tumors of salivary glands

1. AZFAR NEYAZ, JUNIOR RESIDENT
SGPGIMS, LUCKNOW

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7. Serous-type acini of a parotid gland
with dense secretory granules
Histologic section of a submaxillary
gland.

8. Portion of a parotid gland demonstrating multiple foci of sebaceous
differentiation.

9. The intercalated ducts (arrows)
(sectioned longitudinally) lie in
contact with the acinus.
The striated ducts (sectioned
transversely) are lined with a
oncocytic columnar cells.

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 Malignant epithelial tumors

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 Malignant epithelial tumors

12. Benign epithelial tumors

13. Soft tissue tumors
 Hemangioma
Haematolymphoid tumors
Secondary tumors

14. General features of salivary gland tumors in adults and children

16. 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)

17. architectural
pleomorphism

19. 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.

22. • Plasmacytoid hyaline cells :
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 Chondromyxoid stroma

23. 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.

24. An intimate mixture of epithelial and
stromal elements is seen in this mixed
tumor.
The stroma exhibits cartilaginous
differentiation.
Plasmacytoid cells

25. 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.

26. Pleomorphic adenoma showing a
focus of mucous metaplasia.
Focal squamous differentiation with
keratinization is seen amidst
complex glandular structures.

27. Lipomatous pleomorphic adenoma.
Pleomorphic adenoma showing bone
forming by osseous metaplasia in
stroma.

28. Spindly and stellate cells are disposed in a lattice-like fashion within the
myxoid matrix. A myoepithelioma can show a similar appearance.

31. Recurrent pleomorphic adenoma
Typical multinodular growth
pattern.

33. Metastasizing pleomorphic adenoma

34. Signs of malignant transformation:
 Rapid growth,
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Malignant mixed tumor

36. 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.

37. 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).

39. Carcinosarcoma showing mixture of adenocarcinomatous and osteosarcomatous
differentiation

40. basaloid

41. Cut surface of the parotid gland
tumor shows well-circumscribed,
grayish-white, solid mass.

42. Histologically subclassified according to their cellular growth
pattern.
 Solid
 Trabecular
 Tubular,
 Membranous (dermal analogue) types

43. 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).

44. 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.

47. 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).

48. Basal cell adenocarcinoma.
Solid nests of mildly atypical basaloid cells
with peripheral palisading
Basal cell adenocarcinoma.
Focal squamous differentiation with
keratin pearl formations.

51. Myoepithelioma.
The cut surface of a tumor presents as a well-circumscribed, yellow-tan
colored, solid mass in the parotid gland.

53. 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.

54. 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.

55. Spindle-shaped myoepithelial cell forming
a neurilemmoma-like pattern.
Myoepithelial cells forming a reticular
pattern.

59. • Reactivity for cytokeratin and at least one of the other myoepithelial
markers, including SMA , GFAP, CD10, calponin and smooth muscle
actin is required for diagnosis.

60. Myoepithelial carcinoma.
Low-power view showing multinodular
architecture.
Spindle cell type.
The spindle cells arranged in a vaguely
interlacing fascicular pattern.

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

63. Oncocytoma consisting of
characteristic light and dark cells.
Oncocytoma with clear cell change.

65. Oncocytic carcinoma.
This is a destructive infiltrating tumor.
Oncocytic carcinoma showing neural
invasion.

69. 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

71. • 2nd mc tumor
M>F
Radiation smoking.

72. 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).

73. 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.

77. Sebaceous adenoma showing nests of
sebaceous cells with peripheral squamous
differentiation.
Sebaceous adenoma consisting solely of
sebaceous cells of varying sizes.

78. Well-differentiated sebaceous carcinoma consisting of non-specific glandular
cells and cells showing conspicuous sebaceous differentiation.

79. within a background of lymphocytes and
lymphoid follicles

80. Sebaceous lymphadenoma :
Variably shaped epithelial nests with multiple
cystic formations, containing sebaceous cells
,in a lymphoid stroma.
Sebaceous glands in a diffuse lymphoid
background

81. 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.

83. 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

84. 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.

86. 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.

87. arising at the
junction
endophytic growth

88. 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.

89. Intraductal papilloma

90. 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.

92. 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.

93. • 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.

94. • Commonest childhood.

95. 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.

96. Low-grade mucoepidermoid
carcinoma: with a prominent cystic
component. The tumor contains
goblet, intermediate and squamous
cells.

97. 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

98. 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.

99. Mucoepidermoid carcinoma.
Clear cell variant
Oncocytic variant.

100. Mucoepidermoid carcinoma.
Abundant hyalinized stroma is evident.
Extensive secondary lymphoid cell
infiltration, referred to as tumor-
associated lymphoid proliferation.

103. Differential diagnosis

104. perineural invasion.

105. 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

106. The classic cribriform pattern of
adenoid cystic carcinoma.
At higher magnification, the cells are
haphazardly arranged around the
extracellular spaces

107. Adenoid cystic carcinoma.
Tubular variant (20-30%) showing
morphologically similar luminal and
abluminal cells.
Adenoid cystic carcinoma.
Tubular variant showing morphologically
clear abluminal cells.

108. 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.

109. Adenoid cystic carcinoma with
prominent perineurial invasion
Adenoid cystic carcinoma showing
bone invasion

110. 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.

112. Adenoid cystic carcinoma. P63 staining of myoepithelial component.

113. 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

114. DIFFERENTIAL DIAGNOSIS:
 PLG adenocarcinoma
 Basaloid sq. cell carcinoma
 Pleomorphic adenoma
 BC adenocarcinoma

115. serous acinar cell
differentiation

117. Sections through a superficial parotidectomy for an acinic cell carcinoma
reveal a sharply demarcated tumor with a partially cystic appearance.

118. 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

119. 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

120. Microcystic variant.
Follicular variant

121. Acinic cell carcinoma showing focal
clear cell change.
Papillary cystic variant.
There are many hobnail cells and
some vacuolated cell

122. 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.”

125. Tumor invades into the minor
salivary gland parenchyma.
A malignant infiltrative tumor characterized by diverse architectural
patterns but unified by bland-looking tumor cells.

126. 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.

127. 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

128. Papillary configurations of columnar or
cuboidal cells
Polymorphous low-grade adenocarcinoma
‘‘Indian-file’’ growth pattern.

129. Perineural invasion with concentric
targetoid appearance.
Fascicular growth pattern

130. • So variability of growth pattern is the most consistent architectural
feature of the tumor.

132. 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)

133. 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.

134. A) Cytokeratin stain highlighting the luminal
cells.
(B) Calponin staining highlighting abluminal
myoepithelial cells.
Epithelial-myoepithelial carcinoma
showing neural invasion

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

137. 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.

138. 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

139. 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.

140. Salivary duct carcinoma.
Immunohistochemistry.
Carcinoma cells are diffusely positive
for androgen receptor in their nuclei.
Diffuse and strong membranous staining
for HER-2/neu.

143. • 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.

144. Hyalinizing clear cell carcinoma.
Uniform population of cells with clear
cytoplasm forming discrete nests in a
dense fibrous stroma.

145. undifferentiated carcinoma
non-neoplastic lymphoplasmacytic

147. Undifferentiated lymphoepithelioma-like carcinoma of the parotid gland.
The tumor has sharply demarcated margins and grossly resembles a lymphoma.

148. 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

149. 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.

151. 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

153. 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.

154. 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

157. 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

160. Adenocarcinoma NOS: Low grade tumor.
Prominent well-formed glandular
formations.
Intermediate-grade tumor.
Fused glandular formations with focal solid
areas.

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

163. 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

165. 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.

167. 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.

170. Tumor diffusely and uniformly involves the
parotid gland lobules, leaving scattered
striated ducts.
Proliferation of the plump endothelial cells
with mild nuclear atypia.

173. 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.

174. 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

176. 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

177. • 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?

178. Cellular differentiation in various salivary gland neoplasms