Tumors of salivary gland

AZFAR NEYAZ, JUNIOR RESIDENT

SGPGIMS, LUCKNOW

Serous-type acini of a parotid gland

with dense secretory granules

Histologic section of a submaxillary

gland.

Portion of a parotid gland demonstrating multiple foci of sebaceous

differentiation.

The intercalated ducts (arrows)

(sectioned longitudinally) lie in

contact with the acinus.

The striated ducts (sectioned

transversely) are lined with a

oncocytic columnar cells.

Malignant epithelial tumors

Malignant epithelial tumors

Benign epithelial tumors

Soft tissue tumors

Hemangioma

Haematolymphoid tumors

Secondary tumors

General features of salivary gland tumors in adults and children

Major salivary gland Minor salivary gland

Warthin tumor Polymorphous low grade

adenocarcinoma (palate)

Acinic cell carcinoma Canalicular adenoma (lip, buccal

mucosa)

Oncocytoma/oncocytic carcinoma Cystadenoma/cystadenocarcinoma

Epithelial-myoepithelial carcinoma Inverted papilloma

Basal cell adenoma/adenocarcinoma Intraductal papilloma

Salivary duct carcinoma

Lymphoepithelial carcinoma

Sialadenoma papilliferum (palate)

architecturalpleomorphism

Benign mixed tumor of the

submandibular gland demonstrating

a firm, whitish tan, well-encapsulated

mass

Gross specimen of pleomorphic

adenoma. The external surfaces have

been marked with blue dye.

The cut surface of the tumor is tan-

colored and interspersed with brown

areas. Note the glistening quality of the

tumor.

• Plasmacytoid hyaline cells :

Chondromyxoid stroma

There is a small satellite nodule

immediately outside the thin capsule

of the tumor. This represents a tumor

protuberance . This finding is still

compatible with a diagnosis of benign

pleomorphic adenoma.

Double-layered duct-like structures

with a conspicuous abluminal layer

of clear myoepithelial cells.

An intimate mixture of epithelial and

stromal elements is seen in this mixed

tumor.

The stroma exhibits cartilaginous

differentiation.

Plasmacytoid cells

Cellular mixed tumor :

Because of its extreme cellularity, this

tumor may be mistaken for a malignant

tumor

Pleomorphic adenoma with a focus

resembling adenoid cystic carcinoma.

There are some cribriform structures and

tubules sharply demarcated from the

stroma.

Pleomorphic adenoma showing a

focus of mucous metaplasia.

Focal squamous differentiation with

keratinization is seen amidst complex glandular structures.

Lipomatous pleomorphic adenoma.

Pleomorphic adenoma showing bone

forming by osseous metaplasia in

stroma.

Spindly and stellate cells are disposed in a lattice-like fashion within the

myxoid matrix. A myoepithelioma can show a similar appearance.

Recurrent pleomorphic adenoma

Typical multinodular growth

pattern.

Metastasizing pleomorphic adenoma

Signs of malignant transformation:

Rapid growth,

Malignant mixed tumor

Noninvasive carcinoma ex pleomorphic

adenoma showing more extensive

dysplastic change

Noninvasive carcinoma ex pleomorphic

adenoma showing dysplastic cells

replacing the inner duct layer leaving a

benign myoepithelial layer.

Perineural invasion next to remnant of

scarred pleomorphic adenoma.

Note the benign component with

numerous small irregular ducts in a

hyalinized stroma (upper left) and a

focus of adenocarcinoma with

associated necrosis (lower right).

Carcinosarcoma showing mixture of adenocarcinomatous and osteosarcomatous

differentiation

basaloid

Cut surface of the parotid gland

tumor shows well-circumscribed,

grayish-white, solid mass.

Histologically subclassified according to their cellular growth

pattern.

Solid

Trabecular

Tubular,

Membranous (dermal analogue) types

Trabecular type :

Narrow epithelial islands forming an

interconnecting cord-like architecture.

Solid type :

Large sheets & broad bands of basaloid

cells with peripheral palisading.

Detail of a squamous diff. frequently

found in the solid variant (inset).

Tubular type.

Prominent duct-like structures with

intraluminal eosinophilic secretion.

Membranous type.

Thick, hyaline, basement membrane

like material surrounds large lobules.

This material is also present within the

epithelial nests forming coalescing,

hyaline droplets.

Basal cell adenocarcinoma. Islands of basaloid cells infiltrate a fibrous stroma.

Distinction from basal cell adenoma is based on the presence of unequivocally infiltrative growth.As is typical of basal cell adenocarcinoma, some cells have darker nuclei and some have larger paler nuclei.

A focus of perineural invasion is seen

(right of center).

Basal cell adenocarcinoma.

Solid nests of mildly atypical basaloid cells

with peripheral palisading

Basal cell adenocarcinoma.

Focal squamous differentiation with

keratin pearl formations.

Myoepithelioma.

The cut surface of a tumor presents as a well-circumscribed, yellow-tan

colored, solid mass in the parotid gland.

Spindle cell type.

The spindle cells are arranged in an

interlacing fascicular pattern.

Plasmacytoid cell type.

The plasmacytoid cells exhibiting

eccentrically located nuclei and abundant

eosinophilic cytoplasm are surrounded by

a myxoid matrix.

Epithelioid cell type :

Solid and trabecular growth patterns of

polygonal epithelial cells with central nuclei

and eosinophilic cytoplasm

Clear cell type :

Solid growth of polygonal shaped clear

cells with intercellular hyaline depositions.

Spindle-shaped myoepithelial cell forming

a neurilemmoma-like pattern.

Myoepithelial cells forming a reticular

pattern.

• Reactivity for cytokeratin and at least one of the other myoepithelialmarkers, including SMA , GFAP, CD10, calponin and smooth muscleactin is required for diagnosis.

Myoepithelial carcinoma.

Low-power view showing multinodular

architecture.

Spindle cell type.

The spindle cells arranged in a vaguely

interlacing fascicular pattern.

Gross appearance of oxyphilic adenoma.The tumor is well circumscribed, solid, and light brown.

Oncocytoma consisting of

characteristic light and dark cells.

Oncocytoma with clear cell change.

Oncocytic carcinoma.

This is a destructive infiltrating tumor.

Oncocytic carcinoma showing neural

invasion.

Canalicular adenoma is made up of double

rows of interconnecting & branching cords

of tumor composed of bland, basaloid,

cuboidal to columnar cells.

The surrounding stroma is acellular with

very sparse collagen production

• 2nd mc tumor

M>F

Radiation smoking.

Gross appearance of Warthin tumor of

parotid gland.

The presence of multiple large cystic

spaces is characteristic of this lesion.

Warthin tumor is typically tannish

brown, often with cystic spaces.

In addition, this tumor demonstrates

areas of degeneration and necrosis

(yellowish foci).

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

lymphoid stroma.

Sebaceous adenoma showing nests of

sebaceous cells with peripheral squamous

differentiation.

Sebaceous adenoma consisting solely of

sebaceous cells of varying sizes.

Well-differentiated sebaceous carcinoma consisting of non-specific glandular

cells and cells showing conspicuous sebaceous differentiation.

within a background of lymphocytes andlymphoid follicles

Sebaceous lymphadenoma :

Variably shaped epithelial nests with multiple

cystic formations, containing sebaceous cells

,in a lymphoid stroma.

Sebaceous glands in a diffuse lymphoid

background

Lymphadenoma.

A well-circumscribed tumor in the parotid

gland.

Lymphadenoma, nonsebaceous type.

There are multiple nests of basaloid tumor

cells with focal ductal differentiation in a

lymphoid background.

Cystadenoma.

Well-circumscribed tumor composed of

variably sized, multiple cysts with focal

papillary configurations.

The cyst lining epithelium consists of

columnar or cuboidal cells.

The cysts contain eosinophilic,

proteinaceous material

Oncocytic cystadenoma.

Papillary-cystic proliferation of oncocytic

epithelium in the parotid gland.

Note the absence of lymphoid infiltration in

fibrous stroma separating cystic spaces.

The cysts are lined by a double-layered

oncocytic epithelium, resembling that

seen in Warthin tumor.

Cystadenocarcinoma.

Tumor with multiple papillary-cystic

structures invades into the surrounding

salivary gland parenchyma.

Cyst formations accompanied by

prominent intracystic papillary projections

of columnar cells.

arising at the junction

endophytic growth

Inverted ductal papilloma.

This tumor is continuous with the overlying

surface epithelium and grows in an inverting

pattern, forming a smooth-edged, broad-

based mass.

It is composed of immature squamous or

basaloid epithelium

In addition, numerous mucinous goblet

cells are often intermixed with the

basaloid and squamous cells.

Intraductal papilloma

Intraductal papilloma.

A cystically dilated duct with papillary

epithelial projections into the cystic space.

Extending into the lumen of the cystic

space are fronds of columnar epithelium

supported by a central fibrovasacular

core.

Sialadenoma papilliferum demonstrating

the typical exophytic papillary surface and

deeper ductal components.

The bland surface squamous epithelium

communicates with the underlying columnar

epithelium lining the ductal structures.

• Salivary gland anlage tumor manifests in newborns or within the first

few weeks of life with respiratory distress.

• The tumor is postulated to be a hamartoma because the histologic

features are reminiscent of developing salivary gland in embryo.

• Although some investigators favor a teratomatous interpretation.

Salivary gland anlage tumor

The surface is covered by nonkeratinizing

squamous epithelium which extends

downwards into the submucosal tissue,

giving rise to squamous nests, branching

ducts and cystic structures.

• Commonest childhood.

Cut surface of the intermediate-grade

tumor shows gray white, solid mass

accompanied by multiple small cystic

structures and infiltrative borders.

Low-grade mucoepidermoid

carcinomas may have a distinctly

cystic gross appearance.

Low-grade mucoepidermoid

carcinoma: with a prominent cystic

component. The tumor contains

goblet, intermediate and squamous

cells.

Intermediate grade mucoepidermoid

carcinoma.

Solid nests with focal cystic structures

consisting of intermediate cells as well

as epidermoid cells & a few mucous

cells

Low-grade mucoepidermoid carcinoma

Tumor is composed primarily of

markedly pleomorphic epidermoid

cells and a small proportion of

mucous cells.

Periodic acid–Schiff (PAS) stain

showing scattered positive mucous

cells in the solid nests.

Mucoepidermoid carcinoma.

Clear cell variant

Oncocytic variant.

Mucoepidermoid carcinoma.

Abundant hyalinized stroma is evident.

Extensive secondary lymphoid cell

infiltration, referred to as tumor-

associated lymphoid proliferation.

Differential diagnosis

perineural invasion.

Adenoid cystic carcinoma of the

parotid gland has deceptively well-

delineated outlines. Microscopically,

the tumor extends well beyond the

grossly apparent edges of the tumor.

Tan, fleshy, firm, invasive tumor

The classic cribriform pattern of

adenoid cystic carcinoma.

At higher magnification, the cells are

haphazardly arranged around the

extracellular spaces

Adenoid cystic carcinoma.

Tubular variant (20-30%) showing

morphologically similar luminal and

abluminal cells.

Adenoid cystic carcinoma.

Tubular variant showing morphologically

clear abluminal cells.

Adenoid cystic carcinoma.

Solid variant higher power showing

scattered duct-like structures within

the tumor sheet.

Adenoid cystic carcinoma.

Solid variant showing extensive

comedo necrosis.

Adenoid cystic carcinoma with

prominent perineurial invasion

Adenoid cystic carcinoma showing

bone invasion

Adenoid cystic carcinoma with

hyalinization or myxoid change, mimicking

pleomorphic adenoma.

The cribriform island shows deposits of

abundant hyaline material with

strangulation" of the tumor cells.

This pattern differs from the hyalinization

seen in pleomorphic adenomq in that the

process is confined to the cellular island,

which itself is sharply delineated from the

fibrous stroma.

Adenoid cystic carcinoma. P63 staining of myoepithelial component.

The left field depicts the pre-existing

adenoid cystic carcinoma, comprising

Basaloid cells with interspersed

pseudocystics paces.

The right field shows the poorly

differentiated (dedifferentiated) solid tumor

composed of much larger, pleomorphic and

mitotically active cells, associated with

coagulative necrosis

DIFFERENTIAL DIAGNOSIS:

PLG adenocarcinoma

Basaloid sq. cell carcinoma

Pleomorphic adenoma

BC adenocarcinoma

serous acinar celldifferentiation

Sections through a superficial parotidectomy for an acinic cell carcinoma

reveal a sharply demarcated tumor with a partially cystic appearance.

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

Some tumor cells contain basophilic

granules (left lower field).

Most cells are polygonal and many

resemble intercalated duct cells. Note

the bland appearances of the nuclei.

Acinic cell carcinoma with extensive

psammoma body formation

Microcystic variant.

Follicular variant

Acinic cell carcinoma showing focalclear cell change.

Papillary cystic variant.

There are many hobnail cells and

some vacuolated cell

Well-differentiated acinic cell carcinoma

with abundant lymphoid stroma.

favorable prognosis

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

“dedifferentiation.”

Tumor invades into the minor

salivary gland parenchyma.

A malignant infiltrative tumor characterized by diverse architectural

patterns but unified by bland-looking tumor cells.

Sheet-like solid growth of the tumor cells

exhibiting uniform oval nuclei without any

pleomorphism.

Polymorphous low-grade adenocarcinoma.

Low power view showing histologic

diversity within the tumor. Mainly solid and

tubular growth patterns with focal cribriform

and papillary areas.

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

Papillary configurations of columnar or

cuboidal cells

Polymorphous low-grade adenocarcinoma

‘‘Indian-file’’ growth pattern.

Perineural invasion with concentric

targetoid appearance.

Fascicular growth pattern

• So variability of growth pattern is the most consistent architectural

feature of the tumor.

The myoepithelial component is

represented by the cells with clear

cytoplasm

The tumor characteristically invades in

broad fronts (normal salivary gland tissue

seen in right field)

Epithelial-myoepithelial carcinoma with

trabecular arrangement & predominantly

non-canalized ducts.

Epithelial-myoepithelial carcinoma.

Not uncommonly some glandular

structures have dilated lumens or are

thrown into papillary folds.

This feature is practically never seen in

adenoid cystic carcinoma.

A) Cytokeratin stain highlighting the luminal

cells.

(B) Calponin staining highlighting abluminal

myoepithelial cells.

Epithelial-myoepithelial carcinoma

showing neural invasion

Cut surface of the tumor shows gray-white, solid mass with foci of necrosis

Intraductal component comprised of

cribriform structures.

Note that the central portion of the ductal

cell nests undergoes comedo-like necrosis

The invasive component consists of

irregular glands and cords of cells that

elicit a prominent desmoplastic reaction.

Carcinoma cells exhibiting large

pleomorphic nuclei with coarse chromatin

and prominent nucleoli. The cytoplasm is

abundant and granularly eosinophilic

Sarcomatoid salivary duct carcinoma.

There are several nests of typical salivary

duct carcinoma with a prominent

cribriform pattern surrounded by a

markedly pleomorphic, atypical spindle

cell population of tumor cells

Mucin-rich variant.

Mucin lakes containing islands of

carcinoma cells (right) in addition to the

typical salivary duct carcinoma

component.

Invasive micropapillary variant.

Morula-like small cell clusters without

fibrovascular cores, surrounded by a clear

space.

Salivary duct carcinoma.

Immunohistochemistry.

Carcinoma cells are diffusely positive

for androgen receptor in their nuclei.

Diffuse and strong membranous staining

for HER-2/neu.

• The majority of tumors with a predominant population of clear cells

have been diagnosed as epithelial-myoepithelial carcinomas.

• Other differentials:

• clear cell oncocytoma

• mucoepidermoid carcinoma

• acinic cell carcinoma

• sebaceous carcinoma

• metastatic renal cell carcinoma are needed to be excluded.

• It is a diagnosis by exclusion.

Hyalinizing clear cell carcinoma.

Uniform population of cells with clear

cytoplasm forming discrete nests in a

dense fibrous stroma.

undifferentiated carcinoma non-neoplastic lymphoplasmacytic

Undifferentiated lymphoepithelioma-like carcinoma of the parotid gland.

The tumor has sharply demarcated margins and grossly resembles a lymphoma.

Undifferentiated, lymphoepithelioma-like

carcinoma. A large component of tumor

(left) is surrounded by a brisk

lymphoplasmacytic reaction (right).

The neoplastic cells have large, vesicular,

but relatively uniform nuclei. Mitotic figures

are typically easily identified. Cell borders

are indistinct. The epithelial cells are mixed

in a complex fashion with the reactive

lymphoplasmacytic elements

In situ hybridization for EBV-encoded small RNA (EBER). Almost all of the carcinoma cells express strong nuclear EBER hybridization

signals. Note complete absence of signal in the surrounding lymphoid stroma.

Undifferentiated carcinoma

• Rare tumors composed of primitive/anaplastic cells which exhibit no

obvious line of differentiation.

• Focal isolated glandular formation or squamous differentiation does

not exclude this diagnosis.

• Undifferentiated carcinoma can be further subclassified into:

• small cell carcinoma

• large cell undifferentiated carcinoma

• lymphoepithelioma-like carcinoma

Small cell carcinoma.

High-power view showing the tumor cells

with scant cytoplasm and inconspicuous

nucleoli. Mitotic figures are readily

identified.

Small cell carcinoma.

Tumor cells are diffusely immunopositive

for chromograninA.

Paranuclear dot-like pattern of

immunoreactivity for cytokeratin 20.

The tumor cell nuclei are round to oval,

with pale, dispersed chromatin and a well-

defined nuclear membrane

Large cell carcinoma. Sheet-like growth

pattern of large pleomorphic cells with

abundant eosinophilic cytoplasm

and prominent nucleoli

Solid growth with peripheral palisading and

several rosette-like structures.

The tumor cells have large and polygonal

nuclei with vesicular chromatin and

prominent nucleoli

Adenocarcinoma NOS: Low grade tumor.

Prominent well-formed glandular

formations.

Intermediate-grade tumor.

Fused glandular formations with focal solid

areas.

High-grade tumor.Irregularly shaped islands and strands of anaplastic carcinoma cells. Glandular formations are inconspicuous.

Colloid carcinoma

Composed of multiple pools of mucin in a

delicate fibrous stroma that surrounds

atypical pleomorphic carcinoma cells.

Detail of carcinoma nests demonstrating

prominent nucleoli and moderate amounts

of eosinophilic cytoplasm

Low-power view showing multilocular

cystic lesions filled with lamellar keratin

material.

Portion of the cyst wall consists of

stratified squamous epithelium with

keratinization through parakeratotic cells.

The tumor forms sheets of basaloid cells with focal ductal differentiation separated

by fibromyxomatous stroma.. The tumor cells are uniform without mitotic figures or

pleomorphism.

Tumor diffusely and uniformly involves the parotid gland lobules, leaving scattered striated ducts.

Proliferation of the plump endothelial cells with mild nuclear atypia.

well-developed stage of MALT lymphoma

showing scattered lymphoepithelial lesions

in diffuse sheets of monocytoid cells

Lymphoepithelial lesion formed by the

infiltration of monocytoid cells in the

proliferation of duct epithelial cells.

MALT lymphoma.Immunohistochemistry.

(A) The lymphoid tumor cells at both

inside and outside of the

lymphoepithelial lesion diffusely\ express

CD20 (left) but are negative for CD3

(right).

Immunoglobulin light chain restriction.

Many kappa light chain-positive cells are

seen in the left, whereas only scattered

lambda positive cells are identified in the

right

Most important features taken into consideration before making a

diagnosis are :

• Tumor borders

• Cellular composition

• Architectural arrangement

• Cytologic features

• Stromal components

Analytic approach to diagnosis of epithelial tumors of

salivary glands

• Some acinic cell ca and ca-ex-PA have circumscribed borders.

• Pushing type of infiltration – Epithelial myoepithelial carcinoma,

Basal cell adenocarcinoma, acinic cell carcinoma.

• Morphologically bland looking myoepithelial, basal cell, oncocytic

neoplasm if having invasive borders : malignant.

• Warthin's tumor complicated by infarction or inflammation can result

in adhesions to the surrounding tissues, mimicking a -malignant

neoplasm clinically or grossly.

Invasive or not?

Cellular differentiation in various salivary gland neoplasms