has traditionally incited angst in the diagnosing pathologist. The four principal histologic patterns are (1) solid/lobular, (2) microcystic, (3) papillary-cystic, and (4) follicular. Small tumors can be easily missed, because the acinar cells are so well differentiated that they blend into the surrounding normal gland. Two features are classic, however. The first is the characteristic acinic cell, which has blue cytoplasm with abundant serous-type granules and a small, round, centrally placed nucleus ( Fig. 85.6A ). PAS stains will be strongly positive in these cells. A number of other cell types are seen, including pink, clear, and vacuolated cells, such that most tumors are a mixture of different cell types (see Fig. 85.6A ). The second classic feature is a dense lymphoid infiltrate with germinal centers (see Fig. 85.6B ). The periphery of the tumors may or may not be infiltrative but is often “pushing” in nature (see Fig. 85.6C ). Although it could be assumed that lack of an infiltrative border might signal a benign lesion, ACC has no benign equivalent (i.e., there is no acinic cell adenoma). “High-grade transformation” has been described in as many as 20% of ACCs and consists of tumors with areas of classic, “conventional” ACC and an intermixed undifferentiated carcinoma in sheets with large pleomorphic cells, brisk mitotic activity (<2 per 10 hpf), and often, necrosis.

The differential diagnosis includes normal parotid gland. However, ACC will not have the exquisitely lobular architecture, intralesional fatty tissue, or the presence of ducts that normal salivary gland tissue will always have. For the pink and clear cell types, tumors such as oncocytic carcinoma, secretory carcinoma, and clear cell carcinoma not otherwise specified (NOS) must be considered, and the papillary variant of ACC must be differentiated from cystadenocarcinoma. The finding of focal cells with blue, serous-type cytoplasmic granules will confirm the diagnosis of ACC. IHC has relatively limited utility but is very helpful to distinguish ACC from secretory carcinoma. DOG1 is a newer marker of acinic cells and intercalated duct epithelium and shows a classic membrane pattern in cells of ACC. Secretory carcinoma is positive for S-100 and mammaglobin, whereas ACC is negative or patchy for these markers.

FNA biopsy of ACC is difficult because of its frequent resemblance to normal salivary gland tissue. The diagnosis rests on finding a cellular specimen with sheets and clusters of large acinar cells with abundant granular cytoplasm and central round, regular nuclei. There must be a lack of normal ductal epithelial cells and adipose tissue (both of these latter findings are from normal salivary gland tissue), but a prominent background component of lymphocytes is often present as they are recruited by the tumor cells in most cases of ACC.

Surgical resection with negative margins is the most important therapy; still, tumors will recur in approximately one-third of cases. Although classically regarded as low-grade malignancies, overall, 10% to 15% of these tumors will metastasize locally to regional lymph nodes or distantly to the lung and bones. ACCs are also notorious for the timing of recurrence, as they spread years beyond the primary presentation and have a protracted clinical course. Survival curves do not flatten out until after a decade. Survival is approximately 80% at 5 years and 70% at 10 years. Grading of these tumors has been classically thought of as correlating poorly with behavior; however, some more recent studies that have divided tumors into low- and high-grade types based on mitotic activity and necrosis have shown that the majority of high-grade tumors (also termed “with high-grade transformation”) recur and metastasize, whereas 10% or less of the bland-appearing low-grade tumors recur.

Malignant Mixed Tumors

Malignant mixed tumor is the broad term used to encompass three different salivary gland malignancies: (1) carcinoma ex pleomorphic adenoma; (2) true malignant mixed tumor, or carcinosarcoma; and (3) metastasizing pleomorphic adenoma (MPA). As a group, these account for approximately 3% to 5% of all salivary gland malignancies, and carcinoma ex pleomorphic adenoma is by far the most common of these.