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CHAPTER II

LITERATURE REVIEW

A. ANATOMY AND PHYSIOLOGY OF SALYVARY GLAND

Embryology, the major salivary glands develop from the 6th - 8th weeks of

gestation as outpouchings of oral ectoderm into the surrounding mesenchyme.

The parotid enlage develops first, growing in a posterior direction as the facial

nerve advances anteriorly; eventually, the fully developed parotid surrounds CN

VII. However, the Parotid gland is the last to become encapsulated, after the

lymphatics develop, resulting in its unique anatomy with entrapment of

lymphatics in the parenchyma of the gland. Furthermore, salivary epithelial cells

are often included within these lymph nodes. The minor salivary glands arise from

oral ectoderm and nasopharyngeal endoderm. They develop after the major

salivary glands. During development of the glands, autonomic nervous system

involvement is crucial; sympathetic nerve stimulation leads to acinar

differentiation while parasympathetic stimulation is needed for overall glandular

growth (Rosen F. S., 2001).

1. Parotid gland

The parotid gland, the largest of the salivary glands, is palpable over the

ramus of the mandible and is bounded posteriorly by the sternocleidomastoid

muscle (which indents the gland) and the mastoid process. The parotid gland

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extends from the level of the external auditory canal and zygomatic arch to the

angle of the mandible and is separated medially from the carotid sheath by the

posterior belly of digastric muscle, the styloid process, and its associated

muscles (Beale T and Madani G, 2006).

Figure 2.1 Salivary Glands

The Parotid is invested in its own fascia (capsule), which is continuous

with the superficial layer of deep cervical fascia. The Parotid fascia consists of

Superficial layer – extends from the masseter and SCM to the Zygoma, and

Deep layer – extends from the fascia of the posterior belly of the Digastric

muscle, and forms the Stylomandibular membrane separating the Parotid and

Submandibular glands. The Parotid fascia sends septa into the glandular

tissue, which prevents the possibility of separating the glandular tissue from

its investing fascia. The attachments of the Parotid fascia include Anterior >
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Mandible, Inferior > Stylomandibular ligament, Posterior > Styloid process

(Rosen F. S., 2001).

The gland is frequently described as having a superficial and a deep lobe

separated by the facial nerve. A more correct terminology in use is to describe

the gland as superficial when it is external to the mandible and

retromandibular when it is deep to the mandible. The larger superficial

component accounts for the majority of the gland and lies on the lateral

surface of the masseter muscle, which is it self on the lateral surface of the

mandibular ramus. The remaining deeper component extends medially

through the stylomandibular tunnel between the posterior border of the ramus

of the mandible, the stylomandibular ligament, and the skull base superiorly.

When evaluating most parotid masses, it is sufficient to map the expected

course of the nerve using constant anatomical landmarks (such as the

stylomastoid foramen, the retromandibular vein, the posterior belly of

digastric, and the mandibular ramus). One of the simplest methods is the use

of the facial nerve line connecting the lateral surface of the posterior belly of

digastric to the lateral surface of the mandibular ramus5. The contents of the

parotid gland include the following: Lymph nodes, Facial nerve (VII),

External carotid artery, Retromandibular vein (Beale T and Madani G, 2006).

Lymphatic nodes, there are basically two groups of lymphatic tissue

aggregates, namely a series of superficial nodes lying under the external

parotid fascia, and about 15-20 lymph follicles embedded in the gland,

superficial to the facial nerve. The deep lobe may contain one or at the very
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most two of these follicles. Blood supply, the external carotid artery enters the

deep aspect of the gland just above the point where it is covered by the

stylohyoid muscle. It passes vertically upwards in the deepest part of the

gland, giving off the transverse facial, internal maxillary and, finally, the

superficial temporal artery (Rosen F. S., 2001).

Nerve supply, The parotid gland has both sympathetic (mainly

vasoconstrictor) and parasympathetic (secretomotor) innervation. The

sympathetic fibers arise from the carotid plexus and the parasympathetic fibers

arise from the auriculotemporal nerve. The secretomotor component of the

auriculotemporal nerve (a branch of the mandibular division of the trigeminal

nerve) arises from the glossopharyngeal cranial nerve that has joined the

auriculotemporal nerve just below the skull base. The secretomotor

parasympathetic fibers leave the auriculotemporal nerve within the parotid

gland; by the time the nerve crosses the temporomandibular joint, it contains

only sensory (Vth nerve) fibers from the scalp. Taste and mastication are the

principal stimuli (unconditioned reflex) but others such as sight, thought and

smell of food (conditioned reflex) also play a role. Taste and mechanical

stimuli from the tongue and other areas of the mouth excite parasympathetic

nerve impulses in the afferent limbs of the salivary reflex which travel via the

glossopharyngeal (CN IX), facial (CN VII), vagal (CN X) (taste) and the

trigeminal (CN V) (chewing) cranial nerves. These afferent impulses are

carried to the salivary nuclei located approximately at the juncture of the pons

and the medulla. In turn impulses from the salivary centres can be modulated
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i.e. stimulated or inhibited by impulses from the higher centres in the central

nervous system; for example, the taste and smell centres in the cortex and the

lateral hypothalamus where the regulation of feeding, drinking and body

temperature occurs. Also, in stressful situations dry mouth sometimes occurs,

as a result of the inhibitory effect of higher centres on the salivary nuclei. The

secretory response of the gland is then controlled via the glossopharyngeal

nerve synapsing in the otic ganglion, the postganglionic parasympathetic

fibres carrying on to the parotid gland and via the facial nerve synapsing in the

submandibular ganglion and carrying on to the sublingual and submandibular

glands. Parasympathetic stim ulation also increases the blood flow to the

salivary glands, increasing the supply of nutrition (Beale T and Madani G,

2006).

The venous drainage is mainly by means of the retromandibular or

posterior facial vein which is formed by the merging of the superficial

temporal and maxillary veins. This has the same direction as the artery but lies

superficial to it and immediately deep to the facial nerve. It exits at the tail of

the gland, at which point the mandibular branch of the facial nerve crosses

immediately superficial to it before passing downwards and forwards into the

submandibular triangle (Kontis and John, 1998).

2. Submandibular gland

The Submandibular gland weighs ½ the weight of the Parotid. It is often

referred to as the Submaxillary gland because of the tendency of British

anatomists to refer to the mandible as the ‘submaxilla’. This gland lies in the
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submandibular triangle formed by the anterior and posterior bellies of the

Digastric muscle and the inferior margin of the mandible. The gland is

positioned medial and inferior to the mandibular ramus partly superior and

partly inferior to the base of the posterior half of the mandible. The gland

forms a ‘C’ around the anterior margin of the Mylohyoid muscle, which

divides the Submandibular gland into a superficial and deep lobe. The deep

lobe comprises the majority of the gland. The Marginal Mandibular branch of

CN VII courses superficial to the Submandibular gland and deep to the

Platysma. As is the case with the Parotid gland, the Submandibular gland is

invested in its own capsule, which is also continuous with the superficial layer

of deep cervical fascia (Rosen F. S, 2001).

The Submandibular duct (Wharton’s duct) exits the medial surface of the

gland and runs between the Mylohyoid (lateral) and Hyoglossus muscles and

on to the Genioglossus muscle. Wharton’s duct empties into the intraoral

cavity lateral to the lingual frenulum on the anterior floor of mouth. The

length of the duct averages 5 cm. The Lingual nerve wraps around Wharton’s

duct, starting lateral and ending medial to the duct, while CN XII parallels the

Submandibular duct, running just inferior to it. The identification of CN XII,

the Lingual nerve, and Wharton’s duct is absolutely essential prior to resection

of the gland (Holmberg K.V. and Hoffman M. P., 2014).

Innervation to the Submandibular gland derives from 2 important

sources: 1) Sympathetic innervation from the Superior Cervical ganglion via

the Lingual artery, and 2) Parasympathetic innervation from the


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Submandibular ganglion, which is fed by the Lingual nerve. Arterial supply to

the Submandibular gland comes from the Submental branch of the Facial

artery (off of the External Carotid artery). The Facial artery forms a groove in

the deep part of the gland, then curves up around the inferior margin of the

mandible to supply the face. The Facial artery and vein are the first blood

vessels encountered when resecting the Submandibular glands as they cross

superficially over the inferior border of the mandible. The Facial vein courses

over the lateral surface of the Submandibular gland. One method of preserving

the Marginal Mandibular nerve is to identify and ligate the Facial vein 2 - 3

cm inferior to the mandible and elevate the vein and all superior tissue

superiorly (Holmberg K.V. and Hoffman M. P., 2014).

Venous drainage is provided by the Anterior Facial vein, which lies deep

to the Marginal Mandibular branch of CN VII. Lymphatic drainage goes to the

deep cervical and jugular chains of nodes. Perivascular lymph nodes near the

Facial artery are often involved with cancer originating in the Submandibular

gland, and these nodes should be removed with Submandibular resection

(Rosen F. S. 2001).

3. Sublingual Gland

This is the smallest of the major salivary glands. The almond shaped

gland lies just deep to the floor of mouth mucosa between the mandible and

Genioglossus muscle. It is bounded inferiorly by the Mylohyoid muscle.

Wharton’s duct and the Lingual nerve pass between the Sublingual gland and

Genioglossus muscle. Unlike the Parotid and Submandibular glands, the


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Sublingual gland has no true fascial capsule. Also unlike the Parotid and

Submandibular glands, the Sublingual gland lacks a single dominant duct.

Instead, it is drained by approximately 10 small ducts (the Ducts of Rivinus),

which exit the superior aspect of the gland and open along the Sublingual fold

on the floor of mouth. Occasionally, several of the more anterior ducts may

join to form a common duct (Bartholin’s duct), which typically empties into

Wharton’s duct. Of note, the ducts of the sublingual glands are too small for

the injection of contrast, making a sialogram of this gland impossible (Rosen

F. S. 2001). Innervation to the Sublingual gland derives from 2 important

sources:

a. Sympathetic innervation from the cervical chain ganglia via the Facial

artery

b. Parasympathetic innervation, like the Submandibular gland, is derived

from the Submandibular ganglion

Arterial supply to this gland is two-fold:

a. The Sublingual branch of the Lingual artery

b. The Submental branch of the Facial artery

Venous drainage reflects the arterial supply. Lymphatic drainage goes to

the Submandibular nodes (Rosen F. S. 2001).

4. Minor Salivary Glands

Unlike the major salivary glands, the minor salivary glands lack a

branching network of draining ducts. Instead, each salivary unit has its own
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simple duct. The minor salivary glands are concentrated in the Buccal, Labial,

Palatal, and Lingual regions. In addition, minor salivary glands may be found

at the superior pole of the tonsils (Weber’s glands), the tonsillar pillars, the

base of tongue (von Ebner’s glands), paranasal sinuses, larynx, trachea, and

bronchi. The most common tumor sites derived from the minor salivary

glands are the palate, upper lip, and cheek. Most of the minor glands receive

parasympathetic innervation from the Lingual nerve, except for the minor

glands of the palate, which receive their parasympathetic fibers from the

Palatine nerves, fed by the Sphenopalatine ganglion (Kontis and John, 1998).

B. DEFINITION OF SALIVARY GLAND TUMOR

Salivary gland tumors represent a diverse group of neoplasms. They are

uncommon lesions morphologically and clinically diverse, distinct from other

cancers of the head and neck. Salivary gland cancer starts in one of the salivary

glands. Salivary glands make saliva, which contains enzymes to begin the process

of digesting food as well as antibodies and other substances that help prevent

infections of the mouth and throat. There are two main types of salivary glands:

the major salivary glands and minor salivary glands. The major salivary glands

are consisted of three sets, the parotid glands in front of the ears, the

submandibular glands below the jaw and the sublingual glands under the floor of

the mouth and on the sides of the tongue. The minor salivary glands are several

hundreds and are located beneath the lining of the lips, tongue, in the roof of the

mouth, and inside the cheeks, nose, sinuses, and larynx (Dimas et al, 2015).
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Neoplasms of salivary gland origin are tumors that involve mainly major

salivary glands, including the paired parotid, submandibular, and sublingual

glands. Most salivary gland tumors are benign. There are many types of benign

salivary gland tumors, with names such as adenomas, oncocytomas, Warthin

tumors, and benign mixed tumors (pleomorphic adenomas). Tumors in the minor

salivary glands are less common, but they are more often malignant than benign.

These tumors most often start in the palate (Dimas et al, 2015).

C. CLASSIFICATION

1. Benigna salivary gland tumors

a. Mixed Tumor (Pleomorphic Adenoma)

Pleomorphic adenoma is a tumour of variable capsulation

characterized microscopically by architectural rather than cellular

pleomorphism. Epithelial and modified myoepithelial elements

intermingle most commonly with tissue of mucoid, myxoid or chondroid

appearance (Speight et al, 2002).

1) Epidemiology

Pleomorphic adenoma is the most common salivary gland

tumour and accounts for about 60% of all salivary neoplasms

{2439}. The reported annual incidence is 2.4-3.05 per 100,000

population {244, 2053}. The mean age at presentation is 46 years

but the age ranges from the first to the tenth decades {703}. There

is a slight female predominance {703,2711} (Speight et al, 2002).


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2) Clinical features

Pleomorphic adenomas usually are slow growing painless

masses. Small tumours typically form smooth, mobile, firm lumps

but larger tumours tend to become bossellated and may attenuate

the overlying skin or mucosa. Multifocal, recurrent tumours may

form a fixed mass. Pleomorphic adenomas are usually solitary but

they may show synchronous or metachronous association with

other tumours, particularly Warthin tumour, in the same or other

glands {2298}. Pain or facial palsy are uncommon but are

occasionally seen, usually in relation to infarcted tumours. The size

of most tumours varies from about 2-5 cm but some reported cases

have been massive {388}. In the palate, tumours are usually seen at

the junction of the hard and soft palate unilaterally. In the hard

palate they feel fixed due to the proximity of the underlying

mucoperiosteum (Speight et al, 2002).

3) Pathology

Pleomorphic adenomas are composed of neoplastic

myoepithelial cells intermingled with neoplastic ducts and stroma.3

A subset of tumors contain dyplastic cells and/or foci of malignant

cells. Ethunandan et al evaluated 100 consecutive patients treated

with surgery for pleomorphic adenomas at the Queen Alexandra

Hospital (Portsmouth, UK) and found 96 to be benign, 1 apparently

benign tumor contained foci of vascular invasion, 1 lesion


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contained focal dysplasia, and the remaining 2 patients had tumors

with intracapsular invasion. All 4 patients remained disease-free at

15 months, 28 months, 32 months, and 36 months after resection,

respectively. Ohtake et al analyzed 101 patients with pleomorphic

adenoma for cellular atypia, p53 expression, and proliferating cell

nuclear antigen expression. Histologically, 6% had focal cellular

atypia and 45% had scattered atypical cells with no foci. Overall,

cellular atypia was identified in 51% of patients with hematoxyllin

and eosin stains, 56% of patients with p53 immunohistochemical

stains, and 66% of patients with proliferating cell nuclear antigen

stains. Cellular atypia identified via p53 positivity increased with

tumor duration of more than 10 years (P 0.005) and was unrelated

to tumor size. Neural adhesion molecule (N-CAM) is a tumor

suppressor molecule that has been shown to inhibit cell invasion in

various malignancies. Saleh et al analyzed N-CAM expression via

immunohistochemistry in 4 patients with pleomorphic adenoma

and 4 patients with carcinoma ex-pleomorphic adenoma and found

that the luminal cells stained strongly positive for N-CAM in the

former compared with the latter.14 This suggests that

downregulation of N-CAM occurs as part of the process of

malignant transformation that occurs in a small subset of patients

with pleomorphic adenomas. –catenin is a component of the

wingless WNT signaling cascade and is associated with invasion


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and metastases in various neoplasms. It may also play a role in

malignant transformation. do Prado et al found -catenin expression

in 10 normal salivary glands, 16 pleomorphic adenomas, and 3

carcinomas ex-pleomorphic adenomas and found that in all cases

there was membranous and cytoplasmic immunostaining for -

catenin. Further, there was loss of cytoplasmic -catenin expression

in pleomorphic adenomas and cytoplasmic accumulation in

carcinomas ex-pleomorphic adenomas. Thus, loss of the -catenin

adhesion molecule occurs during the development of pleomorphic

adenomas, and cytoplasmic accumulation of -catenin occurs with

malignant transformation.

4) Diagnosis

A history is obtained and a physical examination is performed,

including a thorough head and neck evaluation. Magnetic

resonance imaging is obtained to determine the location and extent

of the lesion and its probable etiology. Fine needle aspiration

biopsy is obtained; if negative and it is thought that the lesion is

most likely pleomorphic adenoma then the patient undergoes

resection with frozen section histopathologic evaluation at the time

of the operation (Ethunandan et al).

b. Whartin Tumor

A tumour composed of glandular and often cystic structures,

sometimes with a papillary cystic arrangement, lined by characteristic


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bilayered epithelium, comprising inner columnar eosinophilic or oncocytic

cells surrounded by smaller basal cells. The stroma contains a variable

amount of lymphoid tissue with germinal centres. (Elledge et al,2009)

1) Epidemiology

In most countries, Warthin tumour is the second

commonest tumour of the salivary glands. In the United States

(US) it comprised about 3.5% of all primary epithelial tumours

(5.3% in the parotid) {668}. Other studies revealed higher

percentages, such as 14.4% of primary epithelial tumours of the

parotid gland in the United Kingdom (UK) {703}, 27% in

Denmark {2075}, and 30% in Penn - sylvania, USA {1765}.

Warthin tumour occurs in Caucasians and Asians {451}, but has a

lower incidence in AfricanAmericans {668} (although this may

now be increasing {2856}) and in Black Africans {2590}. The

mean age at diagnosis is 62 years, (range 12-92) {668}, and it is

rare before 40. The relative sex incidence has changed during the

last half-century: In 1953 the male to female ratio was 10:1 {786},

whereas in 1996 it was 1.2:1 {668}, and in 1992 it was equal

{1765}. In the UK in 1986 the ratio was 1.6:1 {705} (Elledge et

al,2009).

a) Clinical features

Most patients present with a painless mass, on

average, 2-4 cm, although occasional cases have reached 12


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cm {2783}. The mean duration of symptoms is 21 months,

but in 41% of patients it is less than six months {705 Many

patients notice fluctuation in size of the tumour, especially

when eating {1711}. Pain has been reported in 9% {705},

particularly those with the metaplastic variant {2866}.

Facial paralysis is very rare, and is the result of secondary

inflammation and fibrosis, and likewise can be seen in the

metaplastic variant {706,1876}. Warthin tumour is able to

concentrate Technetium (99mTc), appearing as a “hot”

lesion. It is usually well-circumscribed, but secondary

inflammation can cause the edges to become indistinct

(Elledge et al,2009).

b) Pathology

These tumors are well encapsulated lesions with

cystic and solid areas. These tumors consist of an oncocytic

epithelial cell component arranged in double layers, which

develops cysts and papillary projections, and a variable

amount of lymphoid tissue often with germinal centers. The

immunoprofile of the lymphocyte subsets is similar to that

in normal or reactive lymph nodes. A few Warthin's tumors

(about 8%) show areas of squamous cell metaplasia and

regressive changes (Elledge et al,2009).

c) Diagnosis
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A diagnosis of Warthin tumor is often suspected based on

the presence of characteristic signs and symptoms. The

following tests may then be ordered to confirm the

diagnosis and rule out other conditions that cause similar

features:

 X-rays of the salivary gland (called a ptyalogram or

sialogram)

 CT scan, MRI and/or ultrasound

 Salivary gland biopsy

c. Ductal Papilloma

Ductal papillomas are a group of relatively rare, benign, papillary

salivary gland tumours known as inverted ductal papilloma, intraductal

papilloma, and sialadenoma papilliferum. They represent adenomas with

unique papillary features with a common relationship to the excretory

salivary duct system, a nonaggressive biologic behaviour, and a

predilection for the minor salivary glands. They tend to occur in the

middle-aged and elderly and rarely in children. The three types of ductal

papillomas possess distinct clinical and histologic features allowing

differentiation from each other and other adenomas with a papillary

pattern (Brannon et al,2001)

1) Epidemiology

The true incidence of inverted ductal papilloma (IDP) is

unknown, but it is thought to be relatively rare based on the


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sparse number of reported cases. Lesions have arisen in adults

with an age range of 28-77 years and a male predilection {264}

(Brannon et al,2001).

2) Clinical features

IDP typically presents as a painless nodular submucosal

swelling, often with a dilated pore or punctum surfacing the

swelling {1046}. Lesions have been described as being present

from months to several years (Brannon et al,2001).

3) Pathology

The pathogenesis of intraductal papilloma is still uncertain.

(Brannon et al.) stated that these lesions originate from the

salivary gland duct epithelium, most likely the excretory duct.

These tumors usually present as asymptomatic, well-defined

solitary submucosal masses or swellings that vary in size from

less than 1–1.5 cm. The lesion often has a reddish color. The

ages of patients have ranged from 29 to 77 years, with mean

age of 54 years. Gender distribution has remained essentially

even. The minor salivary glands are more frequently involved

than the major glands. Intraductal papillomas are most

commonly found in the lips and buccal mucosa followed by

palate and tongue. Of the major glands, the parotid is most

frequently involved. In contrast to intraductal papillomas,

papillary cystadenomas are morphologically multicystic with


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numerous small-to-medium-sized cystic spaces. In the papillary

cystadenoma, the intraluminal growth is often characterized by

multiple papillary projections with a variety of epithelial cell

types, but usually the papillary growth occupies the lumen to a

limited degree. In inverted ductal papilloma, the character of

the proliferating epithelium is predominantly epidermoid,

whereas in intraductal papilloma, it is columnar or cuboidal

epithelium and/or mucous cells.

4) Diagnosis and Treatment

Complete removal of the lesion was carried out with the

CO2 laser under local anesthesia using 4% articaine with

1:100.000 adrenalin (Laboratorios Inibsa, Barcelona, Spain).

The specimen sent to the pathology laboratory was of a pinkish

color, rounded and measured 1 x 0.5 cm in size. The following

postoperative medication was prescribed: ibuprofen 600 mg in

tablets, one every 8 hours for 5 days (Ibuprofeno 600 mg,

Zambom, Barcelona, Spain) and chlorhexidine gel, three

applications a day for 10 days (Clorhexidina Gel Bioadhesivo

50 ml, Lacer, Barcelona, Spain). The postoperative course was

free of complications, and the patient is presently subjected to

periodic controls to detect possible relapse (Brannon et al.,

2001).
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d. Oncocytoma

Benign tumour of salivary gland origin composed exclusively of

large epithelial cells with characteristic bright eosinophilic granular

cytoplasm (oncocytic cells) (Weber et al, 2002).

1) Epidemiology

Oncocytoma accounts for about 1% of all salivary gland

neoplasms and occurs most commonly in the 6-8th decades

{257}. The mean age of the patients is 58 years. There is no

sex predilection. (Weber et al, 2002).

2) Clinical features

Symptoms vary according to the site of occurrence and

most commonly present as a painless mass, less frequently

nasal or airway obstruction. (Weber et al, 2002).

3) Pathology

Oncocytomas are benign epithelial tumors characterized by

oncocytes with eosinophilic granular cytoplasm rich in

mitochondria. Oncocytic cells are thought to originate from the

transformation of epithelial cells of salivary gland ducts or

acini. They occur most commonly in their sixth to eighth

decades and are slightly predominant in women. (Weber et al,

2002).
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4) Diagnosis and Treatment

CT has been established as the first-line image modality in the

assessment of major salivary gland tumors . Oncocytomas and

Warthin's tumors have very similar imaging features; thus, they

are indistinguishable in standard CT and MR images. The

common CT finding of the parotid oncocytomas described in

the literature is a well-defined parotid mass showing

homogeneous enhancement. The reports on MRI imaging of

parotid oncocytomas describe these tumors as appearing

hypodense on both T1 and T2 sequences. This has been

attributed to the high cellularity and low water content

displaying homogeneous contrast enhancement. Complete

surgical excision with radical or superficial parotidectomy are

the treatments of choice. The extent of the excision is dictated

by preoperative clinical and radiological (CT, MR)

examinations and intraoperative findings. In addition,

radiotherapy may play an important role in the management of

locally advanced, unresectable, or recurrent salivary gland

cancers when surgery is not feasible. Although radiotherapy

can be very effective in achieving tumor shrinkage and

providing symptomatic relief, curative non-operative

approaches have been challenging. The use of systemic

chemotherapy in advanced salivary gland cancer has in general


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been confined to those patients with advanced and incurable

disease. Meaningful exploration of this treatment modality has

been hampered by the diversity of histologic subtypes and the

rarity of the disease. The scientific literature has reported

results from clinical trials using a number of different

chemotherapeutic agents often found in mixed populations,

including patients with different histologic subtypes. Cisplatin-

based regimens have been the most frequently explored, but the

response rates have been modest, and the impact on survival

rate has been impossible to discern. (Weber et al, 2002).

e. Monomorphic Tumors

Monomorphic adenomas are benign salivary gland tumors that

have a predilection for development in the upper lip and parotid gland.

Typically, patients are older persons (mean age, 61 years), but a broad age

range (32 to 87 years) has been reported in the literature. Adequate

treatment consists of superficial or total parotidectomy (depending on

extent and location of the tumor) for parotid lesions and excision with a

limited border of normal tissue for minor gland tumors. Uniform

cellularity, lack of myxoid or chondroid features, and a tendency for

multicentric origin are features which separate these tumors from

pleomorphic adenomas. Monomorphic adenomas have been mistakenly

diagnosed and treated as adenoid cystic carcinomas. Close attention to


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cytologic detail, histomorphology, and growth pattern at the periphery are

important in separating these tumors. (Hadiprodjo et al, 2012).

1) Epidemiology

The frequency of cystadenoma is between 4.2-4.7% of

benign tumours {668,2711}. There is a female predominance

and the average age of patients with cystadenoma is about 57

years (range 12-89). (Hadiprodjo et al, 2012).

2) Clinical features

Cystadenomas of the major glands typically present as slowly

enlarging painless masses. In oral mucosa, these tumours

produce smooth-surfaced nodules that resemble mucoceles.

(Hadiprodjo et al, 2012).

3) Pathology

Cystadenoma of the salivary glands is a rare benign tumor,

usually presenting as a slow-growing mass. The tumor usually

arises in the minor salivary glands (0.9-2% of all minor

salivary gland neoplasms) but is extremely rare in the major

salivary gland. A review reported only three cases of the tumor

arising in major salivary glands, and Tsurumi et al. found that

all four reported cases of salivary gland cystadenoma, between

1985 and 2003, had arisen in the minor salivary glands.

(Tsurumi et al).
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Cystadenoma can be subdivided into mucinous and

papillary types. The latter has well-defined unilocular or

multilocular cysts, with intraluminal papillary projections. The

lining epithelial cells are cuboidal or columnar, and usually two

layers in thickness. Oncocytic differentiation occurs in 1% of

tumors and can be extensive. (Tsurumi et al).

4) Diagnosis

Diagnosis of cystadenoma is strictly histopathological. The

histopathological features described in our case were

characteristic and in general agreement with what has been

reported in the literature for cystadenoma. 25% cases of

cystadenoma have been reported to show a distinct fibrous

capsule, which was not present in our case. Since salivary

gland tumors show great histomorphological diversity,

differential diagnosis of cystadenoma must include intra ductal

papilloma, cystadeno carcinoma, low-grade mucoepidermoid

carcinoma and Warthin's Tumor. (Hadiprodjo et al, 2012).

f. Sebaceous Tumors

It is a rare, usually well-circumscribed tumour composed of

irregularly sized and shaped nests of sebaceous cells without cytologic

atypia, often with areas of squamous differentiation and cystic change.

(Elledge et al, 2009)


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1) Epidemiology

They account for 0.1% of all salivary gland

neoplasms and slightly less than 0.5% of all salivary

adenomas {2301}. The mean age is 58 years (22-90 years)

and the male:female ratio is 1.6:1 {896, 901}. Unlike

cutaneous sebaceous neoplasms {1132,2214}, there is no

increased risk of developing a visceral carcinoma (Elledge

et al, 2009).

2) Clinical features

Patients typically present with a painless mass.

3) Pathology

These tumors vary from a small nodule to an ill-

defined plaque and are usually tan-yellow. Most lesions do

not exceed 1 cm in diameter, with a common range of 0.1

to 9 cm.1 They usually arise in older individuals and in

men slightly more often than in women. Pain or tenderness

is not uncommon, whereas ulceration is rarely found.

Clinically, cutaneous sebaceous adenoma is often

misdiagnosed as basal cell carcinoma.

In an extensive search of the literature on tumors of

the sebaceous glands, cutaneous sebaceous adenoma was

mentioned more commonly and was defined as a


30

component of Muir-Torre syndrome, which is an autosomal

dominant genodermatosis characterized by at least a single

sebaceous gland tumor and an internal malignancy such as

colorectal or genitourinary carcinoma. However, sebaceous

gland tissue is also found in salivary glands, especially the

parotid gland. Rawson and Horn first described 2 tumors of

the parotid gland with a sebaceous gland component.

(Elledge et al, 2009)

4) Diagnosis and Treatment

Biopsy for histologic examination is usually necessary to

reach a definite diagnosis. Clinically, cutaneous sebaceous

adenoma should be differentially diagnosed from sebaceous

hyperplasia, sebaceous epithelioma, sebaceous carcinoma,

histiocytoma, and xanthoma. Computed tomography

scanning may be performed for larger intrasalivary gland

sebaceous adenomas, which could present with a clinical

picture of dermoid tumor, teratoma, lipoma, or liposarcoma

due to its solid, cystic, or keratoacanthoma-like

morphologic patterns. Treatment is adequate excision.

Compared with colorectal or genitourinary carcinoma in the

general population, the clinical course of the same cancers

in Muir-Torre’s syndrome is relatively benign due to the

low-grade malignancy. (Elledge et al, 2009)


31

g. Benign Lymphoepitelial Lesion

An ultrastructural study of a benign lymphoepithelial lesion of the

parotid gland demonstrated that the so-called epimyoepithelial cell islands

were sharply demarcated from the surrounding parenchyma by a thick

basement membrane containing collagen fibers. The hyaline material seen

by light microscopy within the islands was ultrastructurally similar in

appearance to this delimiting basement membrane. The epithelial cells

within the islands were united by well formed desmosomes and many had

prominent tonofilament bundles, but myogenic differentiation was not

observed. Hydropic degeneration was not seen in these epithelial cells;

cells with a perinuclear clear space seen by light microscopy corresponded

to large lymphoid cells ultrastructurally. (Chhieng et al, 2000)

1) Epidemiology

Despite their aforementioned alternative name, BLL are

seen usually in HIV positive patients without AIDS, and are

not an AIDS defining illness. It is relatively common in

the HIV population, with 5% of patients eventually developing

BLL (Chhieng et al, 2000).

2) Clinical features

Patient arrived with a mass which was firm, fixed, and non-

tender, although eliciting related complaints of tightness and

mild pain. Upon assessment of facial features, mild, bilateral


32

enlargement of lacrimal and submandibular glands was

evident, without palpable neck nodes. Clinical features of

Sjögren's syndrome may be manifested by 50% to 84% of

patients with BLEL (Chhieng et al, 2000).

3) Pathology

Thought to arise from dilatation of intraglandular ducts

from obstruction due to lymphoid hypertrophy. They are

bilateral in ~20% of cases. (Chhieng et al, 2000).

4) Diagnosis

In patients with salivary gland enlargement, diagnosis of

BLEL may be difficult due to the many benign inflammatory

conditions that arise and/or the occurrence of salivary cysts or

tumors. For differential diagnostic purposes, imaging

modalities such as CT, ultrasound, technetium scan, and

sialography may be helpful, although such technical

advancements are not routinely utilized in the management of

salivary gland tumors. Fine needle aspiration biopsy is

controversial in this setting, because for many surgeons, the

presence of tumor alone is sufficient indication to operate.

With a sensitivity near 90% and a specificity of 75%, fine

needle aspiration (FNA) biopsy may have a role in

documenting the benign disease of poor-risk patients, thus

avoiding inappropriate surgery. Nevertheless, histologic


33

findings may be precarious. A history of autoimmune disease

or complaints of dry eyes or mouth often are diagnostic clues,

given a heterogeneous lymphoid component. Grounds for

diagnosis of BLEL by FNA include the presence of

epimyoepithelial islands, numerous small lymphocytes, and a

granular proteinaceous background. (Chhieng et al, 2000).

2. Maligna salivary gland tumors

a. Mucoepidermoid carcinoma

Mucoepidermoid carcinomas are the most common type of

salivary gland cancer. Most start in the parotid glands. They develop less

often in the submandibular glands or in minor salivary glands inside the

mouth. These cancers are usually low grade, but they can also be

intermediate or high grade. Low-grade tumors have a much better

prognosis than high-grade ones. (Airoldi et al, 2001)

b. Adenoid cystic carcinoma

Adenoid cystic carcinoma is usually slow growing and often

appears to be low-grade when looked at under the microscope. Still, it’s

very hard to get rid of completely because it tends to spread along nerves.

These tumors tend to come back after treatment (generally surgery and

radiation), sometimes many years later. The outlook for patients is better

for smaller tumors. (Vered et al, 2002)

c. Adenocarcinomas
34

Adenocarcinoma is a term used to describe cancers that start in

gland cells (cells that normally secrete a substance). There are many types

of salivary gland adenocarcinomas. (Begum et al, 2002)

1. Acinic cell carcinoma: Most acinic cell carcinomas start in the parotid

gland. They tend to be slow growing and tend to occur at a younger

age than most other salivary gland cancers. They are usually low

grade, but how far they have grown into nearby tissue is probably a

better predictor of a patient’s prognosis (outlook).

2. Polymorphous low-grade adenocarcinoma (PLGA): These tumors

tend to start in the minor salivary glands. They usually (but not

always) grow slowly and are mostly curable.

3. Adenocarcinoma, not otherwise specified (NOS): When seen under a

microscope, these cancers have enough features to tell that they are

adenocarcinomas, but not enough detail to classify them further. They

are most common in the parotid glands and the minor salivary glands.

These tumors can be any grade.

4. Rare adenocarcinomas: Several types of adenocarcinoma are quite

rare. Some of these tend to be low grade and usually have a very good

outcome:

• Basal cell adenocarcinoma

• Clear cell carcinoma

• Cystadenocarcinoma

• Sebaceous adenocarcinoma
35

• Sebaceous lymphadenocarcinoma

• Mucinous adenocarcinoma

Other rare adenocarcinomas are more likely to be high grade and may

have a less favorable outcome:

• Oncocytic carcinoma

• Salivary duct carcinoma

d. Malignant mixed tumors

There are 3 types of malignant mixed tumors:

• Carcinoma ex pleomorphic adenoma

• Carcinosarcoma

• Metastasizing mixed tumor

Nearly all of these cancers are carcinoma ex pleomorphic adenomas.

The other 2 types are very rare. c

Carcinoma ex pleomorphic adenoma develops from a benign

mixed tumor (also known as a pleomorphic adenoma). This tumor occurs

mainly in the major salivary glands. Both the grade of the cancer and how

far it has spread (its stage) are important in predicting outcome. (Spiro R,

1998)

e. Other rare salivary gland cancers

Several other types of cancer can develop in the salivary glands.

(Schramm et al, 2001)


36

1. Squamous cell carcinoma : This cancer occurs mainly in older

men. It can develop after radiation therapy for other cancers in the

area. This type of cancer tends to have a poorer outlook.

2. Epithelial-myoepithelial carcinoma : This rare tumor tends to be

low grade, but it can come back after treatment or spread to other

parts of the body.

3. Anaplastic small cell carcinoma : The cells in these tumors have

nerve cell-like features. These tumors are most often found in

minor salivary glands and tend to grow quickly.

4. Undifferentiated carcinomas : This group of cancers includes

small cell undifferentiated carcinoma, large cell undifferentiated

carcinoma, and lymphoepithelial carcinoma. These are high-grade

cancers that often spread. Overall, the survival outlook tends to be

poor. Lymphoepithelial carcinoma, which is much more common

in Eskimo and Inuit people, has a slightly better outcome.

D. EPIDEMIOLOGY

Salivary gland tumors account for about 3% of all head and neck cancers,

with the majority affecting the parotid gland. The incidence of salivary gland

tumor has been increasing in men, while it has stayed relatively constant in

women. Although there are many factors that negatively affect the prognosis of

patients with salivary gland tumor, the most important factors are histologic type,

grade, and clinical stage at presentation. The 10-year disease-specific survival for

early-stage parotid gland tumor is 97%, compared with 20% for a late-stage
37

tumor. Therefore, assessing the tumor early and accurately is important for

determining the proper treatment regimen and outcome of patients (Hadiprodjo et

al, 2012).

E. ETIOLOGY OF SALIVARY GLAND TUMOR

Unlike most other head and neck cancers, the causes of salivary gland

tumors are poorly understood. Unlike head and neck squamous cell carcinoma,

these neoplasms have not been positively linked to tobacco and/or alcohol use,

except possibly Warthin’s tumor. Possible involvement of the Epstein-Barr virus

in salivary tumors has been suggested, with reports indicating mixed and

conflicting results (Venkateswaran et al., 2000). Cytomegalovirus, polyoma virus,

human papilloma virus types 16 and 18, type B particles, and type C particles are

other viruses identified as possible etiologic factors. There is a much stronger

indication that ionizing radiation of nuclear weapons, therapeutic radiation used to

treat a benign conditions (hypertrophied tonsils, enlarged thyroid, acne, etc.), and

excess diagnostic radiation are directly related to an increase in the incidence of

salivary gland tumors. Case studies from the 1970s and 1980s reported increased

salivary gland neoplastic risks for people employed in certain occupations, such

as asbestos mining, rubber products manufacturing, woodworking, and plumbing

(Sun et al., 1999). Radiation therapy in low doses has aslso been associated with

the development of parotid neoplasms even 20 years after treatment. In these

cases the incidence of pleomorphic adenomas, mucoepidermoid carcinomas, and

squamous cell carcinomas found to be increased. As with other forms of head and

neck cancer, chromosomal deletions or rearrangements, and genetic factors that


38

control mechanisms of cell division are being studied as possible causes (Olopade

et al., 2000). The discovery of estrogen receptors in both normal salivary glands

and salivary tumors suggests a possible link between endogenous hormones and

salivary gland tumors (Sun et al., 1999). Two theories have also been developed

trying to explain the etiology of the salivary gland tumors: the bicellular stem cell

theory and the multicellular theory. Recent evidence suggests the bicellular stem

cell theory as the more probable etiology of salivary gland neoplasms, that more

logically can explain the development of neoplasms that contain multiple discrete

cell types. According to this theory tumors arise from 1 of 2 undifferentiated stem

cells: the excretory duct or the intercalated duct reserve cell. Excretory stem cells

give rise to squamous cell and mucoepidermoid carcinomas, while intercalated

stem cells give rise to pleomorphic adenomas, oncocytomas, adenoid cystic

carcinomas, adenocarcinomas, and acinic cell carcinomas (Califano and Eisele,

1999).

F. RISK-GROUP CLASSIFICATIONS

1. Older age

The risk of salivary gland goes up as people get older.

2. Male gender

Salivary gland cancers are more common in men than in women.

3. Radiation exposure

Radiation treatment to the head and neck area for other medical

reasons increases your risk of salivary gland cancer workplace


39

exposure to certain radioactive substances may also increase the risk of

salivary gland cancer.

4. Family history

Very rarely, members of some families seem to have a higher than

usual risk of developing salivary gland cancers. But most people who

get salivary gland cancer do not have a family history of this disease.

5. Certain workplace exposures

Some studies have suggested that people who work with certain metals

(nickel alloy dust) or minerals (silica dust), and people who work in

asbestos mining, plumbing, rubber products manufacturing, and some

types of wood working maybe at increased risk for salivary gland

cancer, but these links are not certain. The rarity of these cancers

makes this hard to study.

6. Tobacco and alcohol use

Tobacco and alcohol can increase the risk for several cancers of the

head and neck area, but they have not been strongly linked to salivary

gland cancers in most studies.

7. Diet

Some studies have found that a diet low in vegetables and high in

animal fat may increase the risk of salivary gland cancer, but more

research is needed to confirm this possible link.

8. Cell phone use


40

One study has suggested an increased risk of parotid gland tumors

among heavy cell phone users. In this study, most of the tumors seen

were benign (not cancer). Other studies looking at this issue have not

found such a link. Research in this area is still in progress

(American Joint Committee on Cancer, 2010).

G. PATOFISIOLOGY

It is generally believed that alterations within stem or reserve (basal) cells

of the salivary ductal system are the main source of neoplastic transformation.

The relationship of these semi-pluripotential reserve cells to other suspected and

important contributors of salivary tumors, such as striated duct cells, intercalated

duct cells, myoepithelial cells, and acinar cells, is unclear (Sapp et al. (1997) ; Yu

and Donath (2001)). Recent work has focused on studying protooncogene and

tumor supressor gene interactions, especially the biomolecular models of H-ras, p-

53, epidermal growth factor (EGF), Ki-67, p63, and p73 (Yoo and Robinson

(2000); Vered et al. (2002); Weber et al. (2002); Bilal et al. (2003); Pinto et al.

(2000)). Mutation in p53 have been found in both benign and malignant salivary

gland neoplasms and some evidence suggests that the presence of p53 mutations

correlates with a higher rate of tumor recurrence. RAS is a G protein involved in

growth signal transduction, and derangements in ras signalling are implicated in a

wide variety of solid tumors. H-Ras mutations have been shown in a significant

proportion of pleomorphic adenomas, adenocarcinomas, and mucoepidermoid

carcinomas (Elledge, 2009). Overexpression of certain genes, such as the c-erb-b2

oncoprotein, shows promise as a potential indicator of tumor aggressiveness


41

(Friedman and Lim, 2001). In recent studies vascular endothelial growth factor

(VEGF) was found to be expressed in over 50% of the salivary gland carcinomas

tested and could be correlated with clinical stage, recurrence, metastasis, and

survival Stenner and Klussman, (2009). Chromosomal abnormalities such as

chromosomal loss or chromosomal rearrangements have been often associated

with salivary gland tumors, while more recently research is focusing on factors

that increase tumor invasion and spread.

H. CLINICAL SYMPTOMS

Most benign salivary gland neoplasms present as smooth, uniform, slowly

growing, well demarcated, moveable, non-ulcerated, and/or painless masses. It is

common for these lesions to be present for several years, sometimes decades,

before patients seek treatment. If untreated, parotid tumors can reach remarkable

size and become grossly disfiguring. By comparison, malignant salivary gland

tumors tend to be characterized by nodularity, irregular shapes, rapid growth, poor

demarcation, fixation to surrounding structures, ulceration, and/or pain.

Neurological signs, such as numbness or weakness caused by nerve involvement,

typically indicate a malignancy. Extension of parotid malignancies to involve the

facial nerve is a particularly ominous finding (Regezi et al., 2003). Persistent

facial pain is highly suggestive of malignancy but only a 10% to 15% of

malignant parotid neoplasms present with pain. Other symptoms include fluid

draining from the ear, pain, numbness, weakness, and trouble swallowing (Regezi

et al., 2003).
42

I. CLINICAL EXAMINATION

1. Imaging tests

Imaging tests use x-rays, magnetic fields, or radioactive particles to

create pictures of the inside of your body. Imaging tests may be done for a

number of reasons, including to help find a suspicious area that might be

cancer, to learn how far cancer may have spread, and tohelp find out if

treatment has been effective.

2. X-rays

If you have a lump or swelling near your jaw, your doctor may order

x-rays of the jaws and teeth to look for a tumor. If you have been

diagnosed with cancer, an x-ray of your chest may be done to see if the

cancer has spread to your lungs. This also provides other information

about your heart and lungs that might be useful if surgery is planned.

3. Computed tomography (CT or CAT) scan

A CT scan uses x-rays to produce detailed cross-sectional images of

your body. Unlike a regular x-ray, CT scans can show the detail in soft

tissues (such as internal organs). A CT scan can show the size, shape, and

position of a tumor and can help find enlarged lymph nodes that might

contain cancer. If needed, CT scans can also be used to look for tumors in

other parts of the body. Instead of taking one picture, like a regular x-ray,

a CT scanner takes many pictures as it rotates around you. A computer

then combines these into images of slices of the part of your body that is
43

being studied. Before the scan, you may be asked to drink 1 to 2 pints of a

liquid called oral contrast. This helps outline the intestine so that certain

areas are not mistaken for tumors. This is most often needed for CT scans

of the abdomen or pelvis. You may also receive an IV (intravenous) line

through which a different kind of contrast dye (IV contrast) is injected.

This helps better outline structures in your body. The injection can cause

some flushing (redness and warm feeling). Some people are allergic and

get hives or, rarely, more serious reactions like trouble breathing and low

blood pressure. Be sure to tell the doctor if you have any allergies or have

ever had a reaction to any contrast material used for x-rays. A CT scanner

has been described as a large donut, with a narrow table that slides in and

out of the middle opening. You need to lie still on the table while the scan

is being done. CT scans take longer than regular x-rays, and you might

feel a bit confined by the ring you have to lie in while the pictures are

being taken.

4. Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans make detailed images of soft tissues in the

body. But MRI scans use radio waves and strong magnets instead of x-rays.

The energy from the radio waves is absorbed and then released in a pattern

formed by the type of body tissue and by certain diseases. A computer

translates the pattern into very detailed images of parts of the body. A

contrast material called gadolinium is often injected into a vein before the

scan to better see details. MRI scans can help determine the exact location
44

and extent of a tumor. Sometimes they can help a doctor tell a benign tumor

from a malignant one. They can also help tell if any lymph nodes are

enlarged or if other organs have suspicious spots, which might be due to the

spread of cancer. MRI scans take longer than CT scans – often up to an

hour – and are a little more uncomfortable. You may have to lie on a table

that slides into a narrow tube, which is confining and can upset people who

have a fear of enclosed spaces. Newer, more open MRI machines can

sometimes be used instead if needed. The MRI machine makes buzzing and

clicking noises that you may find disturbing. Some places will provide

earplugs or headphones to help block this noise out.

5. Positron emission tomography (PET) scan

A PET scan looks for areas of high cellular activity (which might be a

sign of cancer), rather than just showing if areas look abnormal based on

their size or shape. This test can help show whether an abnormal lump or

tumor seen on another imaging test may be cancer. If you have been

diagnosed with cancer, your doctor may use this test to see if the cancer

has spread to lymph nodes or other parts of the body. A PET scan can also

be useful if your doctor thinks the cancer might have spread but doesn’t

know where. For this test, you receive an injection of a radioactive

substance (usually a type of sugar known as FDG). The amount of

radioactivity used is very low and will pass out of the body over the next

day or so. Because cancer cells in the body are growing quickly, they

absorb more of the radioactive sugar. After about an hour, you are moved
45

onto a table in the PET scanner. You lie on the table for about 30 minutes

while a special camera creates a picture of areas of radioactivity in the

body. The picture is not finely detailed like a CT or MRI scan, but it can

provide helpful information about your whole body.Some machines are

able to do both a PET and CT scan at the same time (PET/CT scan). This

lets the doctor compare areas of higher radioactivity on the PET scan with

the more detailed picture of that area on the CT scan.

6. Biopsy

Symptoms and the results of exams or imaging tests may strongly

suggest you have salivary gland cancer, but the actual diagnosis is made

by removing cells from an abnormal area and looking at them under a

microscope. This is known as a biopsy. Different types of biopsies might

be done, depending on the situation.

7. Fine needle aspiration (FNA) biopsy

An FNA biopsy is used to remove a small amount of cells and fluid

from a lump or tumor for testing. This type of biopsy can be done in a

doctor’s office or clinic. It’s done with a thin, hollow needle much like

those used for routine blood tests. Your doctor may first numb the area

over the tumor with local anesthesia. The doctor then puts the needle

directly into the tumor and pulls cells and a few drops of fluid into a

syringe. The sample is then sent to a lab, where it’s checked under a

microscope to look for cancer cells. Doctors may use FNA if they are not

sure whether a lump is a salivary gland cancer. The FNA might show the
46

lump is due to an infection, a benign (non-cancerous) salivary tumor, or a

salivary gland cancer. In some cases this type of biopsy can help a person

avoid unnecessary surgery. An FNA biopsy is only helpful if enough cells

are taken out to be able to tell for certain what a tumor is made of. But

sometimes not enough cells are removed, or the biopsy is read as negative

(normal) even when the tumor is cancer. If the doctor is not sure about the

FNA results, a more extensive type of biopsy might be needed.

8. Incisional biopsy

This type of biopsy may sometimes be done if the FNA biopsy does

not get a large enough sample to examine. In this procedure, the surgeon

numbs the area over the tumor, makes a small incision (cut) with a scalpel

and takes out a tiny part of the tumor. The specimen is sent to the lab to be

looked at by the pathologist. These types of biopsies are not done often for

salivary gland tumors.

9. Surgery

As mentioned above, FNA biopsy of a suspected salivary gland cancer

may not always provide a clear answer. If this is the case but the physical

exam and imaging tests suggest that cancer may be present, the doctor

may advise surgery to remove the tumor completely. This can both

provide enough of a sample for a diagnosis and treat the tumor at the same

time (see the “Surgery for salivary gland cancer” section for more

information). In some cases if the exams and tests suggest cancer is likely,

the doctor may skip the FNA biopsy altogether and go directly to surgery
47

to remove the tumor. The specimen is then sent to the lab to confirm the

diagnosis.

(American Joint Committee on Cancer, 2010).

J. TREATMENT FOR SALIVARY GLAND TUMOR

a. Standard Therapies

The treatment of choice for benign salivary gland tumors is

surgical excision, depending though on the type, size, and stage of salivary

gland cancer and patient’s. In most cases involving the parotid gland,

superficial lobectomy with preservation of the facial nerve is the standard

treatment. Enucleation or ‘lumpectomy’ of parotid tumors can result in

persistence of the neoplasm due to breaches in the capsular wall and

multifocal recurrences. Benign neoplasms of the submandibular and

sublingual glands are treated by total resection of the glands. Intraoral

tumors are excised, along with perilesional tissue that occasionally

includes palatal or alveolar bone. Malignant salivary gland tumors are

treated with a minimum of wide local excision. Patients with clinically

positive lymph nodes usually receive a neck dissection. High-grade

neoplasms are often treated with a combination of wide local excision,

radical neck dissection, and post-operative radiation therapy to eradicate

subclinical disease (Spiro (1998); Le et al. (1999), and Schram and Imola,

2001). Salivary gland neoplasms are considered to respond poorly to

chemotherapy. Subsequently adjuvant chemotherapy is currently indicated


48

only for palliation (Spiro, 1998). The most commonly used

chemotherapeutics are doxorubicin and platinum-based agents.

b. Experimental Therapies

Combinations of platinum-based drugs with mitoxantrone or

vinorelbine have been shown to be effective in the control of recurrent

salivary gland tumors Airodi et al. (2001); Gedlicka et al., 2002).

Fluoropyrimidine new form of 5-fluorouracil with increased activity

against malignant cells but fewer gastrointestinal side effects demonstrated

superior efficacy against malignant salivary tumors and to act

synergistically with radiotherapy (Harada et al., 2004). Newer trials with

antimicrotubule agents with and without concomitant radiotherapy have

shown efficacy (Ruzich et al. (2002); Gilbert et al., 2006). Using a

platinum-based agent, cisplatin, and an antimicrotubule drug, docetaxel,

with radiation shows some promise in advanced carcinomas of the salivary

gland. Using paclitaxel (Taxol), another antimicrotubule drug, alone has

had moderate activity against mucoepidermoid tumors and

adenocarcinomas but no effect adenoid cystic carcinoma. Combination

gene therapy studies have also shown some interesting and promising

results (O’Malley and Li, 1998). Targeted biologic agents such as

trastuzumab, imatinib and cetuximab are also currently under investigation

(Mehra and Cohen (2008); Stenner and Klussman, 2009).