SALIVARY GLANDS

0033-8389/98 $8.00

HEAD AND NECK IMAGING

+ .OO

SALIVARY GLANDS Adam R. Silvers, MD, and Peter M. Som, MD

Overall, diseases of the salivary glands are relatively uncommon; however, as an organ system they have one of the greatest diversities of pathology. The vast majority of lesions are of an inflammatory origin; however, some arise from posttraumatic, systemic, or an uncertain pathogenesis. There also is a wide spectrum of benign and malignant neoplasms.74 As a group, the salivary neoplasms account for less than 3% of all head and neck tumors and they account for less than 0.1% of all cancer deaths.I4 The relative incidence of salivary gland tumors is estimated to be that for every 100 parotid tumors, there are 10 submandibular tumors, 10 minor salivary tumors, and 1 sublingual tumor.lo2The parotid, submandibular, and sublingual glands are often referred to as the major salivary glands, whereas the minor salivary glands line the oral cavity and upper aerodigestive tracts. With regards to the pathogenesis of salivary gland neoplasms, it was assumed for decades that there were but two potential stem cells from which the variety of different salivary tumors originated. It was generally thought that because the basal cells of the excretory duct and the intercalated duct cells acted as the reserve cells for the more differentiated cells of the salivary gland unit, all of the epithelial tumors arose from these reserve cells rather than from the acini! Implicit in this concept was the assumption that the differentiated end cells were incapable of further dividing and therefore were incapable of giving rise to tumors? Recent evidence has shown, however, that salivary glands proliferate and regenerate after injury and that the proliferating cells are not confined to one cell type?7 Further, in cell cultures from human salivary glands, all of the differentiated cell types have now been shown to be capable of cycling.Z8 Thus, the once simple theory for the pathogenesis

of the salivary gland tumors appears to be far more diverse than previously thought. EMBRYOLOGY

The parotid anlagen are the first to develop, followed by the anlagen of the submandibular gland and then the sublingual gland. The minor salivary glands do not start to develop until later.@, 61,68,98 The epithelial buds of each gland enlarge, elongate, and branch, initially forming solid structures. They eventually canalize, however, creating lumina. This ductal canalization process is completed before the terminal buds, or eventual acini, develop.98The lining epithelial cells of the ducts, tubules, and acini then differentiate both morphologically and functionally and the contractile myoepithelial cells become placed about the a ~ i n iIt. ~ ~ has also been shown that an interaction of the salivary gland parenchymal and stromal elements with the autonomic system is necessary for normal salivary development and function to occur; sympathetic nerve stimulation leads to acinar differentiation, whereas parasympathetic nerve stimulation is necessary for overall glandular growth.98 Although the parotid anlagen are the first to develop, they become encapsulated after the submandibular and sublingual glands. This delayed encapsulation is critical, because during the period after the submandibular and sublingual glands encapsulate, but prior to the parotid gland encapsulation, the emergence of the lymphatic system occurs in the mesoderm. Because of this, in the adult there are intraglandular lymph nodes and lymphatic channels only within the parotid glands. In addition, during the encapsulation of the intraparotid and periparotid lymph nodes, salivary epithelial cells can be included within these nodes.

From the Mount Sinai School of Medicine, City University of New York, New York, New York ~~~~

~~~~

~~~

RADIOLOGIC CLINICS OF NORTH AMElUCA VOLUME 36 * NUMBER 5 * SEPTEMBER 1998

941

942

SILVERS & SOM

This unusual situation is, in fact, unique to the parotid and periparotid nodes! It is this special embryogenesis of the parotid glands that is believed to play a role in the development of Warthin's tumors and possibly lymphoepithelial cysts. The parotid gland is also unique in that as its epithelial buds grow and branch, they extend between and around the divisions of the facial nerve incorporating the distal portion of this nerve within the adult gland.M, 98 ANATOMY

Parotid Glands

The parotid is the largest of the salivary glands and its superficial portion is palpable as it overlies the ramus of the mandible. The average gland weighs between 14 and 28 g and in men averages 5.8 cm in craniocaudal dimension and 3.4 cm in the ventrodorsal axis; the parotid gland tends to be slightly smaller in women.*,61 Nearly 80% of the gland lies on the outer surface of the masseter muscle and the ascending ramus

and angle of the mandible. This portion of the gland lies caudal to and ventral to the external auditory canal and the mastoid tip. The remaining approximately 20% of the gland extends medially through the stylomandibular tunnel, which is formed ventrally by the posterior edge of the mandibular ramus; dorsally by the anterior borders of the sternocleidomastoid muscle and the posterior belly of the digastric muscle; and more deeply and dorsally by the stylomandibular ligament, which extends from the tip of the styloid process to the angle and posterior edge of the mandible. This stylomandibular ligament also separates the parotid gland from the submandibular gland. Because of these anatomic relationships, the retromandibular or deep portion of the parotid gland lies anterior to the styloid process, its musculature, and the carotid sheath. This places the deep portion of the parotid gland in the prestyloid compartment of the parapharyngeal space (Fig 1).8,61 The parotid gland, despite the commonly used terminology, is not actually anatomically divided into separate superficial and deep lobes. This nomenclature is based on using the facial nerve and its associated interstitial structures as a reference

Figure 1. Normal anatomy of parotid glands. A, Axial CT scan. B, Axial T1-weighted sequence. C, Axial TP-weighted sequence. The retromandibular portion of the gland is indicated by the arrow.

SALIVARY GLANDS

plane within the gland. More recently, an anatomically correct terminology has become more popular. In this system, the superficial portion of the gland is that region that overlies the ramus of the mandible and masseter muscle. The retromandibular portion of the gland refers to the smaller region behind and deep to the mandibular ramus. The main trunk of the facial nerve exits the skull base via the stylomastoid foramen and immediately gives off three small branches: (1)the posterior auricular, (2) the posterior digastric, and (3) the stylohyoid nerves. The facial nerve then courses laterally around the styloid process and follows the lateral surface of the posterior belly of the digastric muscle a variably short distance before the nerve pierces the posterior capsule of the parotid gland. The nerve then continues within the gland lateral to the posterior facial vein and the more medial external carotid artery. It then divides in one of several anatomic patterns into the temporal, zygomatic, buccal, mandibular, and cervical bran~hes?~ In the parotid gland the intercalated ducts are long and thin. By comparison, in the submandibular gland, the intercalated ducts are shorter and wider. The sublingual gland has the shortest and widest intercalated ducts of the major salivary glands. This may relate to the increasing viscosity of the secretions of these three glands. The parotid gland parenchyma also has abundant fatty tissue with a ratio of adipose to acinar tissue of about 1:l. Stensen‘s duct emerges from the anterior parotid gland, courses over the masseter muscle and buccal fat pad, and then turns medially, almost at a right angle, to pierce the buccinator muscle at the level of the second upper molar tooth. As Stensen’s duct passes over the masseter, it may receive the duct of an accessory parotid gland, which is found in about 20% of people overlying the masseter muscle, usually situated cranial to Stensen’s duct. The parotid and periparotid lymph nodes drain primarily into the internal jugular chain nodes, with some drainage also going to the upper spinal accessory chain of nodes. The innervation of the parotid gland is such that sympathetic innervation is mainly responsible for vasoconstriction, whereas parasympathetic fibers are related to secretory function40 Submandibular Glands

The submandibular gland is the second largest salivary gland, being about one half the weight of the parotid gland (Fig. 2). It occupies most of the submandibular triangle of the neck, and the gland is folded around the dorsal free edge of the mylohyoid muscle. Despite the fact that there are no separate lobes to the gland, by convention it is often referred to as being divided into superficial and deep lobes, with the larger superficial lobe lying in the submandibular triangle, superficial and caudal to the mylohyoid muscle, and the deep

943

portion lying above the mylohyoid muscle. It is from the deep portion of the gland that Wharton’s duct extends to the anterior floor of mouth on the sublingual papilla. Along its course, the duct makes an approximately 45-degree angle with both the sagittal and axial planes. As the duct courses upward, the lingual nerve winds around it, being first lateral, then inferior, and finally medial to it. Lying superficial to the gland are the lingual nerve and submandibular ganglion, whereas deep to the gland is the hypoglossal nerve with its accompanying vein. Lateral to the gland are the facial nerve and vein. The submandibular gland is a mixed serous and mucous gland, with about 10% of the acini being mucinous. By comparison with the parotid gland, adipose tissue is not a significant component of the glandular parenchyma. Its lymphatic drainage is into the submandibular nodes.40,75 Sublingual Glands

The sublingual gland is the smallest of the major salivary glands, weighing only about 2 g. It lies just below the sublingual mucosa in the floor of the mouth, lying against the anterior lingual surface of the mandible (Fig. 3). The gland rests on the mylohyoid muscle and its medial contour is separated from the genioglossus muscle by the lingual nerve and Wharton’s duct. There are about 20 individual small ducts, the ducts of Rivinus, which open independently into the floor of the mouth along the sublingual papilla and fold. Occasionally, some of the ducts of Rivinus fuse to form Bartholin’s duct, which in turn opens into Whar61 The gland’s lymph drains into the ton’s submental and submandibular lymph nodes. Minor Salivary Glands

These glands are situated beneath the mucosa of the oral cavity, palate, paranasal sinuses, pharynx, larynx, trachea, and bronchi. They are most numerous in the buccal, labial, palatal, and lingual regions. The gingivae, the anterior aspect of the hard palate, and the true vocal cords have relatively few minor salivary glands. The minor salivary glands have the same basic structure as the major salivary glands but are either entirely mucous glands, on the hard palate, or mixed seromucous glands, as in the sinonasal and oral cavities. It has been estimated that there are more than 750 minor salivary glands. PHYSIOLOGY

The physiologic control of the salivary glands is almost entirely by the autonomic nervous system and parasympathetic effects predominate. If the parasympathetic innervation is interrupted, glan-

944

SILVERS & SOM

Figure 2. Normal anatomy of the submandibular gland. A, Axial contrast-enhanced CT scan. B, Axial T1-weighted sequence. C, Coronal T1-weighted sequence. The facial artery and vein are lateral to the gland (arrow) and the lingual artery is medial (curved arrow).

dular atrophy occurs. If sympathetic innervation is interrupted, there is little, if any, effect on the glandss9 Normal saliva is 99.5% water and the total daily production of saliva is between 1000 and 1500 mL, most of which is produced during meals. Of this total, the parotid glands contribute about 45%, the submandibular glands about &YO, the sublingual glands 5%, and the minor salivary glands 5y0."~Although the minor salivary glands and the sublingual glands together produce only 10% of the total salivary volume, they are responsible for the majority of the mucous secretions and when these glands are affected by either autoimmune disease or irradiation, xerostomia develops.61,114 The antibacterial activity of saliva is accomplished by secretory IgA; enzymes, such as lysozyme, peroxidase, a-amylase, and lactoferrin; and ions, such as thiocyanate and hydrogen. The normal range of salivary pH is 5.6 to 7.61,114

DEVELOPMENTAL ANOMALIES

Developmental anomalies of the salivary glands are rare, are usually associated with other facial abnormalities, and are associated with xerostomia and thus sialadenitis and dental caries. Parotid gland agenesis has been reported with hemifacial microstomia, mandibulofacial dysostosis, cleft palate, and anophthalmia. Atresia of one or more major salivary gland ducts, usually the submandibular or sublingual glands, is very rare and is associated with xerostomia and possibly the development of a retention cyst.", Hypoplasia of the parotid gland has been reported in the Melkersson-Rosenthal syndrome, and congenital fistula formation of the ductal system has been associated with branchial cleft abnormalities, accessory parotid ducts, and diverticula.61 Aberrancy of salivary gland tissue has been reported in a large variety of locations including the

SALIVARY GLANDS

945

Figure 3. Normal anatomy of the submandibular and sublingual glands. A, Axial contrast-enhanced CT scan. B, Axial T1-weighted sequence. C,Axial contrast-enhanced fat-suppressed T1weighted sequence. D, Coronal T1 -weighted sequence.The curved arrows identify the sublingual gland. The genioglossus muscle is medial to the sublingual gland (arrow) and the myelohyoid lateral to the sublingual gland (arrowhead).

middle ear cleft and external auditory canal; the neck; the inner-posterior mandible (Stafne cyst); the anterior mandible; the pituitary; and the cerebellopontine angle.61Congenital intraglandular cysts also occur and these are discussed in the section on nonneoplastic diseases. IMAGING APPROACH

Over the recent two decades, the choice of which imaging modality to use when investigating a patient with major salivary gland disease has changed. The old approach relied on plain films and sialograms, whereas today the emphasis is on CT, MR imaging, and ultrasound. Although there are no set rules in the literature as to when a particular modality should be used in preference to the others, the general rule utilized by many radiologists is that inflammatory diseases are probably best imaged by CT, whereas tumors are best imaged by MR imaging.

Thus, if the patient's history suggests an inflammatory disease, CT not only demonstrates the actual salivary gland disease, but also potential sialoliths that may be responsible for the disea~e.'~, 75 By comparison, if there is clinical finding of a mass, the initial imaging modality that best evaluates the borders of the lesion is usually MR imaging.*Because of concerns regarding radiation in children and adolescents, it has been suggested that ultrasound be used for inflammatory and superficially located disease, whereas MR imaging be utilized for more deeply positioned masses.3oIf a minor salivary gland tumor is clinically suspected, either enhanced MR imaging or CT can serve as the examination of choice. Although most of the CT studies of salivary gland disease utilize contrast, often no new clinically useful information is obtained over that available on a noncontrast study. When MR im*References 18, 20, 26, 52, 56, 59, 63, 66, 72, 73, 86, 88, 95, 100, 103, 107

946

SILVERS & SOM

aging is used, however, contrast may help distinguish a cystic mass from a solid tumor and thus the routine use of contrast may be more justified than with CT. When contrast is used with MR imaging, fat suppression sequences are necessary to improve lesion conspicuity. Contrast is also very useful when evaluating perineural tumor spread from salivary gland malignan~ies.7~ Plain films are rarely used today for the evaluation of salivary calculi because even if a plain film study is normal, a sialolith or soft tissue calcification may be present that can be easily identified by either ultrasound or CT. Even if a calcification is seen on a plain film, another nonvisualized, but clinically important calcification, may still be present. Because of these limitations, today most imaging for soft tissue calcifications involves either CT or ultrasound. Sialography used to be one of the mainstays of major salivary gland imaging and today it remains the most detailed way to image the ductal system. With the improved use of CT and MR imaging, however, the new and more reliable clinical tests available, and the changes in the clinical approach to the management of major salivary gland disease, there is little need to perform sialography today. In addition, if the patient has a clinically active infection or has an allergy to the contrast agents used, the procedure is contraindicated. If a sialogram is performed, a water-soluble contrast agent should be used.%,55 Most CT studies of the major salivary glands and the neck are performed as axial 3-mm contiguous scans. Spiral or helical scans can also be utilized, especially in children and patients who may have difficulty remaining quiet or motionless throughout the examination. At present, however, the soft tissue images from the spiral studies are not as detailed as those of direct sectional images. Coronal scans through the parotid and submandibular glands can also be obtained to complement the axial examination. Unfortunately, image degradation artifact from dental amalgam often makes these coronal images of little diagnostic use. MR imaging studies of the major salivary glands are usually performed as 3-mm-thick slices with a 1-mm interslice gap. Noncontrast T1-weighted and T2-weighted sequences are obtained and then T1weighted, postcontrast, fat-suppressed images are obtained. Fat suppression may be needed for fastspin echo TZweighted scans as well. Axial views are obtained for all sequences, and coronal and sagittal views may be obtained as needed, usually as part of the postcontrast study.20, 56, loo, lol In the adult, the parotid gland normally is a relatively fatty gland with numerous thin interstitial strandlike structures seen interlacing throughout it. These strands represent the interstitial structure of the gland, the facial nerve branches, and the ductal system. In children and in some adults, a clinically normal parotid gland can have a low fat content, which affects its CT and MR imaging appearance. Unfortunately, it is often impossible

to differentiate such a normal less fatty gland from one that has been infiltrated with cells resulting from a variety of causes. The external carotid artery and the more laterally placed posterior facial vein are situated dorsal to the ramus of the mandible. These vessels course from medially to laterally as one goes from the caudal to the cranial portions of the parotid gland. Some variable, but normal glandular lobulations can also be seen primarily in relationship to the sternocleidomastoid muscle and the mastoid tip. Normally, the facial nerve itself is not imaged. The recent use of high-resolution three-dimensional Fourier transform MR imaging, however, has allowed the facial nerve to be consistently visualized on contiguous scans.62The submandibular glands have a less fatty parenchyma than do the parotid glands. As a result, compared with the parotid glands, the submandibular glands are more homogeneous and cellular on imaging. In addition, the thicker mucoid secretions can normally be identified in the major collecting ducts and hilum of the submandibular gland. After contrast, both submandibular glands should enhance to the same degree. If not, one gland is abnormally functioning. CALCIFICATIONS

Solitary or multiple calcifications within the parotid or submandibular glands usually indicate the presence of chronic sialadenitis. The finding is nonspecific and specific etiologies for the sialadenitis cannot be distinguished based on the pattern of calcifications. If the calcification is within a salivary gland mass, however, the most likely lesion is a pleomorphic adenoma. Less often, calcification within a salivary gland mass can be seen in a schwannoma, a mucoepidermoid carcinoma, rarely within parotid lymph nodes in such conditions as posttreatment lymphoma and long-standing amyloidosis, and rarely within a chronic intraglandular hematoma. Ossification within a parotid mass is also rare; the most common lesion is a pleomorphic adenoma. Thus, once a calcification is seen within the parotid or submandibular glands, the localization of the calcification to either the gland parenchyma or to a discrete mass evokes a limited differential diagnosis. The inability of MR imaging to detect such small calcifications is one of the major limitations of this modality when imaging the major salivary glands. DIFFERENTIATING BENIGN AND MALIGNANT MASSES

The distinction between benign and malignant lesions frequently cannot be made based solely on the morphology as demonstrated by CT and MR imaging. By utilizing the imaging and clinical findings, however, such a distinction may be able

SALIVARY GLANDS

to be made in almost 90% of the cases?1,95,105 The imaging difficulties reflect the fact that whereas most benign salivary lesions (i.e., cysts, tumors, and nodes) have a capsule and thus are smoothly contoured and sharply delineated from the adjacent salivary tissues (Fig. 4), the most common low-grade salivary gland malignancies (i.e., lowgrade mucoepidermoid carcinomas, some acinic cell carcinomas, and some adenoid cystic carcinomas) develop pseudocapsules that cause them to appear on sectional imaging as smoothly outlined benign-appearing lesions. Conversely, high-grade malignancies (i.e., highgrade mucoepidermoid carcinomas, adenocarcinomas, undifferentiated carcinomas, and squamous cell carcinomas) have irregular, infiltrating, indistinct margins with the adjacent salivary tissue and it is only rarely that a benign mass is surrounded by inflammation or hemorrhage and presents an aggressive sectional imaging appearance. Thus, based on morphology, a well-delineated mass is most likely benign, although a low-grade tumor cannot be excluded from the diagnosis. An infiltrating, irregularly delineated mass, however, is most likely to be a high-grade malignancy. Whereas the attenuation of most benign and malignant masses is the same on CT, MR imaging may provide a means of differentiating between benign or low-grade masses and high-grade tumors. The benign lesions and low-grade tumors tend to be sufficiently well differentiated that they contain significant regions of watery serous and mucinous secretions. Thus, on MR imaging they have low T1-weighted and high T2-weighted signal intensities (Fig. 5). The highly cellular highgrade malignancies are undifferentiated and thus tend to contain little serous and mucinous secretions. These tumors tend to have low to intermediate signal intensities on all imaging sequences?l Less often, there are other lesions that can have a relatively low T2-weighted signal intensity. Such lesions include fibrosis, granulomas, and rarely some benign tumors. Whenever a salivary mass

947

has a low T2-weighted signal intensity, however, it should alert the radiologist to the possibility that a high-grade malignancy may be present (Fig. 6). Clinically, benign tumors are usually slow growing, painless, nontender, mobile, and firm. Facial nerve paralysis is rarely present with benign masses. Benign cysts usually develop rapidly over several days and are nontender unless infected, in which case they are both tender and painful. These cysts are moderately firm to palpation and often have a history of prior recurrent clinical episodes. By comparison, malignant tumors tend to enlarge over a period of several weeks, and they can be either painless or slightly painful and minimally tender, depending on how rapidly they are enlarging. In general, the faster these malignancies grow, the more symptomatic they are. When palpated, these malignancies are usually rock hard, and they may be fixed in position. There may be an associated facial nerve paralysis. In fact, the overall incidence of facial nerve paralysis with a parotid malignancy is 12% to 14?'0.~~ NEWER IMAGING TECHNIQUES

Three-dimensional MR imaging is a good communication tool when describing pathology to clinicians who have difficulty assimilating serial CT and MR images and the use of MR imaging contrast may improve the identification of salivary masses on such three-dimensional images.'OgLittle if any information, however, is provided to the clinician that aids in the surgical decision-making process and thus this technique is uncommonly used. MR imaging spectroscopy is still a relatively new field as applied to clinical imaging. It has been shown that 31-phosphorus spectroscopy of salivary malignancies has a significant increase in the concentration of phosphomonoesters, phosphodiesters, and inorganic phosphates compared with normal patients, whereas there was a large

Figure 4. Pleomorphic adenoma. (A) Axial and (B)coronal CT. Borders of the lesion (arrowhead) within the leit parotid gland are well-defined with no evidence of infiltration into the surrounding gland.

948

SILVERS & SOM

Figure 5. Pleomorphic adenoma. (A) Axial CT and (B) axial T2weighted sequence. The adenoma has high signal intensity on the T2-weighted sequence (arrow) and is sharply marginated.

reduction in creatine phosphate.lmThis work may lead the way to more pathologic and prognostic information being attainable on MR imaging; however, at present, because of the considerable time necessary to gather sufficient data and the limited clinical application of MR imaging spectroscopy, it is primarily an investigative tool. Ultrasound has traditionally been used to differentiate solid and cystic salivary gland masses and

to identlfy salivary calculi. It can also be used to identify the more advanced stages of autoimmune disease (Sjogren’s syndrome). Although ultrasound can, in some cases, differentiate lymphomatous nodes from nonlymphomatous nodes; biopsy is still necessary. It is fair to say that overall in the last decade, ultrasound has become a more useful imaging technique particularly for the parotid and submandibular glands and especially in

Figure 6. Mucoepidermoid carcinoma. A, Axial T i -weighted sequence. B, Axial T2-weighted sequence. Both demonstrate low signal intensity and slightly irregular margins (arrow) suggesting a more aggressive lesion.

SALIVARY GLANDS

children, where there is a fear of radiation effects from CT. For more extensive lesions that have spread beyond the gland’s capsule, however, ultrasound does not provide the detailed information possible from CT and MR imagingm, 46, 57, 70 Usually, the ultrasound examination is performed with a linear high-frequency (7 to 10 MHz) transducer. This gives higher resolution images, but does not penetrate as deeply as lower megahertz transducers. Radionuclide salivary studies are based on the fact that the salivary glands normally concentrate technetium (Tc) 99m pertechnetate and some masses also excessively accumulate the radionuclide. Such masses, however, are not as accurately localized as on CT or MR imaging studies. In addition, masses that do not highly accumulate the radionuclide are poorly, if at all, seen. As a result, radionuclide sialograms are not routinely utilized to study parotid and submandibular gland masses. The lesions that most concentrate the Tc 99m pertechnetate are Warthin’s tumors and onco23 ~ytomas.’~, The use of skinny needle biopsy of salivary masses is becoming increasingly more accurate and the diagnostic yields are highest when a cytopathologist or a cytotechnologist is present at the time of the procedure to check the specimen for adequacy. The biopsy is performed with a 22gauge needle and can be done with or without CT or MR imaging guidance.’,34, 52 The use of imageguided biopsies of the parotid glands is variable depending on the surgical philosophy of the referring head and neck surgeons. At our institution, most surgeons feel that any parotid or submandibular gland mass should be removed and thus the skinny needle diagnosis is immaterial to the outcome. There is differing surgical opinion, however, as to whether all parotid masses need to be resected and at some institutions needle biopsy is used as a guide for treatment options.

949

NONNEOPLASTIC AND INFLAMMATORY CONDITIONS Viral and Bacterial Diseases

397

As a group, the acute viral and bacterial inflammatory diseases are the most common salivary gland abnormalities. Most of the bacterial infections ascend from the oral cavity and are related to a decrease in the salivary flow. The production of saliva can be decreased by prior infections; dehydration; trauma; surgery; radiation; some medications; and obstruct@g masses, such as stones or tumors.n The most common salivary gland viral disease is mumps.68 It primarily involves the parotid glands but can occur in the submandibular and sublingual glands. The disease is most reliably diagnosed during epidemics, and the diagnosis can be confirmed by measuring serum antibody titers? Other viruses that can cause parotitis include Coxsackie viruses; parainfluenza viruses (types I and 111); influenza virus type A; herpesvirus; echovirus; and choriomeningitis viIUS.~,a, Epstein-Barr virus and cytomegalovirus may be found in the saliva, but these viruses are not believed directly to affect the major salivary glands. Similarly, to date, HIV has not been shown directly to infect the salivary glands.19, When imaging a patient with an acute sialadenitis, the primary clinical concern is to differentiate between a sialadenitis without an abscess, which is routinely treated only with antibiotics, and sialadenitis with an abscess, which requires immediate surgery. This differentiation is easily accomplished on CT, where the involved gland is dense, enhances slightly, and is somewhat enlarged (Fig. 7). If an abscess is present, it is clearly seen as a localized lower-attenuation walled-off region (Fig. 8). The most common offending agents are Staphylococcus aureus, Streptococcus viridans, Haemophilus influenzae, Streptococcus pyogenes, Escherichia coli, 87s

Figure 7. Sialadenitis. A, Axial CT scan, right parotid. 6, Axial CT scan, left parotid. Both cases demonstrate skin thickening, injection of the subcutaneous fat, irregularity of the borders of the parotid gland, and increased attenuation within the gland reflecting cellular infiltration.

950

SILVERS & SOM

Figure 8. Parotid abscess. Axial CT, right parotid gland. There is a mucoid attenuation lesion with a thick wall (arrow) within the right parotid gland. The remainder of the gland shows typical changes of sialadenitis. There are secondary inflammatory changes in the overlying subcutaneous fat and skin.

and Streptococcus pneumoniae. Intraparotid and periparotid lymph nodes may be involved in the inflammatory reaction.64,n It is usually the undiagnosed or incompletely treated acute suppurative sialadenitis that develops an intraglandular abscess. Patients with such abscesses have fever and malaise, and rather quickly the abscess may extend into the parapharyngeal space or upper neck. Calcified sialolithiasis can be clearly identified on CT and may be located within the ductal system of the gland or within Stensen's or Wharton's duct. Occasionally, even a noncalcified stone can be identified in these ducts as the stone obstructs and dilated intraglandular ducts are seen proximally. Between 80% and 90% of salivary gland stones occur in the submandibular gland (Fig. 9), 10% to 20% occur in the parotid glands, and only 1%to 7% occur in the sublingual Most sialoliths are solitary; however, about 25% of patients with one stone have multiple stones.17* 77 In patients with chronic sialadenitis, at least one calculus is present in two thirds of the cases, and 80% of submandibular and 60% of parotid stones are radiopaque on plain films.* Nearly 85% of submandibular gland stones occur within Wharton's duct; 30% near the duct ostium, 20% in the middle portion of the duct, 35% at the bend in the duct as it goes around the back of the mylohyoid muscle, and only 15% occur in the hilum and gland Symptomatic parotid gland stones occur primarily in Stensen's duct; however, incidental asymptomatic small intraparotid ductal calculi are commonly seen on CT scans. If the cause of the interruption to salivary flow is near the buccal orifice of the duct, localized surgery may be curative. If the obstruction is more proximal in the main duct or in the gland, and if repeated infections have occurred, however, today the tendency is surgically to remove the gland. If the obstruction to salivary flow is complete, glandular atrophy

eventually occurs. If an incomplete obstruction occurs, the gland usually continues to produce saliva and a glandular mucocele may develop. The chronic inflammatory diseases of the major salivary glands may be due to recurrent bacterial infection, a granulomatous process, prior irradiation, autoimmune disorders, or be idiopathic. The radiologist should attempt to differentiate the obstructive and nonobstructive diseases, because the treatment and prognosis often vary considerably. The chronic nonobstructive diseases tend to involve the parotid glands with a greater frequency, whereas the obstructive disorders are more common in the submandibular glands. Chronic recurrent sialadenitis is clinically characterized by recurrent diffuse or localized painful swelling of the salivary gland and it is usually associated with an incomplete ductal obstruction. Autoimmune Disease

Sjogren's syndrome is a systemic autoimmune disorder of the exocrine glands that occurs either alone (primary Sjogren's syndrome) or with any of several connective tissue diseases (secondary Sjogren's syndrome). Traditionally, the diagnosis is established when two or more of the following clinical hallmarks are present: keratoconjunctivitis sicca; xerostomia; and a connective tissue disease, which usually is rheumatoid arthriti~."~ The autoimmune diseases represent a diffuse exocrinopathy that primarily affects the lacrimal and salivary glands. Other exocrine glands, however, can also be involved and cause symptoms, such as tracheobronchitis, dry skin, dysphagia, and atrophic vaginitis. Involvement of the glands of the gastrointestinal tract also can occur, but it is less frequent.38,42 Often, the involvement of these other exocrine gland systems is histologically present, but not clinically apparent. The actual incidence of Sjo-

SALIVARY GLANDS

951

Figure 9. Submandibular gland with stone. A, Axial and 6,coronal CT showing calcified stone (arrows) within right submandibular gland and hilum. C,A more caudal axial CT shows dilatation of the intraglandular ducts (curved arrow).

gren’s syndrome is difficult to establish because the symptoms can be nonspecific, and the specific autoimmune antibodies (SS-A and SS-B) may be elevated only during active disease or not at all. Among the autoimmune diseases, however, Sjogren‘s syndrome is considered second in frequency only to rheumatoid Previous terminology referring to this disease is confusing and has included recurrent parotitis in children, Mikulicz’s disease, and sicca syndrome. The childhood form of the disease is one tenth as common as the adult form, and children have a lower incidence of developing the advanced form of parotid disease.I3It is important to establish the diagnosis as early in the course of the disease as possible because many cases spontaneously resolve at puberty and unnecessary surgery prior to puberty can be avoided. There are only a few cases of recurrent parotitis in children that have

progressed into the adult form of Sjogren’s syndrome.6l The adult form of the disease is most common between the ages of 40 and 60 years and nearly 90% to 95% of the patients are women. In adults, the parotid disease tends to be progressive, occasionally requiring a parotidectomy to relieve the symptoms of recurrent infection.”, The incidence of parotid enlargement has varied from 25% to 55% of cases, and either parotid or submandibular gland enlargement occurs in 80% of all patients with Sjogren’s syndrome. The risk of developing non-Hodgkin’s lymphoma is estimated to be about 44 times greater in patients with Sjogren’s syndrome than in control subjects and the lymphoma may develop in both extraparotid and intraparotid sites.%,61 Local irradiation or immunosuppression (either secondary to therapy or a primary disease) further increases the risk of developing lymphoma.

952

SILVERS & SOM

Because Sjogren‘s syndrome initially involves the most peripheral intraglandular ducts and acini, in the initial stages of the disease the sialogram shows a normal central duct system and numerous peripheral punctate collections of contrast material uniformly scattered throughout the gland. These punctate changes are the earliest sialographic findings that are diagnostic of Sjogren‘s syndrome and they cannot be identified on CT or MR imaging. Eventually, larger globular collections of contrast material may also be seen uniformly scattered throughout the gland and once the disease destroys the acini, infection from the mouth results in a destroyed, abscessed gland, the so-called cuvit u y and desfrucfive forms of Sjogren’s syndrome.% If a secretogogue is given at the end of the sialogram, the contrast material drains from the main ducts, but remains within the punctate and globular collections. Occasionally, patients with chronic bacterial or granulomatous infection can develop multiple abscesses within the parotid gland. These collections tend to vary in size, and they are not usually uniformly distributed 96 throughout the On both CT and MR imaging in the earliest stages of Sjogren’s syndrome, the involved glands appear normal. As the disease progresses, glandular enlargement occurs and on CT the gland is denser than normal, a nonspecific finding. As the parotid disease continues to progress, on CT a honeycomb glandular appearance develops.58This CT appearance was once thought to be diagnostic of Sjogren’s syndrome. Other granulomatous diseases and even chronic sialadenitis, however, also can give similar CT findings. On MR imaging, once globular changes are present within the parotid glands, these collections can be seen on T1weighted images as discrete collections of low signal intensity. This MR imaging appearance is

diagnostic of Sjogren’s syndrome. Rarely, diffuse, bilateral macroscopic cystic change can develop. The cysts can vary from a few millimeters to several centimeters in diameter. When this occurs, the CT and MR imaging appearances in the parotid gland may be similar to those of the lymphoepithelial cysts associated with HIV infection (Fig. 10). A distinguishing feature is that in the autoimmune disease there is no diffuse cervical adenopathy, whereas such lymph node enlargement is part of the H N disease process. Sialosis

Sialosis or sialadenosis refers to a nonneoplastic, noninflammatory, nontender, chronic or recurrent enlargement of the parotid glands.13,69 Less commonly, the submandibular, sublingual, and minor salivary glands can also be affected.74The parotid disease is usually bilateral and symmetric, but can be unilateral or asymmetric. The onset is usually insidious and the disease is associated with a variety of endocrine diseases, nutritional states, and certain medications. Sialosis is especially prevalent in patients with diabetes, and the parotid gland enlargement may be the first clinical evidence of the underlying disease. Sialosis has also been associated with a variety of medications. With these pharmacologic sialoses both the submandibular and parotid glands may be involved, and the glandular swelling may be painful.42,60, 69 Sialosis may also lead to x e r ~ s t o m i a It .~~ has been suggested that a degeneration of the autonomic nervous system may be the common pathologic principle in all types of s i a l ~ s i s . ~ ~ On sialography, the parotid gland is enlarged, and the ducts are usually normal in appearance but splayed by the increased gland volume. On

Figure 10. Sjogren’s syndrome. Axial CT scan through the parotid glands of a patient with advanced Sjogren’s syndrome. There are diffuse cysts (arrowheads) throughout both parotids. There was no cervical adenopathy or nasopharyngeal lymphoid hyperplasia present, which distinguishes this from multiple lymphoepithelial cysts associated with HIV infection.

SALIVARY GLANDS

both CT and MR imaging, the parotid glands are enlarged, but may appear either dense or fatty depending on the dominant pathologic change. As such, the CT and MR imaging appearances are nonspecific and the diagnosis requires correlation with the clinical findings and the patient's history.ll1 Postirradiation Sialadenitis

Postirradiation sialadenitis can occur in either an acute or chronic form. Today, the acute type is rare and is characterized by a tender, painful swelling of the gland within 24 hours after it has been irradiated, usually by a single dose of 1000 cGy or more. These manifestations usually subside within 3 to 4 days, and there may be an associated transient xerostomia. The chronic form occurs in glands irradiated as part of a curative treatment plan, usually for oral cavity or pharyngeal tumors? After a full dose of irradiation, the gland atrophies and xerostomia occurs because of direct effects both on the major and minor salivary glands. CT and MR imaging usually show the involved gland(s) to be smaller than normal, cellular, and fibrotic. On CT these glands appear denser than normal, whereas on MR imaging the glands are usually of lower signal intensity than normal on most sequences. Only in the acute phase of this disease does the gland have a higher than normal T2-weighted signal intensity due to edema. External irradiation is a tumor promoter, with an increased incidence of salivary malignancies being found as a late sequela (10 to 25 years) in children who were irradiated for nonmalignant conditions." Granulomatous-type Diseases

These diseases may affect the intraparotid or juxtaglandular lymph nodes. The gland parenchyma can also be directly involved, and this may occur either as an ascending infection from the oral cavity or as part of a systemic process. The so-called granulomatous diseases that may involve the major salivary glands include sarcoidosis, tuberculosis, atypical mycobacterial infection, syphilis, cat-scratch fever, toxoplasmosis, and actinomycosis.n In reality, some of these infections do not actually produce histologic granulomata. Sarcoidosis is a systemic disease of presumed infectious etiology characterized by noncaseating granulomas involving multiple organ systems. The parotid glands are affected in 10% to 30% of patients, and in some cases the parotid disease may be the initial and only manifestation of the disease. In 83% of these patients bilateral parotid gland enlargement is present and in some patients involvement of the minor salivary glands can cause xerostomia.60,77, 94 In most patients a nontender, nonpainful, chronic enlargement of the

953

gland occurs. The gland is often multinodular and clinically may mimic a malignancy. The parotid glands can also be involved in patients with sarcoidosis who have uveitis and facial nerve paralysis. This triad of findings is called Heerfordt's syndrome. Most cases of such salivary gland sarcoidosis usually resolve as the underlying disease is treated. On CT and MR imaging, the parotid disease appears as multiple, benign-appearing noncavitating masses. In fact, these nodes are frequently radiographically described as being "foamy" in appearance and there is often an associated cervical adenopathy. The main differential diagnosis is lymphoma. If the sarcoid granuloma is a solitary parotid mass, however, it cannot be differentiated from the other benipappearing parotid lesions. Primary tuberculous involvement of the salivary glands is rare. For cases that do affect the salivary glands, 70% involve the parotid glands, 27% involve the submandibular glands, and only 3% involve the sublingual glands.= Most often the salivary disease arises from a focus in the tonsils or teeth and spreads to the gland via the regional lymph nodes. The clinical presentation may either be that of an acute tuberculous sialadenitis that can mimic other acute infections or a more indolent disease that may mimic a tumor." Similar to the clinical findings, the imaging findings are nonspecific. Cat-scratch (animal-scratch) fever is a granulomatous disease that may involve the parotid lymph nodes and mimic primary salivary gland disease.n Its radiographic findings can resemble either those of sarcoidosis or tuberculosis. Toxoplasmosis is caused by the protozoa Toxoplasma gondii, and this disease is one of the most common infections occurring in humans, infecting from 5% to 95% of the population, depending on geographic location. Most commonly the disease causes asymptomatic lymphadenopathy, and in the parotid region the disease may be indistinguishable from cat-scratch fever, sarcoidosis, and tuberculosis. Actinomycosis is caused by the bacterium Actinomyces israelii, and the disease in humans usually arises in the oral cavity of patients with poor dentition. The disease i s an indolent, chronic infection that invades the salivary glands from a focus usually in the mandible. Sinus tracts are commonly infected, and nodal disease can occur in and around the parotid gland and in the submandibular lymph nodes.= An inflammatory infiltration of the soft tissues usually occurs in association with the nodal disease, and this reaction usually involves the masticator space. Rarely, the disease can spread to the parotid gland in a retrograde manner from the mouth. The associated sinus tracts and masticator space disease allows this diagnosis to be suggested on CT and MR imaging. Cystic Lesions

Cystic lesions account for up to 5% of all salivary gland masses; however, if neoplasms are ex-

954

SILVERS & SOM

cluded, the number of true cysts is greatly reduced? The majority of the true cysts occur in the parotid gland and may be classified as either congenital or acquired. A cystic salivary gland lesion has a limited differential diagnosis. The imaging character of the cyst wall (i.e., thickness, nodularity) often allows further refinement of the differential diagnosis, which includes primarily Warthin’s tumor (either solitary or multiple) and lymphoepithelial cyst (either solitary as a result of any chronic infection or multiple as seen in HIV infection). Most commonly, with HIV infection there are multiple, bilateral parotid lymphoepithelial cysts with a diffuse cervical adenopathy (Fig. 11). In about one third of patients there are hyperplastic adenoids. The socalled intrapurotid brunchid cleft cyst is most likely a solitary lymphoepithelial cyst, because the parotid gland is not a branchial derivative. It is believed that the lymphoepithelial cyst arises from intranodal salivary inclusions, rather than from branchial cleft remnants.12A solitary lymphoepithelial cyst may develop in response to any chronic inflammatory disease with or without any relationship to an immune disorder. In distinction to those cysts that are entirely within the parotid gland, cysts that have a fistulous connection in or around the external auditory canal are clearly of a first branchial cleft origin. Less often, a cystic region can be seen in a low-grade mucoepidermoid carcinoma, the papillocystic variant of acinic cell carcinoma, an oncocytic cystadenoma, and either an abscessed node or a necrotic metastatic node. Rarely a dermoid cyst occurs and parotid cysts can occur in association with fibrocystic and polycystic disease? Many acquired cysts of the major salivary glands develop as a result of an obstruction to part of the ductal system that may be caused by a postinflammatory stricture, a calculus, trauma, a

postsurgical complication, or a mass. Almost always the ductal obstruction is incomplete or intermittent, because complete obstruction of the glandular ducts results in acinar and glandular atrophy rather than cyst formation.61,74 The resultant thinwalled cyst has been called a retention cyst, a mucocele of the major salivary gland, or an extravasation cyst. These cysts occur most often in the submandibular gland. When such a cyst arises in the sublingual gland, it is called a runulu. A sialocele arises when saliva accumulates within a cyst area that develops secondary to a complete or incomplete traumatic interruption of the excretory ducts draining the region. These sialoceles develop rapidly after trauma, and needle aspiration of saliva from the cyst confirms the diagnosis.22, The term runulu specifically refers to a mucous retention cyst in the sublingual gland, and the ranula occurs in two forms. A simple ranula, which is the most common form, is a retention cyst that remains in the floor of the mouth above the level of the mylohyoid muscle (Fig. 12). The simple ranula is a true cyst because it has an epithelial lining around its entire periphery. The deep or plunging ranula develops from the rupture of the wall of a simple ranula. As such, it usually extends below the level of the mylohyoid muscle, and in reality is a pseudocyst. Pathologically, inflammatory tissue forms part of the cyst wall where the irritating saliva penetrated into the muscles and soft tissues. The simple ranula occurs as a mass in the floor of the mouth, extending from the sublingual gland along the lingual border of the mandible toward the submandibular gland. The portion in the lateral floor of the mouth has been referred to as the tail of the ranula and is a fairly specific imaging finging. Because of the simple ranula’s location, the differential diagnosis includes a lateral der-

Figure 11. HIV-related disease. Axial CT. Numerous bilateral lymphoepithelial cysts (arrow) and cervical adenopathy (curved arrow). The presence of multiple cystic lesions within the parotid glands associated with cervical adenopathy and lymphoid hyperplasia should prompt the evaluation of a patient’s immune status even in patients who deny risk factors for HIV disease.

SALIVARY GLANDS

955

Figure 12. Ranula axial T2-weighted sequence. Ranula (arrow) extending posteriorly from right sublingual gland. The ranula extends from the floor of mouth into the subrnandibular triangle of the neck.

moid or epidermoid cyst, a lipoma, or a salivary gland tumor. The plunging ranula appears clinically as a painless mass in the submandibular or submental triangles of the neck, with or without evidence of a mass in the floor of the mouth. The differential diagnosis includes dermoid and epidermoid cysts, thyroglossal duct cysts, cystic hygroma, and lymphadenopathy (Fig. 13)." The cystic nature of the lesion is easily identified on CT; however, if postcontrast MR imaging is not used, a watery solid mass and a cyst may appear the same. On CT, the cyst contents usually have a watery attenuation and the cyst wall is easily identified. On postcontrast MR imaging, the cyst wall enhances whereas the cyst contents do not enhance. On MR imaging, most of the cysts have low T1-weighted signal intensity, but may have intermediate and even high signal intensity. Virtually all of the cysts have a high T2-weighted signal

intensity. Definition of the cyst wall thickness, smoothness, or uniformity may occasionally be made on T1-weighted images, but this is usually better accomplished on postcontrast fat suppressed studies.85,90, 112 A pneumocele of a major salivary gland results from the retention of air in the gland parenchyma or ductal system. This occurs after an increase in intrabuccal pressure. Although it is uncommonly associated with adult occupations, such as glass blowing and trumpet playing, it commonly occurs in children who cause retrograde insufflation of air into the gland via Stensen's or, less commonly, Wharton's duct.

TUMORS AND TUMORLIKE CONDITIONS Salivary gland neoplasms cause about 750 deaths a n n ~ a l l y . ~A* higher ,~ incidence of salivary

Figure 13. Obstructed submandibular duct simulates a ranula. Axial CT scan through the floor of mouth (A) and the submandibular gland (6)demonstrate a dilated submandibular gland duct. In 6,the duct can be followed back into the gland (curved arrow) confirming that this is not a ranula.

956

SILVERS & SOM

neoplasms has been reported in Eskimos, survivors of atomic bomb blasts, and those exposed to 78 previous radiation.77, Between 70% and 80% of parotid gland tumors, 40% and 58% of submandibular gland tumors, 15% and 30% of sublingual gland tumors, and 20% and 51% of minor salivary gland tumors are benign. Generally, these figures indicate that the smaller the salivary gland involved, the greater the likelihood that a tumor is malignant?,n,78 The TNM staging of salivary gland tumors according to the American Joint Committee on Cancer is weighted heavily on the size of the primary lesion (Table 1). By using this staging system, it becomes evident that the higher the stage, the greater the recurrence rate, the greater the incidence of metastasis, and the lower the survival rate. Although the overall cure rates traditionally are calculated on the basis of no evidence of disease for 5 years, several of the major salivary gland tumors, notably adenoid cystic carcinoma, may have late recurrences. Because of this, statistics citing 5 years of curability must be viewed with 77 Overall for predicting some circum~pection.~~, prognosis, this grading system overrides histology except for salivary ductal carcinoma, which by virtue of its diagnosis indicates a grave prognosis. Although salivary gland tumors are uncommon in children, there is a higher frequency of malignancies in children compared with adults. Of all epithelial and nonepithelial salivary gland tumors

in children, 35% are malig1ant.4~The most common tumors in the pediatric age group are hemangiomas, followed in descending frequency by pleomorphic adenomas, mucoepidermoid carcinomas, lymphangiomatous-type tumors, acinic cell carcinomas, and undifferentiated carcin0mas.4~ For all salivary gland malignancies, the presence of metastatic regional lymph node disease is a poor prognostic finding.4Similarly, facial nerve tumor invasion predicts an increased rate of nodal metastasis (66% to 77%) and thus an unfavorable prognosis. Overall, if the facial nerve is paralyzed at clinical presentation, the 5-year survival rate is only between 9% and 14%.The presence of distant metastasis is also associated with a very poor prognosis and about 20% of all parotid malignancies have distant metastasis.* The presence of pain is not necessarily a criterion of malignancy because 5.1% of benign tumors and 6.5% of malignant tumors present with parotid pain. Pain in a patient with a known malignancy, however, is a very poor sign. Overall, the 5-year survival rate in such patients with pain is 35%, compared with 68% in patients who do not have pain. The pain in these malignancies is principally secondary to neural invasion.8 In the past decade, the treatment philosophy for parotid gland malignancies has changed as the limitations of surgery for the more aggressive neoplasms have become known. Postoperative irradiation is now used frequently to improve local con-

Table 1. PAROTID TNM STAGING SYSTEM Primary Tumor (T) TX = primary tumor cannot be assessed TO = no evidence of primary tumor T1 = tumor 2 cm or less in greatest dimension without extraparenchymal extension T2 = tumor greater than 2 cm but not more than 4 cm in greatest dimension without extraparenchymal extension T3 = tumor more than 4 cm but not more than 6 cm in greatest dimension or tumor having extraparenchymal extension without seventh nerve involvement T4 = tumor more than 6 cm in greatest dimension or tumor invades skull base or seventh nerve Regional Lymph Nodes (N) NX = regional lymph nodes cannot be assessed NO = no regional lymph node metastasis N1 = metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension N2 = metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension, or multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension N3 = metastasis in a lymph node more than 6 cm in greatest dimension

Distant Metastasis (M) MX = distant metastasis cannot be assessed MO = no distant metastasis M1 = distant metastasis Stage Grouping Stage I = T1 or T2, NO, MO Stage II = T3, NO, MO Stage 111 = T1 or T2, N1, MO Stage IV = T4, NO, MO or T3 or T4, N1, MO or Any T, N2 or N3, MO or Any T, Any N, M1 From American Joint Committee on Cancer: Manual for Staging Cancer, ed 5. Philadelphia, JB Lippincott, 1997; with permission from the American Joint Committee on Cancer (AJCC), Chicago, IL.

SALIVARY GLANDS

trol, and chemotherapy is being utilized more often to control distant metastasis! What is clear from the literature is that imaging cannot be relied upon to provide a definitive histologic diagnosis. More important to the clinician than giving a specific pathologic diagnosis based on the imaging is to provide accurate tumor mapping. Has the tumor spread outside the confines of the gland? If so, is there bone or carotid artery invasion? What is the relationship of a parotid mass to the plane of the facial nerve? Are there metastatic lymph nodes? A brief discussion of key imaging findings on some of the more common tumors follows. Epithelial Tumors

The pleomorphic adenoma, also referred to as the benign mixed tumor, is the most common salivary gland tumor and represents 70% to 80% of all benign tumors of the major salivary glands. Of

957

all pleomorphic adenomas, 84% occur in the parotid gland, 8% in the submandibular gland, 6.5% in the minor salivary glands, and 0.5% in the sublingual glands. Of the parotid tumors, 90% arise lateral to the plane of the facial nerve (Fig. 14).74,n Although about 50% of all minor salivary gland tumors are malignant, the pleomorphic adenoma is still the single most common tumor of these glands.74 The lesions are usually solitary, ovoid, well-demarcated masses despite their having a capsule of variable thickness and completeness. The larger tumors may have pedunculated contour. The larger lesions can have sites of necrosis, hemorrhage, and focal calcification or occasionally ossif i ~ a t i o n They . ~ ~ are the most common salivary gland tumors to have calcifications and ossifications within the tumor matrix. Surgical extirpation with an intact capsule is essential to prevent seeding of the operative field. If such seeding occurs, multiple recurrences within the operative bed develop within 5 to 10 years after surgery (Fig. 15).

Figure 14. Pleomorphic adenoma. A, Axial CT. 6,Axial T1-weighted sequence. C,Axial T2-weighted sequence. 0,Axial postgadolinium T1-weighted sequence. W-defined lesion within the left parotid gland showing typical intermediate signal and moderate enhancement on T1-weighted sequences with high signal intensity on T2-weighted sequence.

958

SILVERS & SOM

Figure 15. Recurrent pleomorphic adenoma. A and 6, Coronal T2-weighted sequences showing cluster of grapes appearance (arrows).

Because of their grouping in the operative field, these tumors have been described as appearing as a cluster of grapes.I5,36, 95 The carcinoma ex pleomorphic adenoma is either a malignant change in a benign mixed tumor, in which elements of the benign lesion can still be identified, or the development of a malignant tumor in a patient known to have a previously resected pleomorphic adenoma (Fig. 16). Usually the malignancy is an adenocarcinoma, but any epithe-

lial subtype can and does occur in approximately 2% to 5% of all mixed tumors.74* 95 It has been estimated that left untreated, nearly 25% of all pleomorphic adenomas may undergo malignant change.74,95 The imaging of pleomorphic adenoma shows the typical picture of a benign-appearing mass. The smaller lesions are usually homogeneous in appearance and ovoid. The larger masses most often have a nonhomogeneous appearance, with

Figure 16. Carcinoma ex pleomorphic. A, Axial T1-weighted sequence. 6, Axial T2-weighted sequence. C, Axial T1-weighted sequence postgadolinium with fat suppression. On the axial T2weighted sequence, there is an area of decreased signal intensity (arrow) suggesting that a more aggressive lesion may be present. The area of nonenhancement (curved arrow) on the postgadolinium sequence also raises the possibility of malignant degeneration.

SALIVARY GLANDS

sites of lower attenuation representing areas of necrosis, and cystic change. Localized areas of increased attenuation most often represent sites of recent hemorrhage and are associated clinically with a sudden increase in tumor size and localized pain. The larger tumors tend to develop a lobulated contour that, when present, is highly suggestive of the diagnosis. A carcinoma ex pleomorphic adenoma may have one of several CT appearances. (1) It may look like a large pleomorphic adenoma with no evidence of malignancy. ( 2 ) It may look like a benign mixed tumor with a focally aggressive appearance. This aggressive area has a necrotic center, thick, irregular walls, and infiltrating margins. (3) Last, the tumor may be entirely aggressive in its appearance, with no remaining evidence of any benign pleomorphic adenoma. Warthin’s tumor, adenolymphoma or papillary cystadenoma lymphomatosum, is the second most common benign lesion of the parotid gland, representing 2% to 10% of all parotid tumors.74The lesion is exclusively limited to the parotid gland and the periparotid lymph nodes. As many as 10% of cases have bilateral involvement. It is also the most common lesion to occur as multifocal unilat-

959

eral and bilateral disease. The tumor is benign and most patients are in their fourth to seventh decades of life; this tumor is rarely found in nonwhites. Most Warthin’s tumors appear as small, ovoid, homogeneous, smoothly marginated masses in the posterior and inferior aspect of the superficial lobe (tail) of the parotid gland. Cyst formation is common, especially in larger tumors (Fig. 17). The cyst wall is usually thin and fairly smooth, but at some point there is a focal tumor nodule, differentiating it from a lymphoepithelial cyst. When a Warthin’s tumor is large and arises either from the periphery of the parotid gland or from a juxtaparotid lymph node, imaging confusion with a second branchial cleft cyst or a necrotic node possibly may occur. When multiple lesions are seen either in one parotid gland or bilaterally, the most likely diagnosis is Warthin’s tumors. The differential diagnosis includes lymphoepithelial cysts of HIV-positive patients and possibly multiple cavitated metastatic nodes. If the multiple Warthin’s tumors are solid, the imaging differential diagnosis includes lymphoma; granulomatous disease (primarily sarcoidosis); and benign adenopathy.@ Although mucoepidermoid carcinomas account

Figure 17. Warthin’s tumor. A, Axial CT bilateral and multiple Warthin’s tumor. B, Axial CT unilateral cystic Warthin’s tumor. There is slight nodularity of the cyst wall, differentiating this tumor from a benign cyst. Warthin’s tumors often present as multiple masses within one or both parotids. Cystic changes are common especially in larger lesions.

960

SILVERS & SOM

for less than 10% of all salivary gland tumors, they represent about 30% of the salivary gland malignancies. Nearly 50% of these lesions occur in the parotid gland, and about 45% arise in the minor salivary glands, primarily in the palate and buccal mucosa.5,74 In adults, mucoepidermoid carcinomas are the most common parotid gland malignancy and the second most common malignancy in the submandibular gland after adenoid cystic carcinoma. Mucoepidermoid carcinomas are also the most common salivary gland malignancies in children?*,74, These tumors can be classified histologically as low, intermediate, or high grade, and the grade correlates well with prognosis.4’ The imaging findings of mucoepidermoid lesions vary with the grade of the tumor. Low-grade lesions are benign in appearance. Cystic areas may be present and, rarely, focal calcification may be seen. The appearance is similar to that of a benign mixed tumor. By comparison, the high-grade lesions have indistinct infiltrating margins. Adenoid cystic carcinoma accounts for 2% to 6% of parotid gland tumors, 12% of submandibular gland tumors, 15% of sublingual gland tumors, 30% of minor salivary gland tumors, and 50% of lacrimal gland tumors.5,25, 74 Overall, 4% to 8% of all salivary gland tumors are adenoid cystic carcinomas, and they occur most commonly in the parotid gland, the submandibular gland, and the palate. The tumor usually arises in patients between 20 and 80 years of age and is rare in patients who are under 20 years old. Most patients are in the fifth and sixth decades of life. Although a relentless tumor, it may often have a slow rate of growth, so that prolonged survivals are reported even after metastases are present. Because of this, the true survival must be evaluated by looking beyond the usual 5-year survival figures. Perineural invasion (seen in 50% to 60% of cases) is a pathologic hallmark of this tumor and accounts for the relatively frequent clinical presentation with pain. On imaging, the parotid lesions tend to appear as benign well-delineated tumors, whereas the minor salivary gland neoplasms usually have malignant infiltrative margins. Retrograde tumor extension to the skull base often occurs via the facial nerve or the mandibular nerve. This neural invasion is best demonstrated by postcontrast MR imaging, where nerve enhancement and enlargement signify tumor spread (Fig. 18). Acinic cell carcinoma represents only 2% to 4% of all major salivary gland tumors. They occur almost exclusively in the parotid gland and represent 15% to 17% of all malignant parotid tumors. Bilateral parotid gland tumors occur in 3% of cases, making these tumors second only to Warthin’s tumor as being the most common parotid lesion to occur b i l a t e r a l l ~ .At ~ ~least , ~ ~ 80% of these tumors occur in the parotid gland; 4% in the submaxillary gland; and about 10% intraorally, primarily in the buccal mucosa or lip. These tumors

Figure 18. Perineural spread. Sagittal T1-weighted sequence through the parotid gland demonstrates a tumor within the parotid gland with thickening of the facial nerve (arrow) secondary to perineural spread.

usually occur in patients in their fifth and sixth decades of life. It should be noted, however, that acinic cell carcinomas are the second most common parotid malignancy (after mucoepidermoid carcinoma) in The 5-year survival rate is 80% to 90%, but the 20-year survival rate is only Metastases to regional lymph nodes occur in 10% to 19% of patients, and distant metastases (primarily to lung and bone) occur in nearly 15% of the 74 Tumor stage at the time of presentation is the most important survival pred i ~ t o r The . ~ ~ imaging characteristics of these tumors are nonspecific, with most lesions having a generally benign appearance. Salivary duct carcinoma is an uncommon, extremely aggressive malignancy that has a male predominance and a predilection for the parotid gland. Histologically, this tumor resembles breast carcinoma, replete with intraductal in situ carcinoma and comedonecrosis. This tumor may be confused histologically with mucoepidermoid carcinoma or squamous carcinoma and distant metastasis may develop. Following surgical resection, adjuvant radiotherapy is recommended. Survival is generally very poor and of the limited number of reported cases, 75% of the patients have died of their disease.’” 74 Despite the scores of well-recognized diagnostic categories of salivary tumors, some tumors persist in eluding current classification schemes. Because some form of gland formation is common to most of these tumors, the group is referred to as adenocarcinoma, not otherwise specified. These tumors usually are painful, rapidly enlarging masses and the majority of tumors occur at minor salivary gland sites (68%), followed by the parotid gland (28%) and the submandibular gland (4%). Although squamous epithelium is not a normal component of the salivary glands, squamous metaplasia can arise secondary to chronic inflammation. Primary squamous carcinomas of salivary origin represent 0.1% to 0.5% of all parotid tumors, and

SALIVARY GLANDS

3% to 10% of the malignant parotid neoplasms.", 33, 74 They account for 3% of submandibular gland neoplasms and 4% of the carcinomas. Approximately two thirds of the cases occur in the parotid glands, and most of the remaining cases occur in the submandibular glands. Before establishing the diagnosis of a primary salivary squamous carcinoma, the possibility must be considered of recurrence of a periparotid skin primary or metastasis to periparotid lymph nodes from another source, such as a carcinoma of the upper face or scalp, or much more rarely, an occult primary from the oral cavity, nasal cavity, or nasopharynx. The incidence of metastasis to the parotid gland from squamous cell carcinoma of the skin is believed to be more than twice the incidence of primary salivary gland squamous cell carcin0ma.7~ The imaging characteristics are those of a highgrade infiltrating tumor. Of the major salivary glands, the parotid glands are most frequently involved by metastatic disease. This fact reflects the presence of intraglandular lymph nodes, which drain the face, external ear, and scalp. The most common tumor to metastasize to the parotid glands and the periparotid lymph nodes is melanoma of the temporal scalp, which has such spread in 80% of the cases. In light of this, the diagnosis of primary melanoma of the parotid should virtually never be accepted. Parotid metastasis from melanomas in other areas of the head and neck occurs in approximately 50% of the cases. Less commonly, basal cell carcinomas, metastases from renal cell carcinomas (3% of literature cases), lung carcinomas (4% of literature cases), breast carcinomas (2.5% of literature cases), and gastrointestinal carcinomas YO of literature cases) can occur both to the intraparotid and periparotid lymph nodes.32,37, 43, 74 Nonepithelial Tumors

Nonepithelial tumors of the salivary glands represent less than 5% of all salivary gland neoplasms. In children, however, they may account for over 50% of the lesions.8,74 The only tumors of statistical consequence are hemangiomas, lymphangiomas, lymphomas, neurogenic lesions, lipomas, and sarcomas. Hemangiomas of the parotid gland represent 1% to 5% of all salivary gland tumors, but they are the most common salivary gland neoplasm in children.s,74, lO4 Submandibular gland involvement is rare, and in these cases it has been difficult to distinguish between tumors that arose within the gland and those that arose in the soft tissues adjacent to the gland. The congenital capillary hemangioma is the predominant tumor in the first year of life, representing 90% of parotid gland tumors in this age group. This lesion is usually discovered shortly after birth, is unilateral, compressible, and soft. Rapid enlargement can occur, and a bluish coloration can be seen in the overlying skin, espe-

961

cially when the infant is crying. There also may be an associated hemangioma in the overlying skin. These nonencapsulated and lobulated lesions are more common in girls. The differential diagnosis includes cystic lymphangioma and the rare, malignant hemangioendothelioma,both of which can be distinguished histologically. If possible, surgery is to be avoided until adulthood, because many of these tumors may spontaneously regress.74In addition, there are no known instances of malignant transformation of this lesion.1o4 Cavernous hemangiomas occur in older children and adults, with most patients being older than 16 years of age. These tumors tend to be wellcircumscribed lesions and involve the extraparotid tissues. Surgery is the treatment of choice, because spontaneous regression is unlikely.74Capillary hemangiomas appear to be very rare in the parotid gland. On CT these tumors enhance, are often lobular in contour, may be seen to extend to the overlying skin, or may have phleboliths within the tumor tissues. Often, the mass effect of the tumor on the surrounding soft tissues is relatively minimal, reflecting the soft nature of these lesions. On MR imaging, the majority of the lesions have a low to intermediate, nonhomogeneous T1-weighted signal intensity and a high T2-weighted signal intensity. There may be sites of high signal intensity on both T1-weighted and T2-weighted images, which are caused by prior hemorrhage and slow flow. There also can be vascular flow voids. Lymphangiomas are benign tumors that are composed primarily of lymphatic vessels. These tumors are classified as lymphangioma simplex, cavernous lymphangioma, and cystic lymphangioma or cystic hygroma. All three pathologic types may coexist within the same tumor. Most of the lesions that are found in the head and neck are cystic hygromas. Lymphangiomas represent 5% to 6% of all benign tumors of infancy and childhood, with 50% to 60% of the cases being present at birth. Between 80% and 90% of patients are diagnosed by the age of 2 years. This age range corresponds to the period of greatest lymphatic growth. It is uncommon for cystic hygromas to be reported in adults.7.44.90.97.104 Most commonly, these lesions arise in the posterior triangle of the neck. They can spread to invade the parotid and submandibular glands, muscles, and vessels. Most tumors are painless, soft or semifirm masses, and some fluctuation in size is common. Sudden enlargement is associated with infection or hemorrhage. Facial nerve paralysis can occur either secondary to nerve compression by a parotid lesion with hemorrhage, or secondary to an acute otitis media caused by a lesion obstructing the eustachian tube.97 On CT, these lesions are usually cystic masses filled with homogeneous low-attenuation material. The cysts usually have thin walls and most commonly there are multiple intercommunicating cystic components. Areas of higher attenuation within

962

SILVERS & SOM

the cysts usually correspond to sites of hemorrhage?7 Infection is identified by an enhanced, thickening of the cyst wall and infiltration of the adjacent soft tissues. In cases of multiple repeated infections, the attenuation of the cyst contents may approach that of muscle. On MR imaging, the signal intensities are typically low on T1-weighted images and high on T2-weighted images. Fluidfluid levels are commonly seen on MR imaging. Primary lymphoma of the salivary gland is very rare. This diagnosis can be made only if there is histologic proof of lymphoma in the salivary parenchyma without any evidence of intraglandular or extraglandular nodal involvement. Overall, provided that these patients do not have bone marrow involvement and are therefore stage IV lymphomas, the prognosis of stage I salivary lymphoma is good. At 5 to 8 years, 33% to 50% of patients are disease free.45The mean age is over 50 years, with only 10% of patients being younger than 30 years of age. Womeh represent 64% of the cases (Fig. 19). Secondary lymphomatous involvement of the salivary glands is also rare, with about 80% of the cases involving the parotid gland. The incidence of such salivary gland lymphoma varies from 1% to 8% of the cases of lymphoma. Most commonly, large cell lymphoma is the pathologic tumor type. All forms of non-Hodgkin’s and Hodgkin’s lymphomas, however, have been reported.n Because there is disseminated lymphoma outside of the parotid gland, the prognosis in these patients is poor. There is a well-documented relationship between Sjogren’s syndrome and non-Hodgkin’s lymphoma, as well as with HIV infection and Waldenstrom’s macroglobulinemia. The lymphomas usually are of the large cell type, are extraglandular, and ultimately have a poor prognosis. The CT appearance of secondary lymphoma of the parotid gland varies as the pathologic distribution of the disease. Most commonly, the parotid disease is confined to the intraparotid lymph

Figure 19. Lymphoma. Axial CT of lymphoma,left parotid gland. The appearance of lymphoma within the parotid gland is nonspecific and cannot be differentiated from other aggressive primary lesions of the parotid gland.

nodes. Each node is homogeneous and may enhance slightly on postcontrast CT scans. If the parenchyma is involved, a diffuse infiltration is seen either with poorly defined margins or with involvement of the entire gland. The identification of extraparotid nodal disease can be helpful in suggesting the diagnosis. On MR imaging the lymphoma tends to have a homogeneous intermediate signal intensity on all imaging sequences. Enlargement of an intraparotid lymph node can occur as a result of a variety of causes. These include hyperplastic adenopathy; acute viral or bacterial adenopathy; lymphoma; infectious granulomatous disease; and metastatic disease from primary sites in the scalp, periauricular region, face, or at a distant site below the clavicles. The rapid, painful nodal enlargement that usually accompanies inflammatory adenopathy may simulate a parotid malignancy, especially in children. Because about 5% of facial nerve paralysis is caused by acute otitis media, if there is also an associated ear infection, a facial nerve paralysis can be present. Clinically, the patient has a painful, rapidly growing parotid mass with an accompanying facial nerve paralysis and a tumor, such as a rhabdomyosarcoma, is suspected. In such cases, if an MR image is performed, the node usually has a fairly high T2-weighted signal intensity, whereas the high-grade malignancies tend to have low to intermediate T2-weighted signal intensity. Although this information can be helpful in distinguishing these entities, in most cases needle aspiration or surgery is necessary to establish the diagnosis. Such inflammatory nodes may enhance on postcontrast CT scans and have a slightly irregular margin as a result of the inflammatory reaction, further simulating a malignancy. Even when a parotid node is enlarged with metastatic disease, the mass may simulate a benign lesion on imaging. This is especially true in cases of metastatic melanoma from a facial or scalp primary. Lipomas can arise either within the parotid gland or in the immediate periparotid region. At times, it may be clinically and radiographically impossible to distinguish the true site of origin. Lipomas represent about 1%of parotid gland tumors, and approximately 90% of the cases are ordinary lipomas. The remaining lesions are either infiltrating lipomas, or they occurred as part of a 77, 93 lipomatosis syndrome.44, The ordinary lipomas are discrete lesions that usually have a homogeneously low attenuation ( - 65 to - 125 H). They have no definable capsule on imaging, yet they are easily delineated from the adjacent soft tissues (Fig. 20). The infiltrating lipoma is similar in appearance to the ordinary lipoma except with poorly defined margins and infiltration of adjacent muscles may be demonstrated on imaging. Hemorrhage and fibrotic changes can occur within lipomas; and on CT these changes may cause an increased attenuation that approaches that of muscle. Usually, these

SALIVARY GLANDS

963

Figure 20. Lipoma. Axial (A) and coronal (B) CT scans. This lesion is easily identified as a fat attenuation lesion without a definable capsule but can easily be separated from the more dense underlying structures and parotid gland (curved arrows).

changes are focal within the lipoma; however, the entire lesion may be hemorrhagic, rendering impossible the CT diagnosis. On MR imaging lipomas have a high T1-weighted and an intermediate T2-weighted signal intensity, which may be minimally heterogeneous. An important diagnostic point is that whenever a lipomatous mass has an overall heterogeneously dense matrix, it may represent a liposar~oma.~~ Neurogenic tumors of the parotid gland are the second most common benign mesenchymal neoplasm after vascular or lymphatic tumors. They may be either schwannomas or neurofibromas. Both lesions are usually ovoid, sharply delineated masses that arise primarily from the facial nerve trunk or its branches. The schwannomas are solitary, whereas the neurofibromas often are multiple and associated with other manifestations of neurofibromatosis type 1 (NF-1) or von Recklinghausen’s disease. On CT these tumors can enhance, be cystic, or be isodense with muscle. The cystic changes usually are small and multiple. The neurofibromas may have a low, almost fatty attenuation that may simulate a lipoma. On MR imaging these tumors are indistinguishable from other benign masses.47,48, 92 SUMMARY OF DISEASE PATTERNS

A history of recurrent parotid swelling, with or without associated pain, suggests an inflammatory process. A CT scan may identify a calcified sialolith, show the sialadenitis, or suggest Sjogren‘s syndrome or sialosis. On MR imaging, multiple collections of contrast material that are uniform in size and distribution throughout the gland suggest Sjogren’s syndrome. Salivary tumors in children are uncommon and represent less than 5% of tumors in all age groups. Hemangioma is the most common tumor, representing over 50% of all lesions. Next in decreasing

frequency are pleomorphic adenomas, mucoepidermoid carcinomas, lymphangiomas, and acinic cell carcinomas. Rarely, undifferentiated carcinomas, adenocarcinomas, and adenoid cystic carcinomas can occur. About 30% to 35% of the cases are malignant, a higher percentage than found in adults.8,49, 53,77 A solitary benign-appearing mass in a pediatric patient may also be inflammatory. Masses that result from autoimmune disease and chronic sialadenitis may on occasion simulate a parotid tumor, and intraparotid lymphadenopathy may also mimic a parotid neoplasm. A solitary benign-appearing mass in an adult patient is most likely a benign mixed tumor, a Warthin’s tumor, a low-grade mucoepidermoid carcinoma, a carcinoma ex pleomorphic adenoma, or an adenoid cystic carcinoma. A solitary malignant-appearing mass is most likely to be a highgrade mucoepidermoid carcinoma, an adenocarcinoma, or an undifferentiated carcinoma. Multiple masses suggest Warthin’s tumors, acinic cell tumors, lymphoma, granulomatous disease, oncocytic tumors, pleomorphic adenomas, or metastases. Multiple cystic masses, especially in association with benign cervical adenopathy, suggest that the patient is HIV positive. Multiple partially cystic masses are most likely Warthin’s tumors. A solitary cystic mass most likely is a lymphoepithelial cyst or a Warthin’s tumor. All salivary masses are probably better identified on MR imaging than on CT. Calcifications are better seen on CT, however, and when within the gland ducts indicate sialoliths. Calcification within a mass suggests a benign mixed tumor or, less commonly, a mucoepidermoid carcinoma. Phleboliths indicate a hemangioma. If the tumor accumulates Tc-99m pertechnetate, a Warthin’s tumor or an oncocytoma is present. If a tumor mass has low to intermediate signal intensity on all MR imaging sequences, a high-grade malignancy may be present. Although other entities can give these signal intensities, the high-

964

SILVERS & SOM

grade lesion is the most important one to rule out of the differential diagnosis. References 1. Abemayor E, Ljung BM, Ward PH, et al: CT-directed aspiration biopsies of masses in the head and neck. Laryngoscope 951382-1386, 1985 2. Ahuja A, Ying M, Yang WT, et al: The use of sonography in differentiating cervical lymphomatous lymph nodes from cervical metastatic lymph nodes. Clin Radiol 51:186-190, 1996 3. al-Deeb SM Herpes simplex encephalitis mimicking mumps. Clin Neurol Neurosurg 9549-53,1993 4. Andersen LJ, Therkildsen MH, Ockelmann HH, et al: Malignant epithelial tumors in the minor salivary glands, the submandibular gland and the sublingual gland. Cancer 68:2431-2437, 1991 5. Audair PL, Ellis GL, Gnepp DR, et al: Salivary gland neoplasms. General considerations. In Ellis G, Audair P, Gnepp D (eds): Surgical Pathology of the Salivary Glands. Philadelphia, WB Saunders, 1991 6. Bailey BJ: Trauma. In Cummings CW, Fredrickson JM, Harker LA, et a1 (eds): Otolaryngology-Head and Neck Surgery, vol 2. St. Louis, Mosby-Year Book, 1986, pp 1015-1026 7. Barnes L (ed): Surgical Pathology of the Head and Neck, vol 1. New York, Marcel Dekker, 1985, pp 725-880 8. Batsakis JG: Tumors of the Head and Neck Clinical and Pathological Considerations, ed 2. Baltimore, Williams & Wilkins, 1979 9. Batsakis JG, Chinn E, Regezi JA, et al: The pathology of head and neck tumors: Salivary glands, part 11. Head Neck Surg 1:167-180, 1978 10. Batsakis JG, chi^ EK, Weimert TA, et al: Acinic cell carcinoma: A clinico-pathologic study of 35 cases. J Laryngol Otol 93:325-340, 1979 11. Batsakis JG, Regezi JA: Selected controversial lesions of salivary tissues. Otolaryngol Clin North Am 10:309-328, 1977 12. Bhaskar SN, Bemier J L Histogenesis of branchial cysts: A report of 468 cases. Am J Pathol 35:407423, 1959 13. Bloch KJ: Sjogren’s syndrome. In Stein JH (ed): Internal Medicine. Boston, Little Brown & Co, 1983, pp 10341036 14. Boring CC, Squires TS, Tong T Cancer statistics 1993. In CA Cancer Clin 4338-19, 1993 15. Brandwein MS, Huvos AG: Oncocytic tumors of major salivary glands: A study of 68 cases with follow-up of 44 patients. Am J Surg Pathol 15514 528,1991 16. Brandwein MS, Jagirdar J, Patil J, et al: Salivary duct carcinoma (cribriform salivary carcinoma of excretory ducts): A clinicopathologic and immunohistochemical study of 12 cases. Cancer 65:23072314, 1990 17. Bryan RN, Miller RH, Ferreyro RI, et a1 Computed tomography of the major salivary glands. AJR Am J Roentgenol 139547-554, 1982 18. Casselman JW, Mancuso A A Major salivary gland masses: Comparison of MR imaging and CT. Radiology 165~183-189,1987 19. Chapnik JS, Noyek AM, Berris B, et al: Parotid gland enlargement in HIV infection: Clinical/imaging findings. J Otolaryngol 19:189-194, 1990 20. Chaudhuri R, Bingham JB, Crossman JE, et al: Mag-

netic resonance imaging of the parotid gland using the STIR sequence. Clin Otolaryngol 17211-217, 1992 21. Chen KTK, Hafez G R Infiltrating salivary ductal carcinoma: A clincopathologic study of five cases. Arch Otolaryngol 10737-39, 1981 22. Cholankeril JV,Ravipati M, Khedekar S, et al: Unusually large sialocele: CT characteristics. J Comput Assist Tomogr 13:367-368, 1989 23. Cogan MI, Gill P S Value of sialography and scintigraphy in diagnosis of salivary gland disorders. Int J Oral Surg 10:21&222, 1981 24. Coit WE, Hamsberger HR, Osborn AG, et al: Ranulas and their mimics: CT evaluation. Radiology 163211-216, 1987 25. Conley J, Dingman D L Adenoid cystic carcinoma in the head and neck (cylindroma). Arch Otolaryngol 100:81-90,1974 26. Dalimonte P, Cerofolini E, Leoni A, et al: 1.5T MR in the diagnosis of parotid masses: Comparison with ultrasonography. Eur J Radiol 9:224-230, 1989 27. Dardick I, Burford-Mason AP: Current status of histogenic and morphogenetic concepts of salivary gland tumorigenesis. Crit Rev Oral Biol Med 4:639677, 1993 28. Dardick I, Dardick AM, Mackay AJ, et a1 Pathobiology of salivary glands. IV Histogenetic concepts and cycling cells in human parotid and submandibular glands cultures in floating collagen gels. Oral Surg Oral Med Oral Pathol 76:307-318, 1993 29. Davis RA, Anson BJ, Budinger JM, et al: Surgical anatomy of the facial nerve and parotid gland based upon a study of 350 cervico-facial halves. Surg Gynecol Obstet 102:385-412, 1956 30. Diederich S, Roos N, Bick U, et a1 Diagnostic imaging of the salivary glands in children and adolescents. Radiologe 31:550-557, 1991 31. Donath K: Swellings of the cheek from sialosis. HNO 27113-118, 1979 32. Eneroth C M Salivary gland tumors in the parotid gland, submandibular gland and the palate region. Cancer 271415-1418, 1971 33. Evans RW, Cruickshank AH: Epithelial Tumors of the Salivary Glands. Philadelphia, WB Saunders, 1970, pp 242-278 34. Gatenby RA, Mulbem CB, Strawitz J: CT-guided percutaneous biopsies of head and neck masses. Radiology 146:717-719, 1983 35. Gibson J, Lamey PJ, Lewis M, et al: Oral manifestations of previously undiagnosed non-insulin dependent diabetes mellitus. J Oral Pathol Med 19:284287, 1990 36. Gnepp DR Malignant mixed tumors of the salivary glands: A review. Pathol Annu 28279-328, 1993 37. Gnepp DR Metastatic disease to the major salivary glands. In Ellis G, Auclair P, Gnepp D (eds): Surgical Pathology of the Salivary Glands. Philadelphia, WB Saunders, 1991 38. Godwin J: Benign lymphoepithelial lesion of the parotid gland (adenolymphoma, chronic inflammation, lymphoepithelioma, lymphocytic tumor, Mikulicz disease): Report of eleven cases. Cancer 5:1089-1103, 1952 39. Gooding G A Gray scale ultrasound of the parotid gland. AJR Am J Roentgenol 134:469472, 1980 40. Gray H: Anatomy of the Human Body. Philadelphia, Lea and Febiger, 1959, pp 1237-1241 41. Healey WV, Perzin KH, Smith L Mucoepidermoid carcinoma of salivary gland origin. Cancer 26:368388, 1970

SALIVARY GLANDS 42. Hudson NP: Manifestations of systemic disease. In Cummings CW, Fredrickson JM, Harker LA, et a1 (eds): Otolaryngology-Head and Neck Surgery, vol 2. St. Louis, Mosby-Year Book, 1986, pp 1007-1013 43. Johns ME: Parotid cancer: A rational basis for treatment. Head Neck Surg 3:132-141,1980 44. Johns ME: The salivary glands: Anatomy and embryology. Otolaryngol Clin North Am 10:261-271, 1977 45. Kapadia SB: Hematologic diseases: Malignant lymphomas, leukemias, plasma cell dyscrasias, histiocytosis X, and reactive lymph node lesions. In Barnes L (ed): Surgical Pathology of the Head and Neck, vol 2. New York, Marcel Dekker, 1985, pp 1045-1207 46. Kawamura H, Taniguchi N, Itoh K, et al: Salivary gland echography in patients with Sjogren's syndrome. Arthritis Rheum 33:505-510, 1990 47. Kumar AJ, Kuhajda FP, Martinez CR, et al: Computed tomography of extracranial nerve sheath tumors with pathological correlation. J Comput Assist Tomogr 723574365, 1983 48. Lack EE, Upton Ml? Histopathologic review of salivary gland tumors in children. Arch Otolaryngol Head Neck Surg 114:280-290, 1988 49. Lack EE, Upton Ml? Histopathologic review of salivary gland tumors in children. Arch Otolaryngol Head Neck Surg 11489fb906, 1988 50. Levitt SH, McHugh RB, Gomez-Marin 0,et al: Clinical staging system for cancer of the salivary gland A retrospective study. Cancer 47:2712-2724, 1981 51. Levv DM. ReMine WH. Devine K D Salivarv gland calchi. JAMA 181:1115-1119, 1962 52 Lufkin R, Teresi L, Hanafee W New needle for MRguided aspiration cytology of the head and neck. AJR Am J Roentgenol 149:380-382,1987 53. Luna MA, Batsakis JG, El-Naggar AK Pathology consultation: Salivary gland tumors in children. Ann Otol Rhinol Laryngol 100:869-871, 1991 54. Manashil GB: Clinical Sialography. Springfield, IL, Charles C Thomas, 1978, pp 74-81 55. Mancuso A, Rice D, Hanafee W. Computed tomography of the parotid gland during contrast sialography. Radiology 132:211-213, 1979 56. Mandelblatt SM, Braun IF, Davis PC, et al: Parotid masses: MR imaging. Radiology 163:411414, 1987 57. Mann W, Wachter W Ultrasonic diagnosis of the salivary glands. Laryngorhinootologie 67:355-361, 1988 58. March DE, Rao VM, Zwillenberg D Computed tomography of salivary glands in Sjogren's syndrome. Arch Otolaryngol 115:105-106, 1989 59. Marsot-Dupuch K, Brunereau L, Meyer B, et al: Parotid metastases: Value of imaging. Review of the literature apropos of 4 cases. Ann Otolaryngol Chir Cervicofac 108:338-342, 1991 60. Marx RE, Hartman KS, Rethman KV A prospective study comparing incisional labial to incisional parotid biopsies in the detection and confirmation of sarcoidosis, Sjogren's disease, sialosis and lymphoma. J Rheumatol 15:621-629, 1988 61. Mason DK, Chisolm DM: Salivary Glands in Health and Disease. London, WB Saunders, 1975, pp 37-69 62. McGhee RB Jr, Chakeres DW, Schmalkbrock P, et al: The extracranial facial nerve: High resolution threedimensional fourier transform MR imaging. AJNR Am J Neuroradiol 14465-472, 1992 63. Mees K, Vogl T, Kellermann 0 Magnetic resonance tomography in tumors of the salivary glands-A .I"

965

diagnostic advantage? Laryngolrhinolotologie 6 7 355-361, 1988 64. Miglets AW Infections, Part 111. Clinical entities. In Cummings CW, Fredrickson JM, Harker LA (eds): Otolaryngology-Head and Neck Surgery, vol2. St. Louis, Mosby-Year Book, 1986, pp 999-1006 65. Mihalyka EE: Congenital bilateral polycystic parotid glands. JAMA 18k634-635, 1982 66. Mirich DR, McArdle CB, Kulkarni MV Benign pleomorphic adenomas of the salivary glands: Surface coil MR imaging versus CT. J Comput Assist Tomogr 11:620423, 1987 67. Morris MR, Moore DW, Shearer GL: Bilateral multiple benign lymphoepithelial cysts of the parotid gland. Otolaryngol Head Neck Surg 9787-90, 1987 68. Moss-Salentijn L, Moss ML: Development and functional anatomy. In Rankow RM, Polayes IM (eds): Diseases of the Salivary Glands. Philadelphia, WB Saunders, 1976, pp 17-31 69. Moutsopoulos HM, Chused TM, Mann DL, et al: Sjogren's syndrome (sicca syndrome): Current issues. Ann Intern Med 92212-226, 1980 70. Neiman HL, Phillips JF, Jaques DA, et al: Ultrasound of the parotid gland. J Clin Ultrasound 4:1113, 1976 71. Olsen WL, Jeffrey RB Jr, Sooy CD, et al: Lesions of the head and neck in patients with AIDS CT and MR findings. AJNR Am J Neuroradiol 9:693-698, 1988 72. Panush D, Fulbright R, Sze G, et al: Inversion-recovery fast spin-echo imaging: Efficacy in the evaluation of head and neck lesions. Radiology 187421426, 1993 73. Parker GD, Hamsberger HR: Clinical-radiologic issues in perineural tumor spread of malignant diseases of the extracranial head and neck. Radiographics 11:38%399, 1991 74. Peel RZ, Gnepp D R Diseases of the salivary glands. In Barnes L (ed): Surgical Pathology of the Head and Neck, vol 1. New York, Marcel Dekker, 1985, pp 535-552 75. Pownell PH. Brown OE. Pranskv SM. et al: Connenital abnormalities of the submkdibular duct. k t J Pediatr Otolaryngol 24:161-169, 1992 76. Pretorius D, Taylor A: The role of nuclear scanning. Head Neck Surg 4:427-432, 1982 77. Rabinov K, Weber A L Radiology of the Salivary Glands. Boston, G Hall & Co, 1985, pp 153-166 78. Rankow RM, Polayes I M Surgical treatment of salivary gland tumors. In Rankow RM, Polayes IM (eds): Diseases of the Salivary Glands. Philadelphia, WB Saunders, 1976, pp 239-283 79. Rice DH, Becker T Magnetic resonance imaging of the salivary glands: A comparison with computed tomographic scanning. Arch Otolaryngol Head Neck Surg 113:78-80, 1987 80. Roebker JJ, Hall LC, Lukin RR: Fractured submandibular gland: CT findings. J Comput Assist Tomogr 15:1068-1069. 1991 81. Schall GL: Tke role of radionuclide scanning in the evaluation of neoplasms in the salivary glands: A review. J Surg Oncol 3:699-714, 1971 82. Schall GL, Smith RR, Barsocchini LM: Radionuclide salivary imaging usefulness in a private otolaryngology practice. Arch Otolaryngol 1 0 7 4 0 4 , 1981 83. Scoidt M, Greenspan D, Levy J, et al: Does HIV cause salivary gland disease? AIDS 393194322, 1989 84. Shugar JMA, Som PM, Biller HF Warthin's tumor: A multifocal disease. Ann Otol Rhinol Laryngol 91:24&249, 1982

966

SILVERS & SOM

85. Shugar JMA, Som PM, Jacobson AL, et a1 Multicentric parotid cysts and cervical adenopathy in AIDS patients; a newly recognized entity: CT and MR manifestations. Laryngoscope 98772-775, 1988 86. Sigal R, Monnet 0, de Baere T, et a1 Adenoid cystic carcinoma of the head and neck Evaluation with MR imaging and clinical-pathologic correlation in 27 patients. Radiology 184:95-101, 1992 87. Skolnick PR, Kosloff BR, Hirsch MS: Bidirectional interactions between human immunodeficiency virus type 1 and cytomegalovirus. J Infect Dis 157508-513, 1988 88. Smith FW, Deans HE, McLay JCA, et al: Magnetic resonance imaging of the parotid glands using inversion-recovery sequences at 0.08T. Br J Radiol 61:480-491, 1988 89. Snyderman NL, Suen JY Neoplasms. In Cummings CW, Schuller DE (eds): Otolaryngology-Head and Neck Surgery, vol 2. St. Louis, Mosby-Year Book, 1986, pp 1027-1069 90. Som PM: Cystic lesions of the neck. Postgrad Radiol 7211-236, 1987 91. Som PM, Biller HF: The MR identification of highgrade parotid tumors. Radiology 173:823-826, 1989 92. Som PM, Biller HF, Lawson W, et al: Parapharyngeal space masses: An updated protocol based upon 104 cases. Radiology 153:149-156, 1984 93. Som PM, Scherl MP, Rao VM, et al: Rare presentations of ordinary lipomas of the head and neck: A review. AJNR Am J Neuroradiol 7657-664, 1986 94. Som PM, Shugar JMA, Biller HF: Parotid gland sarcoidosis and the CT-sialogram. J Comput Assist Tomogr 5:674-677, 1981 95. Som PM, Shugar JMA, Sacher M, et al: Benign and malignant parotid pleomorphic adenomas: CT and MR studies. J Comput Assist Tomogr 12:6549, 1988 96. Som PM, Shugar JMA, Train JS, et al: Manifestations of parotid gland enlargement Radiographic, pathologic, and clinical correlations. I. The autoimmune pseudosialectasias. Radiology 141:415419, 1981 97. Som PM, Zimmerman RA, Biller H F Cystic hygroma and facial nerve paralysis: A rare association. J Comput Assist Tomogr 8110-113, 1984 98. Sperber G H Craniofacial Embryology, ed 4. London, Wright, 1989, pp 188-191 99. Spratt JS Jr: Etiology and therapy of acute pyogenic parotitis. Surg Gynecol Obstet 112391405, 1961 100. Tabor EK, Curtin H D MR of the salivary glands. Radiol Clin North Am 27379-392, 1989

101. Teresi LM, Lufkin RB, Wortham DG, et al: Parotid masses: MR imaging. Radiology 163405409, 1987 102. Thackray AC, Lucas R B Tumors of the Major Salivary Glands. Atlas of Tumor Pathology. Washington, DC,Armed Forces Institute of Pathology, 1974, pp 1-15 103. Tien RD, Hesselink JR, Chu PK, et al: Improved detection and delineation of head and neck lesions with fat suppression spin-echo MR imaging. AJNR Am J Neuroradiol 12:19-24, 1991 104. Touloukian RJ: Salivary gland diseases in infancy and childhood. In Rankow RM, Polayes IM (eds): Diseases of the Salivary Glands. Philadelphia, WB Saunders, 1976, pp 284-303 105. Trappe M, Marsot-Dupuch K, Le Roux C: Study of the salivary glands in 1990. Ann Radiol (Paris) 34:114-117, 1991 106. Tunkel DE, Loury MC, Fox CH, et al: Bilateral parotid enlargement in HIV seropositive patients. Laryngoscope 99:545-590,1989 107. Vogl TJ, Balzer J, Grevers G: Magnetic resonance tomography in questionable lesions of the ENT area: Examination technique and results of a prospective study of 1,493 patients. Laryngorhinootologie 71: 439452, 1992 108. Vogl TJ, Dadashi A, Jassoy A, et al: The 31-phosphorus spectroscopy of space occupying lesions of the salivary glands. The clinical results and differential diagnosis. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 158:31-38, 1993 109. Vogl T, Wilimzig C, Assal J, et al: 3D MR imaging with Gd-DTPA in head and neck lesions. Eur J Radiol 1:151-157, 1991 110. Waldhart E, Lynch JB: Benign hypertrophy of the masseter muscles and mandibular angles. Arch Surg 102:115-118, 1971 111. Whyte AM, Bowyer FM: Sialosis diagnosed by computed tomography. Br J Radiol 60400-401, 1987 112. Work WP: Cysts and congenital lesions of the parotid gland. Otolaryngol Clin North Am 10339-343, 1977 113. Work WP, Hecht DW: Inflammatory diseases of the major salivary glands. In Paparella MM, Shumrick DA (eds): Otolaryngology, vol 3, Philadelphia, WB Saunders, 1973, pp 258-265 114. Wotson S, Mandel I D The salivary secretions in health and disease. In Rankow RM, Polayes IM (eds): Diseases of the Salivary Glands, Philadelphia, WB Saunders, 1976, pp 32-53 Address reprint requests to

Adam R. Silvers, MD Department of Radiology Box 1234 The Mount Sinai Hospital One Gustave Levy Place New York, NY 10029