Salivary gland tumors

Introduction
Tumors of the salivary glands are uncommon and represent 2-4% of head and neck
neoplasms. They may be broadly categorized into benign neoplasms, tumor-like
conditions, and malignant neoplasms. The glands are divided into major and minor
salivary gland categories. The major salivary glands are the parotid, the submandibular,
and the sublingual glands. The minor glands are dispersed throughout the upper
aerodigestive submucosa (i.e., palate, lip, pharynx, nasopharynx, larynx, parapharyngeal
space).

Most (70%) salivary gland tumors (SGTs) originate in the parotid gland. The remaining
tumors arise in the submandibular gland (8%) and minor salivary glands (22%). Although
75% of parotid gland tumors are benign, slightly more than 50% of tumors of the
submandibular gland and 80% of minor SGTs are found to be malignant. Pleomorphic
adenomas (benign mixed tumors) are the most common benign SGTs, comprising 85% of
all salivary gland neoplasms.

The ubiquitous deposition of the minor salivary glands complicates the diagnosis and
management of SGTs. The approach for a suspected tumor of the minor salivary glands
begins with a thorough history and a physical examination. Radiographic imaging (CT
with or without MRI) and a histopathologic diagnosis (obtained based on fine needle
aspiration biopsy [FNAB]) often provide useful information prior to definitive surgical
therapy.

CLASSIFICATIONS
1. Adenomas
1 Pleomorphic adenoma
2 Myoepithelioma (myoepithelial adenoma)
3 Basal cell adenoma
4 Warthin’s tumor (adenolymphoma)
5 Oncocytoma (Oncocytic adenoma)
6 Canalicular adenoma
7 Sebaceous adenoma
8 Ductal Papilloma
 Inverted ductal papilloma
 Intraductal papilloma
 Sialadenoma papilliferum

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9 Cystadenoma
 Papillary cystadenoma
 Mucinous cystadenoma
2. Carcinomas
1 Acinic cell carcinoma
2 Mucoepidermoid carcinoma
3 Adenoid cystic carcinoma
4 Polymorphous low-grade adenocarcinoma
5 Epithelial-myoepithelial carcinoma
6 Basal cell adenocarcinoma
7 Sebaceous carcinoma
8 Papillary cystadenocarcinoma
9 Mucinous adenocarcinoma
10 Oncocytic carcinoma
11 Salivary duct carcinoma
12 Adenocarcinoma
13 Malignant myoepithelioma
14 Squamous cell carcinoma
15 Small cell carcinoma
16 Undifferentiated carcinoma
3. Miscellaneous
1 Nonepithelial tumors
2 Malignant lymphomas
3 Secondary tumors
4 Unclassified tumors
5 Tumor-like lesions
 Siladenosis
 Oncocytosis
 Necrotizing sialometaplasia (salivary gland infarction)
 Benign lymphoepithelial lesion
 Salivary gland cysts
 Chronic sclerosing sialedenitis of submandibular gland (Kuttner tumor)
 Cystic lymphoid hyperplasia in patients with acquired immunodeficiency
syndrome
INCIDENCE
Salivary gland tumors …3-4% of all head & neck neoplasm.
70% originate in parotid gland.
> 70%of them are Benign.

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70% of them …plemorphic adenoma.
10% of parotid tumors… mucoepidermoid carcinoma.

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Pathophysiology
I. Multi-cellular theory
 Salivary gland arise from the adult differentiated counter part of salivary gland
unit:
􀂄􀂄 Acinar cell : acinous tumor.
􀂄􀂄 Striated duct cell: oncocytic tumor.
􀂄􀂄 Intercalated duct cell: mixed tumor.
􀂄􀂄 Excretory duct cells: mucoepidermoid carcinoma & squamous cell carcinoma.

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II. Bicellular Theory
 The basal cell of excretory & intercalated duct act as stem cells.
􀂄􀂄 Intercalated duct stem cell: acinous cell carcinoma, adenoid cystic carcinoma, mixed
tumor & oncocytic tumors.
􀂄􀂄 Excretory duct stem cell: squamous cell carcinoma & mucoepidermoid carcinoma.

Aetiology
I. Radiation
 Several studies have implicate radiation associated neoplasm.
 Does-response pattern.
 Mostly parotid
 Commonly mucoepidermoid carcinoma.
II. Epstein-Barr Virus:
 The consistent association of E B V with lymphoepithelial carcinoma of the
salivary gland suggest the virus probably plays causal role
 Similar pathogenesis of nasopharyngeal carcinoma.
 no evidence of a causal role of EBV in other primary tumors of the salivary gland.
III. Genetic Factors:
Many genetic alternation may be responsible for increased likelihood of developing
salivary gland neoplasm as allelic loss, structural rearrangement, monosomy& polysomy.
IV. Other factors:
 Silica dust or wood dust.
 Using Kerosene as cooking fuel.
 Warthin’s tumor is strongly associated with cigarette smoking.
Diagnosis
I. Clinical features:
 Usually present as slowly growing painless swelling
 A sudden increase in size ( infection, cystic degeneration, hemorrhage inside the
mass, or malignant transformation)
 malignant indicators as:Facial nerve paresis or paralysis. Weakness or numbness of
the tongue or in distribution of branches of trigeminal nerve.
 Pain
 Fixation
 Cervical adenopathy
History of malignant skin lesion should be clarified as case of metastatic disease to the
parotid.

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Need full examination especially.
 The mass itself.
 Skin of face or scalp.
 Oropharynx.
 C N S.
 Cervical lymph node.

II. Fine needle aspiration biopsy:

Efficacy is well established
 Accuracy = 84-97%
 Sensitivity = 54-95%
 Specificity = 86=100%
Safe, well tolerated

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Opponents:
 Doesn’t change management
 Surgery regardless of reported diagnosis
 Obscuring final pathologic diagnosis
 Frequency of “inadequate” sampling, requires
 multiple biopsies, prolongs course until definitive
 treatment, increases cost
Proponent:
 Important to distinguish benign vs. malignant nature of neoplasm
 Preoperative patient counseling
 Surgical planning
 Differentiate between neoplastic and non-neoplastic processes
 Avoid surgery in large number of patients
III. Radiology:
 Conventional radiography & sialography are rarely used.
 C T & M R I give better understanding:
o Location & extent of the tumor.
o Its relation to major neurovascular structure
o Perineural spread.
o Skull base invasion.
o Intracranial extension.
o But most of the time can’t be differentiate between benign & malignant
entities.
 Nuclear imaging using Technetium 99m
 pertechnetate is rarely obtained because
 FNAB may provide better information.
 Other imaging studies:
 Ultrasonography.
 Color doppler sonography.
IV. Biopsies:
-Incisional intraoral biopsy of parapharyngeal tumor should not be performed.
-The proper approach to parotid neoplasm is parotidectomy which diagnostic &
curative.
- Open biopsy done rarely & in the patient who not surgical candidate & for whom
FNAB is not diagnostic.

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Benign tumors
Pleomorphic Adenoma
 Most common of all salivary gland neoplasms
 70% of parotid tumors
 4th-6th decades.
 F:M = 3-4:1.
 Slow-growing, painless,firm mass.
 Rarely progresive.
􀂄 Gross pathology
 Smooth
 Well-demarcated
 Solid
 Cystic changes
 Myxoid stroma
􀂄 Histology
 􀂄 Mixture of epithelial, myopeithelial and stromal components
 􀂄 No true capsule
 􀂄 Tumor pseudopods
Warthin’s Tumor
 papillary cystadenoma lymphomatosum
 6-10% of parotid neoplasms
 Older, Caucasian, males
 10% bilateral or multicentric
 3% with associated neoplasms
 Presentation: slow-growing, painless mass
Gross pathology
 Encapsulated
 Smooth/lobulated surface
 Cystic spaces of variable size, with viscous fluid, shaggy epithelium
 Solid areas with white nodules representing lymphoid follicles
Histology
􀂄Papillary projections into cystic spaces surrounded by lymphoid stroma

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Oncocytoma
 < 1%of salivary gand tumors.
 Parotid is the most frequent site.
 Slow-growing , painless mass.
 6th decade.
 M:F = 1:1.
Gross
􀂄 Encapsulated
􀂄Homogeneous, smooth
􀂄Orange/rust color
Histology
 Cords of uniform cells and thin fibrous stroma
 Large polyhedral cells
 Distinct cell membrane
 Granular, eosinophilic cytoplasm
 Central, round, vesicular Nucleus
Monomorphic Adenomas
 < 5% of salivary gland tumors.
 Only one morphologic cell type.
 Subclassified into:
• Basal Cell Adenoma.
• Canalicular Adenoma.
• Myoepithelioma.
• Clear cell adenoma.
• glycogen-rich adenoma.
• Sebaceous adenoma
Basal Cell Adenoma
 Basal cell is the most common
 1.8% of benign epithelial salivary gland neoplasms.
 6th decade.
 M:F = approximately 1:1.
 Caucasian > African American.
 Most common in parotid.
 Histological types: Solid , Trabecular , Tubular , Membranous

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Hemangioma
 Benign of endothelial origon.
 < 5% of salivary gland tumors.
 > 90% of parotid tumors in children < 1year.
 Present at birth.
 Unilateral,painless,rapid-growth .
 F > M.
 CT & MRI are dignostic.
 Spontanouus regression ,surgery if needed.
Malignant
Mucoepidermoid Carcinoma
 Most common salivary gland malignancy.
 5-9% of salivary neoplasms.
 Parotid 80% - 90% of cases.
 3rd-8th decades, peak in 5th decade.
 F>M.
 Caucasian > African American.
 Most common salivary gland tumor in children.
 It contain two major elements: mucin producing cells & epithelial cells of
epidermoid variety & according to that classified into low-grade, high grade &
intermediate.
 Presentation
􀂄􀂄 Low-grade: slow growing, painless mass
􀂄􀂄 High-grade: rapidly enlarging, +/- pain
Gross pathology
-Well-circumscribed to partially encapsulated to unencapsulated
-Solid tumor with cystic spaces
Histology—Low-grade
 􀂄Mucus cell > epidermoid cells
 􀂄 Prominent cysts
 􀂄 Mature cellular elements
Histology—Intermediategrade
 􀂄 Mucus = epidermoid
 􀂄 Fewer and smaller cysts
 􀂄 Increasing pleomorphism and mitotic figures.

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Histology— High-grade
 Epidermoid > mucus
 Solid tumor cell proliferation
 Mistaken for SCCA-Mucin staining
 high chance of locoregional recurrence,distant metastasis & shorter survival rate
compaired with low grade tumors.
Adenoid Cystic Carcinoma
 Overall 2nd most common malignancy
 Most common in submandibular, sublingual and minor salivary glands
 M=F
 5th decade
 Presentation
􀂄􀂄 Asymptomatic enlarging mass
􀂄􀂄 Pain, paresthesias, facial weakness/paralysis
 Subclassified histologically in:Cribriform, tubular, solid
 Perineural involvement is characteristic of adenoid cystic carcinoma & occur in
20-80%.
 Lymphatic spread uncommon 15%.
 Distant metastasis continue to occur for as long as 20 years or more & common in
lung (90%).
Acinic Cell Carcinoma
 3% of all salivary gland neoplasm.
 80-90% in parotid.
 15% of all parotid tumors.
 Main age is 40-50 years.
 2/3 Occur in female.
 3% Shows bilateral involvement.
 Second most common salivary gland in children.
 Well circumscribed tumor with fibrosis tissue macroscopically.
 Four histological patterns identified solid, microcystic, papillary cystic& follicular.
But the type of pattern do not correlate with biologic behavior or prognosis.
 It is generally regarded as relatively low grade malignancy & has more favorable
prognosis.
 They seldom metastasize but they have high tendency to recur locally.

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Malignant mixed tumor
 Epithelial & mesenchymal elements.
 3-12% of salivary gland tumor.
 ¾ in parotid.
 Carcinoma ex-pleomorphic adenoma (most common variety).
 Incidence increase by duration & recurrence of pleomorphic adenoma.
 Microscopic foci of necrosis, hemorrhage, calcification or excessive hyalinization.
 2 Subgroups, invasive & non-invasive:
 Degree of the invasion determine the prognosis which <8-mm 5-year survival rate
is 100%,but > 8- mm show <50%.
 Invasive type show 25% regional & 33% distant metastasis.

Polymorphous low grade adenocarcinoma

 Known also as terminal duct or lobular carcinoma.
 Majority in oral cavity (palate or buccal mucosa).
 Slow growth.
 Common in female 2:1
 Lymph node metastasis 9%
 Local recurrence 17%
 No distant metastasis.
Salivary duct carcinoma
 High grade aggressive tumor from excretory duct cells in major salivary gland
mainly.
 Microscopic feature remarkably similar to mammary intraductal carcinoma.
 35% recurrence.
 62% distant metastasis
 77% died of the disease.
Epithelial-Myoepithelial carcinoma
 1% of salivary gland neoplasm.
 Ductal cell population.
 Mostly involve the parotid at age 50-80 female.
 Sold, tubular & cribriform subtypes.
 High incidence of local recurrence 50% especially with sold type.
 Distant metastasis 25%.
 40% of patient died by their disease.

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Adenocarcinoma
 Ranging from low grade well differentiated to high grade invasive lesions.
 Common in major gland.
 Originate from excretory or striated ducts.
 Cystic or solid, may be papillary or non-papillary in growth pattern.
 Prognosis depend on grade.
Squamous cell carcinoma
 Rare to be primary & common to be secondary from intraparotid lymph node or
direct involvement.
 Should be differentiated from mucoepidermoid carcinoma by presence of mucin on
electron microscope with stain or immunohistochemical test.
 Incidence 0.3% -1.5% in major gland.
 50% nodal metastasis.
 M:F = 2:1.
 7th-8th decades
 TR:surgery + Neck dissection + Postop.XRT.

Undifferentiated Carcinoma
 Lack of histological characteristics.
 High in china
 Indistinguishable histological from
 undifferentiated carcinoma of nasopharynx.
 Linked to E B virus.
Lymphoma
 5% of all extranodal lymphoma affected salivary gland.
 90% occur in parotid.
 85% are N H L.
 Nodal or extranodal in the salivary gland.
 Primary or disseminated.
 Its risk in Sjogren’s syndrome is 44 fold higher & has bad prognosis.
Secondary tumors
The majority of metastasis are caused by
 lymphatic spread from cutanous malignancy of the head & neck.
 Hematogenous metastasis are rare & majority from lung, kidney & breast
 Contiguous extension of facial sarcomas.
10% of malignant parotid gland tumors(2ry).

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40% are SCC, & 40% are melanoma.
2/3 of SCCs, occur in 1st year.
Melanoma correlate with thickness of primary tumor.

Management
Staging

Treatment for salivary gland cancer

The principal treatment of salivary gland tumors is surgical resection with save margins
used either as single modality or conjunction with adjuvant radiotherapy.
I. Surgery:
 Small, localized tumor of the superficial lobe may be adequately treated with
superficial parotidectomy.
 Large tumor and tumor involving the deep lobe usually require total
parotidectomy.

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  The facial nerve is dissected & preserved unless it is directly involved by the
tumor.
􀂄 􀂄 Preoperative weakness or paralysis
􀂄 􀂄 Intraoperative evidence of gross or microscopic infiltration.
 The sacrificing more likely with large & high grade tumor or that one extend from
superficial to deep lobe.
 Surgical margin on distal & proximal nerve stumps should be checked due to the
possibility of perineural spread.
 Tumors extending beyond the parotid gland may require resection of surrounding
structures up to subtotal petrosectomy.
Complication of Parotidectomy
1) Frey’s syndrome (Gustatory sweating):
 Symptoms vary in severity.
 Incidence 35-60%.
 Due to cross re-innervation between the postganglionic secretomotor
parasympathetic fibers to the parotid gland & the postganglionic sympathetic fibers
supplying the sweat glands of the skin.
 Diagnosis depend largely on the patient’s symptoms but can be confirm by
Minor’s starch & iodine test.
 If the symptoms are bothersome we can use antiperspirant, glycopyrrolate lotion,
tympanic neurectomy or muscle flap or sheet of facia between the skin and the
parotid ped.
2) Facial nerve paresis or paralysis.
3) Salivary fistula
 􀂄 Uncommon & self limited.
 􀂄 Clear sialorrhea or fluid collections.
 􀂄 Treated by wound care, pressure dressing, repeated aspiration of fluid
collections or oral anticholinergics.
II. Neck Dissection:
 If there is metastatic cervical L.A.P. the patient need comprehensive cervical
lymphadenectomy.
 But there is controversy about management of clinically negative neck.
 In high-grade or large tumor. The incidence of occult regional disease is relatively
high, so the elective neck dissection or selective (supraomohyoid) neck dissection
should be considered.
 In low-grade malignancy the elective neck dissection not recommended.

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III.Radiotherapy
 Adjuvant radiotherapy is superior to surgery alone & effective in improve
locoregional control & highly recommended in patient with poor prognosis.
 In inoperable tumor the neutron irradiation alone is the therapy of choice &
superior to conventional proton or electron therapy & even superior to debulking
surgical procedure.

IV. Chemotherapy
Although the salivary gland malignancy show some response to various
chemotherapeutic agents, these response have not resulted in significant improvement in
long survival rate.

Prognosis
I- Stage:
The most important factor.
The incidence of local recurrence & regional metastasis are lowest in patient with stageI.
II-Histology & Grade:
 The biologic behavior depend largely on the histologic type of malignancy.
 Squamous cell carcinoma, malignant mixed tumors, undifferentiated carcinoma &
salivary duct carcinoma are considered high-grade tumors while acinic cell
carcinoma & polymorphous low grade adenocarcinoma are considered low-grade
tumor.
 Adenoid cystic carcinoma considered a high grade malignancy although histologic
pattern have different biologic behavior.
 Mucoepidermoid carcinoma highly correlated with tumor grade.
III. Site:
The prognosis & also the local recurrence after treatment have a definite correlations
with primary site of origin which better in major salivary glands than minor salivary
glands mainly due to:
- Present at more advance stage.
- High incidence of extension & fixation.
- Bone involvement.
IV. Nodal metastasis:
 Considered as predictor of poor prognosis.
 Adenoid cyst carcinoma 10&20 years survival rate drop from 62 & 50% to 38 &
8% with nodal metastasis.

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V. Surgical margins:
 Some consider it as the most important factor.
 Microscopic positive margin need radiotherapy to achieve good prognosis.
VI. Perineural spread:
 In squamous cell carcinoma the perineural spread show poor prognosis.
 The effect of perineural spread in the prognosis of adenoid cystic carcinoma still
controversial. But any how the perineural spread in major nerve indicate adverse
prognostic factor.
VII. Facial Nerve paralysis:
Although facial nerve paralysis may not be associated with 100% mortality rate, it is an
indicator of poor prognosis.
VIII. Pain:
 Patients with pain appear to have a less favorable outcome.
 Its presence increase likelihood of local invasion of bone or sensory nerves.
IX. Distant metastasis:
 20% of parotid malignancy.
 Most frequently in adenoid cystic carcinoma & undifferentiated carcinoma.
 Lung, bone & brain.
X. Gender:
Men have poorer outcome.

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