lec. Dr.

Ban Falih Ibraheem

Salivary gland tumors Oral pathology -fourth stage

A- Benign salivary gland tumors

1- Pleomorphic adenoma ( Benign mixed tumor ) ( ICD-O code 8940/0).

It is the most common salivary neoplasm, it accounts for 53 % to 77% of the parotid tumor. They are derived
from a mixture of ductal and myoepithelial elements.

Clinically: typically appears as a slowly growing, painless, firm mass. The patient may be aware of a lesion
for many months or years before seeking a diagnosis. It is most common in young adults with a slight female
predilection. When occurs in the parotid gland, it affects mainly the superficial lobe and presents as swelling
overlying the mandibular ramus in front of the ear. Initially, the tumor is movable. The palate is the most
common site for the minor salivary gland, followed by the upper lip and buccal mucosa. Palatal tumors occur
in the posterior lateral part as smooth surface, dome-
shaped mass.

Immunoprofile: The inner ductal cells in the tubular-

glandular structures are positive for cytokeratin 3, 6, 10,
11, 13, and 16. The neoplastic myoepithelial cells co-
express vimentin and pan-cytokeratin and are variably
positive for S-100 protein, a-smooth muscle actin.

Molecular genetics: The target gene in pleomorphic

adenomas with 8q12 abnormalities is PLAG1.

Histopathology.
The pleomorphic adenoma is a well-circumscribed, encapsulated tumor, although a capsule may be
incomplete or show infiltration by tumor cells. It shows a great variety of histological appearances with a
complex intermingling of epithelial components and mesenchymal-like areas. The diversity and complexity
of appearances account for the term pleomorphic. The tumor is composed of a mixture of glandular epithelial
and myoepithelial cells within a mesenchyme-like background. Microscopically, there is considerable
variation in the arrangement of the epithelial and stromal components between different tumors and within
different areas of the same tumor. The epithelial component may be arranged in duct-like structures or as
sheets, clumps, and interlacing strands. Both epithelial-duct cells and myoepithelial-type cells are present.
Areas of keratinizing squamous cells and mucous-producing cells can be present.

The intercellular material may be fibrous, but the most characteristic feature is the presence of myxoid and/or
chondroid areas. In chondroid areas, isolated rounded cells lie in lacunae within the mucoid material so that
the tissue comes to resemble hyaline cartilage.
Malignant transformation can occur, usually in tumors that have been present for many years, resulting in
carcinoma ex pleomorphic adenoma.

Treatment. Surgical excision for a lesion in the superficial lobe of the parotid gland, superficial
parotidectomy. Tumor of the deep lobe of the parotid, total parotidectomy is usually necessary with the
preservation of the facial nerve. An important aspect of the deficient encapsulation and intra- and
extracapsular nodules is that they influence the surgical management of the tumor. Local enucleation should

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be avoided because the entire tumor may not be removed, or the capsule may be violated., resulting in the
seeding of the tumor bed, leaving behind islands of neoplastic tissues in the tumor bed, which could give rise
to uni- or multifocal recurrence. For these reasons, the tumor is usually excised with a margin of surrounding
normal tissue. With adequate surgery, the prognosis is excellent.

2-Warthin tumor (adenolymphoma, papillary cystadenoma lymphomatosum )( ICD-O code

8561/0)
Clinically: occurs almost exclusively in the parotid gland, representing the second most common benign
parotid tumor. It is mostly seen in the tail of the gland near the angle of the mandible. It is a slow-growing,
painless lesion, and may be firm or fluctuant to palpation. Bilateral parotid tumors occur in some cases. Most
patients are over 50 years of age with a male predilection. In rare cases, it has been reported within
submandibular or minor salivary glands. This tumor has been associated with cigarette smoking.

The pathogenesis of the tumor is uncertain, but it most likely arises from residues of salivary duct epithelium
entrapped within lymph nodes during development or from the proliferation of ductal epithelium associated
with the secondary formation of lymphoid tissue. Recent studies supported the second theory as they found
cytogenetic abnormalities in the epithelial component.

Immunoprofile: Lymphoid marker studies have shown B

(CD20), NK (CD56), and T (CD3) cells, including helper (CD4)
and suppressor (CD8) subtypes. This profile of lymphocyte
subsets is similar to that in normal or reactive lymph nodes

Histopathology.
The tumor characteristically has a papillary cystic structure and
shows multiple irregular cystic spaces containing mucoid
material separated by papillary projections of tumor tissue.
Microscopically, the tumor consists of epithelial and lymphoid
elements. The epithelial component which clothes the papillary processes is double-layered. The luminal
layer consists of a tall columnar cell with a centrally placed nucleus surrounded by a cuboidal layer with a
vesicular nucleus. The epithelial cells have markedly eosinophilic granular cytoplasm. The epithelium is
supported by lymphoid stroma and contains numerous germinal centers

Treatment. Surgical removal, some surgeons prefer local resection, others prefer superficial parotidectomy
to avoid violating the tumor capsule, rate of recurrence is less than 10%. Malignant changes occur but are
rare.

3-Oncocytoma (ICD-O code 8290/0)

The oncocytoma is a benign tumor. It is a rare tumor comprising 1% of all salivary tumors.
Clinically: usually arising in the major salivary gland, especially the parotid gland, but are rare in minor
salivary glands. It occurs in patients over 60 years of age as a firm, slowly growing painless mass.

Histopathology. It is usually a well-circumscribed tumor,

composed of sheets of large polyhedral cells (oncocyte) with
abundant granular ( due to over-abundance of mitochondria)
eosinophilic cytoplasm. These cells form an alveolar or
glandular pattern. These cells have a centrally located nucleus
that varies from small hyperchromatic to large.

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Treatment .surgical excision. In the parotid gland, this requires partial parotidectomy to avoid violation of
the tumor capsule with preservation of the facial nerve. The prognosis after removal is good, with a low
recurrence rate.

4- Monomorphic adenoma. Describe a group of benign salivary gland tumors with a more uniform
histopathologic pattern than pleomorphic adenoma, which includes:

1-Basal cell adenoma (ICD-O code 8147/0)

It derives its name from the basaloid appearance of tumor cells. However, immunohistochemical studies
showed that it is not necessary composed of single-cell types but sometimes a combination of ductal
epithelial and myoepithelial cells.

Clinically: This tumor accounts for about 1-2 percent of all salivary tumors. Unlike canalicular adenoma,
basal adenoma primarily occurs in the parotid gland. About 70 percent occur in the parotid gland, and minor
salivary glands are the second most common sites. It occurs in old age, and appears as a slow-growing,
movable mass similar to pleomorphic adenoma. On palpation, it is firmer than pleomorphic and smaller in
size.

Histopathology: it is well- circumscribed or encapsulated. It consists of multiple islands and cords of

epithelial cells with small stroma between them. Cytologically uniform basaloid cells (cuboidal) are
arranged in a variety of patterns, and the peripheral cells are palisaded and columnar or cuboidal in shape.

2-Canalicular adenoma (ICD-O code 8149/0)

Almost all cases occur in the minor salivary gland of the upper lip. The buccal mucosa is the second common
site. This tumor occurs mainly in patients over 50 years of age, with female predominance. They are slow-
growing, painless mass, firm, or fluctuant.

Histopathology: Thin fibrous capsules often surround the tumor. This tumor consists of anastomosing
strands of single-layer columnar or cuboidal epithelial cells with a basophilic nucleus. Some adjacent rows
of cells may result in the bilayered appearance of tumor cords. These cells enclose duct structures. Or long
canals, the tumor cells are supported by loose connective tissue stroma.

Treatment. Local surgical excision. Recurrence uncommon

Malignant tumors of the salivary gland.

1-Mucoepidermoid carcinoma ( ICD-O code 8430/3)

Mucoepidermoid carcinoma is the commonest malignant salivary
gland malignancy. In the United state, it makes up 10% of all major
salivary gland tumors and 15-21% of minor salivary gland tumors.

Clinically: The tumor occurs over a wide age range from the second
to seventh decades with a slight female predilection. The majority
occurs in the parotid gland as an asymptomatic lesion, pain, or facial
nerve palsy may usually develop in the high-grade tumor. The minor
glands are the second most frequent sites, especially the palate, which sometimes are fluctuant and have blue
color that can be mistaken for mucocele.
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Genetics: Molecular studies of these tumors are few and limited in a number of cases. They show an
infrequent genetic loss at chromosomes 9p21, 8q, 5p, 16q, and 12p. Studies of the H-ras gene in these tumors
have reported 18% mutations at codons 12 and/or 13. Recently a molecular analysis of the translocation of
the following two chromosomes(11:19) (q21;p12) was evident.

Histopathology. The tumors are characterized by 1-squamous(epidermoid) cells, 2-mucus-secreting cells,

and 3-cells of intermediate types, which have the potential for further differentiation towards mucous or
squamous cells. The mucous cells contain abundant foamy cytoplasm, while epidermoid cells have a
squamoid feature with a polygonal shape, intercellular bridges, and rarely keratinization. An associated
lymphocyte infiltration may be prominent. The relative proportions of individual cell types and their
arrangements vary from lesion to lesion, but it is customary to distinguish between well-differentiated (low-
grade) and poorly differentiated (high-grade) tumors.

The low-grade: tumor shows prominent cyst formation, minimal cell

atypia, and a high proportion of mucous cells,
The high-grade tumor: consists of solid islands of squamous and
intermediate cells, with pleomorphism and mitotic activity; mucous
cells are infrequent.
Intermediate: shows feature that fall between high and low grade

The behavior of a mucoepidermoid carcinoma cannot be predicted

with any degree of certainty from its histology. The overall 5-year
survival rate is about 70 percent. However, well-differentiated, low-
grade tumors have a local recurrence rate of less than 10 percent and 5-
year survival of about 95 percent. In contrast, poorly differentiated
(high-grade) tumors have been reported to have local recurrence rates
of 80 percent and 5-year survival rates of only 30-40 percent.

Treatment. Treatment is predicated on the location, histopathologic grade, and clinical staging of the tumor.
Early-stage tumors of parotid are treated by subtotal parotidectomy, while advanced tumors may necessitate
total removal of the parotid by sacrificing the facial nerve.

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2-Adenoid cystic carcinoma (ICD code: 8200/3)
Adenoid cystic carcinomas are one more common and best-recognized salivary malignancy.

Clinically: They are the most common tumor in the minor salivary gland, mainly in the palate. Some cases
are detected in parotid and submandibular glands. Usually arise in middle-aged or elderly patients. They
may present as slowly enlarging tumors indistinguishable from pleomorphic adenomas. Pain is a common
finding, occurring early in the course of the disease because of perineural invasion. Facial nerve paralysis
may develop within parotid gland tumors. The palatal tumor may be ulcerated.

Genetic: Frequent losses at 12q, 6q23-qter,13q21-q22, and 19q regions have been reported. Promoter
methylation of the p16 was found in 20% of these tumors.

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Histopathology. It is composed of a mixture of myoepithelial cells and ductal cells. The tumor has a wide
spectrum of histological appearances. The cribriform pattern is the most common and best-recognized
type, which consists of islands of basaloid epithelial cells containing cyst-like spaces resembling swiss
cheese. These spaces contain basophilic mucoid or hyalinized eosinophilic products. These cells are uniform
in appearance, and mitotic activity is rare. Tubular pattern the tumor cells occur as multiple small ducts
within the hyalinized stroma. And finally solid variant consists of a sheet of tumor cells, unlike cribriform
and tubular, this pattern shows cell pleomorphism and mitotic activity. Highly characteristic feature of this
tumor is the perineural invasion.

Treatment. Surgical excision, however, is characterized by local recurrence and distant metastasis.

3-Acinic cell adenocarcinoma (ICD-O code 8550/3)

The acinic cell carcinoma is an uncommon neoplasm, as this malignancy occurs mostly in serous acini, so the
great majority arise in the parotid gland. It acts in a non-aggressive fashion and is associated with a good
prognosis, or it represents low-grade malignancy.

Clinically: Most common in the parotid gland, occurs in a wide age range, and appears as a slow-growing
mass. However, associated pain and tenderness can be noted.

Histological appearances, This tumor may be well-

circumscribed. However, some show infiltrative growth. It
has a variable appearance. The solid variety consists of
sheets of serous acinar cells of large, basophilic, granular
cytoplasm, with a round dark nucleus with a uniform
appearance similar to the serous acinar cells of normal
salivary glands. Other tumors may show a cystic pattern.
These multiple cysts contain mucin or eosinophilic material.

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4-Carcinoma arising in pleomorphic adenoma (ICD-O code 8941/3)
Characterized by malignant transformation of epithelial component of previously benign pleomorphic
adenoma
Clinically: It occurs in middle-aged and old adults. The patient had already mass present for years and
undergo rapid growth and ulceration., or others with short duration. Almost most cases occur in the parotid
gland.

.Histopathology: Areas of typical benign pleomorphic adenoma can be seen with an area of malignant
changes of the epithelial component characterized by cellular pleomorphism, an abnormal mitotic activity,
often has an aggressive pattern with capsular invasion and infiltration in surrounding tissues.

Treatment. Invasive carcinoma needs wide excision with local lymph node dissection and adjunctive
radiotherapy.

Grading of salivary gland carcinomas

Most grading is done using general cytomorphologic features (pleomorphism, mitoses, necrosis) and is thus
highly individualized. Even when grading systems exist, there may be several to address the same tumor
type, none of which correlate exactly with one another.

Adenoid cystic carcinoma is graded quickly and simply in that it is based solely on the growth
pattern. Subsequently, the grading of this tumor has evolved into three grades of increasing aggressiveness
based on predominant growth pattern: grade 1: tubular, grade 2: cribriform, and grade 3: solid. Regardless of
grade, all adenoid cystic carcinomas are treated with surgery plus irradiation because, locally, they are
aggressive and ‘high risk. Though there is some evidence to suggest that solid/grade 3 adenoid cystic
carcinomas have a higher likelihood of lymph node metastasis

Mucoepidermoid carcinomas are graded by most into low, intermediate, and high grade.. which depends on
cytomorphologic and architectural and may include perineural and angiolymphatic invasion. Assigning point
values to each adverse histologic parameter and with ascending point scores equating to a higher grade.

5-Mammary analogue secretory carcinoma

Is a newly known salivary gland malignancy with histopathologic features similar to secretory carcinoma of
the breast.

Clinical Features; The mean age of the tumor is 47 years, with a male predilection. It affects most
commonly the parotid gland, while the minor salivary glands and submandibular glands are affected less
frequently. It appears as a slowly growing, painless mass.

Histopathology: This tumor shows histopathological

features similar to those of secretory carcinoma of the
breast. The tumor cells have bland, vesicular nuclei
surrounded by slightly granular or vacuolated cytoplasm.
These cells revealed various patterns of arrangement;
solid, tubular, microcystic, or large cystic structures.
Papillary infolding of tumor cells in cystic space is seen
with a “hobnail” appearance.

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Immunostaining: The tumor cells show diffuse immunoreactivity for S-100 protein, vimentin, and
mammaglobin.

6-Polymorphous low-grade adenocarcinoma

Clinical features: It is almost exclusively a tumor of the minor salivary glands. Most commonly detected
in the hard or soft palate, followed by the upper lip and buccal mucosa. It is most commonly seen in old
adults. This tumor is characterized by slow growth and appears as a painless mass.

Histopathology: Tumor cells have a deceptively uniform appearance. They are round to polygonal in shape,
with indistinct cell borders and pale to eosinophilic cytoplasm. The nuclei may be round, or ovoid.. The cells
can display different growth patterns, hence, the polymorphous term. The cells may show solid patterns, form
cords, ducts, or larger cystic spaces. In some tumors, a cribriform pattern can be produced that mimics
adenoid cystic carcinoma.

Immunostaining: Polymorphous low-grade adenocarcinoma shows a significantly weaker expression of

CD43 and c-kit (CD117) than adenocystic carcinoma.

Treatment and prognosis: It is best treated by wide surgical excision; the overall prognosis is relatively
good

Polymorphous low-grade adenocarcinoma showed various

morphological patterns of solid (A), cribriform (B), tubular (C),
trabecular (D).X100