2. Anatomy and histology
• 3 pairs of major salivary glands.
• Other locations include lateral margins of tongue, palate,
lips, buccal mucosa.
• Seromucous glands of nasal cavity, larynx and bronchi
histologically similar to minor salivary glands
3. • The fundamental structure of all salivary glands is the
acinar-ductal unit.
• Acini are variably composed of serous or mucous cells or
both.
• Ductal unit include
– Striated duct
– Intercalated duct
– Excretory duct
• Acini and intercalated ducts are surrounded by
myoepithelial cells.
• Preservation of the lobular architecture is an important
feature favoring a diagnosis of a non-neoplastic process
over a tumor.
4.
5. • Myoepithelial cells:
• Physiologically and functionally modified epithelial cells.
• Possess a duel epithelial and smooth muscle phenotype.
• Produce extracellular matrix.
• Anti-invasive effect in neoplasms by promoting epithelial
differentiation, secreting protinase inhibitors and
supressing angiogenesis.
• Basal cells:
• Maintain multidirectional differentiation and play a role in
the process of regeneration and metaplastic changes.
6. Introduction
• Tumors of the salivary glands are:
– Most heterogeneous group of tumors.
– Greatest diversity of morphologic features.
• Relatively uncommon.
• The majority of these neoplasms are benign 80% and only
20% are malignant.
• The various types of salivary gland tumors are best
distinguished by their histologic patterns.
7. Epidemiology
• Uncommon neoplasms
• 2%-6.5% of all head and neck neoplasms.
• Global annual incidence varies from 0.4-13.5 cases per
100000 people.
• Most salivary gland tumors originate in the parotid glands
(64%-80%), malignancy (15%- 32%).
• 7-11% occur in the submandibular glands, malignancy
(37%- 45%).
• less than 1% in the sublingual glands, malignancy (70%
90%)
8. • 9%-23% in the minor glands.
• Benign tumors account for 63% to 78% of all salivary
gland neoplasms.
• Most common benign tumor: Pleomorphic adenoma -53%-
77% of all cases occurs in parotid glands.
• Warthin’s tumor- 6%-14% of all cases
• Most common malignancy- Mucoepidermoid carcinoma.
9. • Most common minor salivary gland tumor site: Palate,
(42%- 54%).
• The proportion of malignant tumors varies significantly by
site and is the greatest in the sublingual glands, tongue,
floor of the mouth, and retromolar area.
• Most common among children: Mucoepidermoid
carcinoma.
10. • RULE OF 80S
– 80% of parotid tumors are benign
– 80% of parotid tumors are Pleomorphic adenomas
– 80% of salivary gland Pleomorphic adenomas occur in
the parotid
– 80% of parotid Pleomorphic adenomas occur in the
superficial lobe
– 80% of untreated Pleomorphic adenomas remain
benign
11. Etiology
• Viruses- EBV, CMV, Polyoma virus,
• Ionizing radiation.
• Increased occupational risks- asbestos, nickel compounds
or silica dust.
• Employment in the woodworking, rubber industries and
beauty saloons.
• Lifestyle- Warthin’s tumors showed a strong association
with cigarette smoking.
• Endogenous hormones.
13. • Cell differentiation results in three basic models of benign
or malignant salivary gland neoplasms.
– 1) In one form of differentiation, tumor cell population
results in a dual population that combines recognizable
luminal and/or acinar cells with myoepithelial and/or
basal cells
– 2) A second pattern results primarily in
luminal/glandular cells that resemble to some extent
normal duct epithelial and/or acinar cells
– 3) The third process produces tumor cells resembling
normal myoepithelial and/or basal cells.
17. Pleomorphic adenoma/ mixed tumor
• Name suggested by Willis.
• Most common neoplasm of salivary gland tumor.
• Benign neoplasm- consisting of cells exhibiting the ability
to differentiate to epithelial (ductal and nonductal) cells
and mesenchymal (chondroid, myxoid, osseous) cells.
• Other names: Branchioma, enclavoma, teratoma,
cyindroma, myxochondrocarcinoma.
• Salivary gland tumor origin: EPITHELIAL
• Shows cytogenic abnormalities in chomosomes- 12q13-15.
• Putative pleomorphic adenoma gene(PLAG1) has been
mapped to chromosomes 8q12.
18. • HISTOGENESIS
• Numerous theories have been proposed
• The tumor is centered around myoepithelial cells and
reserve cells
• Ultrastructural studies have confirmed the presence of
ductal and myoepithelial cell.
• According to Hubner and associates cell responsible for
morphological diversity is myoepithelial cell which
produces fibrous, mucinous, chondroid, and osseous areas
19. • According to Regezi and Batsakis
• Intercalated duct reserve cell can differentiate into ductal
and myoepithelial cells.
• This cell in turn can undergo mesenchymal metaplasia.
• According to Dardick and his associates
• Neoplastically altered epithelial cells with the potential for
multidirectional differentiation might be histogenetically
responsible for pleomorphic adenoma.
20. • CLINICAL FEATURES
• Most common tumor.
• Rate of occurance:
– 60-70%- parotid glands
– 40-60%- submandibular glands
– 40-70%- minor salivary glands
– seldomly- sublingual glands
• Age: 30-50 years
• Sex: female> male – 3:1 – 4:1
• In parotid- presents in the lower lobe of the superior lobe
as a mass over the angle of the mandible, below and infront
of the ear.
21. • CLINICAL PRESENTATION:
• painless, slow growing, firm mass, initially small in size
and begins to increase in size.
• Initially movable but with continued growth become more
nodular and less movable.
• Recurrent tumor- multinodular, fixed on palpation.
• Palate – intraorally common site.
• Seldom ulcerated- unless secondarily traumatized.
25. • GROSS PATHOLOGY
• Benign tumor showing well encapsulated mass
• Cut surface of the tumor is tan coloured and glossy in
appearance
26. • HISTOPATHOLOGIC APPEARANCE
• HALLMARK: Morphologic Diversity.
• Charecterized by- Variable, Diverse, Structural &
histologic patterns.
• It demonstrate glandular epithelium and mesenchyme like
tissue and the proportion of each component varies widely.
• Typically a well-circumscribed encapsulated tumor
• The epithelium often forms ducts and cystic structures or
may occur as islands or sheets of cells , anastomosing cords
and foci of Keratinizing squamous cells and spindle cells .
27.
28. • Foote and Frazell (1954) categorized PA into:
• a) Primarilly myxoid (36%)
• b) Myxoid and cellular component in equal proportions (30%)
• c) Predominantly cellular (22%)
• d) Extremely cellular (12%)
29. • Myoepithelial cells are major component of PA.
• Have variable morphology- sometimes appearing as
angular or spindled, some with eccentric nucleus
resembling plasma cells are responsible for characteristic
mesenchyme like changes.
• Vacuolar degeneration of myoepithelial cells can produce a
chondroid appearance.
• the stroma exhibits areas of an eosinophilic hyalinized
change, fat or osteoid also is seen.
35. • TREATMENT AND PROGNOSIS
• Surgical excision
• Superficial parotidectomy with preservation of the facial
nerve
• Local enucleation should be avoided - resulting in seeding
of the tumor bed.
• Deep lobe of the parotid- total parotidectomy is usually
necessary also with preservation of the facial nerve.
36. • Submandibular tumors - Total removal of the gland with
the tumor.
• Malignant degeneration is a potential complication,
resulting in a carcinoma ex pleomorphic adenoma.
• The risk of malignant transformation is probably small,
but it may occur in as many as 5% of all cases.
37. Warthims tumor
• Papillary Cystadenoma Lymphomatosum or
Adenolymphoma
• 5-14% of parotid neoplasms, 2nd most common benign
tumor..
• Pathogenesis is uncertain..
– Believed to arise from heterotrophic salivary gland
tissue found within the parotid lymph nodes.. OR..
– Proliferation of salivary gland ductal epithelium that is
associated with secondary formation of lymohoid
tissue…
• Risk factor - Smokers have 8 fold greater risk..
- EBV
38. • CLINICAL FEATURES
• Almost exclusively restricted to the parotid glands
• Appears as painless, slow growing, nodular mass..
• Firm or fluctuant on palpation
• Tail of parotid is the common site
• Unique characteristic = occurs bilaterally (5-14%)
• Rare in sub-mandibular/lingual glands..
• Older, Caucasian, males… 6th – 7th decade..
• M:F = 10:1..
39. • GROSS PATHOLOGY
– Encapsulated
– Smooth/lobulated surface
– Cystic spaces of variable size, with turbid fluid, caseous
debris, & tenaceous mucoid material with shaggy
epithelium…
– Solid areas with white nodules representing lymphoid
follicles…
40. • HISTOPATHOLOGIC APPEARANCE
• Epithelium: mixed ductal with lymphoid stroma..
• Double cell layer..oncocytic in nature..
– Luminal cells= tall columnar, centrally placed,
palisaded…
– Basal cells= cuboidal, with more vescicular nuclei..
• Lining epithelium demonstrates papillary projections into
cystic spaces surrounded by lymphoid stroma…
• Stroma: mature lymphoid follicles with germinal centers
• Focal areas of metaplsia may be seen..
48. Mucoepidermoid carcinoma
• 5% of all salivary gland tumors
• Commonest malignant tumor in adult and childhood.
• 1st to 9th decade peaking in 4-5th decade
• Females
• Parotid gland (45%) And palate (21%)
• Malignant glandular epithelial neoplasm characterized by
mucous cells, intermediate cells, and epidermoid cells.
49. • Etiology:
– Therapeutic Radiation
– Lipoidal installation
– Presence of other foreign material
• Origin:
– Cells of the salivary gland excretory and intercalated
duct
50. • CLINICAL FEATURES:
• Age: 3rd – 5th decade
• Sex: females> male
• Site: parotid is most commonly affected. Intraorally:
palate
• Most common salivary gland neoplasm in children
51. • CLINICAL FEATURES:
• Low grade: slowly enlarging, painless mass, seldom
exceeds 5cm in diameter in low grade.
• not completely encapsulated, often contains cysts- filled
with viscoid, mucoid material.
• may be mistaken as mucocele.
• High grade: grows rapidly, facial nerve paralysis
• ulceration, trismus, draining from the ear, dysphagia.
• metastasis to regional lymph node, lung, bone, brain,
suncutaneous tissue.
52. Blue-pigmented mass of the posterior
lateral hard palate.
Mucoepidermoid carcinoma.
Mass of the tongue
53. • GROSS PATHOLOGY
Low-grade mucoepidermoid carcinomas
may have a distinctly cystic gross
appearance.
-Cystic spaces- viscid, mucoid material
-Areas of hemorrhage seen.
Cut surface of the tumor shows gray
white, solid mass accompanied by
multiple small cystic structures and
infiltrative borders.
54. • HISTOPATHOLOGICAL FEATURES:
• Characterized by: variety of cell types and growth patterns
• Composed of-
– a)mucous secreting cells
– b)epidermoid cells
– c)intermediate cells
– d)columnar or clear cells
• Grades:
– a) low grade
– b) intermediate grade
– c) high grade
55. • Mucous cells- vary in shape, abundant pale foamy
cytoplasm that stains positive for mucin stains.
• relatively large, may assume round, cuboidal, ovoid,
columnar or goblet shapes.
• stains positive for mucicarmine and PAS stain.
• Epidermoid cells- squamous features, polygonal shape.
• Intermediate cells- larger than basal cell, smaller than
squamous cell. Proginitor of epidermoid and squamous
cells.
• Clear cells- larger, polygonal and defined cytoplasmic
borders.
56. • Histopathological Grades are based on-
– Amount of cyst formation
– Degree of cytoplasmic atypia
– Relative number of mucous, epidermoid & intermediate
cells.
57.
58. • Low grade: Hallmark- prominent cystic structures
accompanied by the presence of numerous mature cellular
element including mucous cells and extracellular matrix.
– Mucous cell predominate
– squamous cell lining the cystic spaces seen.
– Size, shape & staining characteristics of cells are
uniform
• Intermediate grade: intermediate cells predominate with
scattered mucous cells and zones of epidermoid cells
forming large, solid islands of tumor.
– Mitotic figures- rare.
62. • High grade: nearly solid cellular proliferation of
epidermoid & intermediate cells
– Noticiable degree of cellular atypia
– N:C ratio altered
– nucleoli prominent, mitosis- numerous
• 2 differentiation pattern:
• a)Resemble a MDSCC
• b) variety of cell types that are most often dominated by
• intermediate cells.
64. varients
• 1)Sclerosing MEC:
• Extremely rare, characterized by intense central sclerosis
that occupies the entirety of an otherwise typical tumor,
frequently with an infiltrate of plasma cells, eosinophils,
and/or lymphocytes at its peripheral region.
• 2 mechanism: Tumor infarction and extravasation of
mucins resulting in reactive fibrosis.
65. • 2) Intraosseous MEC:
• Primary intraosseous mucoepidermoid carcinoma (PIOC)
of the jaw bones is an extremely rare malignant salivary
gland tumor, comprising 2–3% of all mucoepidermoid
carcinomas reported.
– commonly seen in the posterior part of the mandible
– Histologically low-grade cancers
– Radiographically seen as uniocular or multiocular
lesions.
67. • TREATMENT AND PROGNOSIS:
• Conservative excision with preservation of facial nerve
• Submandibular gland- removal of the gland
• Minor salivary gland- surgical
• Matastatis- 12% of cases
• Prognosis- fairly good.
68. Adenoid cystic carcinoma
• Cylindroma, adenocystic carcinoma, adenocystic basal cell
carcinoma, psuedo adenomatous basal cell carcinoma,
basaloid mixed tumor.
• The adenoid cystic carcinoma is one of the more common
and best- recognized salivary malignancies.
• Slow growing but aggressive neoplasm with a remarkable
capacity of recurrence.
• Marked propensity for perineural invasion.
• Adenoid cystic carcinoma is a “basaloid tumour consisting
of epithelial and myoepithelial cells in variable
morphologic configurations, including tubular, cribriform,
cystic and solid patterns
69. • CLINICAL FEATURES:
• Age: 5th- 7th decade
• Sex: F>M
• Site: 50-60% within minor salivary gland- palate> tongue,
buccal mucosa.
• Slowly growing mass.
– Pain is a common and important finding
– Patients often complain of a constant , low-grade, dull
ache, which gradually increases in intensity.
– Facial nerve paralysis may develop with parotid
tumors.
– Palatal tumors can be smooth surfaced or ulcerated.
– Tumors arising in the palate or maxillary sinus may
show radiographic evidence of bone destruction
71. • HISTOPATHOLOGIC FEATURES:
• The adenoid cystic carcinoma is composed of a mixture of
myoepithelial cells and ductal cells that can have a varied
arrangement.
• Three major patterns are recognized;
– (1) Cribriform
– (2) Tubular
– (3) Solid.
• Usually a combination at these is seen, and the tumor is
classified based on the predominant pattern.
72. • Cribriform pattern:
• The cribriform pattern is the most classic and best
recognized appearance, characterized by islands of
basalaid epithelial cells that contain multiple cylindrical,
cyst like spaces resembling Swiss cheese or honeycomb
pattern.
73. • These spaces often contain a mildly basophilic mucoid
material a hyalinized eosinophilic product , or a combined
mucoid hyalinized appearance.
• Sometimes the hyalinized material also surrounds these
cribriform islands.
Adenoid cystic carcinoma.
The tumor cells are
surrounded by hyalinized
material
74. • Tubular pattern:
• Tubular structure that are lined by stratified cuboidal
epithelium.
• Longitudinal section- ductal structures are viewed as ducts
or tubules.
• Lumina contains mucinous substance- PAS positive
• Cribriform pattern may exist with tubular pattern.
75.
76. • Solid pattern:
• Solid groups of cuboidal cells with little tendency towards
ducts or cyst formation.
• Arranged in nests or sheets of varying size and shape.
• Areas of necrosis seen
• Cellular pleomorphism, mitosis observed.
81. • TREATMENT AND PROGNOSIS
• Surgical excision
• Adjunct radiation therapy may slightly improve patient
survival in some cases.
• Prognosis- poor
82. Polymorphous low grade adenocarcinoma
• Lobular carcinoma, terminal duct carcinoma.
• Evans and Batsakis first used the term
• PLGA occurs almost exclusively in the minor salivary
glands
• Characterized by: Bland, uniform nuclear feature, diverse
by characteristic architecture, infiltrative growth and
perineural invasion.
83. • CLINICAL FEATURES:
• Age: 50-80 years
• Sex- F:M=2:1
• Site: 50-60%- palate, 16%- buccal mucosa, 12%- upper
lip, major SG- parotid
• c/p- Most often appears as a pain less mass that may have
been present for a long time with slow growth.
– Associated with bleeding, discomfort, telangiectasia,
ulceration.
– Tumor can erode or infiltrate the underlying bone.
85. • GROSS PATHOLOGY:
• Firm, circumscribed, but non-encapsulated, yellow tan
lobulated nodule, average size 2.2cms.
• Bony invasion may be seem in large lesion in the hard
patate, may impinge upon the maxillary bone and cause
bone resorption and laterally medullary invasion
86. • HISTOPATHOLOGIC FEATURES:
• Characterized by: Infiltrative growth with diverse
morphology & Uniform nuclear appearance
• At low power, the tumor sometimes appears well
circumscribed.
• peripheral cells are usually infiltrative, invading the
adjacent tissue in a single- file fashion.
• Difference growth pattern- hence the name polymorphous.
• Variety of growth patterns- solid, ductal, cystic, tubular or
cribriform
88. • Tumor stroma- varies from mucid to hyaline and in some
areas Separated by fibrovascular stroma.
• In some tumors, a cribriform pattern can be produced that
mimics adenoid cystic carcinoma .
• Mitotic figures are uncommon.
• Perineural invasion common
90. • TREATMENT AND PROGNOSIS
• The polymorphous low-grade adenocarcinoma is best
treated by wide surgical excision, sometimes including
resection of the under lying bone.
• Metastasis to regional lymph nodes is relatively
uncommon, occurring in just under 10% of patients.
• Therefore, radical neck dissection seems unwanted
• Distant metastasis is rare.
