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lymphoid component is often less pronounced in these extraparotid sites, the pathologist should exercise caution to avoid overdiagnosis of a lesion better classified as a papillary cystadenoma or salivary duct cyst with oncocytic ductal metaplasia
Differential Diagnosis. The differential diagnosis consists of BCA, polymorphous low-grade adenocarcinoma (PLGA), adenoid cystic carcinoma (AdCC), and, rarely, pleomorphic adenoma (PA). Parallel rows of tumor cells are not usually a feature of BCA and should allow appropriate classification. If necessary, immunohistochemistry should be helpful because BCA, unlike canalicular adenoma, frequently has myoepithelial cells that stain with appropriate markers. Also rarely both BCA and canalicular adenoma may occur in the same patient.256 PLGA and AdCC also do not have large areas with parallel rows of tumor. In addition, they, unlike canalicular adenoma, infiltrate adjacent tissues in a destructive fashion and are frequently associated with perineural invasion and may have myoepithelial cells that can be demonstrated immunohistochemically. PA, unlike canalicular adenoma, will frequently have cartilaginous foci and a myoepithelial cell–populated myxoid stroma. In addition, the border between the epithelial elements and myxoid matrix within PA is blurred by myoepithelial cells. This is different from the sharp border between the tubules and canaliculi and matrix of canalicular adenoma.
Tumors of the salivary glands are:
-Most heterogeneous group of tumors.
-Greatest diversity of morphologic features.
The majority of these neoplasms are benign 80% and only 20%
The various types of salivary gland tumors are best
distinguished by their histologic patterns.
A broad morphologic spectrum exists between different tumor
types and sometimes even within an individual tumor mass.
Certain neoplastic processes have obvious histologic,
functional, immunohistochemical, and/or ultrastructural
markers that allow pathologists to assemble nonologic
groupings that function somehow like a taxonomic system.
The inherent complexity, together with the relative
infrequency of salivary gland tumors, contributes to a
situation in which diagnostic dilemmas are almost
inevitable and unfortunately occur all too frequently.
2%-6.5% of all head and neck neoplasms.
Global annual incidence varies from 0.4-13.5 cases per 100000
Most salivary gland tumors originate in the parotid glands
(64%-80%), malignancy (15%- 32%).
7-11% occur in the submandibular glands, malignancy (37%-
less than 1% in the sublingual glands, malignancy (70%-90%)
9%-23% in the minor glands.
Benign tumors account for 63% to 78% of all salivary gland
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.
Most common minor salivary gland tumor site: Palate, (42%-
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.
Rule of 80’s:
-80% of parotid tumors are benign
-80% of parotid tumors are Pleomorphic adenomas
-80% of salivary gland Pleomorphic adenomas occur in the
-80% of parotid Pleomorphic adenomas occur in the superficial
-80% of untreated Pleomorphic adenomas remain benign
Viruses- EBV, CMV, Polyoma virus,
Increased occupational risks- asbestos, nickel compounds or
Employment in the woodworking, rubber industries and beauty
Lifestyle- Warthin’s tumors showed a strong association with
Cell of origin for a neoplasm rather than the
developmental process underlying the tumor
The formation or development of tissue from the
undifferentiated cells of the germ layers of the
Basal cells of both excretory and intercalated duct
responsible for differentiation of functional units.
Basal cells of excretory duct responsible for development of all
remaining salivary gland units.
The outer (basal) layer of cells give rise to the inner (luminal)
Eversole in 1971, refined by Batsakis and colleagues.
2 Cells- excretory duct reserve cells
intercalated duct reserve cells.
- were presented as the hypothetical cells of origin for salivary gland
From Excretory duct - Mucoepidermoid carcinoma,
Primary SCC and
Salivary duct carcinoma
From Intercalated duct- Pleomorphic and monomorphic adenoma
Polymorphous low grade adenocarcinoma,
Basal cell adenocarcinoma (BCA),
Adenoid cystic carcinoma (AdCC) and
Acinic cell carcinoma (ACC).
Adenocarcinoma, not otherwise specified (NOS) (AdC NOS) - arise
from either of these reserve cells.
carcinoma ex pleomorphic adenoma - uncertain histogenesis.
Myoepithelial cells were responsible in part for the wide histologic
variation of these neoplasms.
Acinar secretory cell play a minimal role in the parencymal renewal
and thus, was incapable of a significant role in tumor induction.
Differentiated cells at all levels of the gland, including acinar
and basal cells, are capable of cell division and metaplastic
The process of differentiation inherent in the neoplasms and the
resulting histopathology characteristic for that particular tumor.
The evaluation and development of form, as the development
of the shape of a particular organ or part of a body or
developments undergone by individuals who attain the type to
which the majority of the individuals of the species
and ductal cells)
Patterns of tumor differentiation reflect the bilayered cells
composed of luminal or acinar cells and outer basal and/or
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
3) The third process produces tumor cells resembling normal
myoepithelial and/or basal cells.
Myoepithelial cells :
Physiologically and functionally modified epithelial cells
located between the luminal cells and basement membrane.
Stellate shaped with cytoplasmic processes embracing the
acini, or spindle shaped surrounding the intercalated ducts.
Possess a dual epithelial and smooth muscle phenotype.
Produce an extracellular matrix.
Exert an anti-invasive effect in a neoplasm promoting epithelial
differentiation, secreting proteinase inhibitor and suppressing
P-63, high molecular weight cytokeratin (CK-14) are positive
for myoepithelial cells.
Other myoid markers are calponin, actin, myosin, S-100 and
Glial Fibro Acidic Protein (GFAP).
CD117/c-kit is negative in the normal salivary gland cells,
however, is interestingly positive in the luminal (glandular)
cells of various types of salivary gland tumors.
Readily highlighted by immunostaining for cytokeratin,
carcinoembryonic antigen (CEA), and epithelial membrane
Abluminal cells :
Basal cells that differs ultastructurally from myoepithelial cells
in the absence of myofilaments.
Maintain the capacity of multidirectional differentiation and
play an important role in regeneration and metaplastic changes.
Immune reactive for p-63 and high molecular weight
1) Chromosomes 3p21, 8q12 and 12q13-15 rearrangements and
the PLAG-1 and HMGI-C genes in pleomorphic adenomas
2) Translocations of chromosomes 11q21 and 19p13 in both
Warthin tumour and mucoepidermoid carcinoma.
3) Structural and molecular alterations at 6q, 8q, 12q in adenoid
cystic and carcinoma ex-pleomorphic adenoma.
4) Elevated HER-2 gene expression and gene amplification in
mucoepidermoid, salivary duct and adenocarcinomas
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,
Salivary gland tumor origin: EPITHELIAL
Shows cytogenic abnormalities in chomosomes- 12q13-15.
Putative pleomorphic adenoma gene(PLAG1) has been
mapped to chromosomes 8q12.
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.
Clinical presentation: painless, slow growing, firm
mass, initially small in size and begins to increase in
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.
Slowly growing tumor of
The parotid gland.
Tumor of the
Firm mass of the hard
palate lateral to the
Tumor of the
Benign mixed tumor demonstrating a
firm, whitish tan, well-encapsulated
The cut surface of the tumor is tan-
colored and interspersed with
brown areas. Glossy quality of the
HALLMARK: Morphologic Diversity.
Charecterized by- Variable, Diverse, Structural & histologic
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 .
Foote and Frazell (1954) categorized PA into:
a) Primarilly myxoid (36%)
b) Myxoid and cellular component in equal proportions
c) Predominantly cellular (22%)
d) Extremely cellular (12%)
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
Vacuolar degeneration of myoepithelial cells can produce a
the stroma exhibits areas of an eosinophilic hyalinized change,
fat or osteoid also is seen.
Mixed tumor with prominent
and surrounding ducts and
Ductal structures (left) with
background (right) .
(right) with adjacent
ductal epithelium and
Cellular mixed tumor :
Because of its extreme cellularity, this
tumor may be mistaken for a
Pleomorphic adenoma showing
bone forming by osseous
metaplasia in stroma.
Many of the ducts and myoepithelial cells are
surrounded by a hyalinized. Eosinophilic background
Pleomorphic adenoma showing a
focus of mucous metaplasia.
Focal squamous differentiation
with keratinization is seen amidst
complex glandular structures.
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.
Submandibular tumors - Total removal of the gland with the
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.
Term used by Sheldon in 1943.
Uncommon- <1% of all salivary gland tumors.
it represents “one-sided” varient at the opposite end of the
spectrum from Pleomorphic adenoma
Defined as a tumor composed entirely or predominantly of
Similar to Pleomorphic Adenoma
Seen among adults
equal frequency in males and females.
Site: parotid most common, palate most common intraorally.
typically present as slowly enlarging, asymptomatic masses.
Masses usually 1 to 5 cm in diameter.
Composed exclusively or almost exclusively of neoplastic
Microscopically, the neoplastic cells are arranged in sheets,
irregular collections, nests, interconnecting trabeculae, or
ribbons, giving solid, myxoid, reticular, microcystic, and
cribriform growth patterns.
The component cells may be spindle shaped, plasmacytoid ,
clear, polygonal, epithelioid, basaloid, or oncocytic
A, The typical plasmacytoid pattern contains eccentric nuclei and abundant
B, The spindle cell pattern is made up of a uniform population of interlacing
bundles of spindle cells with moderate amounts of light eosinophilic cytoplasm.
C, The reticular type is composed of numerous interconnecting ribbons
of myoepithelial cells.
D, The clear cell variant is composed of a somewhat uniform sheet of
cells with a moderate amount of clear cytoplasm
Benign tumor composed of large epithelial cells known as
oncocytes- with granular eosinophilic cytoplasm and a large
number of atypical mitochondria.
It is a rare neoplasm, representing approximately 1% of all
Except salivary gland oncocytes are also seen thyroid,
Age: predominantly a tumor of older adults, 50-80 years.
Sex: slight female predilection
Site: primarily in the major salivary glands, parotid gland- 85% to
Oncocytomas- minor salivary glands are exceedingly rare.
C/P- The tumor appears as a firm, slowly growing, painless mass
that rarely exceeds 4 cm in diameter.
Parotid oncocytomas usually are found in the superficial lobe and are
clinically indistinguishable from other benign tumors.
bilateral tumors can occur.
Gross appearance of oxyphilic adenoma.
The tumor is well circumscribed, solid, and light brown.
well-circumscribed tumor that is composed of sheets of large
polyhedral cells (oncocytes), with abundant granular,
Arranged in sheets, nests or cords which form an alveolar or
cells have centrally located nuclei that can vary from small and
hyperchromatic to large and vesicular.
little stroma is present, usually in the form of thin fibrovascular
Granularity of the cells is created by an overabundance of
These granules also can be identified on light microscopic
examination with a phoshotungstic acid -hematoxylin (PTAH)
The cells also contain glycogen- periodic acid-Schiff (PAS)
variable numbers of cells with a clear cytoplasm. – clear cell
Oncocytoma is composed of a sheet of oncocytic cells with uniform,
predominantly centrally located nuclei and abundant eosinophilic
Clear cell oncocytoma composed predominantly of sheets of clear cells,
usually with focal areas containing typical oncocytic cells .
Mucoepidermoid carcinoma (MEC)
pleomorphic adenoma (PA)
prominent oncocytic metaplasia may also be seen in
-basal cell adenoma (BCA)
-acinic cell carcinoma (ACC)
The prognosis after removal is good with a low rate of
Oncocytomas of the sinonasal glands can be locally aggressive
and have been considered to be low-grade malignancies
Second most common tumor in salivary glands.
First recognized by Albrecht in 1910.
Quoted by Ellis and Auclair in 1991
Later described by Warthin in 1929
Occurs exclusively in the parotid gland.
Accepted theory: Tumor arises in the salivary gland tissue
entrapped within paraparotid or intraparptid lymph nodes
According to Allerga, it is most likely delayed hypersensitivity
diseases, lymphocytes being an immune reaction to the salivary
ducts which undergo oncocytic change.
According to Hsu and coworkers, lymphoid component of the
tumor is an exaggerated secretory immune response.
studies that have found cytogenetic abnormalities in the
Smokers- eight fold greater risk for Warthin’s tumor than do
Epstein-Barr virus also has been implicated in the pathogenesis
Appears as a slowly growing, painless, nodular mass of the parotid
firm or fluctuant to palpation.
occurs in the tail of the parotid near the angle of the mandible
occur bilaterally, 5% to 14% of cases.
bilateral tumors do not occur simultaneously but are metachronous
(occurring at different times).
In rare instances, submandibular gland or minor salivary glands.
lymphoid component is often less pronounced in these extraparotid
Age: 60-80 years
Lower in blacks than in whites
Sex: male>female predilection
Warthin tumors have been associated with cigarette smoking.
This association with smoking also may help explain the frequent
bilaterality of the tumor because any tumorigenic effects of
smoking might be manifested in both parotids.
Gross appearance of Warthin tumor of parotid gland.
The presence of multiple large cystic spaces is characteristic of
The tumor is composed of a mixture of ductal epithelium and a
Exhibit cyst formation, with projection into the cystic space and a
lymphoid stroma showing germinal centers.
Arranged in two layers.
The inner luminal layer consists of tall columnar cells, finely
granular eosinophilic cytoplasm with centrally placed, palisaded and
slightly hyperchromatic nuclei.
The outer layer cells are oncocytic triangular and occasionally
fusiform basaloid cells.
Focal areas of squamous metaplasia or mucous cell prosoplasia
may be seen.
Eosinophilic coagulum present within cystic spaces.
Lymphoid stroma- germinal center formation.
Warthin’s tumor showing
papillary cystic tumor with
dense lymphoid stroma
The papillae and glands are
typically lined by columnar
oncocytic luminal cells in which
the nuclei are often polarized
towards the lumen. Beneath the
luminal cells is a layer of basal
cells, which are sharply
demarcated from the underlying
Occasionally, foci of prominent squamous metaplasia (left
inset) and mucinous metaplasia (right inset) may be seen
within this tumor
local resection with minimal surrounding tissue
superficial parotidectomy to avoid violating the tumor capsule .
6% to 12% recurrence rate
Malignant Warthin tumors (caretnoma ex papillary cystadenoma
Iymphomatosum) have been reported but are exceedingly rare.
Neoplasm of uniform population of basaloid epithelial cells
arranged in solid, trabecular, tubular or membranous pattern.
1st reported by: Kleinsasser and Klein in 1967
Histological source: Intercalated duct or reserve cell.
Monomorphic adenomas- term should be avoided. Because
ultrastructural and immunohistochemical studies have shown
that basal cell adenomas are not necessarily composed of only
one cell type but sometimes of a combination of salivary ductal
epithelium and myoepithelial cells.
Age: middle aged- 57.7 years
Site: Parotid – 75%- superficial lobe.
Intraorally- Upper lip & Buccal mucosa.
C/p- Slowly growing, freely movable mass, less than3cm in
- firm in consistency which may be cystic and compressible.
One subtype, Membranous BCA-
Often occurs in combination with skin appendage tumors-
Dermal Cylindromas & Trichoepitheliomas.
Multiple bilateral tumors- Because these tumors often bear
a histopathologic resemblance to the skin tumors- Dermal
Round to ovoid, well-circumscribed, with smooth surface
capsule, firm in consistency- similar to lymph node.
Membranous Basal cell adenoma- Multinodular.
Cut surface- homogenous, solid appearance that may be
interrupted by cysts of varying sizes, filled with brown/ red
mucinous or blood, gray white to pink red or brown in color.
Basal cells that make up this lesions are uniform and
2 morphological forms:
1) small cells- scanty cytoplasm, round deeply basophilic
2) large cells- amphophilic to eosinophilic cytoplasm,
ovoid pale staining nucleus.
larger (pale) cells predominates with the small (daker)
cells, located in the peripheral portion of the epithelial
tumor nests, cords or islands.
4 morphologic pattern:
a) solid b) trabecular c) tubular d) membranous.
2 consistant features seen:
Sharp demarcation between the neoplastic epithelial
cells and the surrounding connective tissue
Palasiding of peripheral cuboidal or slightly columnar
cells that accentuates epithelioconnective tissue
Solid type :
Large sheets & broad bands of basaloid cells demonstrating palasiding
pattern, Cells demarcated from the connective tissue stroma by a basement
Inner portion- Epithelial cells-parallel to basal cells- tends to produce
scattered whorled eddies.
Eddies mature into squamous cells- produce keratin to give appearance of
Detail of a squamous differentiation frequently found in the solid variant
(a) Clinical examination: Small nodule behind the left ear.
(b) basaloid cells in nests sheets and trabeculae (PAP stain; ×100).
(c) peripheral palisading of cells (red arrows) and bare nuclei in background (PAP,
(d) basement membrane material around cell clusters (green arrows) (PAP, x400
Trabecular type :
Narrow epithelial islands forming an interconnecting cord-like
architecture- reticular pattern.
Prominent multiple duct-like structures with intraluminal eosinophilic
occurs in conjugation with trabecular pattern to form a
Presence of thick, hyaline, basement membrane like material
surrounds large lobules. This material is also present within the
epithelial nests forming coalescing, hyaline droplets.
Epithelial islands produce JIGSAW PUZZLE PATTERN
Hyaline material- PAS STAIN POSITIVE.
Treatment and Prognosis
similar to that of pleomorphic adenoma, complete surgical removal
Recurrence is rare
membranous subtype has a 25% to 37% recurrence rate
malignant counterpart - basal cell adenocarcinoma
A number of salivary gland tumors can be characterized
microscopically by a papillomatous pattern.
The sialadenoma papilliferum, intraductal papilloma , and
inverted ductal papilloma are three rare salivary tumors
that also show unique papillomatous features.
viral - human papillomavirus
on occasion, the common squamous papilloma of the oral
mucosa will arise at the site where a minor salivary gland
merges with the surface epithelium.
Because of this location, such squamous papillomas also
contain scattered mucous cells within the exophytic
papillary growth, and these lesions - "ductal papillomas”
Sialadenoma Papilleferum- minor salivary glands, especially on the palate,
among major glands- parotid gland.
older adults., M:F-1.5:1
Biphasic growth pattern exophytic papillary and endophytic components.
exophytic, papillary surface growth that is clinically similar to the common
Intraductal Papilloma- ill- defined lesion that often has been confused with
the papillary cystadenoma.
occurs in adults, minor salivary glands- lower lip
No gender predilection
c/p- submucosal swelling, appears to arise from excretory duct.
Inverted Ductal Papilloma- rare tumor that has been described
only in the minor salivary glands of adults.
Site: most common lower lip and mandibular vestibule
Appears to arise from excretory duct near mucosal surface.
asymptomatic submucosal nodule, may show a pit or
indentation in the overlying surface mucosa.
Sialadenoma papilliferum is somewhat similar to the squamous
papilloma , exhibiting multiple exophytic papillary projections that are
covered by parakeratotic stratified squamous epithelium.
This epithelium is contiguous with a proliferation of papillomatous
ductal epithelium found below the surface and extending downward into
the deeper connective tissues.
demonstrating the typical exophytic
papillary surface and deeper ductal
Multiple ductal lumina are formed, which characteristically are lined
by a double- rowed layer of cells consisting of a luminal layer of tall
columnar cells and a basilar layer of smaller cuboidal cells.
These ductal cells often have an oncocytic appearance. infiltrate of
plasma cells, lymphocytes, and neutrophils is present.
The bland surface squamous epithelium
communicates with the underlying columnar
epithelium lining the ductal structures.
Sialadenoma papilliferum . Low-
power view showing a papillary
surface tumor with associated
ductal str uctures in the
superficial lamina propria.
Sialadenoma papilliferum. High-
power view of cystic areas lined by
papillary, oncocytic epithelium
Inverted ductal papilloma is composed primarily of a proliferation of
squamoid epithelium with multiple thick, bulbous papillary projections
that fill the ductal lumen.
Well defined tumor mass within the lamina propria that has an
Basaloid and squamous cells are arranged in thick, bulbous proliferation
that project in papillary configuration into a luminal cavity.
Pushing interface with the connective tissue stroma of the lamina propria
and the submucosa.
Lumina is often narrow.
Small microcysts within the epithelium is evident.
Inverted ductal papilloma.
This tumor is continuous with the overlying
surface epithelium and grows in an inverting
pattern, forming a smooth-edged, broad-
It is composed of immature squamous or
In addition, numerous mucinous goblet
cells are often intermixed with the
basaloid and squamous cells.
Intraductal papilloma exhibits a dilated, unicystic structure
that is located below the mucosal surface.
Papilloma appears to arise in the duct system more distant from
the mucosal surface.
Cyst wall is lined by a single or double row of cuboidal or
columnar epithelium, which has multiple arborizing papillary
projections into the cystic lumen.
Extending into the lumen of the cystic space are fronds of columnar
epithelium supported by a central fibrovasacular core.
Treatment and Prognosis
conservative surgical excision.
Recurrence is rare.
Transformation of ductal and acinar cells to oncocytes.
Uncommon before the age of 50
oncocytes are a common finding in the salivary glands
Oncocytosis refers to both the proliferation and accumulation
of oncocytes within salivary gland tissue.
It may mimic a tumor both clinically and microscopically.
Considered to be a metaplastic process rather than a neoplastic
Site: parotid gland, in rare instances, it may involve the
submandibular or minor salivary glands.
may be extensive enough to produce clinical swelling.
proliferation is multifocal and nodular, sometimes entire gland can
be replaced by oncocytes- Diffuse hyperplastic oncocytosis.
oncocytosis occurs most frequently in older adults
Focal nodular collections of oncocytes with in the salivary gland
Enlarged cells are polyhedral and demonstrate abundant granular,
eosinophilic cytoplasm as a result of the proliferation of
These cells may have a clear cytoplasm from the accumulation of
The multifocal nature of the proliferation may be confused with that
of a metastatic tumor, especially when the oncocytes are clear in
Oncocytosis. Multifocal collections of clear oncocytes (arrows) in
the parotid gland
Oncocytosis is a benign condition and often is discovered only as
an incidental finding.
No further treatment is necessary, and the prognosis is excellent.
exclusively in the minor salivary glands
Defined as- tumor composed of columnar epithelial cells arranged
in thin, anastomosing cords often with a beaded pattern and a
characteristic paucicellular stroma.- WHO
Age: older people, 7th decade
Sex: F:M- 1.2-1.8:1
Site: upper lip , 75% occurring in this location.
Buccal mucosa is the second most common site.
c/p: slowly growing, pain less mass that usually ranges from several
millimeters to 2 cm, firm or somewhat fluctuant to palpation.
- The overlying mucosa may be normal in color or bluish and can be
mistaken for a mucocele.
- In some instances. the lesion has been noted to be multifocal.
Varies from discrete encapsulated nodule to lesions that
are circumscribed but encapsulated.
Pink-tan to tan, brown or yellow
Sometimes cystic spaces with gelatinous material seen
Monomorphic in nature, single- layered cords of columnar or cuboidal
epithelial cells with deeply basophilic nuclei, adjacent parallel rows of
cells may be seen, resulting in a bilayered appearance of the tumor cords,
showing ‘party wall’.
These cells enclose ductal structures, form of long canals, larger cystic
Epithelium may demonstrate papillary projections into the cystic lumina.
Tumor cells are supported by a loose connective tissue stroma with
A thin fibrous capsule often surrounds the tumor, although satellite
islands are observed in the surrounding salivary gland tissue .
Epithelial proliferations result in various cystic structures.
Lining of cyst- varies from flattened to tall columnar cells,
and cuboidal, mucous, and oncocytic cells seen.
Lining thickness- 1-3 epithelial cells
Limited papillary growth with central connective tissue
Eosinophilic or slightly hematoxyphilic secretions are
seen in the stroma
Dense fibrous connective tissue stroma with scattered
inflammatory cells seen.
Well-circumscribed tumor composed of
variably sized, multiple cysts with focal
The cyst lining epithelium consists of
columnar or cuboidal cells.
The cysts contain eosinophilic,
Most common malignant salivary gland neoplasm.
2nd most frequent of occurence of all salivary gland
Term was 1st used by Stewart, Foote and Becker in 1945.
5% of all salivary gland neoplasm
Presence of other foreign material
Cells of the salivary gland excretory and intercalated
Age: 3rd – 5th decade
Sex: females> male
Site: parotid is most commonly affected
Most common salivary gland neoplasm in children.
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,
Blue-pigmented mass of the posterior
lateral hard palate.
Mass of the tongue
Infrequent genetic loss at chromosomes 9q21, 8q, 5p, 16
H-ras gene have been shown mutation at codon 12 or 13
Cut surface of the tumor shows gray
white, solid mass accompanied by
multiple small cystic structures and
carcinomas may have a distinctly
cystic gross appearance.
-Cystic spaces- viscid, mucoid
-Areas of hemorrhage seen.
Characterized by: variety of cell types and growth
Composed of- a)mucous secreting cells
d)columnar or clear cells
Grades: a) low grade
b) intermediate grade
c) high grade
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
Clear cells- larger, polygonal and defined cytoplasmic
Histopathological Grades are based on-
Amount of cyst formation
Degree of cytoplasmic atypia
Relative number of mucous, epidermoid & intermediate
Low grade: Hallmark- prominent cystic structures
accompanied by the presence of numerous mature
cellular element including mucous cells and
- Mucous cell predominate
- squamous cell lining the cystic spaces seen.
- Size, shape & staining characteristics of cells are
Intermediate grade: intermediate cells predominate
with scattered mucous cells and zones of epidermoid
cells forming large, solid islands of tumor.
- Mitotic figures- rare.
carcinoma: with a prominent
Mucus cells - mucicarmine stain,
Clear cells - PAS
Intermediate-grade mucoepidermoid carcinoma with few mucus
cells and prominent population of intermediate and epidermoid cells
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
High-grade mucoepidermoid carcinoma with poorly differentiated,
irregular nests of tumor cells and very focal mucinous differentiation.
Abundant hyalinized stroma is evident.
Extensive secondary lymphoid cell
infiltration, referred to as tumor-
associated lymphoid proliferation.
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.
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
commonly seen in the posterior part of the mandible
Histologically low-grade cancers
Radiographically seen as uniocular or multiocular
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.
The acinic cell adenocarcinoma is a salivary gland
malignancy with cells that show serous acinar
Abrams and his coworker, concluded – tumor of this
type have atleast a low grade malignant potential.
Defined by cytologic differentiation towards serous acinar
cells whose characteristic feature is cytoplasmic PAS
positive Zymogen type secretory granules.
17% of primary salivary gland malignancy
6% of all salivary gland neoplasm
By Eversole, later by Regezi and Batsakis, hypothesizes
that ACC develops from stem or reserve epithelial cells
located at the tubuloacinar terminal of salivary gland
duct unit, i.e, intercalated duct region.
Age: Middle age, 44 years
Sex: female>male (3:2)
Site: parotid- 80%
Intraorally- lips & buccal mucosa
c/p: slow growing, mobile or fixed mass of variable
- Asymptomatic usually, pain and tenderness seen over a
third of patient.
- Facial muscle weakness can be seen
- Bilateral synchronous tumors have been reported
Acinic cell adenocarcinoma. Small, nodular mass of the hard palate.
Sections through a
reveal a sharply
demarcated tumor with a
partially cystic appearance.
Primary ACC –mononodular, well circumscribed, 2-4 cm in diameter
Multinodularity is not infrequent
Color: Grayish white or reddish gray
May be solid or cystic,
Consistency- firm to soft, somewhat friable.
Highly variable morphologic feature
Well circumscribed and encapsulated, may exhibit
infiltrative growth pattern
Characteristic cell: serous acinar cells, with abundant
granular basoplilic cytoplasm and round and darkly
stained eccentric nucleus.
Mitotic figures- uncommon
Solid growth pattern:
Most easily recognised
Contain large number of Well Differentiated acinar cells
and most closely resemble normal parotid gland
Composed of sheets of tumor cells that frequently have an
Groups of tumor acinar cells are separated and surrounded
by very thin fibrous septa that contain small, nearly
Clear cells often grow
Acinic cell adenocarcinoma. Parotid
tumor demonstrating sheet of
granular, basophilic serous acinar
Acinic cell adenocarcinoma. High-
power view of serous cells with
basophilic, granular cytoplasm.
Acinic cell carcinoma.
The cells have an abundant cytoplasm
filled with basophilic zymogen granules
Acinic cell carcinoma.
Periodic acid Schiff stain highlighting
zymogen granules on the luminal aspect
Extensive in 1/3 of ACC
Numerous small cystic spaces.
Acinar cells still frequent, may be dominating type.
Vacuolated and intercalated duct like cells are prominent
Mucinous material may pool in the cystic space
Papillary- cystic pattern:
Cystic structure that contain proliferations of the epithelium,
projecting into lumina.
Some epithelial projections have fibrovascular cores, where as others
appear to be masses of epithelium without apparent supporting
Epithelial proliferations vary in thickness
Intercalated duct like and non specific glandular cells predominate,
vacuolated cells also seen.
Apical portion of the lumen lining cells bulge into lumen- produce a
hobnail like configuration.
Variable size- ovoid to round cystic spaces lined by cuboidal to
low columnar epithelial cells.
Cystic space- contain proteinaceous material that stimulate the
appearance of colloid
Intercystic areas –usually occupied by epithelial cells that are
nonspecific glandular cells with some vacuolated and acinar
Curious feature- frequent association with a lymphoid
infiltrate in the supporting stroma, geminal centres may be
Arise within intraparotid lymph node.
Acinic cell carcinoma with extensive psammoma body formation
Acinic cell carcinoma
showing focal clear cell
This otherwise typical acinic cell carcinoma
shows an area (upper) of higher grade
carcinoma with small-cell features.
This phenomenon has been referred to as
Treatment and prognosis
Total excision with preservation of facial nerve- parotid
Lymph node dissection
Surgical excision- intraoral tumors
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
Age: 5th- 7th decade
Site: 50-60% within minor salivary gland- palate> tongue,
c/p: 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
Adenoid cystic carcinoma. Painful mass of the hard palate and
maxillary alveolar ridge.
Adenoid cystic carcinoma of the
parotid gland has deceptively well-
Microscopically, the tumor extends
well beyond the grossly apparent
edges of the tumor.
White or grayish white color,
firm, invasive tumor.
Areas of hemorrhage seen.
The adenoid cystic carcinoma is composed of a mixture
of myoepithelial cells and ductal cells that can have a
Three major patterns are recognized;
(1) cribriform ,
(2) tubular, and
Usually a combination at these is seen, and the tumor is
classified based on the predominant 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.
These spaces often contain a mildly basophilic mucoid material
a hyalinized eosinophilic product , or a combined mucoid
Sometimes the hyalinized material also surrounds these
Tubular structure that are lined by stratified cuboidal
Longitudinal section- ductal structures are viewed as ducts or
Lumina contains mucinous substance- PAS positive
Cribriform pattern may exist with tubular pattern.
Adenoid cystic carcinoma.
Tubular variant showing morphologically
clear abluminal cells.
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.
Adenoid cystic carcinoma.
Solid variant higher power showing
scattered duct-like structures within
the tumor sheet.
Adenoid cystic carcinoma.
The tumor cells are
surrounded by hyalinized
Adenoid cystic carcinoma. Perineural
Dedifferentiation of adenoid cystic carcinoma
- Recently defined, rare varient.
- characterized histologically by 2 component
1. Conventional low grade adenoid cystic carcinoma
2. high grade dedifferentiated carcinoma.
Because of frequent recurrence and matastasis, the
clinical course is short, similar to AdCC with a
predominant solid growth pattern.
Histologically low grade AdCC merges gradually into
extensive dedifferentiated component that is composed
of solid sheets and cords of anaplastic tumor cell with
focal gland formation..
p53 gene alteration plays a pivotal role.
Treatment and Prognosis
Adjunct radiation therapy may slightly improve patient
survival in some cases.
Epithelial myoepithelial carcinoma (EMEC) is a rare low-grade
malignant salivary gland neoplasm.
less than 1% of all salivary gland neoplasms.
ORIGIN: intercalated duct
A malignant tumor composed of variable proportions of two
cell types, which typically form duct-like structures.
The biphasic morphology is represented by an
- Inner layer of darker cells, that represent intercalated duct
- Outer layer of clear, myoepithelial-type cells.
Age: older, 6th- 7th decade of life.
Site: parotid- 75%> submandibular gland
intraorally: palate, tongue.
c/p: Asymptomatic, or painful salivary gland swelling with
a history of steady increase in size over an extended period
Facial paralysis & Localized swellings
Locally infiltrative, destructive growth pattern & frequent
rate of recurrence.
Facial deformity & nasal obstruction- incase of maxillary
Increased risk of secondary primary tumor- either in
salivary gland or in separate site
Single, well circumscribed, firm, lobulated neoplasm that
ranges from 2-8 cm
On cross section- multinodular growth pattern with
irregular cystic spaces.
Recurrent tumors- multicentric growth with irregular
tumor borders and central areas of necrosis.
Multinodular growth pattern with islands of tumor cells
separated by dense band of fibrous connective tissue.
Islands of tumor cells composed of small ducts lined by
cuboidal epithelium that is surrounded by clear cells that
interface with thickened hyaline like basement membrane.
Inner- luminal cuboidal cells have finely granular, dense,
eosinophilic cytoplasm and central or basally located
- Columnar cells and squamous foci may also be seen
proliferating within cystic and microcystic space that often
contain material that reacts positivity to PAS stain.
Outer- clear myoepithelial cell vary in shape from
columnar to ovoid, well defined cell borders, eccentrically
located vesicular nuclei located towards the basement
- Clear myoepithelial predominates
mitotic figures- rare
Vascular invasion & neurotropism may be seen.
Higher magnification showing luminal intercalated Duct like cells and
abluminal clear cells.
Another area Showing luminal cuboidal cells and abluminal clear cells and dense
hyalinised basement membrane (Original magnification,)
Epithelial-myoepithelial carcinoma with
trabecular arrangement & predominantly
Not uncommonly some glandular
structures have dilated lumens or are
thrown into papillary folds.
This feature is practically never seen in
adenoid cystic carcinoma.
S – 100 immunohistochemistry
Recently recognized type of salivary malignancy that was first
described in 1983.
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
Age: 50-80 years
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,
- Tumor can erode or infiltrate the underlying bone.
Polymorphous low-grade adenocarcinoma. Ulcerated mass of
the posterior lateral hard palate
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
Gross image shows bone invasion in
a large tumor in the hard palate
Characterized by: Infiltrative growth with diverse
morphology & Uniform nuclear appearance
At low power, the tumor sometimes appears well
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
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.
Histopathological image shows
uniform nuclei, round to ovoid,
with ground-glass type nuclear
Histopathological image shows
whorling around small neurovascular
bundles; a targetoid appearance
adenocarcinoma . This
medium-power view shows a
cribriform arrangement of uniform
tumor cells with pale-staining nuclei
Pale-staining cells which
infiltrate as single-file cords.
Tubular structures are predominantly lined
by a single layer of small cuboidal cells.
Multiple pseudocystic spaces with pale
staining amphophilic mucoid contents
resulting in a cribriform appearance
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.
Surgical pahology of the salivary glands, Gary L Ellis,
Paul L Auclair.
Shafer’s textbook of oral pathology, 6th edition.
Oral and maxillofacial pathology, 3rd edition, Neville.
Color/Atlas text of salivary gland tumor pathology,
Gnepp, diagnostic surgical pathology of the head and