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Home , Acinus, Buccal fat pad, Duct (anatomy), Gland, Hard palate, Palate

1 THE NORMAL SALIVARY

The salivary system is composed of This text focuses on the salivary glands proper exocrine glandular arranged as three but recognizes the relationship to the airway paired, large aggregations, known collectively seromucous glands. as the major salivary glands, and numerous, The basic structure of a tissue nonuniformly distributed, small aggregations in is a branching tubule or that has the princi- the mucosa of the oral cavity, referred to as the pal secretory cells, the acinar cells, at the ends of minor salivary glands. The major salivary glands the branches and an opening into the oral cavity are the parotid, submandibular (submaxillary), at the other end of a single collecting duct. The and sublingual glands. The major and minor basic salivary gland unit has morphologically and salivary glands produce the fuids that consti- functionally varying segments: , intercalated tute oral . All salivary glands share a basic duct, striated duct, and excretory duct (fg. 1-1). structure, but there are site-specifc variations in These segments have a bilayered cellular compo- function, , and gross and microscopic sition of luminal cells and abluminal peripheral features that infuence the frequency and types cells. The abluminal cells are identifiable as of associated . myoepithelial cells in the distal portion of the The seromucous glands of the , gland (acinus and intercalated duct) and basal , larynx, and bronchi are morpholog- cells in the proximal portion of the gland (ex- ically and functionally similar to many of the cretory duct). There are two types of acinar cells, oral minor salivary glands but, strictly speaking, serous and mucous, whose secretions differ; the are not salivary glands because they do not proportion of each type varies by anatomic contribute to the saliva. Some investigators, site. The chemical composition of the saliva from however, include tumors of the airway seromu- a specifc gland is dependent on the relative pro- cous glands in discussions of salivary neoplasia portion of these two acinar cell types. Table 1-1 because some tumors in these sites are similar is a simplistic description of the distribution of or identical to tumors of the salivary glands. acinar cell types among various salivary glands.

Figure 1-1 SCHEMATIC OF BASIC SALIVARY GLAND UNIT Cytomorphologic features of various portions of the salivary system from the secretory end piece, left, to the oral cavity, right.

1 Tumors of the Salivary Glands

Table 1-1 ACINAR CELL TYPES IN VARIOUS SALIVARY GLANDS

Salivary Gland Type of Acinia Parotid Serous Submandibular Serous and mucous Sublingual Mucous and serous Mucous Mucous and serous Mucous and serous Buccal mucosa Mucous and serous

aPredominant type frst.

DEVELOPMENT All salivary glands, major and minor, are de- rived from the mucosal of the oral cavity. Salivary gland development begins in the ffth to sixth weeks of embryonic life when the primordia appear. This is fol- lowed by the appearance of the submandibular primordia at the end of the sixth week and the sublingual primordia at about the seventh to eighth weeks (23,29,36). The numerous intra- oral minor salivary glands develop during the third month of gestation (23). The salivary gland primordia initiate as buds of proliferative epithelium from the primitive (oral cavity). The stomodeal epithe- lium is part ectoderm and part endoderm. The parotid gland primordia develop from the oral ec- toderm while the submandibular and primordia probably arise from endoderm Figure 1-2 (23,36). The parotid gland epithelial buds form FETAL DEVELOPMENT OF SALIVARY GLANDS between the maxillary and mandibular processes Top: The origin of the parotid gland, submandibular of the mandibular arch in the area of the future gland, and sublingual gland from the epithelial lining of right and left . The primordia of the sub- the primitive stomodeum is illustrated in the schematic drawing of the oral cavity in a 9-week-old embryo. mandibular glands grow from the foor of the Bottom: Section through the fetal tongue, linguogingival oral cavity between the lower and tongue, groove, and buccal mucosa shows the proliferative epithelial the linguogingival groove, on each side of the cord of the developing parotid gland (arrow). midplane. The sublingual gland primordia arise as several epithelial buds adjacent to the develop- ing submandibular glands (fg. 1-2). The epithe- At the end of each solid cord of epithelium lial buds continue to proliferate as strands into of the developing salivary glands, a cluster of the underlying oral ecto mesen chyme, which epithelial cells forms the terminal bulb. Clefts increases in cellularity around the developing develop in the terminal bulbs, and these newly glands and has a role in the lobular organization formed bulbs proliferate into the ectomesen - of the glands and encapsulation of the parotid chyme as branches from the original cord. and submandibular glands (23,36). This process of cord-like proliferation, bulb

2 The Normal Salivary Glands

Figure 1-3 Figure 1-4 FETAL PAROTID GLAND FETAL PAROTID GLAND Many tubules of epithelium within a loose connective The epithelial tubules are composed of a double layer tissue stroma are in the early stages of luminization, but of cells. The inner cells differentiate into duct-luminal and cellular differentiation into acini, intercalated ducts, and serous acinar cells while the peripheral cells differentiate striated ducts is not evident at this stage of development. into myoepithelial and basal cells.

formation, bulb clefting, and further prolifera- After luminization but before cellular differ- tion continues in a repetitive manner (23). Each entiation, the terminal bulbs are referred to as new cord of epithelium remains contiguous terminal tubules and saccules. The epithelium with the preceding cord so that continuity with of the terminal tubules and saccules has two the oral epithelium is maintained. layers (fg. 1-4). The inner, luminal layer of Initially, the epithelial cords and bulbs are cells, differentiates into acinar and intercalated without lumens. Lumin ization occurs frst in duct cells, and the outer layer differentiates into the epithelial cords and progresses to the ter- myoepithelial cells (23). Complete maturation minal bulbs (fg. 1-3). Along with lumen devel- of the salivary glands does not occur until after opment, cellular differentiation results in the birth (36). characteristic features of excretory ducts, striat- At about the third month of gestation the pa- ed ducts, intercalated ducts, and acini (23). The rotid gland is colonized by lymphocytes. These proximal branched cords become excretory and eventually develop into several intraparotid and main ducts, the distal branched cords become periparotid nodes and lymphoid nodules striated ducts, and the luminized terminal bulbs that lack the complete organization of a lymph become intercalated ducts and acini. node (36).

3 Tumors of the Salivary Glands

is confned by the styloid process and stylo- mandibular ; , stylohyoid, stylopharyngeal, and digastric muscles; and ca- rotid sheath. Anteriorly, this deep portion of the gland lies against the medial pterygoid muscle (fg. 1-6). Laterally, the gland is only covered by and subcutaneous adipose tissue. Fibrous and adipose tissues from the deep cervical fas- cia encapsulate the gland. The gland is in close contact or embraces several important struc- tures including the internal jugular and branches, external carotid and branches, lymph nodes, auriculotemporal branch of the trigeminal , and (20,23,29,36). The secretions of the gland fow through a duct system that converges to a single duct, the Stensen duct, which is 4 to 7 cm in length. This duct exits the gland along its anterior edge, traverses across the lateral surface of the mas- seter muscle, penetrates the buccal pad and just anterior to the anterior edge of the , and opens into the oral cavity on the buccal mucosa opposite the . Accessory parotid gland tissue is found along the anterior portion of the Figure 1-5 gland and Stensen duct in about 20 percent of ANATOMIC RELATIONSHIP OF PAROTID people (fg. 1-5) (36). AND SUBMANDIBULAR GLANDS Although the parotid gland is a single con- The anatomic position and relationship of the parotid tiguous structure, surgically it is convenient to and submandibular glands to the , zygomatic arch, , and masseter muscle are seen in a lateral view conceptualize a superfcial (or lateral) and a deep of the head. The parotid gland duct (Stensen duct) crosses (or medial) that are separated by the course the masseter muscle and penetrates the buccal tissues. of the facial nerve through the gland (20,29). Lobules of accessory parotid tissue are located along the The majority of neoplasms occur in the super- course of the duct. fcial portion of the gland. The facial (cranial nerve VII) nerve emerges from the stylomastoid GROSS ANATOMY foramen and immediately enters the posterome- dial surface of the parotid gland. As it enters the Parotid Gland gland, the nerve divides into two main trunks The parotid gland is the largest of the salivary that further branch and then course in superior, glands and in adults weighs 15 to 30 g (23,36). anterior, and inferior directions in a generally It is roughly triangular shaped, with the apex similar mediolateral plane. The posterior edge just inferior to the and of the ramus of the mandible also impinges the more superior base of the triangle along the upon the gland, and the gland narrows from zygomatic arch (fg. 1-5). The anterior portion of the superfcial to the deep portions. For tumors the gland lies along the ramus of the mandible, that arise in the deep portion of the gland, the slightly over the posterior edge of the masseter path of least resistance for expansion is into the muscle. Posteriorly, the gland is bounded by . These tumors, therefore, the ear, the mastoid process, and the anterior manifest as pharyngeal swellings rather than edge of the sternocleidomastoid muscle. The the facial swellings that develop with the more deep, medial portion of the gland extends into frequently occurring tumors of the superfcial the retroman dibular parapharyngeal area and lobe (fg. 1-6) (29).

4 The Normal Salivary Glands

Figure 1-6 ANATOMIC RELATIONSHIP OF PAROTID GLAND Left: A horizontal section through the lateral portion of the pharynx and mandible at the level of the mastoid process shows the parotid gland traversed by the facial nerve. The deep portion of the gland narrows and is bounded by the posterior ramus of the mandible, muscles of the styloid process, and medial pterygoid muscle. Right: Tumors that arise within the deep portion of the gland may expand into the lateral pharyngeal space and produce swelling of the lateral pharyngeal wall.

Secretomotor innervation of the parotid gland is by parasympathetic nerve fbers via the ninth cranial nerve, although the nerve fbers enter the gland by way of the and after a complicated course (2,20). Sympathetic fbers accompany the vessels. Interruption of the parasympa- thetic nerve pathways results in atrophy of the gland (2,20). The blood supply and drainage are via branches of the external carotid and (29,36). The intimate relationship between parenchy- mal and lymphoid tissue in the parotid gland is unique among salivary gland tissues. During embryonic development, the parotid gland is seeded with lymphoid cells that develop into several lymph nodes within and around the parenchymal tissue (fg. 1-7) (36). In a study of parotid glands from adult cadavers, McKean et al. (40) found that the number of parotid lymph nodes varied from 3 to 24 per gland. Not all lymphoid tissue in the parotid gland develops the complete structural organization of most lymph nodes, such as a capsule and subcapsular and medullary sinuses. So the count of lymph Figure 1-7 nodes in the parotid gland is infuenced by how strict is one’s defnition of a . Over GLANDULAR LYMPH NODES 90 percent of the parotid lymph nodes that The parotid gland has several periparotid and intraparotid these researchers found were lateral to the facial lymph nodes that drain portions of the ear, temporal region, lateral , eyelids, and conjunctiva. They in turn drain nerve, in the superfcial portion of the gland. into the internal jugular lymph nodes. The submandibular These lymph nodes drain the anterolateral lymph nodes are all extraglandular.

5 Tumors of the Salivary Glands

Figure 1-8 THE MAJOR SALIVARY GLANDS The medial surface of the mandible and shows the relationship of the submandibular, sub-lingual, and parotid glands. The (Wharton duct) runs anteriorly to the anterior foor of the .

portion of the auricle and external auditory me- within this capsule, but three to six lymph atus, skin of the temporal and fronto temporal nodes lie adjacent to the gland in the subman- region, root of the , eyelids and conjuncti- dibular triangle (fg. 1-7) (41). These lymph va, tympanic cavity, and the parotid gland itself nodes receive afferent vessels from the nose, (61). These lymph nodes drain into the cervical , , lateral part of the foor of the mouth, lymph nodes along the anterior aspect of the anterior and lateral portions of the tongue, sternocleidomastoid muscle. and , and send efferent vessels into the along the Submandibular Gland and sternocleidomastoid The submandibular gland is the second larg- muscle (41,61). The blood supply and drainage est salivary gland and weighs approximately 7 of the gland are by the lingual and facial arteries to 15 g (23,29,36). It occupies a large portion of and the anterior (29). The gland is the , which is formed innervated by parasympathetic secretomotor by the inferior border of the mandible and the fbers of the facial nerve and sympathetic anterior and posterior bellies of the digastric (36). Unlike the parotid gland, no large nerves muscle (fg. 1-5). Superiorly, the submandibular course through the parenchyma of the gland. space is bounded by the mylohyoid muscle. The Sublingual Gland posterior extension of the submandibular gland rises upward and around the posterior edge of the The sublingual gland is the smallest of the mylohyoid muscle and into the major salivary glands and weighs about 2 to 4 of the foor of the oral cavity (fg. 1-8) (23,29). g (23,29,36). It lies above the mylohyoid muscle Like the parotid gland, the duct system con- in the lingual sulcus of the foor of the mouth, verges into a single main excretory duct, the between the tongue and the sublingual fossa Wharton duct. This duct extends about 5 cm of the mandible (fg. 1-8). Its superior aspect is from the superior portion of the gland in an covered only by . Unlike the parotid anterior direction in the lingual sulcus to an and submandibular glands, the sublingual gland opening, the sublingual caruncula, adjacent to has several ducts that connect to the oral cavity. the lingual frenum in the anterior foor of the The largest of these, the Bartholin duct, opens mouth. The openings of the paired subman- into the submandibular duct just posterior to dibular glands are only a few millimeters apart the sublingual caruncula (23). Several smaller (fg. 1-9) (29,36). ducts, the Rivinus ducts, open directly into the The submandibular gland is enveloped in a oral cavity (23,36). The blood supply is from the fne fbrous capsule. There are no lymph nodes sublingual and submental arteries, and venous

6 The Normal Salivary Glands

Figure 1-9 WHARTON DUCTS The right and left submandib- ular ducts (arrows) course antero- medially in the foor of the mouth to openings at the lingual carun-culae, which are only a few milli-meters apart.

drainage is via tributaries of the (36). Innervation is from parasympathetic fbers of the facial nerve (36). Minor Salivary Glands It is estimated that there are 500 to 1,000 lobules of minor salivary gland tissue dispersed within the mucosa of the oral cavity (23,29). These intraoral glands usually are not clinically evident, although salivary lobules often can be palpated in the lips. For the most part, salivary gland lobules are 1 to 5 mm in size and are sep- arated from one another by . Glands in the posterior are more Figure 1-10 numerous and more confuent. Most lobules PAROTID GLAND ACINI have individual excretory ducts that open into The rounded acini are serous type and composed of the oral cavity, but these duct orifces are not several pyramidal-shaped cells with basal nuclei and bluish usually perceptible on the normal oral mucosa. purple, granular cytoplasm (hematoxylin and eosin [H&E] stain). six cells in a two-dimensional plane of section Parotid Gland (fg. 1-10). Each acinus surrounds a tiny lumen, Within the parotid gland, the main excretory although it is frequently not discernible in the duct branches into smaller interlobular ducts, plane of section, and the acinus itself is sur- which in turn branch into many, even smaller, rounded by a basement membrane. The serous intralobular striated ducts. The striated ducts cells are roughly triangular or trapezoidal in likewise divide into numerous intercalated shape, with the narrowest part of the cells at ducts, which are connected to the terminal the luminal surface. secretory structures, the acini. The acini of the The abundant cytoplasm contains numerous parotid gland are nearly 100 percent serous, basophilic zymogen granules, the secretory although occasionally there are a few mucous granules (fg. 1-10), but the number of cytoplas- type acini. The serous acinar cells are arranged mic granules varies with the secretory phase of in small, roughly spherical clusters of three to the cell. The granules stain with the periodic

7 Tumors of the Salivary Glands

Figure 1-11 Figure 1-12 PAROTID GLAND ACINI INTERCALATED DUCT The cytoplasmic zymogen granules stain with periodic The luminal cells of the intercalated duct (arrow) surround acid–Schiff (PAS) and resist diastase , but they are a small lumen. They are smaller than acinar cells, cuboidal, negative with the mucicarmine stain. and eosinophilic to amphophilic with central nuclei. acid–Schiff (PAS) stain and are resistant to dia- membrane are myoepithelial cells. Some in- stase digestion (fgs. 1-11). They are unreactive vestigators also have identifed myoepithelial with the mucicarmine and Alcian blue stains. cells in association with striated and interlob- The nuclei are uniform, round, and located in ular excretory ducts (8,12). Myoepithelial cells the basal half of the cells. are fattened, stellate- and spindle-shaped cells The intercalated ducts are longer and more with cellular processes that extend in “basket conspicuous in the parotid gland than in any fashion” around the acini and intercalated of the other salivary glands, but their small ducts. The myoepithelial cells have histologic size in comparison to the acini and striated and ultrastructural features of both epithelium ducts makes them more diffcult to discern. and smooth muscle, and are believed to have The intercalated ducts are lined by low cuboidal contractile properties that aid in the cells with scant cytoplasm and uniform, round of saliva. These cells are diffcult to visualize in nuclei (fg. 1-12). Since their nuclei are about routine hematoxylin and eosin (H&E)-stained the same size as the nuclei of acinar cells, the tissue sections. nuclear to cytoplasmic ratio is much greater The striated ducts are much larger than the in the intercalated duct cells than acinar cells. intercalated ducts, about three to six times The cytoplasm is amphophilic to eosinophilic. the size of an acinus. Striated ductal cells are Located between the basal surface of acinar columnar and intensely eosinophilic. The nu- and intercalated duct cells and the basement clei are uniform and round, and located in the

8 The Normal Salivary Glands

Figure 1-13 Figure 1-14 STRIATED DUCT STRIATED DUCT The striated duct is much larger than the intercalated duct. The striated ducts stain with phosphotungstic acid– The luminal cells are columnar, with eosinophilic cytoplasm hematoxylin because of numerous cytoplasmic mito- and central nuclei. The vertical cytoplasmic striations in the chondria. basal half are due to folds in the basal plasma membranes. center or luminal half of the cells. Fine vertical cells are intermingled among the pseudo- striations, for which the cells are named, can be stratified columnar cells (fig. 1-15). As the seen with high magnifcation light microscopy excretory duct merges with the oral mucosal in the basal half to two thirds of the cells (fg. epithelium, the luminal epithelium becomes 1-13). These striations are the result of promi- stratifed squamous epithelium. nent basal folds in the plasma membranes. The The glandular parenchyma is segregated into striated duct cells react more intensely with the varying sized lobules by septa of fbrous tissue, phosphotungstic acid–hematoxylin stain than which also form a capsule around the entire other cellular constituents because they contain gland. A variable amount of fat is found in both a large number of mitochondria (fg. 1-14). Oc- intralobular and extralobular locations. The casional myoepithelial cells and scattered basal clusters of acinar cells are closely apposed and cells are located between the striated cells and very dense in young persons, but the amount basement membrane. of interstitial adipose tissue increases, while the For the most part, interlobular and extra- parenchymal tissue decreases, with advancing glandular excretory ducts are lined by pseudo- age (fg. 1-16). It has been reported that the stratifed columnar epithelium (fg. 1-15). Small T1-weighted signal intensity of magnetic reso- basal cells are distributed along the basement nance images (MRIs) of parotid glands increases membrane, and occasional goblet type mucous with age due to the increasing amount of fat in

9 Tumors of the Salivary Glands

Figure 1-15 INTERLOBULAR EXCRETORY DUCT Left: This large excretory duct is lined by pseudostratifed columnar epithelium and supported by dense fbrous connective tissue. Right: Excretory ducts sometimes contain goblet-like mucous cells (PAS stain).

Figure 1-16 INTRAGLANDULAR ADIPOSE TISSUE IN PAROTID GLAND A: The parotid gland from a neonate contains no discernible adipose tissue. B: There is a moderate amount of intralobular adipose tissue in the parotid tissue from a middle-aged adult. C: The intraparotid adipose tissue is quite prominent in the gland from an elderly person.

the glands (69). Since the secretory capacity of Lymphoid tissue in the form of small, un- the parotid gland exceeds normal requirements, structured nodules and lymph nodes is found the decreasing parenchyma to fat ratio rarely scattered within and around the parotid gland results in unless some intercurrent (fg. 1-17). As previously noted, some of the disease alters the function of the gland. small lymphoid nodules lack the capsules and

10 The Normal Salivary Glands

Figure 1-17 Figure 1-18 PAROTID LYMPH NODES SEBACEOUS CELLS IN PAROTID GLAND Intraparotid and periparotid lymphoid tissues vary from Foci of sebaceous cells occur in most parotid glands, but developed lymph nodes to nodules with little structure they are so few that they are not commonly noticed in tissue (inset). sections from surgical excision specimens. subcapsular and medullary sinuses of true Branches of the facial nerve are often in lymph nodes. The periglandular lymph nodes contact with, or in close proximity to, parotid lie within the capsule of the gland. In the study parenchymal tissue (fg. 1-19). of McKean et al. (40), only about one fourth of Submandibular Gland the parotid lymph nodes, which they distin- guished from unstructured lymphoid nodules, The lobular architecture and parenchyma of had germinal centers. Glandular tissue is fre- acini, intercalated ducts, striated ducts, inter- quently entrapped in the medullary region of lobular ducts, and main excretory duct of the these lymph nodes. submandibular gland are very similar to those of Foci of sebaceous glands or small collections the parotid gland (fg. 1-20). Unlike the parotid of sebaceous cells are present in most parotid gland, mucous acini constitute a signifcant por- glands, but they are infrequently encountered tion of the acini, about 5 to 10 percent (fg. 1-21). in routine examination of surgical The majority of acinar cells are serous. Acini with specimens because there are so few of them (fg. mucous cells are generally not purely composed 1-18). Unlike mucous cells, sebaceous cells are of mucous cells but are a mixture of mucous unreactive with the mucicarmine stain. While and serous cells. The serous cells are typically sebaceous cells are a normal, albeit very minor, arranged as crescent-shaped caps, called demi- constituent of parotid glands, their functional lunes, at the periphery of the mucous acinar signifcance is unknown. cells. The mucous cells have abundant, clear to

11 Tumors of the Salivary Glands

Figure 1-19 Figure 1-20 FACIAL NERVE BRANCHES IN PAROTID GLAND SUBMANDIBULAR GLAND Segments of peripheral nerve often are in close proximity Although there is less fat in the adult submandibular to parotid parenchyma. gland than in the parotid gland, the lobular architecture is similar.

Figure 1-21 SUBMANDIBULAR GLAND ACINI Left: Mucous acini comprise 5 to 10 percent of the acinar tissue. Serous cells are frequently located at the periphery of mucous acini. Striated ducts are more prominent and the intercalated ducts are shorter than those in the parotid gland. Right: The mucicarmine stain highlights the mucous cells while the serous cells are unreactive.

12 The Normal Salivary Glands

Figure 1-22 Figure 1-23 SUBLINGUAL GLAND MINOR SALIVARY GLANDS IN TONGUE The sublingual gland acini are typically more elongated In the tongue, lips, and buccal mucosa, lobules of salivary than those of the parotid and submandibular glands. The gland tissue are located beneath the mucosal epithelium and acini are predominantly composed of mucous cells with within the deeper skeletal muscle. These glands are unen- serous cell demilunes. capsulated and in contact with the adjacent muscle tissue. faintly basophilic, fnely granular to furrowed tissue, as in the parotid gland. In fact, using MRI cytoplasm with basally oriented, round nuclei. studies, Sumi et al. (69) found that the sublin- Mucous cells are reactive with PAS, mucicar- gual gland undergoes an age-related decrease in mine, and Alcian blue stains (fg. 1-21). size. Several collecting ducts connect to the oral The intercalated ducts are shorter in length mucosa and submandibular gland duct. and less discernible than their counterparts in Minor Salivary Glands the parotid gland while the striated ducts are more conspicuous. Again, the myoepithelial The intraoral minor salivary glands are scat- cells are obscure in routine-stained tissue sec- tered as small lobules within the oral mucosal tions. For any specifc age group, the amount and submucosal tissues of the buccal mucosa, of intraglandular adipose tissue is less than in lips, foor of mouth, hard and soft , ton- the parotid gland. Lymph nodes, lymphoid sillar pillars, and tongue. The minor glands are nodules, and large peripheral nerves are not mostly unencapsulated and lie in close contact present within the gland. with the structures around them, especially the muscles of the tongue and lips (fg. 1-23). This Sublingual Gland intramuscular, unencapsulated morphology is Unlike the parotid and submandibular a factor to be considered in the histologic eval- glands, most of the acini of the sublingual gland uation of invasive growth and malignancy in are of mixed type, composed of mucous cells minor salivary gland neoplasms. The anterior with serous cell demilunes (fg. 1-22). These se- hard palate and gingiva are generally devoid of cretory end pieces are frequently elongated rath- salivary glands, but the retromolar mandibular er than spherical like acini in the parotid and ridge does contain salivary glands. submandibular glands. The lobular architecture The glands in the posterior hard palate con- is less organized, and both the intercalated ducts sist of pure mucous type acini without serous and striated ducts are shorter than in either of cells (fg. 1-24). In the tongue, the salivary gland the other major salivary glands. tissue located on the anterior ventral portion, Similar to the submandibular gland, lym- called the Blandin and Nunn glands, is of mu- phoid tissue and large peripheral nerves are cous type, while the tissue in the region of the not usually evident within the substance of circumvallate papillae on the posterior dorsal and the gland. Also, there does not appear to be an lateral portion, called the von Ebner glands, is age-related increase in intraglandular adipose of serous type. Most of the other minor salivary

13 Tumors of the Salivary Glands

Figure 1-24 MINOR SALIVARY GLANDS OF THE PALATE Left: The palate contains the largest foci of intraoral minor salivary gland tissue. These glands are composed only of mucous acini, without serous acini. Right: Each rounded acinus is surrounded by a thin layer of connective tissue. The mucous cells surround small central lumens, are pyramidal shaped, and have pale, granular cytoplasm with basally located nuclei. glands are mixed mucoserous glands in which Mucous acinar cells are similar to serous cells the mucous cells predominate. but the secretory droplets are often larger, more irregularly shaped, and more electron lucent ULTRASTRUCTURE than those in serous cells. The number and size of secretory droplets and prominence of the Acinar Cells Golgi apparatus and endoplasmic reticulum At the ultrastructural level, the most notable vary with the functional stage of the cell. The feature of serous acinar cells is the numerous secretory droplets often fuse to form very large cytoplasmic secretory granules, known as zy- droplets. Rough endoplasmic reticulum, Golgi mogen granules, located predominantly in the apparatus, and mitochondria are mostly located apical portion of the cell (fg. 1-25). These are in the basal portion of the cell. The lateral inter- round, membrane-bound structures of varying cellular inter digitations are less complex than electron density and diameter. The number of those of serous cells. The basal plasma mem- granules depends upon the secretory phase of brane folds are more complex in mucous cells of the cell. The extensive array of rough endo- the submandibular and sublingual glands than plasmic reticulum and Golgi apparatus is basal in mucous cells of the minor salivary glands, but and lateral to the nucleus, and mitochondria minor salivary gland mucous cells have more are modestly numerous. The is complex lateral interdigitations (11,23,37). located along the basal surface except where Myoepithelial Cells myoepithelial cells lie between the acinar cells and basal lamina. When the acinar cell is not Myoepithelial cells are situated between distended with secretory product, the basal the basal plasma membrane of the acinar and plasma membrane demonstrates numerous intercalated duct cells and the basal lamina. folds. Microvilli extend from the luminal surface They have a fattened, elongated shape with into the intercellular space that is continuous cytoplasmic processes that extend over the with the lumen. In the intercellular space are surface of acinar and duct cells, although the complex inter digitations of plasma membranes myoepithelial cells adjacent to intercalated of adjacent cells. There are junctional complexes duct cells have fewer cytoplasmic processes (fg. at the apical end of the cells and desmosomal 1-26). The nuclei are elongated or irregularly attachments at sites along the lateral borders shaped. The cytoplasmic processes and the basal (11,23,37). portion of the cell bodies contain numerous

14 The Normal Salivary Glands

Figure 1-25 ULTRASTRUCTURE OF SEROUS ACINAR CELL Variably sized secretory granules occupy most of the apical portion of the cytoplasmic compartment. Parallel arrays of rough endoplas- mic reticulum lie adjacent to the basally located, round nucleus. The intercellular space contains inter-digitations of adjacent cells and represents a canaliculus that is connected to the acinar lumen and is actually the beginning of the duct system.

microflaments with focal densities. There are focal densities and pinocytotic vesicles along the basal plasma membrane (fg. 1-27). Mito- chondria, endoplasmic reticulum, Golgi vesi- cles, and lysosomes are concentrated about the nuclei. Desmosomes attach the myoepithelial cells to the acinar and ductal cells, and tonofl- aments are present in some cells (12). Intercalated Duct Cells Unlike the acinar, myoepithelial, and striated duct cells, which have unique and characteristic features, intercalated duct cells are distinguished by their simplicity and absence of special ultra- Figure 1-26 structural features. A few cells in proximity to acinar cells contain some secretory granules; ULTRASTRUCTURE OF ACINAR otherwise, within the scant cytoplasm are basal- AND MYOEPITHELIAL CELLS ly located rough endoplasmic reticulum, apical- A (arrow) is situated between the basement membrane and basal plasma membrane of the ly located Golgi apparatus, and mitochondria. serous acinar cells. It has elongated cytoplasmic processes The lateral cell membranes interdigitate with that extend over the surface of the acinar cells.

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