SALIVARY GLAND TUMORS

Glands are those organs or tissues in which the cells are engaged in synthesis, storage and discharge of
secretory products.
Salivary glands are the compound, tubuloacinar, merocrine, exocrine glands whose ducts open
into the oral cavity.
All these are derived from atleast 2 primary germ layers.

1) Endoderm / ectoderm  Secretory cells and lining of the duct.

2) Mesoderm  Connective tissue part of the gland which carries the blood and nerve supply to the
gland.
Salivary gland tumours have a special status in human neoplasia. They are likely have the most
complex histopathology of any organ / tissue and they are histologically heterogenous group of tumours
and the have greatest diversity of morphologic features among their cells and tissue.
Is the presence of unique myoepithelial cell in organs such as salivary, sweat and mammary glands a factor
responsible for the diversity of squamous tumours?
Tumours may be derived from salivary epithelium (parenchyma) or supportive stroma (mesenchymal).
70% occur in major salivary gland and 30% occur minor salivary gland  mainly palate, bone
marrow, upper lip, oropharynx, lower lip, tongue.
Benign parenchymal tumours  Adenoma
Malignant  Adenocarcinoma
Parotid  Mainly benign salivary gland tumours
Submandibular and minor salivary gland  malignant = benign.
Histologically these glands can be regarded as having two main types of cells.
Luminal and Non luminal, organized in a specific relationship.
Luminal : Refers to the secretary cells comprising acini and the lining or lumen fusing cells of ductal
system, ductal cells and
Non-Luminal : Similarly has two main components myoepithelial and basal.

In routinely stained histologic sections, luminal cells are readily recognized at all functional levels
of the gland and non luminal cells can be difficult to identify in the intercalated ducts and acini of salivary
gland lobules whereas apparent in the interlobar and main excretory ducts.

CLASSIFICATION :
World Health Organization Histological Classification of Salivary Gland Tumours (1991) :
1) Adenomas
- Pleomorphic adenoma
- Myoepthelioma
 - Basal cell adenoma
- Warthins tumour
- Oncocytoma
- Canalicular adenoma
- Sebaceous adenoma
- Ductal papilloma
- Inverted ductal papilloma
- Intraductal papilloma
- Sialadenoma papilliferum
- Cystadenoma
- Papillary cystadenoma
- Mucinous cystadenoma
2) Carcinomas
- Acinic cell carcinoma
- Mucoepidermal carcinoma
- Adenoid cystic carcinoma
- Polymorphous low grade
- Epithelial myoepithelial carcinoma
- Basal cell adenocarcinoma
- Sebaceous carcinoma
- Papillary cystadenoma
- Mucinous adenoma
- Oncocytic carcinoma
- Salivary duct carcinoma
- Adenocarcinoma
- Malignant myoepithelioma
- Carcinoma of pleomorphic adenoma
- Squamous cell carcinoma
- Small cell carcinoma
- Undifferentiated carcinoma
- Other carcinoma
3) Non-epithelial tumours
4) Malignant lymphomas
5) Secondary tumours
6) Unclassified tumours
7) Tumour like lesions
- Sialadenosis
- Oncocytosis
- Necrotizing sialometaplasia
- Benign lymphoepithelial lesion
- Salivary gland cysts
- Chronic sclerosing sialadenitis of submandibular glands (Kuttner tumour)
- Cystic lymphoid hyperplasia in AIDS

ETIOLOGY:
1) Viruses : Epstein barr virus, polyoma virus, cytomegalovirus type C and type B particles, human
papilloma virus 16 and 18 types.

2) Radiation :
• 483 rads given 1 cm below the parotid skin.
• Excessive use of dental and medical diagnostic radiograph
3) Occupation : Asbestos, Rubber products, plumbing and wood working.
4) Life style :
• Severe malnutrition i.e. Kwashiokar causes salivary gland enlargement and has a risk for
carcinoma
• Smoking association with Warthins tumour
5) Hormones

DIFFERENCES :
Benign Malignant

Clinical Features :
1. Smooth, uniform surface 1. Nodular surface
2. Normal surface colouration 2. Surface telangiectasia
3. Round, dome shaped 3. Irregularly shaped
4. Intact overlying mucosal skin 4. Ulcerated
5. Movable 5. Fixed and indurated
6. Asymptomatic 6. Occlusal nerve deficits

Histological Features :
1. Distinct and intact capsule 1. Lacks encapsulation
2. Uniformity of cells 2. Cells irregular in size and shape
3. Tissue structure resembles normal 3. Altered tissue patterns
4. Neoplastic cells, displace nerves 4. Invades nerves
 5. Normal stroma 5. Lacks sufficient stroma
6. No necrotic areas 6. Occlusal areas of necrosis

Neoplastic cells in the participation of squamous tumours

(based on ultrastructural and/or immuno cytochemical evidence)
Neoplasm Types of Cells
1) Pleomorphic adenoma Luminal
Acinar
Myoepithelial
2) Myoepithelioma Myoepithelial
Rare luminal
3) Basal cell adenoma Luminal
Myoepithelial / basal
Acinar
4) Warthins tumour Luminal
Basal / myoepithelial
5) Epithelial – Myoepithelial carcinoma Luminal
Myoepithelial
6) Acinic cell carcinoma Acinar
Intercalated duct
Myoepithelial
7) Mucoepidermoid carcinoma Goblet
Luminal
Squamous
Myoepithelial / basal
8) Salivary duct carcinoma Luminal
Myoepithelial
9) Polymorphous low grade adenocarcinoma Luminal
Myoepithelial
10) Adenocarcinoma, Nos Luminal
Myoepithelial
11) Malignant mixed tumour Luminal
Squamous
Myoepithelial

Note :
Myoepithelial cells : Ferritin, GFAP, Actin, Myosin, Fibronectin, Elastin, Laminin and Vimentin.
Ductal epithelial cells : Keratin, S-100 (Intercalated cells and acinar cells), BMP (Luminal cells of
tubuloglandular structure), CEA and Lactoferrin (Ductal epithelial cells).

Histogenesis:
 Histos  Web (a combining form denoting relation to tissue).
Genesis  Production.
The formation or development of tissues from the undifferentiated cells of germ layers of the
embryo.
In pathology, this term has become synonymous with the “cell of origin” for a neoplasm rather
than the development process underlying the tumour.

CONCEPTS OF SALIVARY GLAND TUMOUR HISTOGENESIS :

(By Eversole and Attie and Sciubba-1990)
Various concepts bearing on the positioning of proliferating cells in the salivary glands.
1) Basal reserve cell theory : Basal cells of both excretory and intercalated ducts are responsible for
differentiation of functional units.
2) Pluripotential unicellular reserve cell therapy : Basal cells of excretory duct are responsible for
developing of all remaining salivary gland cell
3) Semipluripotential bicellular reserve cell theory : Certain reserve cells in specific segments of the
duct system of major and minor salivary glands are critical to the develop of neoplasm in these glands.
This concept was based on histologic observation of developing bilayered major ducts in human fetal
salivary gland with the implication that the outer (basal) layer of cells gave rise to inner (luminal)
layer.
It was further refined and developed by Batsakis and Colleagues as follows ;
Excretory duct reserve (basal) cells were postulated to originate only tumours such as mucoepidermoid
carcinoma, SCC. Whereas intercalated duct reserve (luminal) cells were stated to be responsible for
pleomorphic and monomorphic adenoma, ACC, and acinic cell carcinoma. Theere was little or no
direct evidence to support the hypothesis.
4) Multicellular theory: Differentiated cells at all the levels of the gland, including acinar and basal cells
are capable of cell division.
Observations of DNA synthetic and mitotic activity in developing rat and human salivary gland
and autoradiographic studies of induced cell proliferation in rat salivary gland.
Autoradiography of neonatal rat salivary gland after tritiated thymidine administration and
electron microscopy of these tissues, reveals that as well as duct basal cells, luminal cells at all levels of
duct system and even acinar cells are capable of DNA synthesis and mitosis. Indeed, in such studies more
luminal than basal cells are seen in mitosis.
In adult rat salivary gland induced to undergo hyperplasia, more acinar cells than intercalated duct
cells are in S.phase of the cell cycle. Similar findings are present in fetal and adult human salivary gland.
From such observations it is evident that dividing cells are not limited to basal cells of excretory
ducts and luminal cells of intercalated ducts, so there is no support for the semipluripotential bicellular
reserve cell hypothesis.
 However, there is considerable evidence for a multicellular theory of tumour histogenesis. That is,
any of “multiplicity of cell types in normal salivary gland have the potential to give rise to any of various
types of tumour occurring in this organ”.
In terms of tumour induction it should be appreciated that “differentiated cells are capable of
metaplastic alterations”.
Eg. Epidermoid metaplasia has been demonstrated in acinar and myoepithelial cells of the salivary gland of
the rat and in secretory cells of hamster tracheal mucosa. These data suggests that any of the various cells
found in normal salivary gland could serve as a precursor for neoplasia, thus this is a multicellular
histogenetic concept.

Morphogenetic Concepts:
In the simplest possible scenario based on the ducto-acinar unit.
Tumour cell differentiation results in three basic models of benign or malignant salivary gland
neoplasm.
1) In one form of differentiation, tumour cell population results in a dual population that combines
recognizable luminal and/or acinar cells with myoepithelial and/or basal cells.
2) A second different pattern results primarily in luminal / glandular cells that resemble to some extent
normal duct epithelial and /or acinar cells.
3) The third process produces tumour cells resembling normal myoepithelial and/or basal cells.

Superimposed on these three basic patterns of differentiation is the lack of or production of

extracellular materials by neoplastic myoepithelium, either alone or in association with ductal luminal cells.
( Proteoglycans, collagens, GAG, basal lamina and elastins)
So histomorphology of many salivary gland tumours as viewed in light microscope have five main
categories.
Solid : Preferential differentiation of myoepithelial / basal cells.
Tubular : Combination of luminal and myoepithelial / basal cells of normal ductoacinar unit is replicated
in tubular.
Cribriform : Production of excess basal lamina and glycosaminoglycans in association with myoepithelial
basal cell.
Myxoid regions : Variable production of basal lamina and glycosaminoglycans leads to gradual separation
of tumour cells leading Myxoid areas.
Chondroid : Metaplastic processes associated with the development of myxomatous area results in
chondroid.
(More extensive according of mucoid material around individual myoepithelial cells and vascular
degeneration of cell results in cartilaginous appliances).

PLEOMORPHIC ADENOMA/ MIXED TUMOR / ENCLAVOMA / BRANCHIOMA /

ENDOTHELIOMA / ENCHONDROMA :

HISTOGENESIS:
• Intercalated duct reserve cells can differentiate in to ductal or myoepithelial cells.
• Either ductal or myoepithelial or both play a role in the histogenesis of the tumor.
• Myoepithelial cells are responsible for the morphologic diversity of the tumor in the production of
fibrous mucinous , chondroid or osseous areas.
• it shows cytogenetic abnormalities involving chromosome region 12q13-15.
• Putative pleomorphic adenoma gene ( PLAG1) has been mapped to chromosome 8q12.

CLINICAL FEATURES:
• Most common tumor of salivary glands.
• It Accounts 53 – 77% Parotid Tumors, 44 – 68% Sub mandibular tumors and 38 – 43 % minor
gland tumors.

Age:
• 4 -6th decade of life, rletively common in young adults also.

Sex:
• Female predominance.

Location:
• Most common - parotid gland – in the lower pole of the superficial lobe of the gland ..
• May occur in any major or accessory glands but rare in sublingual gland.
• Minor salivary salivary glands - palate is most common site
Clinical presentation:
• Presents as small , painless, quiescent nodule which slowly begins to increase in size, some times
show intermittent growth.
• It presents as swelling overlying the ramus in front of the ear.
• Lesion between ascending ramus and sylomandibular ligament results in dumblee- shaped tumor
on the lateral pharyngeal wall or soft palate.
• Irregular nodular lesion , firm in consistency although areas of cystic degeneration may be
palpated superficially.
• Lesion is not fixed to either deeper tissues or to the overlying skin.
• Intra oral lesions may cause difficulty in mastication, talking and breathing.
• Palatal pleomorphic adenoma is fixed to underlying bone but not invasive.

HISTOPATHOLOGIC FEATURES:

Macroscopic features :
• Irregular to ovoid mass with well defined borders.
 • Cut surface is rubbery , fleshy, mucoid or gelatinous with a homogeneous tan or white in colour.

Microscopic features:
• Capsule may be incomplete or show infiltration by tumor cells.
• Characteristically show morphologic diversity.
• Show combination of epithelium and mesenchymal like tissues

• Foote and Fraell categorized the tumor in to

o Principally myxoid
o Myxoid and cellular components present in equal proportions
o Predominantly cellular
o Extremely cellular
• Epithelial cells occur in the form of cellular nests, sheets of cells , anastmosing cords and fici of
keratinizing squames or spindle cells, they may also form ducts are cysts.
• Myoepithelial show variable morphology appearing angular or spindled, plasmacytoid / hyaline
cells ( cells are more rounded and have eccentrically placed nucleus)
• Extensive accumulation of mucoid material around the individual myoepithelial cell gives myxoid
appearance. Vacuolar degeneration of these myoepithelial cells results in cartilaginous in
appearance.
• Stroma may show foci of hyalinization, bone and even fat cells.
• Highly cellular tumor with absence of pleomorphic pattern is called cellular adenoma.
• Accumulation of mucoid material between the tumor cells leads to myxomatus background,
vacuolar degeneration of cells in these areas produce a chondroid appearance.

MYOEPITHELIOMA / MYOEPITHELIAL ENDOTHELIOMA:

ETIOPATHOGENESIS:

CLINICAL FEATURES

• Uncommon salivary gland tumor.

Age:
• Adults

Sex
• Equal gender predilection.

Location- most common

• Major glands – pleomorphic adenoma
• Minor salivary glands – palate.

Clinical presentation:
• Similar to pleomorphic adenoma

HISTOPATHOLOGY:

• Composed exclusively of neoplastic myoepithelial cells which are predominantly plasmacytoid or

spindle shape.
• May show epithloid or clear cells.
 • Chondroid and myxoid areas are absent

BASAL CELL ADENOMA:

ETIOPATHOGENESIS:
• Intercalated or reserve cells is the histogenic source.

CLINICAL FEATURES
• Show uniform population of basaloid epitheloid cells arranged in solid, trabecular, tubular or
membranous pattern.

Age:
• Peak sixth decade of life

Sex:
• Female predominance.

Location:
• Predominantly in major salivary glands – parotid gland.
• Second most common site – minorsalivary glands – lip and buccal mucosa.
Clinical presentation:
• Painless slow growth, firm, may be cyatic and compressible.

HISTOPATHOLOGY:

Macroscopic features:
• Single well defined nodule
• Membranous type – multifocal
• Tumor in major salivary glands – well defined capsulated
• In minor glands - less well defined.
• Cut surface – gray to brown, may have cystic areas.

Microscopic features:
• Two morphologic forms of basal cells are present
• Small cell with scanty cytoplasm and round basophilic nucleus.
• Large cell with eosinophillic cytoplasm and an ovoid pale staining nucleus.
• Depending on the morphologic appearance it is of four types
o Solid
o Tubular
o Trabecular
o Membranous
Solid :
 Most common type
 Basaloid cells , form islands ( occasionally show keratin pearls) and cords that have broad,
rounded, lobular pattern.
 Peripheral cells of the islands are palisaded and cuboidal to columnar in shape., hyper chromatin
 Central cells have palar staining nuclei.
 These are sharply demarcated from the connective tissue stroma by basement membrane
Tubular pattern:
 
Multiple small, round duct like cells structures lined by two distinct distinct layer of cells, inner
cublidal ductal cells surrounded by an outer layer of basoloid cells.
 Least common
Membranous type:
 Characterized by the presents of abundant, thick, eosonophillic hyaline layer that surrounds and
separates the epithelial islands. ( hyaline material is the reduplicated basement membrane).
 Multiple large lobular Epithelial islands are arranged in jigsaw puzzle pattern.
Menbranous basal cell adenoma / dermal analogue tumors - appear to be hereditary, offen associated with
skin appendage tumors lke dermal cylindromas and trichoepitheliomasa.

ONCOCYTOMA / ONCOCYTIC ADENOMA / ACIDOPHILIC ADENOMA / OXYPHILIC

ADENOMA:

• Rare benign tumor composed of oncocytes with granular eosinophillic cytoplasm and large no of
atypical mitochondria.

CLINICAL FEATURES
Age:
• Peak bet 51 – 80 YRS

Sex:
• Slight female predominance.

Location:
• Major salivary glands ( most common) -Parotid gland
• Minor salivary glands ( rare) - lip and buccal mucosa.
Clinical presentation:
• Discrete encapsulated mass
• Pain is generally absent

HISTOPATHOLOGY:
• Characterized by large polyhedral cells with abundant granular eosiniphillic cytoplasm and
distinct cell membrane arranged in narrow rows or cords.
• Oncocytes arranged in sheets or nests and cords form alveolar or organoid pattern.
• Cellular atypia, nuclear hyperchromatism and plemorphis are seen.
• Lymphoid cells are frequently present but not the integral part of the lesion.
• Oncocytic cystic adenoma – chiefly composed of numerous duct like structures lined with
oncocytes
• Clear cell oncocytoma – show marked clear cell changes.
• Granularity in oncocytoma is due to abundant mitochondria can be stained by PTAH
• Presents of glycogen give rise to PAS positive stain.

CANALICULAR ADENOMA:
Uncommon neoplasm composed of columnar epithelial cells arranged in a single or double layer forming
branching cords in a loose stroma.

CLINICAL FEATURES
Age:
• 34 – 65yrs
Sex:
• Female predominance.

Location:
• Most common in intraoral accessory salivary glands – upper lip ( majority) followed by buccal
mucosa.

Clinical presentation:
• Slowly growing, well circumscribed , firm nodule, not fixed to the tissue moves through the tissue
for some distance.
• Overlying mucosa may be of normal colour or slightly bluish in colour.

HISTOPATHOLOGY:
• Surrounded by thin fibrous capsule.
• Composed of long columns or cords of cuboidal or columnar cells in a single layer
• The single layer of cells are parallel, forming long canals .
• Party wall may be formed by the double wall of cells.
• Cystic spaces are filled with eosinophillic coagulum
• Stroma is loose and fibrillar with delicate vascularity.

SEBACEOUS ADENOMA:

CLINICAL FEATURES
Age:
• Mean -58YRS

Sex:
• Male predominance.

Location:
• Both major and minor salivary glands.

Clinical presentation:

HISTOPATHOLOGY:
• Sebaceous cell nests show minimal atypia and pleomorphism and has no tendency to invade local
structures.
• Many tumor are microcystic and may be composed of ectactic salivary duct with focal sebaceous
differentiation.
• Tumor may exhibit - oncocytic metaplasia and histiocytes and /or forign body giant cells

DUCTAL PAPILLOMA:
It includes three rare group of benign papillary salivary gland tumors they are
• Inverted ductal papilloma
• Intra ductal papilloma
• Sialadenoma papilliferum

Inverted ductal papilloma:

Very rare tumor.

CLINICAL FEATURES
Age:
• Adults

Sex:
• No gender prediliction

Location:
• Only in minor salivary gland tumors. – lower lip followed by buccal vestibular mucosa.

Clinical presentation:
• Presents as submucosal nodule which may have a pit or indentation in the overlying mucosa.

HISTOPATHOLOGY:
• Basaloid and squamous cells arranged in thick, bulbous papillary proliferation that projects in to
ductal lumen.
• Lumen of the tumor is narrow and may communicates to the exterior of the mucosal surface
through the constricted opening.

Intra ductal papilloma:

• Ill defined lesion, arise from excretory ducts at a deeper level than inverted ductal papilloma.

CLINICAL FEATURES
Age:
• Adults, mean – 54 yrs

Sex:
• No gender predilection

Location:
• Minor salivary glands – lower lip followed by upper lip, palate and buccal mucosa

Clinical presentation:
• Submucasal swelling.

HISTOPATHOLOGY:
• Show unicystic dialated structure.
• Cyst wall lined by a single or double row of cuboidal columnar cells which extend in to the cyst
lumen as papillary projections having fibro vascular stroma.

SIALADENOMA PAPILLIFERUM:

CLINICAL FEATURES:
Age:
• Adults – 56 yrs

Sex:
Male predilection

Location:
• Most commonly involve minor salivary glands.

Clinical presentation:
• Characteristically presents as exophytic , papillary surface lesion.
HISTOPATHOLOGY:
• Exhibits both exophytic and endophytic proliferation of ductal epithelium.
• Papillary projections of the surface epithelium is supported by the fibrovascular core having
inflammatory cell infiltrate of lymphocytes , plasma cells and neutrophills.
• , covered by parakeratotic stratified squamous epithelium.
• Ductal lumen are lined by tall columnar cells resting on the cuboidal basal layer of cells.

CYSTADENOMA:
• Characterized by formation of multiple cystic structures

CLINICAL FEATURES

Age:
• Older age group – 8th decade

Sex
• Female prediliction

Location:
• Both major and minor salivary glands.

Clinical presentation:
• Painless slightly compressible swelling

HISTOPATHOLOGY:
• Lining of the cystic structure varies from flattened to tall columnar cells and cuboidal, mucous
and oncocytic cells
• Limited papillary growth with central connective tissue
• Dense scattered fibrous connective tissue stroma are present with scattered inflammatory cells.

MALIGNANT TUMORS OF THE SALIVARY GLANDS

ACINIC CELL CARCINOMA / ACINAR CELL OR SEROUS CELL ADENOMA

ADENOCARCINOMA:
Third most common malignant salivary gland tumor after mucoepidermoid carcinoma and
adenocarcinoma.

ETIOPATHOGENESIS:
Here the malignant cells show acinar differentiation.
Def:
Acinic cell carcinoma is defined by cytologic differentiation towards serous acinar cells, whose
characteristic feature is cytoplasmic PAS – positive zymogen – type sceretory granules.

CLINICAL FEATURES
Age
 • Middle age group. mean – 44yrs

Sex
• Female predominance – 3;2 ratio.

Location:
• more than 80% occur in the parotid gland.
• Common intraoral sites – lip and buccal mucosa.

Clinical presentation:
• Slow growing , mobile or fixed mass of various duration
• Rare features – facial muscle weakness, bilateral synchronous tumors.

HISTOPATHOLOGY
• Well differentiated cells bear remarkable resemblance to normal acinar cell
• Less differentiated cell resemble embryonic ducts and immature acinar cells.
• Show four growth patterns:
Solid – numerous well differentiated acinar cells arranged in a pattern that resemble
normal parotid gland tissue.
Papillar cystic – large cystic areas that are lined by epithelium having papillary
projections in to cystic spaceses.
Follicular – appear similar to that of thyroid tissue.
Microcystic – show multiple small cystic spaces having some mucinous or eosinophillic
material.

• Characteristically cells resemble acinar cells with abundant granular basophilic cytoplasm and
round darkly stained eccentric nucleus.
• Presents of intercalated duct like cells, which are smaller and vacuolated cells are unique to the
acinic cell carcinomas
• Delicately fibrovascular collagenous tissue.
• Parotid acinic cell carcinoma show lymphoid elements.

MUCOEPIDERMOID CARCINOMA:
Most common malignant salivary gland tumor in both major and minor salivary glands. ( 29 – 34%)
Tumor consists of both mucous secreting cells and epidermoid type cellsin varying proportions.

CLINICAL FEATURES
Ionizing radiation increase the risk of developing mucoepidermoid carcinoma.

Age:
• 3rd or 5th decade of life.
• Most common salivary gland tumor of children.

Sex:
• Slight female prediliction

Location:
• Major salivary glands - parotid is the most common site
• Minor salivary glands – palate is the most common site.

Clinical presentation:
 • Low – grade malignancy appear as slowly enlarging painless mass .
• High –grade malignancy grows rapidly and does produce pain as an early symptom, facial nerve
paralysis in parotid gland tumors.
• Rare features - trismus, drainage from the ear, dysphagia, nubness of the adjacent areas and
ulceration ( particularly in minor salivary glands)
• Intraosseous tumors also may develop.
• Distant metastasis to lung, bone, brain and subcutaneous tissue are also common.

HISTOPATHOLOGY
• It characteristically contain
• Mucous sercreting cells
• Epidermoid cells( squamous cells)
• Intermediate cells.
• Mucous cells are of various shape and have abundant, pale, foamy cytoplasm that stain positive
for mucin stain.
• Epidermoid cells have squamoid feature demonstrate polygonal shape, intercellular bridges and
rarely keratinization
• Intermediate cells are larger than basal cells and smaller than the squamous cells
• Progenitors of epidermoid and mucous cells.
• Occasionally show clear cells ar seen which are mucin and glycogen free.
• Lymyphoid infiltrate can be seen in few cases.

Denpending up on
Amount of cyst formation
Degree of cytologic atypia
Relative no of mucous, epidermoid and intermediate cells
It is devided in to three grades.
Low-grade
Intermediated-grade
High -grade
Low grade:
• Show well formed glandular structure and prominent mucin filled cystic spaceses, minimal
cellular atypia and a high proportion of mucous cells
Intermediate grade:
• Show solid areas of epidermoid cells or squamous cells with intermediate basaloid cells. Cyst
formation is less prominent than in low grade mucoepidermoid carcinoma
• Intermediate cells are prominent.
High-grade:
• Show solid nests and cords of intermediate basaloid cells and epidermoid cells.
• Prominent nuclear pleomorphism and mitotic activity is noted
• Cystic component is less than 20%
• Glandular component predominates rarely
• Necrosis and perineural invasion is present
Grading parameters and point values

Histologic variants
Sclerosing mucoepidermoid carcinoma
Intraosseous mucoepidermoid carcinoma

Parameter Point values

Intra cystic components < 20% +2
Neural invasion +2
Necrosis present +3
Four or more mitoses per 10 HPF +3
Anaplsia present +4

GRADE TOTAL POINT SCORE

LOW 0-4
INTERMEDIATE 5-6
HIGH 7-14

Sclerosing mucoepidermoid carcinoma:

• Pathogenesis _ due to tumor infarction and extravasation of mucin resulting in reactive fibrosis
• Rare variant
• Characterized by an intense central sclerosis that occupies the entirety of the tumor and frequently
show inflammatory infiltrate of plasma cells , eosinophils and or lymphocytes in the peripheral
region.

Intraosseous mucoepidermoid carcinoma/ Central mucoepidermoid carcinoma:

• Central mucoepidermoid carcinoma - Originate with in the jaw
• Pathogenesis – malignant transformation of the epithelial lining of the odontogenic cysts.
• Age – middle age adults
• Site- common in mandible – molar ramus area.
• R/F- Radioluscent
• H/F: Low grade malignancy

WARTHINS TUMOR/ PAPILLARY CYSTADENOMA LYMPHOMATOSUM/ ADENOLYMPHOMA:

Second most common tumor.

ETIOPATHOGENESIS:
Tumor arises in the salivary gland tissue entrapped with in paraparotid or intrparotid lymphnode during
embryogenesis. / lymphoid component is the exaggerated secretory immune response.
Strongly associated with smoking.
EBV may be associated with the disease.

CLINICAL FEATURES:

Age:
• 6 and 7th decade of life.

Sex:
• Male predominance.

Location:
• Almost exclusive in parotid gland. – tail region – at the angle of the mandible.

Clinical presentation:
• Slow growing nodular masss.
• Painless, firm in palpation.

HISTOPATHILOGIC FEATURES:
• Macroscopic examination:
• Soft parotid mass, well encapsulated , contain variable no of cysts that contain clear fluid.
Chocolate coloured fluid can be seen.
Microscopic features:
• Show two histologic components epithelial and lymphoid.it shows papillary projections in to the
cystic space and lymphoid matrix showing germinal centers.
• Cyst lined by bilayered papillary proliferation of oncocytes
• Inner layer is tall columnar with finely granular and eosinophilic cytoplasm due to presence of
mitochondria and centrally placed pallisaded, slightly hyperchromatic nuclei.
• Outer layer of cells are triangular and occasionally fusiform basaloid cells.

ADENOID CYSTIC CARCINOMA/ CYLINDROMA / ADENOCYSTIC CARCINOMA / ADENOID

CYSTIC BASAL CELL CARCINOMA /PSEUDOADENOMATUS BASAL CELL CARCINOMA
/BASALOID MIXED TUMOR:
Characterized by proliferation of ductal ( luminal) and myoepithelial cells in cribriform,tubular, solid and
cystic pattern.
Fifth most common malignant epithelial tumor of the salivary glands..

CLINICALFEATURES

Age:
• 5TH AND 6TH decade of life.

Sex:
• Female predominance

Location:
• Major glands- parotid,sub maxillary glands
• Acessary glands – palate,tongue.

Clinical presentation
• Local pain,facial nerve paralysis in the case of parotid.
• Fixation to the deeper structures and local invasion.
• Intra oral lesions may exhibit ulcerations.
• Show marked tendency to spread through perineural space.
• Tumor in palate or maxillary sinus may radiographic evidence of bone distruction.

HISTOPATHOLOGY:
Myoepithelial and ductal cells show varying arrangement.
Characteristically show perineural invasion
Morphologically show 3 growth patterns:
Cribriform pattern
Tubular pattern
Solid pattern
Cribriform pattern:
• Basalpid epithelial nests form multiple cyst like patterns resembling a swiss cheese or honey comb
pattern.
• Classic and best recognized pattern
 • Lumen contain PAS positive mucopolysaccharide secretion.
Tubular pattern:
• Structures are lined by stratified cuboidal epithelium.
Solid pattern:
• Show little tendency of cyst formation
• Least common type
• High grade lesion

Variants:
Dedifferentiated adenoid cystic carcinoma:
• Rare variant
Histologically characterizedby two components

Conventional low-grade adenoid cystic carcinoma

High- grade dedifferentiated carcinoma
Histologically low-grade adenoid cystic carcinoma merges gradually in to an extensive dedifferentiated
component.
IHC:
Over expression of p53, cyclin D1,Ki 67

POLYMORPHOUS LOW GRADE ADENOCARCINOMA / LOBULAR CARCINOMA/ TERMINAL

DUCT CARCINOMA:
Characterized by bland ,uniform nuclear feature, diverse but characteristic architecture;infiltrative growth
and perineural infiltration.
Previously termed terminal duct carcinoma,lobular carcinoma,papillary carcinoma and trabecular
carcinoma.

CLINICALFEATURES

Age:
• 50 – 79 years

Sex
• Female predominance (2;1)

Location
• Most common in minor salivary gland tumors – 60% - hard and soft palate, 16% buccal mucosa,
12% upper lip.

Clinical presentation:
• Firm, non-tender swelling.
• Occasionally – discomfort, bleeding, telangiectasia or ulceration over the mucosa can be seen.

HISTOPATHOLOGY:
• Characterized by infiltrative growth with diverse morphology and uniform cytologic features.
• Polymorphic nature of the lesion refers to variety of growth patterns like – solid, ductal, cystic and
tubular.
• Or cribriform pattern resembling adenoid cystic carcinoma.
• Composed of cuboidal to columnar isomorphic cells that have uniform ovoid to spindle – shaped
nuclei,with scant to moderate amounts of eosinophilic cytoplasm.stroma – fibrovascular or mucoid
to hyaline
 • Show perineural invasion.

EPITHELIAL – MYOEPITHELIAL CARCINOMA / ADENOMYOEPITHELIOMA / CLEAR CELL

ADENOMA / TUBULARSOLID ADENOMA / GLYCOGEN RICH ADENOMA/ GLYCOGEN RICH
ADENOCARCINOMA:
Uncommon,biphasiclow-grade epithelial neoplasm composed of variablepraportion of ductaland
large,clear-staining,differentiated myoepithelial cells

CLINICALFEATURES

Age
• Mean – 60yrs

Sex
• Female predominance

Location
• Most common in parotid gland.

Clinical presentation:
• Slow growing localized swelling.
• Occasionally patient experience facial weakness or pain

HISTOPATHOLOGY:
• Histopathology varies from Solid lobules separated by bands of hyalinized fibrous tissue to
irregular,papillary cystic arrangements with tumor cells which partially or completely fill the
cystic spaces
• Islands of tumor cells composed of small ducts lined by cuboidal epithelium that is surrounded by
clear cells which interfere with a thickened , hyaline like basement membrane.

BASAL CELL ADENOCARCINOMA/BASALOID SALIVARY CARCINOMA/ CARCINOMA

EXMONOMORPHIC ADENOMA/ MALIGNANT BASAL CELL TUMOR / BASAL CELL
CARCINOMA :

Un common low grade malignant neoplasm that is cytologically similar to basal cell adenoma but is
infiltrative and has a small potential for metastasis.

CLINICALFEATURES
Age:
• Mean age 60yrs

Sex
• No gender prediliction

Location
Most common in major salivary gland tumors
- parotid gland (90%)
- rare – buccal mucosa, palate and respiratory tract.

Clinical presentation
• Swelling of the affected site.
 • Rarely sudden increasein size.

HISTOPATHOLOGY:
Histologically show four subtypes.
Solid
Ductal
Trabecular and
Membranous

• Solid neoplasticaggregatesshow peripheral cell palisading arrangement

• Neoplasticclustersshow small darkcells and largepale cells
• Predominant small dark cells arepresent peripherally to large paler cellsoccasionally perineural
and perivascular invasion is seen

SEBACEOUS CARCINOMA:

CLINICALFEATURES
Characterized by malignant sebaceous cells arranged in sheete and/or nests

Age
• Bimodaldistribution- 3rd decade, 7-8th decade.

Sex
• Equal gender predilection.

Location
• Most common- parotid gland.

Clinical presentation
• Paiful mass with varying degree of facdialnerve paralysis
• Occasionally fixed to the underlying skin

HISTOPATHOLOGY:
• Well or partially encapsulated with pushing or infiltrating masses.
• Cellular pleomorphism and cellular atypia are uniformly present.
• Multiple large foci or sheets of tumor cells have hyperchromatic nuclei surrounded by abundant
clear to eosinophilic cytoplasm

PAPILLARY CYSTADENOCARCINOMA/ CYSTADENOCARCINOMA/ MUCUS-

PRODUCINGADENOPAPILLARY ( NONEPIDERMOID) CARCINOMA/LOW GRADE PAPILLARY
ADENOCARCINOMA OFPALATE,PAPILLARY ADENOCARCINMA:

Rare malignant tumor characterized by prominent cystic and frequently ,papillary growth.
CLINICALFEATURES
Age:
• Average 59 years

Sex
• Equal gender predilection

Location
• Major salivary glands- primarily parotid gland

Clinical presentation
• Slow growing asymptomatic mass.

HISTOPATHOLOGY:
• predominately show cystic growth pattern.
• Lumen often filled with mucus and hemorrhage
• Rarely focal dystrophic calsifications are present
• Lining cells of the tumor are cuboidal to columnar
• Tumor cells may contain basaloid, oncocytic, clear and mucus cells to form adenomatous or
nodular ,solid areas
• Tumor may infiltrate either as cyst like structure or as solid islands
• Majority of them are low grade lesions.

MUCINOUS ADENOCARCINOMA:

CLINICALFEATURES
Rare malignant neoplasm charatarized by large amountof extracellular epithelial mucin that contain
cords,nests,and solitary epithelial cells
Age

Sex

Location:
• Major salivary glands primarily –subandibular gland.

Clinical presentation
• May be associated with pain and tenderness.
• Presents as soft, spongy masses

HISTOPATHOLOGY:
• Grossly specimens aremucoid with slimy texture and may ooze mucoid material.

• Characteristically in low power view show islands and cordsof tumorcells appearto befloating
with in the poolsof palestaining mucinpools of mucin may be devided in to irregular lobules by
fibrous connective septa.
• Tumor cells are moderately large,cuboidal and polygonal with eosinophilic to amphophillic
cytoplasm
• The tumor islands aresurrounded by pale-staining mucoid substance.
• Mucoid substance stain with mucicarmine, periodic-acid –schiff and alcian blue at PH 2

.
ONCOCYTIC CARCINOMA/ ONCOCYTIC ADENOCARCINOMA:
Rare high grade tumor

CLINICALFEATURES

Age
• Average age 63 years.

Sex

Location
• Major glands- parotid, submandibular glands
• Minor glands-palate.nasalcavity,ethmoidalandmaxillary sinuses.

Clinical presentation:
• Skin overlying the gland occasionally discoloured or wrinkled

HISTOPATHOLOGY:
• Show significant component of oncocytes
• Characterized by oncocytes with marked cellular atypia, frequent mitosis, distruction of the
adjacent structures, perineural invasion and distant or regional lymph node metastasis.

SALIVARY DUCT CARCINOMA/ SALIVARY DUCT ADENOCARCINOMA:

CLINICALFEATURES
Rare high grade tumor

Age
• Seventh and eight decade of life.

Sex
• Male predominance.

Location
• Most common is parotid gland.

Clinical presentation
• Parotid swelling is the common feature.
• Facial nerve disfunction or paralysis occur in fewcases
• High grade variant is most aggressive type, typified by localinvasion,lymphatic and
hematogenous spread with poor prognosis.

HISTOPATHOLOGY:
• Tumor cells may have small lumina or cribriform arrangement or frequently have solid, irregular
shaped cell aggregates.
• Neoplastic epithelial cells are cuboidal and polygonal with a moderate amount of eosinophilic
cytoplasn and are accompanied by dense fibrous connective tissue stroma that may be hyalinized
in some areas.invasion of nerves,blood vessels and salivary glands and extrasalivary gland tissue
occurs
ADENOCARCINOMA:
• Rare but aggressive tumor.

CLINICALFEATURES

Age:
• Average age – 40 years

Sex
• Equal sex prediliction

Location:
• Major salivary gands – parotid
• Minor salivary glands –palate, lip, tongue

Clinical presentation
• Enlarging mass
• App 25% of patients complaints of pain or facial paralysis.

HISTOPATHOLOGY:
• Solid tumor with out cystic spaces
• Commonly show formation of glandular structures
Based on degree of cellular differentiation it is graded in to
Grade I
Grade II
Grade III
Grade I have well formed ductal structures
Grade III have more solid growth pattern.and few glandular structures.

MALIGNANT MYOEPITHELIOMA/ MYOEPITHELIAL CARCINOMA:

Defined as malignant epithelial neoplasm whose tumor cells demonstrate cytologic differentiation towards
the myoepithelial cells and lack ductal or acinar differentiation.

CLINICALFEATURES

Age
• Mean age 55 yrs

Sex

Location
• Most common parotid gland

Clinical presentation
• Painless mass
• Clinically Presents as intermediate to high –grade tumor and does not correlate with histological
grades.

HISTOPATHOLOGY:
 • Individual cells are resemble tumor cells in myoepithelioma amd myoepithelial cells of mixed
tumor.
• Tumor cells are spindle shaped or plasmacytoid.
• Tumor is quite cellular resembling sarcoma than carcinoma
• Show infiltrative , destructive growth, increased mitotic activity and cellular pleomorphism.
• IHC – S100, smooth muscle actin, occasionally glial fibrillary acidic protein.

CARCINOMA IN PLEOMORPHIC ADENOMA / MALIGNANT MIXED TUMOR

It includes three distinct clinicopathologic entities.
Carcinoma ex plemorphic adenoma
Carcinosarcoma and
Metastasizing mixed tumor (rare)

CARCINOMA EX PLEOMORPHIC ADENOMA/ CARCINOMA EX MIXED TUMOR/ MALIGNANT

MIXED TUMOR:
Most common of the three.
6th most common malignant salivary gland tumor after mucoepidermoid carcinoma, adenocarcinoma, acinic
cell carcinoma, polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma
Characterized by malignant transformation of the epithelial component of a previously benign plemorphic
adenoma.

CLINICAL FEATURES:
Age:
• 6th to 8th decade of life
Sex:
• Slight female predominance

Location
• Major salivary glands – parotid followed by submandibular gland
• Minor salivary glands - palate

Clinical presentation:
• Painless mass / rapid enlargement of long – standing nodule
• May be associate with facial paralysis.

HISTOPATHOLOGY:
• Malignant appearing cells occur afjacent to a typically appearing pleomorphic adenoma.
• Malignant portion may transform in to any epithelial malignancy ( like undifferentiated carcinoma
or adenocarcinoma) except acinic cell

CARCINOSARCOMA/ TRUE MALIGNANT MIXED TUMOR

Rare malignant salivary gland neoplasm that contain both carcinoma and sarcoma components.
Mmetastatic component has both stromal and epithelial component.

Origin
• Denovo
• In association with benign mixed tumor

CLINICAL FEATURES
Age:
• Average 60 years
Sex:
• Equal gender predilection

Localtion
• Major salivary glands

Clinical presentation:
• Swelling, pain, nerve palsy and ulceration.
•
HISTOPATHOLOGY:
• Tumor shows both sarcomatus and carcinomatus component.
• Sarcoma – chondrosarcoma is most common
• Carcinoma – undifferentiated or high grade ductal carcinoma.

METASTASIZING MIXED TUMOR:

• Benign acting plemorphic adenoma that develop metastatic deposits
• Primary neoplasm is single , well- defined mass
• Recurrent lesion may be multiple and show a long interval between the primary tumor and the
metastatic tumor.
• Histological features are with in the spectrum of features typifying pleomorphic adenoma.