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Home , Salivary gland atresia, Salivary gland fistula, Sialocele, Submandibular triangle

ISSN: 1812–1217

Diseases of Salivary Glands: Review

Alhan D Al-Moula Department of Dental Basic Science BDS, MSc (Assist Lect) College of Dentistry, University of Mosul

اخلالضة امخجوًف امفموي تُئة رطبة، حتخوي ػىل طبلة ركِلة من امسائل ثدغى انوؼاب ثغطي امسطوح ادلاخوَة و متأل امفراغات تني ااطَة امفموًة و األس نان. انوؼاب سائل مؼلد، ًنذج من امغدد انوؼاتَة، اذلي ًوؼة دورا" ىاما" يف اافظة ػىل سالمة امفم. املرىض اذلٍن ؼًاهون من هلص يف األفراز انوؼايب حكون دلهيم مشبلك يف األلك، امخحدث، و امبوع و ًطبحون غرضة مألههتاابت يف األغش َة ااطَة و امنخر املندرش يف األس نان. ًوخد ثالثة أزواج من امغدد انوؼاتَة ام ئرُسة – امغدة امنكفِة، امغدة حتت امفكِة، و حتت انوساهَة، موضؼيا ٍكون خارج امخجوًف امفموي، يف حمفظة و ميخد هظاهما املنَوي مَفرغ افرازاهتا. وًوخد أًضا" امؼدًد من امغدد انوؼاتَة امطغرية ، انوساهَة، اتحنكِة، ادلىوزيًة، انوساهَة احلنكِة وما كبل امرخوًة، ٍكون موضؼيا مألسفل و مضن امغشاء ااطي، غري حماطة مبحفظة مع هجاز كنَوي كطري. افرازات امغدد انوؼاتَة ام ئرُسة مُست مدشاهبة. امغدة امفكِة ثفرز مؼاب مطيل غين ابألمِالز، وامغدة حتت امفكِة ثنذج مؼاب غين اباط، أما امغدة حتت انوساهَة ثنذج مؼااب" مزخا". ثبؼا" ميذه األخذالفات، انوؼاب املوحود يق امفم ٌشار امَو مكزجي. ح كرَة املزجي انوؼايب مُس ثس َطا" واملادة األضافِة اموػة من لك املفرزات انوؼاتَة، اكمؼدًد من امربوثُنات ثنذلل ثرسػة وثوخطق هبدروكس َل األتُذاًت مألس نان و سطوح ااطَة امفموًة. ثبدأ أمراض امغدد انوؼاتَة ػادة تخغريات اندرة يف املفرزات و ام كرتَة، وىذه امخغريات ثؤثر اثهواي" من خالل جشلك انووحية اجلرثومِة و املوح، اميت تدورىا ثؤدي اىل خنور مذفش َة وأمراض وس َج دامعة. ىذه األمراض ميكن أن ثطبح شدًدة تؼد املؼاجلة امشؼاغَة ألن امؼدًد من احلاالت اجليازًة )مثل امسكري، امخوَف اهكُيس( ثؤثر يف اجلراين انوؼايب، و ٌش خيك املرض من حفاف يف امفم. ػىل أًة حال امغدد انوؼاتَة ثطبح أكل فؼامَة مع امخلدم ابمؼمر، نوخغريات اهكبرية اميت ثطُة املفرزات انوؼاتَة. الثوخد دراسات ػىل املفرزات انوؼاتَة أو ػىل أشخاص ثشلك فردي، حىت امخغريات امدرشحيَة مع امخلدم ابمؼمر جسوت مضن امغدد انوؼاتَة هفسيا. ثغريات حشمَة، ثوَف، و مكَات ملفِة مذطورة يف امغدد انوؼاتَة ميكن ان حتدث. اخلالاي امبرشًة ميكن أن حرى حتت اير مع امخلدم ابمؼمر هكن ال ًوخد أساس ػومي ذلكل. يف امؼادة ىذه امخغريات يف تىن املنوات اططة نوغدد انوؼاتَة،

ميكن أن ثخطور اىل أورام. ABSTRACT The oral cavity is a moist environment, a film of fluid called constantly coats its inner surfaces and occupies the space between the lining and the teeth. Saliva is a complex fluid, pro- duced by the salivary glands, whose important role is maintaining the wellbeing of the mouth. Patients with a deficiency of salivary secretion experience difficulty eating, speaking, swallowing as well as become prone to mucosal and rampant caries. In human there are three pairs of major encap- sulated salivary glands – (parotid, submandibular, and sublingual). Located outside the oral cavity, with extended duct systems to discharge their secretion. There are also a multitude of smaller minor unen- capsulated salivary glands. (labial, lingual, palatal, buccal, glossopalatine and retromolar). Located just below and within the mucous membranes, characterized by short duct systems. Secretion of each major is not the same, the parotid glands secrete a rich amylase (watery serous saliva), whereas the produces mucinous saliva, and the sublingual gland produces viscous saliva. Because of these variations, saliva found in the mouth is referred to as mixed secretions, as many pro- teins are rapidly removed as they adhere to hydroxyl apatite of teeth and to the oral mucosal surfaces. Diseases of the salivary glands usually bring about changes in the rate of salivary secretion and compo- sition. These changes have a secondary effect in that they lead to the formation of a plaque and calcu- lus, which in turn has a direct bearing on the initiation of caries and . In addition to it, effect in the healthy condition of oral mucosal surfaces. There are many systemic conditions (e.g., diabetes, cystic fibrosis) affect salivary flows, a patient complaining of dry mouth must be thoroughly investigated. These diseases may become severe after therapeutic irradiation in and around the mouth. The salivary gland become less active with age while is problematic, because such a great variation exists in the secretion of saliva, but no longitudinal studies have thus far been reported. Even so, histo- logical changes associated with age have been reported within the salivary glands. Fatty degenerative changes, fibrosis and the progressive accumulation of lymphocytes in the salivary glands are thought to occur. Oncocytes – epithelial cells that can be identified by there marked granularity and acidophilia under the light microscope, are thought to represent as age change, although their significance has not

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been established, beside accumulation of structurally altered mitochondria. Oncocytes are found in acini intercalated and striated ducts of salivary glands and which may give rise to neoplasms. The aim of this review is to provide athorough knowledge of anatomy, embryology and pathophysiology in ne- cessary to treat patient appropriately. Examines the cause, diagnostic methodology, radiographic evalu- ation and management of a variety of salivary gland. Keyword: Salivary gland, Histopathology of salivary glands, salivary gland disorders.

Al- Moula AD. Diseases of Salivary Glands: Review. Al–Rafidain Dent J. 2010; 10(2):214-230. Received: 11/1/2009 Sent to Referees: 12/1/2009 Accepted for Publication:16/3/2009

INTRODUCTION Anatomy of Salivary Glands (Figure 1):

A B

Figure (1): Anatomy of the major salivary glands. A, . B, Submandibular and sublingual glands (Snell R.S.)

Parotid Gland: Parasympathetic secretomotor fibers The parotid gland is the largest sali- from the inferior salivatory nucleus of the vary glands, which lies superficial to the ninth cranial nerve supply the parotid posterior aspect of the masseter muscle gland. The nerve fibers pass to the otic and the ascending ramus of the mandi- ganglion via the tympanic branch of the ble.(1) The deep part of the gland may ex- ninth cranial nerve and the lesser petrosal tend forward between the medial pterygoid nerve. Postganglionic parasympathetic process.(1) fibers reach the parotid gland via the auri- The parotid gland is a lobulated mass culotemporal nerve, which lies in contact surrounded by a connective tissue capsule, with the deep surface of the gland. Post- and enclosed by a dense fibrous capsule ganglionic sympathetic fibers reach the derived from the investing layer of deep gland as a plexus of nerves around the ex- cervical .(1) ternal carotid artery.(1) Blood Supply: Submandibular Gland: The external carotid artery and its ter- The submandibular gland is located in minal branches: 1) posterior auricular arte- the submandibular triangle of the , ries, 2) superficial temporal 3) and trans- this triangle is formed by the anterior and verse facial arteries, while the veins drain posterior bellies of the diagastric muscles into the retromandibular vein.(1) and the inferior border of the .(1) Lymph drainage: Blood supply: The lymph vessels drain into the paro- The arteries are branches of the facial tid lymph nodes and the deep cervical and lingual arteries. The veins drain into lymph nodes.(1) the facial and lingual veins. Nerve supply: Lymph drainage:

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The lymph vessels drain into the sub- have a spherical, basally situated nucleus mandibular and deep cervical lymph and surround a small, central lumen. The nodes.(1) basal cytoplasm stains with basophilic Nerve supply: dyes, and the secretory granules in the Parasympathetic secretomotor supply apical cytoplasms usually stain with aci- from the superior salivatory nucleus of the dophilic dyes. Fat cell spaces are often seventh cranial nerve. The nerve fibers seen in sections of the parotid gland.(2) In- pass to the submandibular ganglion and tercalated ducts are numerous and long in other small ganglia close to the duct via the parotid gland, they are lined with cu- the chorda tympani nerve and the lingual boidal epithelial cells and have lumina that nerve. Postganglionic parasympathetic are larger than those of acini. The striated fibers reach the gland either directly or ducts are numerous and appear as slightly along the duct. Postganglionic sympathetic acidophilic. The ducts consist of a simple fibers reach the gland as a plexus of nerves columnar epithelium, with round, centrally around the facial and lingual arteries, from placed nuclei, the lumina are larger rela- superior cervical ganglia.(1) tive to overall size of the ducts.(2) Small Sublingual Gland: ducts from various regions of the gland The sublingual gland is the smallest of coalesce at the anterosuperior aspect of it the three main salivary glands, it lies be- to form (major Stensen's duct), which is neath the mucous membrane of the floor about 1-3mm in diameter and 6 cm in of the mouth, close to the midline. The length, this duct opened intra orally adja- sublingual ducts are 8-20 in number and cent to the upper molar tooth(2). most of them open into the oral cavity on Submandibular Gland: the summit of the sublingual fold, but a The submandibular gland composed of few may open into the submandibular a mixture of serous end pieces and mucous duct.(1) tubules capped with serous demilunes. Blood supply: Although the serous end pieces are similar The gland is supplied by branches of in structure to those found in the parotid the facial and lingual arteries. The veins gland, with abundant secretory granules, a drain into the facial and lingual veins. (1) spherical nucleus and basophilic cytop- Lymph drainage: lasm. The mucous secretory cells are filled The lymph vessels drain into the sub- with pale – staining secretory material, and mandibular and deep cervical lymph little cytoplasm, while the nucleus is com- nodes. (1) pressed against the basal cell membrane Nerve supply: and contains densely stained chromatin. Parasympathetic secretomotor supply The intercalated and striated ducts are less from the superior salivatory nucleus of the numerous than those in the parotid gland, . The fibers pass to the sub- and its major duct known as Warton's duct mandibular ganglion via the chorda tym- passes forward in the sublingual space, pani nerve and the lingual nerve. Postgan- and opened into the mouth behind lower glionic parasympathetic fibers pass to the incisor teeth.(3) gland via the lingual nerve. Postganglionic Sublingual Gland: sympathetic fibers reach the gland as a The sublingual gland is also a mixed plexus of nerves around the facial and lin- gland, but mucous secretory cells predo- gual arteries, from superior cervical gan- minate, while the mucous tubules and ser- glia.(1) ous demilunes resemble those of the sub- Histological feature of the Major Sali- mandibular gland. The intercalated ducts vary Glands: are short and difficult to recognize. Whe- Parotid Gland: reas the Interlobular ducts are fewer in In the parotid gland, the spherical se- numbers than in the parotid or submandi- cretory end pieces are all of serous type, bular glands.(2) (Figure 2). and their pyramidally shaped acinar cells

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Figure (2): Architecture of salivary gland ducts, secretory end pieces and the main features of the paranchymal cells (Antonio N.) The acinar ducts (Bartholin's ducts) of the Salivary gland weak point (clinical con- sublingual glands are coalesce to form 8- sideration): 20 ducts (Rivinus ducts), which are short Parotid salivary gland and lesions of the and small in diameter and open directly facial nerve: into the anterior floor of the mouth.(3) The terminal branches of the facial Development of the Salivary Glands: nerve lie between the superficial and deep All the salivary glands have the same part of gland and a benign parotid neop- plan of origin and development.(2) lasm rarely, if ever, causes facial palsy. A The minor salivary glands begin to de- malignant tumor of the parotid gland is velop around the fortieth day in utero, usually highly invasive and quickly in- whereas the larger major glands begin to volves the terminal branches of the facial develop slightly earlier.(2) They arise at nerve, causing unilateral facial paralysis.(1) about the 7th week as solid out growths of cells from the wall of the developing Parotid gland infections: mouth, these cells grow into the underly- The parotid gland may become acutely ing mesenchymes. inflamed as a result of retrograde bacterial The epithelial buds branch repeatedly from the mouth via the parotid to form solid ducts, the ends of which duct. The gland may also become infected round out to form solid ducts, the ends of via the blood stream, as in . The which round out to form secretory acini. swollen gland extends behind the tempo- Later, the solid ducts and acini become romandibular joint, is responsible for the canalized. The surrounding mesenchyme pain in acute when eating.(1) condenses to form the capsule and divides Submandibular salivary gland(calculus each gland into lobes or lobules. The ducts formation): and acini of the parotid gland are derived The submandibular salivary gland is a from ectoderm, and those of the subman- common site of calculus formation, while dibular and sublingual glands are from it is rare in the other salivary gland. The endoderm.(2) stone can be palpated in the duct, which

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lies below the mucous membrane of the ranges from 24-63 years. The clinical floor of the mouth.(1) presentation is a unilateral swelling of the Sublingual salivary gland and cyst for- hard and/or soft . This lesion is mation: asymptomatic, broad based and covered The sublingual salivary gland, which with intact mucosa of normal color and lies beneath the sublingual fold of the floor quality.(5,6) of the mouth, opens into the mouth by 3. Other disturbances are aplasia, atresia, numerous small ducts. Blockage of one of aberrancy which are rarely caused(2). these duct is believed to be the cause of Physiology of salivary glands: cysts under the .(1) Secretion of saliva: Developmental disturbances of salivary Daily secretion of saliva normally glands: ranges between 800-1500 milliliters, with 1. Xerostomia: average value of 1000 milliliters, and con- Dry mouth or xerostomia, is a frequent tain two major types of protein secretion: clinical complaint. A loss of salivary func- 1. A serous secretion that contain ptyalin tion or a reduction in the volume of se- (an α-amylase) which is an enzyme for creted saliva may lead to the sensation of digesting starches. oral dryness. Many drugs cause central or 2. Mucus secretion that contains mucin peripheral inhibition of salivary secretion for lubricating and for surface protec- and destruction of salivary gland tissue is tive purposes. another common cause of xerostomia. Saliva has a ph between 6.0 and Loss of gland function occurs after radia- 7.0 a favorable range for the digestive ac- tion therapy for head and neck cancer, be- tion of ptyalin.(7) cause the salivary glands often are in- Secretion of ions in saliva: cluded in the radiation fields. Chemothe- Saliva contains especially large quanti- rapy for cancer or associated with bone ties of potassium and bicarbonate ions. marrow transplantation also may cause The concentration of both sodium and reduced salivary function. Autoimmune chloride ions are several times less than in diseases, in particular Sjogren's syndrome, saliva than in plasma. Under resting condi- may cause progressive loss of salivary tions; the concentration of sodium and function from the invasion of lymphocytes chloride ions in the saliva are only about into the gland and the destruction of epi- 15mEq/L each and about 1/7 to 1/10 their thelial cells. Treatment patient with xeros- concentration in plasma. Conversely, the tomia may include genetic modification of concentration of potassium ions is about salivary gland cells to increase fluid and 30mEq/L, seven times as in plasma, while protein secretion.(2,4) the concentration of bicarbonate ions is 2. Hyperplasia of the palatal glands: about 50-70 mEq/L, about two to three It is a non neoplastic enlargement of times that of plasma. During maximal se- the minor salivary glands of the hard pa- cretion; the salivary ionic concentration late, with unknown cause, although there change considerably because the rate of is some evidence to suggest that trauma formation of primary secretion by the acini plays a role.(5,6) can increase as much as 20 –fold. This Clinical features: acinar secretion then flows through the The palate is the main site of involve- ducts as rapidly that the ductal recondi- ment of this salivary gland hyperplasia. tioning of the secretion is considerably There is a male predominance and age reduced. The sodium chloride

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Al- Moula AD concentration rises only to one half of 2/3 tration rises to only four times that of that of plasma, and the potassium concen- plasma.(7,8) Table (1):

Table (1) Daily saliva production by salivary gland Submandibular gland 70% Parotid gland 25% Sublingual gland 3 – 4% Minor gland Trace

Function of saliva for oral hygiene: vorite foods, salivation is greater than 1- Helps wash away pathogenic bacteria as when disliked food is smelled or eaten. well as food particles that provide Salivation also occurs in response to ref- their metabolic support (Cleansing ac- lexes originating in the stomach and upper tion). small intestines. Sympathetic stimulation 2- Thiocyanate ions and anothers are sev- can also increase salivation a slight eral proteolytic enzymes –most impor- amount, much less so than does parasym- tant, lysozyme – that (a) attach the pathetic stimulation. The sympathetic bacteria, (b) aid the thiocyanate ions in nerves originate from the superior cervical entering the bacteria where these ions ganglia and travel along the surface of the in turn become bacteriocidal, and (c) blood vessel walls to the salivary glands. digest food particles, thus helping fur- A secondarily factor that also affects sali- ther to remove the bacterial metabolic vary secretion is the blood supply to the support. glands because secretion always requires 3- Saliva often contain significant amounts adequate nutrients from the blood. The of protein antibodies that can destroy parasympathetic nerve signals that induce oral bacteria.(7) (antibacterial action). copious salivation also moderately dilate Nervous regulation of salivary secre- the blood vessels. In addition, salivation tion: itself directly dilates the blood vessels, The salivary glands are controlled thus providing increased salivary glands mainly by parasympathetic nervous sig- nutrition as needed by the secretory cells. nals from the superior and inferior saliva- Part of this additional vasodilator effect is tory nuclei in the brain stem. Many taste caused by kallikrein secreted by the acti- stimuli, especially the sour taste (caused vated salivary cells, which in turn acts as by acids), elicit copies secretion of saliva an enzyme to split one of the blood pro- often 8 - 20 times the basal rate of secre- teins, an alph 2 – globulin, to form brady- tion, also, certain tactile stimuli, such as kinin, a strong vasodilator.(7) the presence of smooth objects in the Salivary gland radiology: mouth (e.g., a pebble), cause marked sali- 1. Plain film radiographs: vation, where as rough objects cause less The primary purpose of plain films in salivation and occasionally even inhibit the assessment of is salivation. Salivation can also be stimu- to identify salivary stones (calculi) al- lated or inhibited by nervous signals aris- though only 80% to 85% of all stones are ing in the salivatory nuclei from higher radiopaque and therefore visible radio- centers of the central nervous system. For graphically Table (2). instance, when a person smells or eats fa-

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Table (2): Incidence of radiopaque stones Submandibular gland 70% 30% Parotid gland A mandibular occlusal film is in the anterior floor of the mouth (Figure most useful technique to detect the calculi 3). (9)

A B

Figure (3): A, Mandibular occlusal radiograph shows a radiopaque sialolith (arrow). B, Sub- mandibular sialolith after intraoral removal is demonstrated.

Panoramic radiographs can reveal located submandibular stones (Figure 4). stones in the parotid gland and posteriorly

Figure (4): Panoramic radiograph demonstrates a right submandibular sialolith (arrows)

Periapical radiographs can show calculi in ficial structures to determine whether a all salivary (major and minor) glands or mass lesion that is being evaluated is solid their ducts, depending on film placement or cystic (fluid – filled) in nature.(9) and in most instances, the radiographic 3. Sialography: image corresponds in size and shape to the Sialography is indicated as an aid actual stone. (9) in the detection of radiopaque stones. Sia- 2. Ultrasonography: lography is also useful in the assessment Is relatively simple, with poor de- of the extent of destruction of the salivary tail resolution. The primary role of ultra- duct or gland or both as a result of obstruc- sonography is in the assessment of super- tive, inflammatory, traumatic and neoplas-

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Al- Moula AD tic disease, and also to detect any dilata- dilation of the salivary duct secondary to tion or narrowing or constriction of the epithelial atrophy as a result of repeated duct (9,10). inflammatory or infections processes, with Sialography is a technique in irregular narrowing caused by reparative which the salivary duct cannulated with a fibrosis (i.e.," Sausage link" pattern) (Fig- plastic or metal catheter (Figure 5). It a ure 6)

Figure (5): Cannulation of Stensen's duct with a plastic catheter

Figure (6): Sialogram of right parotid gland. The characteristics "Sausage link" appearance of the duct is demonstrated

Sialogram are specialized radiographic thyroid scan.(9) studies performed by oral and maxillofa- 4. Computed tomography: cial surgeons and some interventional ra- The use of computed tomography (CT) diologists trained in the technique(10). The has been generally reserved for the as- three contraindication of performing a sia- sessment of mass lesions of the salivary logram are (1) acute salivary gland infec- glands. Although CT scanning results in tions, (2) Patients with a history of iodine radiation exposure to patients, it is less sensitivity, (3) before a thyroid gland invasive than sialography and does not study, because retained iodine in the require the use of contrast materi- vary gland or ducts may interfere with the al.(9)(Figure 7)

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Figure (7): Computerized tomographic scan of the mandible and floor of mouth shows a post- erior submandibular sialolith (arrow)

5. Magnetic resonance imaging (MRI): biopsy has been shown to demonstrate Is superior to CT scanning in delineat- certain characteristic histopathologic ing the soft tissue detail of salivary gland changes that are seen in the major gland in lesions, specifically tumors, with no radia- ss. The procedure is performed using local tion exposure to the patient or the necessi- anesthesia, and approximately 10 minor ty of contrast enhancement.(91) salivary glands are removed for histologi- 6. Salivary scintigraphy (radioactive iso- cal examination.(3,9,11) tope scanning): 9. Fine – needle aspiration biopsy: The use of nuclear imaging in the form This procedure has a high accuracy of radioactive isotope scanning, or salivary rate for distinguishing between benign and scintigraphy, allows a thorough evaluation malignant lesions in superficial locations. of the salivary gland parenchyma, with Fine – needle aspiration biopsy is per- respect to the presence of mass lesions and formed using a syringe with a 20 –gauge the function of the gland itself. This study or smaller needle. After local anesthesia uses a radioactive isotope [usually, techne- the needle is advanced into the mass le- tium (TC) 99m] injected intravenously sion, the plunger is activated to create a (IV), which is distributed throughout the vacuum in the syringe, and the needle is body and taken up by a variety of tissues, moved back and forth throughout the including the salivary glands.(9) mass, with pressure maintained on the 7. Sialochemistry: plunger. The needle is withdrawn, and the An examination of the electrolyte cellular material with fluid are expelled composition of the saliva. Principally the onto a side and fixed for histological ex- concentration of sodium and potassium, an amination. (3,9) elevated sodium concentration with a de- Salivary gland infections: creased potassium concentration may indi- Viral parotitis or mumps: cate an inflammatory .(9) Mumps is the most common viral in- 8. Salivary gland biopsy: fection which characterized by a painful, A salivary gland biopsy, either inci- non erythematous swelling of one or both sional or excisional, can be used to diag- parotid glands that begins 2-3 weeks (in- nose a tumor of one of the major salivary cubation period) after exposure to the vi- glands, but it is usually performed as an rus. This disease occurs most commonly in aid in the diagnosis of Sjogren syndrome children between ages of 6-8 years and its (ss). The lower labial salivary gland signs and symptoms include preauricular

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Al- Moula AD pain and swelling, fever, chills and head- lesion usually involves the minor salivary ache. Viral parotitis usually resolves in 5- glands of the hard or soft palate, present- 12 days after its onset. Providing suppor- ing as a painful nodule that is covered by tive and symptomatic care for fever, head- intact, erythematous mucosa. (13,16) ache and malaise with antipyretic, analges- Histopathological feature: ic and adequate hydration treats viral paro- Subacute necrotizing sialadenitis is titis. (3,6,12) characterized by a heavy mixed inflamma- Sialadenitis: tory infiltrate consisting of neutrophils, Inflammation of the salivary glands lymphocytes, histocytes and eosinophils. (sialadenitis) can arise from various and There is loss of most of acinar cells and non infectious causes. The most bacterial many of remaining exhibit necrosis, while infections arise as a result of ductal ob- the ducts tend to be atrophic and do not struction or decreased salivary flow.(13) show hyperplasia or squamous metaplasia. One of the more common causes of (13) sialadenitis is the recent surgery (especial- Chelitis glandularis: ly abdominal surgery), when acute paroti- Is a rare inflammatory condition tis (surgical mumps) may arise after such of the minor salivary glands, with uncer- operation because the patient has been tain cause, although several etiologic fac- kept without food or fluids and received tors have been suggested, including actinic atrophy during the surgical proce- damage, tobacco, syphilis, poor hygiene, dure.(3,6,13) and hereditary.(3,13,17) Acute bacterial sialadenitis: Clinical features: Histopathological feature: Chelitis glandularis characteristically Patient with acute sialadenitis, charac- occurs on the lower lip and the affected terized by accumulation of neutrophilis individuals experience swelling and rever- within the ductal system and acini. (3,13,14) sion of lower lip as a result of hypertrophy Chronic sialadenitis: and inflammation of the gland. The open- Recurrent or persistent ductal ob- ings of the minor salivary ducts are in- struction (most commonly caused by sialo- flamed and silated, beside pressure on liths) can lead to chronic sialadentitis. Pe- glands may produce mucopurulent secre- riodic swelling and pain occur within the tions from the ductal openings. The condi- affected gland, which usually developed at tion most often has been reported in mid- mealtime when salivary flow is stimu- dle – aged and older men, although cases lated.(15) have been described in women and child- Histopathological feature: ren. However, some of the childhood cases Chronic sialadentitis is characterized may represent other enities such as exfo- by scattered or patchy infilteration of the liative . Chelitis glandularis has salivary parenchyma by lymphocytes and been classified into three types, based on plasma cells. Atrophy of the acini is com- the severity of the disease: mon, as ductal dilatation and if associated 1. Simple. with fibrosis, the term chronic sclerosing 2. Superficial suppurative (Baelz's) disease. sialadentitis is used.(13) 3. Deep suppourative (Chelitis glandulais Subacute necrotizing sialadenitis: apostematosa). Is a recently recognized form of sali- The latter two types represent progres- vary inflammation that occurs most com- sive stages of the disease with bacterial monly in teenagers and young adults. The involvement and are characterized by in-

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creasing inflammation, suppuration, ulce- stones is twice as common in men between ration, and swelling of the lip.(13,17) age 30-50 years. But it is rare in children (salivary calculi; salivary and the boys are more commonly affected stones): than girls whereas the submandibular Sialoliths are calcified structures that gland is most commonly affected. Mul- develop within the salivary ductal system. tiple stone formation occurs in approx- They are believed to arise from deposition imately 25% of patients.(3) of calcium salts around a nidus of debris Histopathological feature: within the duct lumen and this debris may On gross examination, sialoliths ap- include inspissated mucus, bacteria, ductal pear as hard masses that are round, oval, epithelial cells, or foreign bodies. The or cylindrical and typically yellow, al- cause of sialoliths is unclear, but their though they may be white or yellowish – formation can be promoted by chronic sia- brown. Submandibular stones tend to be ladenitis and partial obstruction. Their de- larger than those of the parotid or minor velopment is not related to any systemic glands. Sialoliths are usually solitary, al- derangement in calcium and phosphorus though occasionally two or more stones metabolism.(13,18,19) may be discovered at surgery. Micro- The pathogenesis of salivary calculi scopically, the calcified mass exhibits progresses through a series of stages be- concentric laminations that may surround ginning with an abnormality in calcium anidus of a amorphous debris. The duct metabolism and salt precipitation, with obstruction frequently is associated with formation of organic and inorganic materi- an acute or chronic sialadenitis of the feed- al to form a calcified mass. .(3,18,19) The in- ing gland.(3,13,18) cidence of stone formation varies from The sublingual gland is examined by 80%, 19% and 1% in submandibular, pa- obstruction and bimanual palpation of the rotid and sublingual glands respectively (3) anterior third of the floor of the mouth. A variety of factors contributes to the The minor salivary glands are ex- higher incidence of submandibular calculi. amined by observation and palpation of Salivary gland secretion contain water, the mucosal surfaces of the , buccal electrolytes, urea, ammonia, glucose, fats, mucosa, palate, and floor of the mouth. proteins and other substances. In general, Obstruction of the sublingual gland is parotid secretions are more concentrated unusual, but if it occurs, it is usually sec- than those of the other salivary glands and ondary to obstruction of Wharton's duct on the main exception is the concentration of the same side of the oral cavity. Although calcium, which is about twice as abundant stone formation is rare in the sublingual in submandibular saliva as in parotid sali- and minor salivary glands, the treatment is va. In addition, the alkaline ph of subman- simple excision of the stone and associated dibular saliva may further support stone gland.(3) formation. Also the Wharton's duct of Other diseases that affect salivary gland: submandibular gland is the longest sali- Sjogren's syndrome: vary duct, therefore saliva has a greater Sjogren's syndrome (ss) is the expres- distance to travel before emptied into the sion of an autoimmune process that results oral cavity and it has two sharp curves in principally in dry eyes (xerophthalmia) its course and, as well as the flow of saliva and dry mouth (xerostomia) owing to secretion occurs against the force of gravi- lymphocyte – mediated destruction of la- ty.(3) The occurrence of salivary gland crimal and salivary gland parenchyma, in

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addition rheumatoid arthritis, may also be by an associated with malignant transfor- seen in this syndrome.(6) So (ss) is a multi- mation to lymphoma. This may occur in system disease process with available approximately 6% - 7% of cases and it is presentation and classified into two types: more common in those with only the sicca 1. Primary (ss) (sicca syndrome); characte- component of the syndrome. Less com- rized by xerostomia (dry mouth) and (xe- monly observed is transformation of the rophthalmia) (dry eye). epithelial component to undifferentiated 2. Secondary (ss): composed of primary carcinoma. Generally, the course for (ss) is (ss), associated with connective tissue dis- one of chronicity, requiring long – term order, most commonly rheumatoid arthri- symptomatic management and careful fol- tis. Although the cause of (ss) is unknown, low-up by a dentist, ophthalmologist and there appear to be a strong autoimmune rheumatologist.(3,6,20) influence, and it shows a female predilec- Traumatic salivary gland injuries: tion of 9:1 with over 80% of affected indi- Traumatic injuries, particularly lacera- viduals being females with a mean age of tions, involving the salivary glands and 50 years.(3,6,20) their ducts may accompany a variety of Generally, the first symptoms to ap- facial injuries, including fractures. Injuries pear are arthritis complaints, followed by that occur in close proximity to one of the ocular symptoms and late in the disease major salivary glands or ducts require process, salivary gland symptoms. The careful evaluation. Facial lacerations may involvement of the salivary and lacrimal involve not only parotid gland and its duc- glands results from a lymphocytic re- tal system, but also branches of the facial placement of the normal glandular ele- nerve and branches of major facial vessels. ments, therefore, xerostomia results from a These structures require meticulous atten- decreased function of both the major and tion for appropriate diagnosis and prompt minor salivary glands, with the parotid repair. Repair may include ductal anasto- gland being the most sensitive.(3,6) moses, in which the proximal and distal The histopathologic changes seen in portions of the duct are identified, a plastic the minor glands are similar to those in the or metal catheter is placed as astent, and major (parotid) glands. Keratoconjuctivitis the duct is sutured over the stent. The ca- sicca is suggested by the patient's com- theter usually remains in place for 10 - 14 plaints and a schirmer's test for lacrimal days for epithelization of the duct to occur. flow.(3,4,6,11,20) Additionally, nerve anastomoses may be Diagnosis depends on the correlation required and performed by placing epi- between the patient history and laboratory neural sutures, using magnification, to data, clinical examination and assessment reapproximate the nerve stimps. The lace- of salivary function. An important consid- rations are closed in a usual layered fa- eration concerns the clinical manifestation shion, after debridment of the soft tissue of xerostomia, although this is the main wounds to cleanse the site of entrapped oral symptom and clinical sign in (ss), particles, such as glass or dirt. Potential other considerations of dry mouth must be sequelae of trauma involving the major evaluated. In addition, major salivary salivary glands include infections, facial gland enlargement is a feature of (ss) but paralysis, cutaneous , may be episodic in nature and in some pa- formation and duct obstruction as tients it may not be present at all.(3,6,11,20) a result of scar formation, with eventual The prognosis of (ss): is complicated glandular atrophy and decreased function.

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The involved gland may eventually require that appears as a vesicle filled with a clear surgical removal.(3,13) or blue – grey mucus. The patient fre- (Reactive Lesions): Mucous retention quently relates a history of the lesion fill- and extravasation phenomena: ing with fluid, rupture of fluid collection, Mucocele: and refilling of these lesions. Many Is a clinical term that include mucus stances of mucocele formation regress extravasation phenomenon and mucus re- spontaneously without surgery, while in tention cyst. Because each has a distinctive case of persistent or recurrent lesions, pathogenesis and microscopy, they are ferred treatment is required for excision of considered separately. the mucocel and the associated minor sali- Salivary ducts, especially those of the vary glands that contributed to its forma- minor salivary glands, are occasionally tion. Usually local anesthesia is adminis- traumatized, commonly by lip bitting, and tered via a mental nerve block, and an severed beneath the surface mucosa. Sub- cision is made through the mucosa. sequant saliva production may then extra- ful dissection around the mucocele may vasate beneath the surface mucosa into the permit its complete removal, however, in soft tissues. Overtime, secretions accumu- many cases the thin lining ruptures and late within the tissues and produce a pseu- decompresses the mucocele before remov- docyst (without a true epithelial lin- al. The regional associated minor salivary ing)(2,3,8,21) that contain thick, viscous sali- glands are removed and sent for va and these lesions are most common in thological evaluation. After surgical the mucosa of the lower lip and known as moval the recurrence rates of mucocele mucoceles (Figure 8). The second most may be as high as 15% - 30%, which common site of mucocele formation is the sibly caused by incomplete removal or buccal mucosa. Which results in an ele- repeat trauma to the minor salivary vated, thinned, stretched overlying mucosa glands.(3,21)

Figure (8): Mucocele of left lower lip

Ranula: The simple is confined to the The most common lesion of the sub- area occupied by the sublingual gland in lingual gland is the ranula, which may be the sublingual space, superior to the mylo- considered a mucocele of the sublingual hyoid muscle. The progression to a plung- salivary gland. result from either ing ranula occurs when the lesion extend mucous retention in the sublingual gland beyond the level of the ductal system or mucous extravasation as into the . Ranulas a result of ductal disruption and divided may reach a larger size than mucoceles, into simple and plunging types. because their overlying mucosa is thicker

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Al- Moula AD and the trauma that would cause their rep- ill – fitting dentures. Patients with new ture is less likely in the floor of the mouth. dentures often experience excess saliva As a result a plunging ranula has the po- production until they become accustomed tential to extend into the neck and com- to the prosthesis. Sialorrhea is a well – promise the airway, resulting in a medical known clinical feature of rabies and heavy emergency.(3,13, 6,22-25) metal poisoning, as well as a consequences Sialocyst (salivary duct cyst): of certain medications, such as lithium and The salivary duct cyst is an epithelium cholinergic agonists.(13) – lined cavity that arises from salivary Clinical features: gland tissue and unlike the more common The excess saliva production typically mucocele, it is a true cyst because it is produce and choking, which may lined by epithelium. The cause of such cause social embarrassment. In children cysts is uncertain, but some cases may with mental retardation or cerebral palsy, represent ductal dilation secondary to duc- the uncontrolled salivary flow may lead to tal obstruction (e.g., mucus plug) which macerated sores around the mouth, chin creates increased intraluminal pressure. and neck that can become secondarily in- Some authors refer to such lesions as mu- fected. cus retention cyst, while other cases ap- An interesting type of supersalivation pear separate from the adjacent normal of unknown cause has been tremed idi- salivary ducts.(13) opathic paroxysmal sialorrhea. Individuals Clinical features: with this condition experience short epi- Salivary duct cysts usually occur in sodes of excessive salivation lasting from adults and can arise with either the major 2 - 5 minutes, and associated with a pro- or minor glands. Cysts of the major glands dram of nausea or epigastric pain.(13) are most common within the parotid gland, Salivary gland tumor: presenting as slowly growing, asympto- A- Benign salivary gland tumors: matic swellings. Intraoral cysts can occur 1. Benign mixed tumor or pleomorphic at any minor gland site, but most frequent- adenoma (Figure 9): ly they develop in the floor of the mouth, Is the most common salivary gland buccal mucosa, and lips. They are often tumor with mean age of occurance 45 look like mucoceles, and characterized by years, and a male to female ratio of 3:2. In soft, fluctuant swelling that may appear the major glands, the parotid gland is in- bluish, depending on the depth of the cyst volved in over 80% of cases, in the minor below the surface and some cysts may feel glands the most common intraoral site is relatively firm to palpation. Cysts in the the palate. Pleomorphic adenomas are floor of the mouth often arise adjacent to usually slow – growing, painless masses the submandibular duct and sometimes with two cell type; 1) the ductal epithelial have an amber color. (13) cell and 2) the myoepithelial cell, which Sialorrhea: may differentiate along a variety of cell Sialorrhea, or excessive salivation, is lines pleomorphic mean many form. The an uncommon condition that has various treatment involves complete surgical exci- causes. Minor sialorrhea may result from sion with a margin of normal involved tis- local irritations, such as apthous ulcers or sue.(3,13,26,27)

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Figure (9): of the right palate

2. Papillary cyst adenoma lymphoma 3:2. The clinical presentation is a submu- (Warthin's tumor): cosal mass that may be painful or ulce- Almost exclusively affects the parotid rated with a bluish tinge because of muc- gland and specifically its tail with peak ous contained within the lesion. An intra- incidence in the sixth decade of life and a osseous form of mucoepidermoid carci- male to female ratio 7:1, the lesion of may present as a multilocular radi- Warthin's tumor presents as a slow grow- olucency of the posterior mandible. The ing – soft, painless mass. Which is be- histopathology shows three cell types (1) lieved to be caused by entrapped salivary mucous, (2) epidermoid, and (3) interme- epithelial rests within developing lymph diate (clear) cells. The proportion of each nodes. The histopathology shows an epi- cell type helps to grade the mucoepider- thelial component in a papillary pattern moid carcinoma as a high – inter mediate and a lymphoid component with germinal or low grade lesions. The higher grade, the center.(3,28,29) more predominance of epidermoid cells 3. Monomorphic adenoma: and pleomorphism, lack of mucous cells Is an uncommon solitary lesion com- and cystic areas, and over all more aggres- posed of one cell type, affecting predomi- sive behavior.(11, 30-32) nately the upper lip minor glands (basal 2. Polymorphous low – grade adenocarci- cell adenoma). The mean age of occur- noma: rence is 61 years and the lesion usually Is the second most common intraoral presents as a symptomatic, freely movable salivary gland malignancy, which was first mass. The histopathology reveals an en- described in 1983 and before its identifica- capsulated lesion composed of one type tion, many cases were probably misdiag- (monomorphic) of salivary ductal epitheli- nosed as . The al cell. (3,6,13) most common site is the junction of the B- Malignant salivary gland tumors: hard and soft with male to female 1. : ratio of 3:1, with a mean age of 56 years. The mucoepidermoid carcinoma is the These tumors present as slow – growing, most common malignant salivary gland asymptomatic masses that may be ulce- tumor. It comprises 10% of major gland rated. The histopathology shows many cell tumors (mostly parotid gland) and 20% of shapes and patterns (polymorphous). Pa- minor gland tumors (mostly palate). This tients experience an infiltrative prolifera- lesion may occur at any age, but the mean tion of ductal epithelial cells in an "Indian age is 45 years. The male to female ratio is file" pattern. This lesion shows a predilec-

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Al- Moula AD tion for invasion of surrounding Development, Structure and Function. th nerves.(3,13,30,33,34) 6 edition. 2003; Pp. 299 – 328. 3. Adenoid cystic carcinoma: 3. Larry J P, Edward E, James R. H. Diag- nosis and Management of Salivary Is the third most common intraoral sali- Gland Disorders Contemporary Oral vary gland malignancy, with a mean age and Maxillofacial Surgery, 4th edition. of 53 years and a male to female ratio of Mosby. 2003; Pp. 434 – 455. 3:2. Approximately 50% of these tumors 4. Vanderwaal IE. Diseases of the Salivary occur in the parotid gland, whereas the Glands. J Oral Maxillofacial Surg. 1997; 34: 15. other 50% occur in the minor glands of the 5. Arafat A, Brannon RB, Ellis GL. Ade- palate. These present as slow growing, non nomatoid hyperplasia of mucous sali- ulcerated masses, with an associated vary glands. Oral Surg Oral Med Oral chronic dull pain. Occasionally, parotid Path. 1981; 52: 51 – 55. lesions may result in facial paralysis as a 6. Joseph AR, James JS, Richard CKJ, Fred C. Oral Pathology (Clinical Pa- result of facial nerve involvement. The thologic Correlation), 4th edition. WD histopathology demonstrates an infiltrative Saunders, 2003; Pp. 183 – 217. proliferation of basaloid cells arranged 7. Arthur CG, John EH. Secretory Func- distant in a "cribriform" (Swiss cheese) tions of the Alimentary Tract: Text th pattern. As seen in the polymorphous low Book of Medical Physiology. 11 edi- tion. Vol. 2, 2006; Pp. 793 – 806. – grade , there may be 8. Tandler B, Gresik EW, Nagato T, Phi- (3) perineural invasion. Because the tumor lips CJ. Secretion by striated ducts of is prone to late recurrence and metastasis, mammalian major salivary gland: re- as well as 5 years survival rate has little view from histological, functional and significance and does not equate to a cure, evolutionary prespective. Anat Rec. 2001; 264: 121. this rate may be as high as 70%, but it con- 9. Noyek AM. Head and Neck Radiology. tinues to decrease overtime and by 20 Gower medical publishing. London. years, only 20% of patients are still a live. 3rd edition. 1991; 312 – 324. Tumors with a solid histopathologic pat- 10. Stephens LC, Schulthesis TE, Price tern are associated with a worse out look RE, et al. Radiation apoptosis of ser- ous acinar cells of salivary and lacrim- than those with a cribriform or tubular ar- al glands. Cancer. 1991; 67: 1539 – rangement. With respect to site, the prog- 1543. nosis is poorest for tumors arising in the 11. Abaza N. The role of labial salivary maxillary sinus and submandibular gland. gland biopsy in the diagnosis of Sjo- Most studies have shown than microscopic gren's syndrome: report of three cases. J Oral Maxillofacial Surg. 1993; identification of perineural invasion has 51(5): 574. little effect on the prognosis. Death usually 12. Goldberg MH, Bevilacqua RG Infec- results from local recurrence or distant tions of the salivary glands. J Oral metastasis, which commonly occurs to the Maxillofac Surg. 1995; 7: 423. lungs and bones, while tumors of the pa- 13. Brad W N, Douglas DD, Carl MA, Jerry E.: Oral and Maxillofacial Pa- late or maxillary sinus eventually may in- thology. 2nd edition. 2002; Pp. 675 – (13) vade up ward to the base of the brain. 679. 14. Blitzer A. Inflammatory and obstruc- REFERENCES tive disorders of salivary glands. J 1. Snell RS. Clinical Anatomy for Medical Dent Res. 1987; 66 (Supp 1): 675 – Students. 7th edition. SMHS Washing- 679. ton. 2004; Pp. 773 – 788. 15. Koudelka BM. Obstructive Disorders: 2. Antonio N. Ten Cate's Oral Histology, Ellis GL, Auclair PL, Gnepp DR (eds). Surgical pathology of the salivary

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