Pictorial Essay Salivary Gland Imaging In Nuclear

Pictorial essay: Salivary gland imaging

Rajul Rastogi,Sumeet Bhargava,1Govindarajan Janardan Mallarajapatna,2 and Sudhir Kumar Singh3

Yash Diagnostic Center, Yash Hospital and Research Center, Moradabad, India

1Department of Radiology and Imaging, Subharti Medical College, Meerut, India

2Department of Imaging and Interventions, Health Care Global Bangalore Institute of Oncology, Bangalore, Karnataka, India

3Department of ENT, Kothiwal Dental College and Research Center, Moradabad, Uttar Pradesh, India

Correspondence: Dr. Rajul Rastogi, Yash Hospital and Research Center, Moradabad, Uttar Pradesh - 244001, India. E-mail: moc.liamg@igotsarahsee

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Abstract

Salivary glands are the first organs of digestion secreting their digestive juices into the oral cavity. Parotid, submandibular, and sublingual glands are the major paired salivary glands in the decreasing order of their size. In addition, multiple small minor salivary glands are noted randomly distributed in the upper aerodigestive tract, including paranasal sinuses and parapharyngeal spaces. The imaging is directed to the major salivary glands. Commonly used imaging methods include plain radiography and conventional sialography. Recently, high-resolution ultrasonography (HRUS) is being increasingly used for targeted salivary gland imaging. However, the advent of cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have revolutionized the imaging of salivary glands. This article illustrates the role of imaging in evaluating the variegated disease pattern of the major salivary glands.

Keywords: Computed tomography, imaging, magnetic resonance imaging, salivary glands

Introduction

Parotid, submandibular, and sublingual glands are the major paired salivary glands of the body acting on the first step of the digestion process.

The parotid gland is the largest salivary gland and is composed of adipose and glandular tissues in nearly equal proportions, making it appear nearly isodense/isointense to fat on computed tomography/magnetic resonance imaging (CT/MR) images. The parotid gland is divided into the larger superficial and smaller deep lobes by the retromandibular or facial vein. It is located posterior to the ramus of mandible and drains via the Stenson's duct traversing superficial to the masseter muscle and passing through the buccinator muscle before finally opening into the oral cavity at the ipsilateral 2nd maxillary molar. The distal part of facial nerve and its terminal branches passes through the parotid parenchyma. Multiple nodes are located superficially and within the parotid gland. Accessory parotid gland is noted in 20% subjects and is usually located anterior to the main parotid and superior to the Stenson's duct draining in to the latter through an accessory duct.

The submandibular gland is the second largest salivary gland and is located in the floor of the mouth adjacent to the posterior body of mandible along the free edge of the mylohyoid muscle. The amount of adipose tissue is relatively lower than that of parotid gland. The lingual nerve and submandibular ganglion are noted superficial to the submandibular gland while the hypoglossal nerve lies deep to it. It drains through the Wharton's duct in the anterior sublingual region at the papilla in paramidline location.

Sublingual gland is the smallest major salivary gland. It lies submucosally adjacent to the anterior mandible in parasymphyseal location. The Wharton's duct and lingual nerve separate the sublingual gland from the medial genioglossus muscle. It opens via multiple ducts usually 20 in number (known as ducts of Rivinus) directly into the floor of mouth along sublingual papillae and folds. Occasionally, some of the ducts unite to form the Bartholin's duct that drain into the Wharton's duct.

The common clinical indications of salivary gland imaging are pain and swelling. Imaging is useful in identifying the masses of salivary glands and also in differentiating them from the masses/pathologies of adjacent cervical spaces, especially parapharyngeal, masticator, and submental spaces and mandibular lesions. Nodal masses, peripheral nerve schwannomas, and masseteric hypertrophy may mimic tumors of salivary glands clinically. In proven cases of salivary gland tumors, imaging helps in delineating the extent of the lesion and invasion of adjacent cervical spaces, skull base, mandible, and nerves/meninges. The disease of major salivary gland can be broadly categorized into the inflammatory, neoplastic, systemic, and congenital conditions.

Imaging Armamentarium for Salivary Gland Imaging Includes:[1,2,3]

  • Plain radiography

  • Sialography (conventional, CT, MRI)

  • High-resolution ultrasonography (HRUS)

  • Computed tomography (CT)

  • Magnetic resonance imaging (MRI)

  • Radionuclide scintigraphy

Plain Radiography

This is the simplest, oldest, and cheapest way of studying the salivary glands. It is useful in detecting ductal calculi, calcifications (as in hemangioma and lymph nodes), and adjacent osseous lesions. Only one-fifth of the salivary ductal calculi are radiolucent.

Parotid gland radiography requires posteroanterior projection with extended chin, open mouth, and cheeks blown out to delineate Stenson's duct lesion. Submandibular gland radiography requires posteroanterior and ipsilateral oblique projection with extended chin, open mouth, and tongue depressed by patients’ finger [Figure 1].

Figure 1(A, B)

Plain radiograph of the submandibular region in AP (A) and lateral oblique (B) projection showing soft tissue swelling associated with a small calculus (arrow) visible on lateral oblique view taken with depressed tongue

Sialography

It refers to the evaluation of the ductal system of the salivary glands. It is considered the gold standard technique for studying the ductal morphology. It is commonly used for parotid and submandibular glands and its main indication is chronic sialadenitis unrelated to sialolithiasis [Figure 2]. Acute sialadenitis is a contraindication for sialography. Irregular pooling of contrast and ductal obstruction without presence of calculus are indirect signs of malignancy.

Figure 2(A, B)

Conventional sialography of submandibular (A) and parotid glands (B) showing ductal system

Sialography is rarely used for sublingual imaging because of numerous small ducts opening directly into the floor of mouth. Sublingual glands may however be visualized in an anatomic variation where the Bartholin's duct is outlined following injection of the contrast medium into the Wharton's duct.

It is usually performed through digital subtraction method following retrograde intracannular injection of the water-soluble, iodinated, contrast medium into the Stenson's/Wharton's duct opening to opacify the ductal system. However, 3DCT performed especially with cone-beam CT following injection of the contrast medium into the ductal system without intravenous injection of contrast can provide images similar to or better than conventional sialography and is often referred to as CT sialography.[4] MR Sialography, by contrast, delineates the ductal system of the gland without injection of ductal/intravenous contrast by utilizing the highly fluid-sensitive sequences similar to that used for magnetic resonance cholangiopancreatography (MRCP) [Figure 3]. MR Sialography can be performed in patients of acute sialadenitis. Prior administration of a sialogogue agent may improve ductal visualization in MR Sialography.[5] MR Sialography has poor spatial resolution as compared to conventional sialography.[6]

Figure 3

MR sialography shows bilateral Stemson's duct (arrows)

High-resolution Ultrasonography

It is a quick and noninvasive method of evaluating parotid and submandibular glands. Both glands appear homogeneously hyperechoic on HRUS, and retromandibular vein can be noted within the parotid gland [Figure 4]. It is performed by a high-frequency linear (7-10 MHz) transducer. It helps in differentiating cystic from solid lesions and also aids in guiding the exact site of Fine N eedle A spiration C ytology (FNAC) in suspected salivary gland lesions.[7]

Figure 4

HRUS images showing normal parotid and submandibular glands (top row) and retromandibular vein in the parotid gland (arrow)

When combined with color Doppler imaging, it helps in assessing the vascularity and nature of the lesion (malignant lesions of salivary glands are highly vascular as compared to their benign counterparts – peripheral vascularity with hypovascular central area in the tumoral lesion is highly suggestive of pleomorphic adenoma). RI and PI values of greater than 0.7 and 1.2, respectively, coupled with high PSV (greater than 44.3 cm/s), ill-defined margins, and nodal involvement with central vascularity are highly indicative of malignant salivary gland lesion.[8,9]

In experienced hands, it helps in differentiating intra-parotid nodes from true intraparenchymal lesions, picking soft calcifications/diffuse lesions and detecting major ductal dilatation with intraductal calculi [Figure 5]. However, it cannot optimally evaluate the deep lobe of the parotid gland.

Figure 5

HRUS images show altered echopattern of the parotid gland with ductal dilatation (thin arrow) and small calculus (thick arrow) at its terminal end

CT and MRI

These cross-sectional studies help in true and near complete imaging of the salivary glands [Figures ​6-​8]. MRI, because of its multiplanar capability and higher soft tissue resolution, has an upper hand over CT in demonstrating the extent of lesion and their perineural/meningeal spread. However, CT (especially cone-beam CT) demonstrates the osseous lesions/extension and calcification/calculus better than MRI. Noncontrast CT may be enough in cases of sialolithiasis. However, ductal system is not optimally evaluated by any of these techniques.

Figure 6

Non-contrast axial CT image showing submandibular sialolithiasis on right side (white arrow) and normal gland on left side

Figure 8

Non-contrast T2W axial & coronal images (top row) and T1W axial and coronal images showing parotid (thick white arrows) and submandibular glands (thin white arrow)

Figure 7

Non-contrast axial CT image show normal appearing parotid (white arrows) gland in a young subject

These studies are often performed after intravenous injection of the contrast media for better delineation of the anatomy and the extent of lesion. Diffusion-weighted (DW) images and gadolinium-enhanced dynamic MR (Gd-MRI) imaging have proven to be very useful in differentiating benign from malignant tumors.[10,11] DW images can be used to calculate apparent diffusion coefficient (ADC) values, which are different for different salivary gland tumors. Gd-MR with dynamic imaging using 120 s as cut-off for time to peak enhancement and 30 % wash-out ratio can differentiate benign and malignant tumors as the latter take less time for peak enhancement and show rapid wash-out. Plateau type of time–intensity curve in dynamic Gd-MR coupled with low ADC values is also highly suggestive of malignancy. Proton MR Spectroscopy has also been described for differentiation of benign from malignant tumors by some authors. Choline/creatinine ratios are significantly lower in malignant than in benign salivary gland tumors.[12]

Radionuclide Imaging

It is a rarely used technique for salivary gland imaging. Sodium pertechnetate (Tc[99]) is actively concentrated and secreted by salivary gland cells while it is not taken up by majority of neoplastic lesions, hence the latter appear as cold spots. Warthin's tumor is an exception to the rule and appears as a hot spot.

Actively dividing cells take up Gallium-67; hence it is useful in detecting diffuse inflammatory/neoplastic processes such as sarcoidosis and lymphoma.

Positron emission tomography (PET) imaging using 2-deoxy-2-[18F] fluoro-d -glucose (FDG) can be used to differentiate benign from malignant tumors of the salivary glands as the former appear as cold spots with the exception of Warthin's tumor and oncocytoma.[13]

Inflammatory Diseases of Salivary Glands

Sialolithiasis is the second commonest cause of sialadenitis next only to mumps and probably the commonest cause of unilateral enlargement of the salivary glands. Sialolithiasis is commonest in the submandibular gland and may cause diffuse or focal enlargement of the gland. Imaging is useful in detecting and defining the location of nonpalpable/multiple calculi. Rarely, a mucus plug instead of the calculus may be a cause of ductal obstruction and consequent acute sialadenitis, often referred to as Kussmaul disease.

Conventional sialography, HRUS, and CT can detect sialolithiasis with a high degree of sensitivity.[14] HRUS is however inferior to CT in differentiating a solitary large ductal calculus from a cluster of small calculi. MRI sialography is useful in cases of chronic sialadenitis when sialolithiasis has been ruled out by the aforementioned studies, especially to look for strictures following passage of calculus. Autoimmune sialadenitis reveals pruning/truncation of major ducts and globular peripheral collections on MR sialography as periphery of the gland is the usual site of initiation of this pathologic process. Presence of microabscesses may mimic peripheral collections of the autoimmune process.

HRUS shows diffusely enlarged and tender gland with diffuse decrease in echogenicity, heteroechoic pattern (due to small focal lesions) and with diffuse increase in vascularity with or without abscess formation in acute stages [Figures ​9-​11]. In chronic stages, the gland may be normal or small in size with reduced echogenicity and vascularity and heteroechoic pattern.

Figure 9

3D HRUS image shows enlarged submandibular gland with altered echopattern in a case of sialadenitis

Figure 11

HRUS image shows submandibular gland abscess (white arrows)

Figure 10

3D HRUS image shows parotid gland with altered echopattern and small calculi in a case of sialadenitis

Sialadenitis manifests as moderate to intensely enhancing, diffusely enlarged salivary gland with or without abscess formation, and intraparenchymal/regional lymphadenopathy on CT/MR imaging [Figures ​12–14]. There is associated soft tissue stranding/thickening of adjacent fat and cervical fascia. As MRI is more sensitive to edema, it picks up early sialadenitis and even inflammation of ductal walls (sialodochitis). MRI in coronal plane is very helpful in delineating the relationship of salivary gland lesions with other structures in the floor of mouth as in ranula (a mucous retention cyst) and in demonstrating the invasion of skull base especially in parotid lesions.

Figure 12

Contrast-enhanced axial CT image shows hypodense, enlarged right submandibular gland with calculus (thick white arrow) and thickening of adjacent fascia (thin white arrow)

Figure 14

Contrast-enhanced axial MR image shows severe parotitis on left side (white arrows)

Figure 13(A, B)

Contrast-enhanced coronal CT image (A) shows submandibular mucocele on right side (thick white arrow) while axial CT image (B) shows right sublingual gland mucocele (thin white arrows)

Ranula refers to a mucus retention pseudocyst occurring in the floor of the mouth within the sublingual space commonly from the sublingual gland following traumatic extravasation of the salivary secretions or following obstruction of the draining duct. Ranula is said to be plunging when it extends anteriorly into the submental space or posteriorly into the submandibular space through either the dehiscence or the posterior free margin of the mylohyoid muscle. It appears as a smooth-walled and fluid-dense/fluid-intense lesion devoid of internal septations on CT/MR images. Presence of anterior tapering into the sublingual space (tail sign) is typical of ranula when it plunges posteriorly. Presence of enhancing walls is indicative of superadded infection.

The important differential diagnosis of abscess within the salivary glands is superinfected cysts in HIV patients, suppurative nodes in the parotid gland, and cystic degeneration/superinfection of the existing neoplasm.

Chronic sialadenitis usually manifests as reduction in parenchymal volume of gland associated with multifocal intraglandular calcifications and rarely a solitary large ductal calculus.

Neoplastic Diseases of Salivary Glands

Salivary gland neoplasms usually present as painless, solitary masses. The risk of malignancy is usually higher in the smaller salivary glands. Majority of the benign lesions are pleomorphic adenoma with Warthin's tumor, monomorphic adenoma, oncocytoma, myoepithelioma, lipoma, and hemangioma accounting for the other small number of benign lesions. Pleomorphic adenoma is more common in middle-aged females. Oncocytoma and Warthin's tumor are predominantly noted in parotid gland. Multifocal masses within the parotid gland are either enlarged lymph nodes or Warthin's tumor.

Malignant lesions include mucoepidermoid carcinoma, adenoid cystic carcinoma, undifferentiated carcinoma, adenocarcinoma, and squamous carcinoma. Most common malignant lesion occurring in parotid gland is mucoepidermoid carcinoma while in submandibular gland, adenoid cystic carcinoma is the commonest associated with high propensity for perineural extension.

Malignant lymphadenopathy within the parotid may be secondary to cutaneous malignancies, especially basal cell carcinoma, squamous cell carcinoma, and melanoma; lymphoma and rarely secondary to malignancies involving upper aerodigestive tract.

CT and MRI are the usual investigations used for evaluating known/suspected salivary gland masses [Figures ​15-​17]. Imaging cannot distinguish between different histologic types as all tumors are isoattenuating to glandular parenchyma on CT and hypointense to gland on T1W MR image and all of them enhance on postcontrast CT and MR images. However, both the modalities can sensitively differentiate between solid and cystic lesions.

Figure 15

Contrast-enhanced axial CT image shows enlarged left submandibular gland (thick white arrow) associated with destruction of the adjacent mandible (thin white arrow) in a case of adenoid cystic carcinoma

Figure 17

Non-contrast T2 & T1W axial images (upper row) and T2W coronal & DW axial images (lower row) show pleomorphic adenoma of right parotid gland (white arrows)

Figure 16

Contrast-enhanced axial CT image shows malignant pleomorphic adenoma of right parotid gland (white arrows

MRI examination is preferred over CT when associated neural (facial, trigeminal, hypoglossal, and lingual nerves) and meningeal involvement is suspected. The signs of malignancy on imaging include invasion of adjacent structures (nerves, bone, skull base, meninges, and adjacent cervical spaces) and rupture of capsule in pleomorphic adenoma, all of which are better delineated by MRI. Postgadolinium, fat-suppressed T1W images are preferred for determining the invasion. Ill-defined margins of the tumor on postcontrast images are also highly suggestive of malignancy.[15]

Pleomorphic adenoma is usually homogeneously hyperintense on T2W, while presence of mass with low-to-intermediate intensity on T2W images is more indicative of a malignant lesion. Warthin's tumor is an exception appearing hypointense on T2W images. Oncocytoma is isointense to the glandular parenchyma on fat-suppressed T2W and postcontrast T1W images.[16]

Radionuclide scintigraphy is preferred in suspected Warthin's tumor and oncocytoma as they appear as hot spots in contrast to all the other benign and malignant lesions. Multiple salivary gland lesions are an indication of scintigraphy to detect Warthin's tumor among the multiple lesions as they can be followed conservatively.

Salivary Gland Involvement in Systemic Disease

Major systemic diseases involving salivary glands are autoimmune processes predominantly including Sjögren's syndrome (including Mikulicz disease) and sarcoidosis. Salivary gland involvement can also occur in HIV disease and following radiation exposure. Imaging reveals diffuse enlargement of the gland in early stages with/without the presence of focal masses, nodules, cysts, nodes, calculi, or calcifications and features of chronic sialadenitis in later stages. Sarcoidosis and Sjögren's syndrome are associated with high incidence of calculi while the latter has a high propensity for lymphoma of parotid. Recently, MR microscopy has been tried to study and stage the parotid gland involvement in patients with Sjögren's syndrome.

MR microscopy refers to the imaging of the parotid gland with small surface coil less than 100 mm in diameter to obtain images of higher spatial resolution (47 mm in a study by Takagia, et al.) than that obtained by usual coils.[17] This allows better evaluation (quantitative rather than qualitative assessment) of parotid gland in patients of Sjögren's disease to determine the severity of disease.[17] The parameters usually involved are the quantification of glandular fat, intact glandular lobules, and number of sialectatic foci.

Bilateral, diffuse, and painless enlargement of the salivary gland referred to as sialosis occurs in diabetes mellitus, chronic alcoholism, hypothyroidism, malnutrition, and rarely secondary to certain drugs (antibiotic, antipsychotics. and diuretics).[18] HRUS reveals a hyperechoic gland without increased vascularity or focal lesions.

Multiple granulomatous diseases including Wegener's disease, tuberculosis, syphilis, and fungal infections may involve salivary glands either diffusely or focally [Figures ​18 and ​19].

Figure 18

HRUS images show bilateral diffusely hypoechoic parotid gland with small hypoechoic nodular lesions in a patient of granulomatous parotitis

Figure 19

Non-contrast T1W axial images show intraparotid adenopathy (white arrows) with altered appearance in a case of tuberculosis of left parotid gland

Kimura disease (combination of eosinophilia and lymphoid proliferation of cervical nodes and salivary glands), actinomycosis, amyloidosis, and hematogenous metastases (usually thyroid and renal in origin) are very rare causes of salivary gland involvement especially the parotids.

CT reveals hyperattenuating glandular parenchyma in both acute and chronic stages associated with enlargement in acute and loss of glandular volume in chronic stages. However, on MRI images, the gland is hyperintense on T2W images in acute and relatively hypointense in chronic stages.

Congenital Lesions of the Salivary Glands

These include cysts (type I branchial cyst, salivary cysts, dermoid, and epidermoid cysts), lipoma, hemangioma, lymphangioma, sialolipoma, and sarcoma [Figure 20].[19] Majority occur in the parotid glands and some of them such as lipoma, hemangioma, dermoid cyst, and lymphangioma reveal characteristic features on CT and MR imaging as elsewhere in the body and other show nonspecific imaging features.

Figure 20

T2W sagittal MR image shows a sublingual epidermoid cyst (white arrows)

Conclusion

A variety of disease patterns involve the major salivary glands with few characteristic features on imaging. HRUS should be the first screening imaging tool followed by sialography, if required. CT is the mainstay of imaging in sialolithiasis while MRI is more optimal for neoplastic processes with associated invasion. CT and MRI are equally good in imaging of the cystic and inflammatory lesions especially abscesses.

Footnotes

Source of Support: Nil

Conflict of Interest: No.

References

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SALIVARY GLANDS DEVELOPMENT AND ANATOMY

The development of the parotid gland starts from 4-6th week, the submandibular gland at 6th week and the sublingual gland including minor salivary glands develops at 8-12 wk of embryonic life. The various developmental stages are: Bud formation, Epithelial cord formation, Branching and glandular differentiation, canalization and cyto differentiation. The parotid is ectodermal while the submandibular and sublingual glands are endodermal in their origins. The parotid represents the largest of the salivary gland which is situated between the external acoustic meatus between the ramus of the mandible and sternocleidomastoid muscle. Each gland is encapsulated and is composed of fat tissue and cells that secrete mainly the serous fluids. The major duct of each parotid gland is called Stensen’s duct which opens into the vestibule of the mouth opposite the crown of the upper second molar tooth. The parotid gland being primarily serous in secretion secretes watery serous saliva[2].

The submandibular glands are located along the side of the lower jawbone in the anterior part of digastric triangle. Each gland has a major duct called Wharton’s duct which opens on the floor of the mouth, on the summit of sublingual papilla at the side of frenulum of the tongue. Each of these glands is covered by a capsule which gives off mixed serous and mucous secretion in nature. The sublingual glands are the smallest of the major salivary glands which lies above mylohyoid and below the mucosa of the floor of the mouth. They are not covered by a capsule and are therefore more dispersed throughout the surrounding tissue. Their secretions are drained by many small ducts known as Rivinus’s ducts that exit along the sublingual fold at the floor of the mouth. Sometimes, few anterior ducts may join to form a common duct called Bartholin’s duct, their secretion being mixed in nature which empties into Wharton’s duct. The sublingual and minor salivary glands are primarily mucous in nature.

Types

Salivary glands can be classified according to size as major and minor glands. The major salivary glands are of three pairs namely the parotid, submandibular and sublingual glands are shown in Figure 1. There are a numerous minor glands present in labial, buccal, glosso palatine, palatine and lingual areas in the oral cavity.

Figure 1 Major Salivary Glands and their related structures.

Based upon the type of secretion salivary glands may be predominantly serous, mucous or mixed depending on the type of secreting cells. Parotid and Von Ebners glands are purely serous while minor salivary glands like glosso palatine, palatine and anterior lingual glands are purely mucous. The mixed types of salivary glands are submandibular, sublingual, labial, buccal and posterior lingual glands.

Histology of salivary glands

Each gland has the secretory unit which is mainly composed of acinus, myoepithelial cells, intercalated duct, striated and excretory ducts. The acinus could be serous, mucous or mixed. These acini contain amylase granules in serous and granules with mucin in mucous glands and are responsible for producing primary secretion is shown in Figures 2 and 3. The secretory granule in mixed salivary glands contains serous demilunes, capping mucous acinar cells (Demilunes of Gianuzzi or Heidenham) producing sero mucous saliva. The ductal system of the salivary gland has a varied network. The three classes of ducts are intercalated, striated, and excretory each with different structure and function.

Figure 2 Mucous secreting cell showing Mucigen vesicle.

Figure 3 Serous secreting cell with secretory granules.

Saliva: It is mainly secreted and produced by the salivary gland. The total volume of saliva secreted daily in an adult person is 600-1000 mL out of which 60% is secreted by the submandibular glands, 30% by the parotid, 5% by the lingual and 7% by the minor salivary glands with a pH in the range of 6.0-7.0. However, the salivary secretion is a reflex action arising from the salivary centres dependent on afferent stimulation. The sublingual and minor salivary glands spontaneously secrete saliva though the bulk of this secretion is nerve mediated. The normal average salivary flow rate ranges from 0.1-0.3 mL per minute[3].

Composition

Saliva is mainly composed of the following components. Electrolytes like sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate, thiocynate, and fluoride. Secretory proteins/Peptides like Amylase, proline rich proteins, mucins, histatin, cystatin, peroxidase, lysozyme, lactoferrin, glycoproteins, lysozyme, defensins, and cathelicidin LL37. They also contain secretory immune globulins-(IgA), IgG, IgM, organic components like, glucose, amino acids, urea, uric acid, and lipid molecules. The other components that are present are epidermal growth factors, epithelial cells, insulin, cyclic adenosine monophosphate, binding proteins and serum albumin. In addition, biologically active peptides such as leptin, ghrelin and endothelin which are identified in saliva are of supreme importance to general health and also oral health in particular[4-9]. Functions: saliva mainly helps in lubrication for the movement of oral tissues against each other and the food, aids in digestion, in taste perception, neutralises by its buffering action the bacterial acids and thereby promotes remineralisation by reducing dissolution of enamel by inhibition of calcium phosphate precipitate. The saliva over all protects the teeth and the oral mucosa by the presence of immunoglobulin’s tissue repair factors and antibacterial system[4].

Oral diagnostic approaches to the patients with salivary gland disorders: (1) Past and Present History: to enquire about the history of patient who had undergone any surgery/radiotherapy, or have any underlying systemic problems/the patient is under any medications, etc. A thorough medical history and physical examination are also essential; and (2) Clinical Examination; a study by Navazesh suggests four clinical measures to diagnose the hypo function in the salivary gland. They are dryness of the lips and buccal mucosa, absence of saliva produced by the gland, bimanual palpation, and DMFT scores[5].

For evaluations of Dry mouth and a salivary mass or enlarged salivary gland, the following diagnostic approached may be applied: (1) Imaging of salivary glands; (2) Sialography; (3) Special imaging; (4) Sialochemistry; and (5) Biopsy and culture.

Salivary gland disorders: (1) Developmental-Aplasia, Atresia, Aberrancy; (2) Functional Disorders-Xerostomia, Sialorrhea (Ptyalism); (3) Inflammatory-infectious conditions; acute and chronic bacterial infection; Sialadenitis, Viral infection; Mumps, Human immunodeficiency virus associated salivary gland disorder; Post irradiation Sialadenitis, chronic sclerosing Sialadenitis, cheilitis glandularis; (4) Traumatic/Obstructive-Mucocele, salivary duct cyst (mucose retention cyst, Ranula), Nicotinic stomatitis, Sialolithiasis; (5) Autoimmune-Sarcoidosis, Sjogrens syndrome, Mikulicz’s disease; (6) Neurological-Frey’s syndrome; (7) Degenerative-idiopathic Sialolithiasis; (8) Non inflammatory non neoplastic-Sialadenosis; (9) Vascular-Necrotizing sialometaplasis; (10) Neoplastic-Benign: Papillary Cystadenoma Lymphomatosum, Pleomorphic Adenoma, BasalCell Adenomas, Oncocytoma, Canalicular Adenoma, Myoepithelioma, Sebaceous Adenoma, and Ductal Papilloma. Malignant: Adenoid Cystic Carcinoma, Hyalinising Clear Cell Carcinoma, Mucoepidermoid Carcinoma, Acinic Cell Carcinoma, Adeno carcinoma, Carcinoma[3,6]; and (11) Classification of Salivary Gland Tumours according to WHO 2005 is listed in Table 1.

Developmental disorders

Atresia is the congenital occlusion or absence of salivary ducts which leads to xerostomia or mucous retention cyst.

Aplasia is the complete absence of one or more salivary gland which leads to xerostomia, and affected patients are more susceptible to dental caries. This condition could be an isolated finding or associated with other disorder like hemi facial microsomia or Treacher Collins syndrome. Recent studies suggest that mutation in fibroblast growth factor 10 (FGF10) affecting the FGF receptor signalling, has been linked with this condition[7]. Enamel hypoplasia, extensive occlusal wear of teeth or congenital absence of teeth are other oral manifestations of salivary agenesis. However the treatment is supportive.

Aberrancy: it is an anatomic variant wherein the normal salivary gland develops at an abnormal position. Sometimes they are found adjacent to lingual surface of the mandible within a depression. Ex: Staphne’s bone cyst or Staphne’s bone cavity: It is thought to be created by an ectopic portion of salivary gland tissue which causes remodelling of the mandibular bone. This creates an apparent cyst like radiolucent area seen on the radiographs[8]. It appears below the inferior alveolar nerve canal in the posterior region of the mandible.

This lesion is not discovered during routine examination, as it causes no symptoms and do not require intervention. However, surgical intervention is recommended in atypical regions in which the diagnosis is unclear and a tumor is suspected.

Functional disorders

Xerostomia: It is defined as the subjective sensation of oral dryness that may or may not be associated with a reduction in salivary output. The condition may be transient, prolonged or permanent depending upon the duration of the condition.

Aetiology: Temporary causes are: (1) Psychological causes due to anxiety and depression; (2) Drug therapy-Drugs that exert anti-anticholinergic and decrease the volume of serous saliva are: anticholinergic ex:atropine, anti-hypertensive ex: reserpine, methyldopa, antihistamine ex: diphenhydramine, antidepressant: amitryptiline, antipsyschotics: diazepam, anti parkinsonian drugs: procyclidine, anti-emetics: hyoscine and antispasmodics: tizandine. Drugs that exert sympathomimetic action and produce more viscous mucinous saliva with less volume are: Nasal decongestants, appetite suppressants, bronchodilators, and amphetamines. Some drugs may also exert their neural effects in higher centres of the brain, by stimulation of adreno receptors in the frontal cortex that can produce inhibitory effects on salivary nuclei’s; (3) Duct calculi: a blockage of the duct of a major salivary gland (submandibular) can produce dryness on the affected side with pain and swelling in the gland on stimulation. If left untreated it can cause progressive fibrosis of the gland and permanent xerostomia; (4) infections; Sialadenitis is the inflammation of the salivary gland, acute infections like mumps and post-operative parotitis, chronic conditions like swellings related to nutritional deficiency, and iodine hypersensitivity, wherein in all these conditions causes hypo salivation[3,9].

Permanent causes: (5) Salivary gland aplasia, Sjogrens syndrome: causes dry eyes, dry mouth and often associated with rheumatoid arthritis. Other systemic disorders like diabetes mellitus, Parkinson’s disease, cystic fibrosis, sarcoidosis, vitamin A, riboflavin, nicotinic acid deficiencies and in anaemia’s; (6) Surgery or trauma to the ducts may also impair secretion; and (7) Radiotherapy: hypo salivation occurs on exposure of major salivary glands to radiation bilaterally in head and neck cancer. At radiation doses > 3000 cGy, the patient is at risk if all major glands are in the field of radiation. Irreversible effects occur at a dose of 6000 cGy for 5 wk. Radiation causes acinar cell atrophy and fibrosis, changes in vascular connective tissue and neurologic function. The degree of salivary gland alteration depends on dose volume factor, patient age, and time of exposure to radiation. Serous acini are affected before mucous acini resulting in thick viscous secretion. Depending on the amount of salivary tissue in the field, xerostomia may resolve within 6 mo and sometimes may be permanent. There can also be changes in salivary composition, decreased secretory IgA and buffering capacity with increased magnesium, calcium, potassium and sodium chloride in post radiotherapy cases[9-11].

Signs and symptoms: Lips are often cracked, peeling and atrophic; Buccal mucosa may be corrugated and pale: (1) Tongue may be smooth and reddened, cracked or fissured, with loss of papillation; (2) Increase in erosion and caries, particularly decay on root surfaces and even cusp tip involvement; (3) Erythematous form of candidiasis is frequent; (4) Lipstick sign: occurrence of shed epithelial cells on the labial surfaces of maxillary anterior teeth as the mucosa adheres to the teeth due to reduced saliva; (5) Tongue blade sign: when held against buccal mucosa, the tissue adheres to the tongue blade as it is lifted away; (6) Viscous sticky saliva with difficulty in speaking and swallowing; (7) Halitosis, altered taste and smell, gingivitis; (8) Complaint of burning mucosa, lips or tongue; (9) Ulceration of oral mucosa; (10) No accumulation of saliva in the floor of the mouth; (11) Poorly fitting prosthesis; and (12) Enlargement of salivary glands.

Xerostomia associated problems are: Dental Caries, Dry mouth, Dysgeusia, Dysphagia, oral Candidiasis, and Bacterial infections[12].

Treatment of xerostomia associated problems: Dental caries; use of fluorinated dentifrice (0.05% NaF)/fluoride gel in the concentration of 1% NaF, 0.4% Stannous fluoride application of 0.5% sodium fluoride varnish to teeth, regular use of re mineralising tooth paste. Dental examination every 6 mo and bitewing radiograph once a year for early diagnosis of dental caries. The recent advances in chair side diagnostics test kits are GC Salivary check-Buffer Kit that identifies, measures, and assesses patient for caries risk based on saliva conditions like hydration, consistency, pH of resting saliva and flow, and buffering capacity of stimulated saliva[13]. GC Saliva Check Mutans Kit is another chair side diagnostic kit used for rapid detection of high levels of S.mutans without the need for incubation is possible within 15 min. In a study, Gopinath et al[14] evaluated the effect of salivary testing in dental caries assessment using salivary testing kit (GC Asia Dental Pvt Ltd, Japan) and recommended adopting this test in patients with high caries risk.

A similar study conducted by Wennerholm et al[15] compared Saliva-Check Mutans and Saliva-Check IgA Mutans with the Cariogram for caries risk assessment and the data suggested that the combination of Saliva-Check Mutans and Saliva-Check IgA Mutans could be used for caries risk assessment.

Kanehire et al[16] aimed to develop a simple screening technique for the diagnosis of hypo salivation by estimation of capsaicin-stimulated salivary flow using filter paper. Five spots containing starch and potassium iodide on filter paper with or without capsaicin and a colouring reagent was designed in this assay system. The study suggested that this test would be useful for evaluating the retained functional ability of salivary glands and screening of hypo salivation with dry mouth.

Dry Mouth should be hydrated regularly using water or lozenges with citric acid to stimulate salivation, artificial salivary substitutes, lubricants such as lanolin based product Vaseline, olive oil, vitamin E or lip balm, oral gels such as oral balance, Dry mouth gel (GC Asia Dental Pvt Ltd, Japan) which can be applied on buccal and lingual surfaces of teeth and oral mucosa which can be applied any time during the day as needed. Even mouthwashes and sprays, sugar free gums, mints water or ice chips are recommended[6,12,17]. Sialogogues like pilocarpine 5 mg 3 times a day, cevimeline 30 mg 3 times a day, bromhexine, bethanecol, and anethole trithione are prescribed. Use of Salivary substitute’s solutions mainly containing electrolytes stimulates natural saliva, example Salivart, Oralube, Xerolube, Plax may also be recommended.

Application, in children 1 spray whereas in adult 2-3 sprays should be directed into the back of the mouth and tongue for the relief of dry mouth symptoms. The characteristics features that these substitutes possess are that they have electrolytes and pH similar to saliva and low viscosity allowing electrolytes particularly calcium to travel through matrix of saliva substitute which helps in remineralisation process. Mucin containing saliva orthana and Glycerate polymer are also suggested for xerostomia. There are studies suggesting the role of acupuncture therapy for improvement in salivation as a treatment option for patients responding to muscarinic agonists[17].

Measuring biofilm activity is possible by using recently introduced simple chair side adenosine triphosphate (ATP) bioluminescence test, CariScreen (Oral BioTech, Albany, Ore) the caries susceptibility test to assess cariogenic bacterial activity and their levels in caries free and caries active patients in about 15 s measurement with a meter[18].

Inflammatory

Sialadenitis is an inflammation condition affecting the salivary glands. Parotid salivary glands are most commonly affected in adolescents and in children, debilitated adults, or patients with medication on tricyclic antidepressants and tranquilizers.

Aetiology: The main etiologic factors for sialadentis can be either infectious or non-infectious factors. Bacterial and viral agents can cause of sialadenitis. Bacterial sialadenitis is caused because of retrograde spread of infection secondary to decreased salivary flow or ductal obstruction. Decreased salivary flow can be secondary to medications, dehydration or debilitating conditions. Ductal obstruction can be due to sialolithiasis, strictures within the ductal system and common in submandibular salivary glands or due to pressure effect from adjacent tumors.

Staphylococcus aureus is the most common etiologic agent for acute bacterial parotitis in addition Staph.Pyogenes, Strep. Viridians and other microorganisms can also cause sialadenitis. Viruses causing sialadenitis include paromyxo viruses (mumps-most common), Coxsackie virus, cytomegalo virus, etc. The patient may present with fever and dehydration[19]. Clinical features: clinically there is sudden pain at the angle of the jaw which is unilateral with glandular enlargement and tender to palpation with purulent discharge over Stensens duct.

Treatment includes administration of salivary stimulants, antibiotics and surgical drainage.

Acute postoperative parotitis: Aetiology is a form of sialadenitis which occurs after a major surgical procedure where in the patient depends only on intravenous fluids. In addition these patients are on atropine which is a pre anaesthetic medication for drying the secretions and this may contribute to dryness of mouth and subsequent inflammation of parotid salivary glands. Non-infectious causes of salivary gland inflammation are sarcoidosis and Sjogrens syndrome.

Clinical features: Parotid gland is the most common salivary gland involved in acute bacterial sialadentitis. The patient presents with painful, usually bilateral swelling of the parotid salivary glands with low grade fever. In addition the patient may also complain of difficulty in opening the mouth. On clinical examination the skin over the parotid region may be inflamed and intra orally purulent discharge may be observed from parotid duct. Treatment-The condition usually resolves in about 48 h. However, symptomatic treatment is recommended.

Mumps is an acute paramyxo virus induced infection of parotid salivary glands. Aetiology- It is a contagious infection spreading through airborne droplets or direct contact of saliva. The peak incidence of mumps is reported during winter and spring season[20]. Clinical features: The infectivity of the mumps virus ranges from 3 to 4 d after the onset of the disease[21,22]. During the prodromal phase of the disease, the patient may complain of low grade fever, muscle pain, head ache and malaise[20] followed by unilateral or bilateral enlargement of parotid salivary glands associated with pain which is severe during mastication. The inflammation of the salivary gland starts reducing by the end of 1st week and the patient returns to normal by 10 d[21]. Epididymoorchitis, Oophoritis, pancreatitis and acute meningitis are the complications of mumps[21]. Treatment is symptomatic and Mumps vaccination (MMR) may decrease the incidence of this infection and considered as preventive measure.

Chronic recurrent parotitis: The proposed etio pathogenesis for this disorder include, congenital[23,24] and acquired factors like ductal obstruction secondary to inflammation infection and autoimmune diseases[25,26].

Chronic sclerosing sialadenitis: Also known as Kuttner’s tumour was identified by Kuttner in 1896. Aetiology-The condition is a chronic inflammatory reaction secondary to ductal obstruction and subsequent salivary stasis. However, salivary flow obstruction is proposed to be the main factor in the pathogenesis of this disorder[27].

Clinical feature: Clinically the condition presents as a painful, hard swelling of submandibular salivary gland. The pain and swelling may be present for a variable duration of time. The differential diagnosis includes chronic sialadenitis, sialolithiasis, and benign lymphoepithelial lesions. Treatment-The condition is managed by surgical excision of the involved gland and chances of recurrence of the lesion or changing into malignancy is found to be rare[27].

Hepatitis C virus associated sialadenitis: Aetiology-hepatitis C virus (HCV) is found to affect the salivary glands and cause the glandular inflammation. Clinical feature: The affected patients may present with mild swelling of the parotid gland with minimum or no symptoms of dry eyes and dry mouth[27,28]. The diagnosis of HCV is by the detection of HCV DNA and anti HCV antibodies. Treatment- Hepatitis associated sialadenitis is treated symptomatically[29].

Human immunodeficiency virus infection: In Human immunodeficiency virus (HIV) infected patients salivary gland lesions commonly occur which may be neo plastic or non-neoplastic in nature. AIDS related tumours such as lymphoma and Kaposis sarcoma and a Sjogrens syndrome like condition occurs in these patients and are described as “HIV salivary gland disease” (HIV-SGD) is considered to be due to reactivation of a latent virus. Various studies have expressed the strong association between salivary gland dysfunction seen in HIV affected patients and Human Cytomegalovirus (CMV) saliva. Clinical feature: The condition is characterised by xerostomia with unilateral or bilateral salivary gland enlargement with reduced tear production. Diagnosis is by biopsy of the major gland which shows the presence of hyperplastic lymph nodes with lymphocytes and cystic cavities obtained from patients affected from HIV-SGD[6,28]. Treatment-Administration of oral sialagogues/frequent sipping of water are recommended for xerostomia. Anti-retroviral therapy may be administered for the management of HIV. Rarely radiotherapy and parotidectomy may be beneficial in advanced condition.

Iodine 131 indiced sialadenitis: Aetiology-high dose of oral Iodine 131 in treatment of thyroid carcinomas can adversely affect the salivary glands leading to sialadenitis. The incidence of acute salivary gland inflammation range from 24%-67% and that of chronic salivary gland inflammation range from 11%-43%[29-31]. Clinical feature: The patients present with pain and swelling of the salivary glands with or without dry mouth condition[32]. Treatment- Administration of oral sialagogues/oral hydration, serotonin receptor blocker and dexamethasone are recommended.

Sialadenosis: Sialadenosis also known as sialosis is an enlargement of salivary glands which is non-inflammatory and non-neoplastic more commonly affecting the parotid salivary glands.

Etiology: This condition can be associated with: Endocrine disorders: (1) Diabetes mellitus and insipidus; (2) Accromegaly; (3) Hypothyroidism; and (4) Pregnancy. Nutritional status: (1) Anorexia nervosa; (2) Bulimia; (3) Chronic alchoholism; and (4) General malnutrition. Medication induced sialadenosis[33]: (1) Psychotropic medications; (2) Antihypertensive drugs; and (3) Sympathomimetic drugs. Clinical features- Patient presents with a slowly progressing bilateral (rarely unilateral) swelling of parotid salivary glands which may be asymptomatic[34]. Rarely patients may complain of reduced salivary flow. Treatment-Management of underlying systemic condition may help in reversing the sialdenosis.

Traumatic: Mucocele

Aetiology-They is caused due to rupture of a salivary gland duct mostly due to trauma resulting in spillage of mucin into the surrounding tissues. Clinical features: Clinically a mucocele appear as bluish thin walled lesion which is fluctuant, and the most common site of occurrence is on the lower lip. Ranula: is a special type of mucocele which grows in the floor of the mouth, usually unilateral and is called due to its similar appearance to enlarged abdomen region of a frog. Treatment-in case of superficial recurrent or deep mucoceles, surgical intervention is indicated while large ranulas are treated by marsupialization. A study by Wilcox et al[6] recommends intra lesional corticosteroids administration before surgery.

Nicotinic stomatitis: Aetiology-The long standing habits of tobacco and or alcohol/hot liquid consumption. Clinical feature: Exhibits whitened areas of the hard palate due to hyperkeratosis caused by the thermal irritation. This irritation also causes inflammation and dilatation of the duct openings of the minor salivary glands of the palate manifesting as red patches or spots on a white background[1]. Treatment- discontinuation of the habits reverses the condition back to normal.

Autoimmune: Sarcoidosis

Aetiology-is an autoimmune chronic granulomatous inflammatory condition which causes destruction of the tissue by T lymphocytic, mononuclear phagocytic infiltration and granuloma formation[6]. The parotid salivary glands are affected in 10%-30% of cases. Clinical feature: The patient presents with a hard, bilateral enlargement of the parotid gland usually asymptomatic in nature. Sarcoidosis of parotid glands along with uveitis and facial nerve paralysis is termed as Heerfordt’s syndrome or uveo parotid fever[35]. The patient may complain of dry mouth and minor salivary gland biopsy confirms the diagnosis. Treatment- palliative treatment primarily relieving of the symptoms of salivary component of sarcoidosis is advised.

Corticosteroid or with Chloroquine has been recommended. Immunosuppressive and immune modulatory medications are administered in patients who do not respond the corticosteroids.

Sjogrens syndrome: Aetiology-is an autoimmune disorder associated with HLA-DR3 AND HLA-B8. The disease was described by Henric Sjogren in 1933. Clinical feature: The primary Sjogren syndrome/sicca complex exhibit dry eyes and mouth. The secondary Sjogren syndrome develops SLE, polyarteritis nodosa, polymyositis, rheumatoid arthritis and in scleroderma.

This condition is most commonly seen in women over 40 years with male: female in the ratio of 1: 10.

Sjogrens syndrome case definition[6,34] requires at least 2 out of the following 3 criteria as mentioned in Table 2. Laboratory findings: Anti salivary duct antibodies, anti-nuclear antibodies, rheumatoid factor increased ESR, Lip biopsy-lymphocytes around salivary glands. The other tests are Schirmer test, Rose Bengal dye test, Sialography and sialochemistry[6]. Treatment-to limit the harmful effects of the disease especially the ocular and oral conditions, symptomatic relief of administration of artificial tears, saliva substitutes, fluoride applications and oral hygiene measures are suggested[6,34].

Mikulicz’s disease: Aetiology-Mikulicz’s disease of unknown aetiology was first reported by Johann von Mikulicz-Radecki in 1888. However, it has been demonstrated that autoimmune, viral, and genetic factors may contribute to the pathogenesis of the disease. Clinical feature: Patients suffering from Mikulicz’s disease present with asymptomatic, bilateral swelling of the parotid, and submandibular salivary glands along with lacrimal glands. This disease closely resembles Sjogren’s syndrome. However the lacrimal and salivary secretion depletion is very minimal in Mikulicz’s disease. Histologically the disease resembles Sjogren’s syndrome, but lacks the characteristic anti-SS-A and anti-SS-B antibodies of Sjogren’s syndrome. Studies have found increased levels of IgG4 antibodies in the serum of patients with Mikulicz’s disease. Treatment- Mikulicz’s disease is very much responsive for steroid therapy particularly to[35] methylprednisolone.

Neurological

Frey’s syndrome also known as Auriculo temporal syndrome which is characterized by sweating in the pre auricular and temporal areas after gustatory stimulation.

Aetiology-the condition most commonly caused due to faulty regeneration of sympathetic and parasympathetic nerve fibres which were injured during parotid tumor surgery or ramus resection. Clinical feature: Post-surgery the parasympathetic fibres start innervating the sweat glands and vasculature of the skin around the parotid area. The symptoms usually appear within few minutes of the start of mastication or during stimulation of saliva and may remain up to 30 min after discontinuing mastication. The diagnosis of the syndrome can be confirmed by starch iodine test[36]. Treatment- Reassurance to the patient is advocated in most of the cases. Intra cutaneous injection of botulin toxin is found to be effective in severe condition and Tympanotomy[23] may be the treatment of choice with severe symptoms.

Degenerative

Sialolithiasis-is a condition of unknown aetiology. However, there could be several coexisting causes leading to the salivary stone formation. Some of these cofactors may be related to disturbed pH of saliva, abnormalities in the sphincter mechanism related to salivary duct opening and abnormal calcium metabolism[5,6]. Clinical Feature: This condition most often will not produce any signs and symptoms. Rarely, it may cause complete ductal obstruction, pain and swelling of the salivary glands. Treatment- Large salivary stone are managed by extracorporeal or intracorporal lithotripsy[6,17] procedure.

Non inflammatory non neoplastic

Sialadenosis is a non-infectious, non-inflammatory gland enlargement usually affecting the parotid bilaterally. This condition is most often seen in women causing salivary hypo salivation which can occur due to systemic disorders[6,12].

Vascular

Necrotizing sialometaplasia: Aetiology-The probable cause could be due to vascular infarction of the salivary gland lobules and is often mistaken for oral cancer[37]. Vascular compression is caused by a necrotic myocutaneous reconstruction of the flap used in palatal surgeries and embolization from carotid endarterectomises, Berger’s disease, Raynaud’s phenomenon. Predisposing factors are dental injections, ill-fitting denture, traumatic injury, previous surgery and upper respiratory tract infections. Clinical feature: appears as a non-neoplastic lesion that usually arises from a minor salivary gland in the lips, posterior part of the palate, and retro molar regions. Treatment: The condition is self-limiting and the healing of the lesion normally takes about 6-8 wk.

Neoplastic

Benign: Pleomorphic Adenoma, Papillary Cystadenoma Lymphomatosum (warthins tumor), Basal Cell Adenomas, Oncocytoma,Canalicular Adenoma, Myoepithelioma, Sebaceous Adenoma, Ductal Papilloma.

Malignant: Adenoid Cystic Carcinoma, Hyalinising Clear Cell Carcinoma, Mucoepidermoid Carcinoma, Acinic Cell Carcinoma, Adeno carcinoma, Pleomorphic Adenoma, Lymphoma[5,6,12].

Oral diagnostic approaches to the patients with salivary gland disorders: (1) Imaging of salivary glands: Salivary gland is one of the main soft tissue structures in the maxillofacial area. Imaging is useful in identifying the masses of salivary glands and also in differentiating them from the masses/pathologies of adjacent cervical spaces, especially para pharyngeal, masticator, submental spaces and mandibular lesions. Conventional radiography has a very limited role in the diagnosis of salivary gland pathology which includes plain radiography. It aids in identifying mainly salivary stones and calcifications. Gland plain radiography like in postero anterior skull projection with cheeks blown out to delineate the parotid duct and submandibular gland radiography includes lateral oblique radiograph with mouth wide open; and (2) Sialography was used as the sole imaging technique before the advent of advanced imaging techniques which include ultrasonography, elastography, computed tomography, scintigraphy, and magnetic resonance imaging. Sialography, an imaging technique of salivary gland, uses contrast medium to delineate the ductal system of salivary glands. Due to use of contrast medium this technique is not suitable and is contraindicated in acute conditions of salivary glands[38]. However sialography is found to be useful in assessment of salivary gland dysfunction secondary to obstructive disorders of the gland[39].

Studies have suggested other various diagnostic methods-magnetic resonance (MR) sialography is a non-invasive technique useful in evaluating the hypo functioning of salivary glands. Sialo endoscopy assist in detecting ductal anomalies that may not be[40] possible to detect by means of either traditional or new imaging techniques.

Sialography, Sialoendoscopy, and MR Sialography are indicated for evaluation of the ductal system of the salivary glands.

Ultrasonography, computed tomography, magnetic resonance imaging is helpful in assessment of the parenchyma of the salivary glands[41]. However; all these diagnostic aids have their own limitations in the diagnosis of salivary gland lesions.

Ultrasonography: Ultrasound examination of salivary glands with a high resolution transducer is found to be a highly sensitive, a non-invasive method for salivary gland evaluation[42]. It is a cost effective imaging tool which displays high definition images useful in evaluating the superficial structures particularly the peripheral areas of the affected salivary gland. High frequency linear probes of 7.5-12 MHz are used in imaging of salivary glands[43]. In acute conditions such as acute radiation induced sialadenitis, the gland appears swollen and show anoechic appearance on ultrasonography[44]. In a recent clinical study ultrasonography was found useful in diagnosing lymph node and salivary gland enlargement in submandibular region and suggested that it also helps in identifying the salivary glandular tissue in accessory salivary gland and salivary calculi[45].

Shock-wave lithotripsy: Shock-wave lithotripsy is a non-invasive diagnostic tool suggested for the management of sialolithiasis. Iro et al[46] in 1989 introduced the application of extracorporeal shock-wave lithotripsy (ESWL) in the management of salivary gland. Sialolithotripsy helps in removing salivary stones into smaller particles and thereby removal by flushing action is possible from the salivary duct system or after salivation induced by citric acid or other sialagogues. The shock-waves are generated extra-corporeally by using Piezoelectric and electromagnetic techniques or intra-corporeally using electro-hydraulic, pneumatic or laser endoscopic devices[46].

Sonoelastography: Elastography is an ultrasonography technique which measures the tissue elasticity in vivo. This imaging technique measures the elasticity of the glandular parenchyma and is useful in evaluating the hypo function of saliva especially in post radiation hypo function of salivary glands[41].

Computed tomography: Computed tomography (CT) scans of the salivary glands are useful in delineate the extent of the lesion and its relation to adjacent structures[47]. Multi detector CT scans help in characterizing tumours of salivary glands like Warthin tumor which demonstrates peak enhancement of signals after administration of contrast agents which is not found in other tumors of salivary glands. However CT scans perform poorly in characterizing the histopathologic nature of the tumors. CT scans help in differentiating the benign and malignant neoplasms of salivary glands. The irregular tumor margin and surrounding tissue infiltration is the characteristic feature of malignancy[48]. However studies have found overlap of CT scan characteristics between malignant and benign lesions. Apart from tumor identification CT scan also aids to view dystrophic calcifications in salivary glands.

CT sailography: Interpretation of sailography findings depend on the imaging technique used to acquire sailography images. Traditionally plain radiographs were used for assessment of salivary glands after injection of the contrast medium. Introduction of CT and MRI scans in maxillofacial imaging have shifted the focus from plain radiography to these advanced imaging techniques. However CT sialography may have limited applications due to the accessibility and cost factors. Moreover the prolonged image acquisition time of CT scans may jeopardize the viewing of CT contrast medium uptake[49]; (3) Special imaging; cone beam computed tomography (CBCT): some of the limitations of CT sialography have been addressed by use of CBCT technology with sialography. A study reported the usefulness of CBCT in demonstrating the secondary structures of submandibular salivary glands in comparison with plain radiography coupled with sialography. The same study reported that the effective dose from CBCT scans were comparable to that of plain radiography when a smaller field of view (FOV) was used[50].

Magnetic imaging resonance (MRI) scans are useful in assessment of salivary glands. The wide variety of soft tissue signals differences and multi planar image acquisition have made MRI an effective imaging modality for assessment of salivary gland tumors. This imaging modality is helpful in assessment of tumors affecting the deep lobes of parotid glands, skull base invasion of the tumours of salivary glands, evaluation of recurrent pleomorphic adenomas and much more[51]. Also high resolution MRI scans delineate the intra parotid course of facial nerve which is an important landmark for surgeons operating on parotid glands[52].

Magnetic resonance sialography-Major limitations of conventional sialography include use of iodine based contrast agents and inability of the contrast agent in overcoming the strictures within the ductal system of the salivary gland which in turn prevent the visualization. These limitations can be overcome by switching on to MR sialography which uses patients own saliva as a contrast medium. MR sialography also demonstrates the actual ductal diameter due to non-use of contrast agents[53].

Scintigraphy-Salivary gland scintigraphy uses Tc-99m pertechnetate which helps in assessment of salivary gland dysfunction in disorders like Sjogrens syndrome. This technique is valuable in assessment of xerostomia[54].

The minimally invasive techniques for preserving the glandular tissue which are currently being used in the management of obstructive salivary disease are sialoendoscopy, shockwave lithotripsy, interventional radiology, endoscopically video-assisted trans-oral and surgical retrieval of stones, and botulinum toxin therapy. Three dimensional reconstruction imaging (MR sialographic) and MR virtual endoscopy have recently been suggested for salivary gland ducts studies on par with their applications in medical field[55].

Emerging imaging based diagnostics: Positron emission tomography (PET) scan: A PET scan focuses for areas of high cellular activity suggesting a sign of cancer growth. It also helps to diagnosed cancer, and to assess its spread to lymph nodes or any other parts of the body. This test requires an injection of a very small quantity of radioactive substance usually a type of sugar known as FDG, which will be excreted by the body later in a day. As cancer cells growth is faster in the body, they absorb more of the radioactive sugar. After about an hour, the patient is moved onto a table and made to lie for about 30 min. Meanwhile a special camera captures a picture of areas of radioactivity in provide helpful information about whole body. It is also possible to take a PET and CT scan at the same time (PET/CT scan). This enables the doctor compare areas of higher radioactivity on the PET scan with the more detailed picture of that particular area on the CT scan[56]; (4) Sialochemistry and Sialometry: Sialochemistry deals with chemical analysis of saliva whereas Sialometry is concerned with measuring salivary flow rates and these two measurements of saliva helps in assessment of functioning of salivary glands. The normal volume of the saliva produced by both the major and minor salivary glands constitutes around 600 to 1000 mL per day[57]. This volume varies in different individuals and it may alter in different systemic conditions.

Sialometry can be in relation to whole saliva or gland specific saliva. Whole saliva is a mixture of salivary gland secretions, non salivary secretions including serum transudates, gingival crevicular fluid, food debris and oral microbes[58]. Most often clinicians assess the salivary gland functions through collection of whole saliva. This method is easy to perform and does not require any special equipment. However, whole saliva analysis is of limited value due to its low sensitivity in detecting gland specific dysfunction and gland specific changes in salivary chemical composition[59]; and (5) Salivary gland biopsy or fine needle aspiration (FNA) helps to determine whether the tumor is benign or malignant. In some cases this type of biopsy can help a clinician to avoid unnecessary surgery. Incisional biopsy; is a type of biopsy sometimes preferred if the FNA biopsy does not get a large enough sample to examine. For salivary gland tumors these types of biopsies are not done often. Surgery can both provide enough of a sample for a diagnosis and treat the tumor at the same time[6,17].

WHO classification of salivary glands neoplasm is listed in Table 1

Salivary gland neoplasm-Salivary gland cancers include tumors of different patho histologic characteristics and biological behaviour. The most prevalent salivary gland tumors[6,60-62] are: (1) Benign Condition: Pleomorphic Adenoma, Papillary Cystadenoma Lymphomatosum (Warthins Tumor), Basal Cell Adenomas, Oncocytoma; and (2) Malignant tumors: Muco Epidermoid Carcinoma, Adenoid Cystic Carcinoma. Salivary gland neoplasms according to study report represent less than 3% of all tumors.

Prevalence: The tumors can arise in about 80% in parotid gland, 15% in submandibular gland and 5% in the sublingual and minor salivary gland. 65% of submandibular, 50% of minor salivary gland and 20% of sublingual gland tumors are benign[6,12,60]. Aetiology: of the salivary gland neoplasm is not known. However, certain environmental factors and abnormalities are implicated. Environmental factors such as radiation, viruses, extensive use of tobacco and their products, molecular changes and genetic factors are considered as the causative factors. Clinical features: Subjects with benign tumor of parotid gland present with a unilateral, asymptomatic swelling of the involved gland and rarely suffer from pain, difficulty in swallowing and extrusion of fluid from the ears. The benign tumor of other types of salivary glands also present as asymptomatic mass of the affected gland without compromising the functions of the individual.

Malignant tumor of the salivary glands may also present as asymptomatic mass and in advanced stages may cause pain and mucosal/skin ulceration. One third of patients with parotid gland malignancy most often present with facial nerve paralysis[60]. The signs of malignancy in a previous benign tumor of parotid gland can be a sudden increase in the size of the mass, with facial nerve paralysis and shows ulceration of the skin overlying the parotid mass[61].

Pleomorphic adenoma: this tumor has many names-Mixed tumor, Endothelioma, etc. which was termed by Willis. In 90% of the cases the tumors affects the parotid gland, most often present in lower pole of superficial lobe of the gland. It occurs more frequently in females than in males between 4-6 decade with average of 43 years. Clinical features: The lesion presents as small, painless quiescent nodules which slowly begin to increase in size, sometimes showing intermittent growth. Surgical excision is the treatment of choice. Treatment: Based on factors like the high recurrence rate, the patient’s age, and extensiveness of resection, XRT may be a useful therapy for this type of tumor.

Papillary cystadenoma lymphomatosum (warthins tumor): is the most common tumor in salivary glands first recognised by Albrecht in 1910 and later in 1929 it was described by Warthins. Clinical features: The tumor occurs mainly in parotid, seen over 60 years of age with the sex prediction is male to female 5:1 ratio. Clinically seen bilateral in 6%-12% of patients as painless lesion unless it is secondarily affected[6,12]. Treatment is mostly by surgical excision.

Basal cell adenomas: Clinical features: a benign salivary gland adenoma constitute to about 1%-2% of the salivary adenomas occurring mostly in the parotid gland and upper lip of the minor salivary gland. The other types of fewer occurrences of benign salivary adenomas are Canalicular Adenoma, Myo Epithelioma, Ductal Papilloma, and Sebaceous Adenomas. Oncocytoma is another benign tumor particularly affecting the parotid bilaterally seen in both men and women[6,61-63]. Treatment is by conservative surgical excision.

Muco epidermoid carcinoma is the most common malignant tumor of the salivary gland mostly affecting the parotid gland and these accounts for 5% of salivary gland tumor. Clinical features: This tumor also affects minor salivary gland in 15% of these cases. They are seen in the age group of 40-50 years with female predilection. The tumor is classified as low grade or high grade depending on the ratio of epidermal cells to mucous cells. In this type of tumor the most common cytogenic abnormality is the recurrent translocation between chromosomes 11 and 19 to form CRTCI-MAML2 fusion protein[34,61]. Treatment is the surgical excision of the tumor with post-operative radiotherapy[61].

Adenoid cystic carcinoma accounts for 30% of tumors in minor salivary glands and 6% affecting the parotid gland. Clinical features: It occurs in the middle and older individuals. The tumor has the ability to infiltrate the nervous tissue and spread along the nerve pathways. Biomarkers of epithelial to mesenchymal transition (EMT) such as Snail and Slug appear to be helpful in the diagnosis of adenoid cystic carcinoma[62,64-68].

Treatment is the radical surgical excision followed by Photon beam radiotherapy has shown to be effective.

Adenocarcinoma is the tumor which takes its origin from epithelium of the salivary duct[62]. This group of salivary gland tumors includes specific lesions, like polymorphous low grade adenomacarcinoma, salivary duct carcinoma, Cribiform adenoma carcinoma, etc. These tumors present a painful swelling of the affected gland and are very rare in occurrence. Management of these tumors depends on the histologic type of the tumors.

Cribriform adenocarcinoma of the tongue and minor salivary glands (CATMSG) is a low grade salivary gland tumor affecting the minor salivary glands of the oral cavity. This tumor was earlier described by Michal et al[64

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