malignant tumors of the salivary glandsdental.subharti.org/oral_path/e-lecturers/dr preeti...adenoid...
TRANSCRIPT
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MALIGNANT
TUMORS OF THE
SALIVARY GLANDS
Dr Preeti Sharma, MDS
Associate Professor
Dept of Oral & Maxillofacial Pathology & Oral
Microbiology,
Subharti Dental College & Hospital
Swami Vivekanand Subharti University
Meerut, UP
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What you will Learn
Malignant Salivary gland Tumours:
1. Mucoepidermoid carcinoma
2. Adenoid cystic carcinoma
3. Polymorphous low grade adenocarcinoma
4. Carcinoma ex pleomorphic adenoma
5. Adenocarcinoma NOS
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Tumor like Lesions:
A. Sjogren’s syndrome
B. Mickulicz Disease
C. Necrotizing sialometaplasia
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Tumors of salivary glands constitute a heterogeneous group of lesions of great morphologic variation.
These tumors are relatively uncommon
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HISTOGENESIS OF SALIVARY GLAND NEOPLASMS
Semipluripotential bicellular reserve cell hypothesis
Specific reserve or basal cells of the excretory and intercalated ducts or both are responsible for replacement of all types of cells in normal gland and hence are the sole source for neoplastic transformation.
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Multicellular histogenetic concept
Any of the various cells found in the normal salivary gland could serve as a precursor for neoplasia; thus, this is a multicellular histogenetic concept.
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HISTOLOGICAL CLASSIFICATION OF SALIVARY GLAND TUMORS (WHO, 2005)
1. BENIGN EPITHELIAL TUMOURS
Pleomorphic adenoma (mixed tumour)
Myoepithelioma
Basal cell adenoma
Warthin tumour
Oncocytoma
Canalicular adenoma
Sebaceous adenoma
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Sebaceous adenoma
Sebaceous Lymphadenoma
Ductal papillomas
- Inverted ductal papilloma
-Intraductal papilloma
-Sialadenoma papilliferum
Cystadenoma
- Papillary cystadenoma
- Mucinous cystadenoma
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2. MALIGNANT EPITHELIAL TUMOURS
Acinic cell carcinoma
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Polymorphous low grade adenocarcinoma
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Epithelial-myoepithelial carcinoma
Basal cell adenocarcinoma
Sebaceous carcinoma
Sebaceous lymphadenocarcinoma
Cystadenocarcinoma
Low-grade cribriform cystadenocarcinoma
Mucinous adenocarcinoma
Oncocytic carcinoma
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Salivary duct carcinoma
Adenocarcinoma, NOS
Myoepithelial carcinoma
MALIGNANT MIXED TUMOURS
A. Carcinoma ex pleomorphic adenoma
B. Carcinosarcoma
C. Metastasizing pleomorphic adenoma
Squamous cell carcinoma
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Small cell carcinoma
Lymphoepithelial carcinoma
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Malignant pleomorphic adenoma
Clinical features
Most common in middle age & older adults
Rapid growth with associated pain or ulceration
Often fixation
Slight female predilection
Tumor of high grade malignancy grows rapidly & produces pain
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Facial n. paralysis frequent in parotid tumors
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Three categories:
Carcinoma ex pleomorphic adenoma
Carcinosarcoma
Metastasizing Mixed tumor
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Histologic features
Carcinoma ex pleomorphic adenoma
Malignant component appears to overgrow benign
Bulk of tumor appear benign
Areas of malignant degeneration of the epithelial component, characterized by cellular pleomorphism & abnormal mitotic activity
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Malignant component has an aggressive growth pattern with capsular invasion & infiltration into surrounding tissues.
Carcinosarcoma
Biphasic tumor demonstrating both carcinomatous and sarcomatous areas.
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Metastasizing mixed tumor
Has microscopic features of a benign pleomorphic adenoma, within both the primary and metastatic sites. Malignant histopathologic changes are not observed.
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MUCOEPIDERMOID CARCINOMA
One of the most common salivary gland malignancies; most common malignant salivary gland tumor in children.
Clinical features
Most common in parotid salivary gland
Minor glands – 2nd most common site especially the palate
Asymptomatic swelling
Pain or facial n. palsy may develop
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2nd to 7th decade
Slight female predilection
Some tumors associated with history of radiation therapy
Trismus, drainage from the ear, dysphagia, numbness of the adjacent areas & ulcerations
Not encapsulated, tends to infiltrate the surrounding tissue, & tends to matastasize to regional lymph nodes
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HISTOLOGIC FEATURES
Mucus secreting cells, epidermoid type cells and intermediate cells.
Mucous cells of various shapes seen.
Epidermoid cells have squamoid features
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Intermediate cells –progenitor of epidermoid and mucous cells.
Clear cells may be seen.
Epidermoid and mucous cells may be arranged in a glandular pattern.
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Three histopathologic grades based on the following:
1. Amount of cyst formation
2. Degree of cytologic atypia
3. Relative numbers of mucous, epidermoid and intermediate cells.
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GRADED AS
Low grade –
Well formed glandular structures & prominent mucin filled cystic spaces, minimal cellular atypia & high proportion of mucous cells
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Intermediate grade –
Solid areas of epidermoid cells or squamous cells with intermediate basaloid cells.
Cyst formation is seen but is less prominent
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High grade –
Consist of cells present as solid nests & cords of intermediate basaloid cells & epidermoid cells
Prominent nuclear pleomorphism & mitotic activity noted
Cystic component very less
Glandular component rare
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PARAMETER POINT VALUE
Intracystic component <20%
Neural invasion present
Necrosis present
Four or more per 10 HPF
Anaplasia
+2
+2
+3
+3
+4
GRADE TOTAL POINTS SCORE
Low
Intermediate
High
0 – 4
5 - 6
7 - 14
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Variants of tumor
Sclerosing type –
Characterized by an intense central sclerosis with inflammatory infiltrate of plasma cells, eosinophils & lymphocytes.
Intraosseous –
May originate within the jaws.
Central mucoepidermoid carcinoma.
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Treatment -
Conservative excision with preservation of the facial nerve
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Adenoid cystic carcinoma
(Cylindroma) Clinical features
50% in minor salivary glands
Palate – most common site for minor gland tumor
Parotid (2-3%)& submandibular (12-17%)
Middle aged adults – most common
Equal distribution between men & women
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Appears as a slowly growing mass
Pain is common finding
Facial nerve paralysis may develop with parotid tumors
Palatal tumors are smooth & ulcerated
Tumors arising in palate or maxillary sinus may show radiographic evidence of bone destruction
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Histologic features
Mixture of myoepithelial & ductal cells
3 patterns
Cribriform
Most classic
Islands of basaloid epithelial cells that contain cylindric cyst like spaces resembling swiss cheese
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These spaces often contain a mildly basophilic mucoid material, a hyalinized eosinophilic product or combined mucoid - hyalinized appearance
Small strands of tumor cells are seen within hyalinised stroma
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Tubular pattern
Tumor cells occur as multiple small ducts within a hyalinised stroma
Tubular lamina lined by one or several layers of cells, & some times both a layer of ductal cells & myoepithelial cells can be seen
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Solid variant
Consists of large islands or sheets of tumor cells that show little tendency towards cyst formations
Cellular pleomorphsim & mitotic activity may be observed
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Dedifferentiation of Adenoid cystic Carcinoma
Solid sheets and cords of anaplastic tumor cells with focal gland formation
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Perineural invasion –
Highly characteristic feature of adenoid cystic carcinoma is its tendency to show perineural invasion
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Polymorphous low grade adenocarcinoma
Malignant epithelial tumor that is essentially limited in occurrence to minor salivary gland sites and is characterized by bland, uniform nuclear features, diverse but characteristic architecture; infiltrative growth; and perineural infiltration.
Recently described in 1983.
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In minor gland sites PLGA is twice as frequent as ACC.
Average age is 59 years; female predilection.
Firm, nontender swelling involving mucosa of hard & soft palates.
Discomfort, bleeding, telangiectasia or ulceration of the overlying mucosa.
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Histologic features
Infiltrative growth with diverse morphology & uniform cytologic features.
Well circumscribed but unencapsulated & infiltrate into adjacent structures.
Polymorphic nature refers to variety of growth patterns including solid, ductal, cystic and tubular.
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Pseudocribriform pattern in some tumors resembling ACC.
Cuboidal to columnar isomorphic cells that have uniform ovoid to spindle-shaped nuclei.
Scant to moderate amounts of eosinophilic cytoplasm seen.
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Perineural invasion is common that makes this tumor mistaken as ACC.
Indian file arrangement shows streaming cords of cells.
Treatment
Conservative wide surgical excision.
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ACINIC CELL CARCINOMA ACINIC CELL ADENOCARCINOMA
Cells show serous acinar proliferation
CLINICAL FEATURES
85% occur in the parotid gland
This neoplasm makes up 1-3% of all parotid gland tumors
One study showed -8.6% of all parotid tumors.
Less common in submandibular glands
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9% develop in oral minor salivary glands with the buccal mucosa, palate, lips being the most common sites.
Seen in 2nd -7th decade
Mean age- middle 40
Slow growing mass
Asymptomatic
Facial nerve paralysis- an infrequent sign.
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Histologic features Variable microscopic appearance
Well circumscribed & sometimes encapsulated
Some tumors show an infiltrative growth pattern
Most characteristic cell is serous acinar cell
These cells are uniform in appearance, and mitotic activity is uncommon.
Other cells may resemble intercalated duct cells.
Some tumors have cells with a clear, vacuolated cytoplasm.
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Several growth patterns seen-
Solid variety consists of numerous well-differentiated acinar cells .
Microcystic- multiple small cystic spaces are created that may contain some mucinous or eosinophilic material.
Papillary – cystic- larger cystic areas formed that are lined by epithelium having papillary projections into the cystic spaces
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Follicullar- appearance similar to thyroid tissue.
Lymphoid elements sometimes seen.
Treatment / prognosis
Surgical excision
Poor prognosis if features like pain or fixation, gross invasion seen
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Adenocarcinoma (NOS) not otherwise specified
Rare but aggressive tumors.
Clinical features
Present in patients over 40 years of age.
Mostly seen in parotid gland.
Palate most common in minor salivary gland sites.
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Histopathology
Demonstrate a wide range of growth patterns, and somewhat difficult to classify.
All adenocarcinomas have in common the formation of glandular structures.
Grades I, II or III depending upon the degree of cellular differentiation.
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TUMOR LIKE LESIONS
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Mickulicz disease reserved for cases associated with benign lymphoepithelial lesions.
Mickulicz Syndrome –cases of parotid and lacrimal enlargement secondary to other disease like tuberculosis, sarcoidosis and lymphoma.
These terms should no longer be used.
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Benign lymphoepithelial lesion
Mikulicz disease is a chronic condition characterized by the abnormal enlargement of the salivary and lacrimal glands.
Uncommon
Inflammatory & neoplastic
Autoimmune disease
Often occurs in combination with Sjogren syndrome.
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CLINICAL FEATURES
Xerostomia, difficulty in swallowing and result in tooth decay.
Enlarged lacrimal glands, leading to decreased tears.
Painless swellings of the salivary glands.
Recurring fevers accompanied by dry eyes.
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Unilateral / bilateral enlargement (85%)
Associated with salivary gland pathology such as sialoliths and benign or malignant epithelial tumors.
85% cases occur in the parotid gland. Onset – fever, infection
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Diffuse enlargement of salivary gland
Size – few cm in diameter
Asymptomatic or associated with mild pain
Women affected more
Middle or later life- mean age 50yrs
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Histologic features
Lymphocytic infiltration destroying or replacing the acini,
Germinal centers may or may not be seen.
Acini replaced by epithelial cells
Lymphoid element diffuse
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Cellular proliferation & loss of polarity
Solid nests/ clumps of poorly defined epithelial cells
Epimyoepithelial islands throughout the lymphoid proliferation.
Eosinophilic material in epithelial islands-seen in advanced lesions.
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Treatment
Surgical excision
Radiation
Mild cases – no treatment
Persistent cases – surgical excision
Prognosis – good
Associated malignancy- a malignant lymphoepithelial lesion or lymphoepithelial carcinoma.
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Sjogren’s syndrome
Chronic , systemic autoimmune disorder that involves the salivary and lacrimal glands.
Triad of
- Keratoconjunctivitis sicca
- Xerostomia
- Rheumatoid arthritis
Two forms- Primary / Secondary
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PRIMARY- sicca syndrome alone: no other autoimmune disorder present
SECONDARY- patient shows sicca syndrome in addition to another associated autoimmune disease.
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Etiology
Genetic
Hormonal
Infection
Immunological
EBV
HLA Ag-HLA-DRw52 associated with both forms of the disease.
HLA-B8 and HLA-DR3 seen in primary form of the disease.
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Clinical features
> 40 years or in middle aged adults.
10 : 1 female male ratio
Dryness of mouth & eyes
Painful burning sensation of oral mucosa
Difficulty in swallowing, altered taste or difficulty in wearing dentures.
Fissured tongue & atrophy of the papillae.
Denture sore mouth & angular cheilitis
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Dental decay, especially cervical caries
Secretory glands involved
Parotid enlargement
Lymphadenopathy
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Histologic features
Lymphocytic infiltration of the salivary gland
Destruction of the acinar units.
Proliferation of ductal & myoepithelium
Atrophy of gland
Antisalivary duct antibody
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Lab Findings
Primary
- Hyperglobulinemia
- Cryoglobulins
- Multiple organ / tissue specific antibodies
- Increased ESR
- Antisalivary duct antibody more in
secondary
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X - RAY
Sialography
Formation of cavitary defects
Cherry blossom
Branchless fruit- laden tree
Reduced salivary flow – sequential salivary scintigraphy
Sialochemistry – IgA, K, Na levels are elevated
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Treatment
No satisfactory treatment
Symptomatically
Ocular lubricants- methylcellulose
Saliva substitutes
Dental caries
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Oral hygiene
Surgery in cases of enlargement
Complications are:
Pseudolymphoma & malignant lymphoma
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Necrotizing sailometaplasia
Uncommon
Destructive inflammatory condition
Ischemia
Mimics malignancy
ETIOLOGY
Traumatic injuries
Radiation therapy
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Dental infections
Ill fitting dentures
Upper respiratory infection
Adjacent tumors
Previous surgery
Tobacco use.
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Clinical features
Palatal glands
75% posterior palate, hard palate
2/3rd unilateral
Other minor glands & occasionally parotid and submandibular gland.
Mean age - 46 years
Males affected twice
Nonulcerated swelling
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Lesions often painless.
Some lesions present as a submucosal swelling, without ulceration of the overlying mucosa.
Necrotic tissue slough out.
Crateriform ulcer of the palate that simulates a malignant processes.
Destruction of the underlying palatal bone.
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Histopathologic features
Acinar necrosis
Acinar cells lack nuclei, appear pale & basophilic
Squamous metaplasia of ducts
Lobular architecture preserved
Liberation of mucin
Inflammatory response
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Scattered neutrophils & foamy histiocytes
Pseudoepitheliomatous hyperplasia of the overlying mucosa can also be present.
DIFFERENTIAL DIAGNOSIS
Squamous cell carcinoma
Mucoepidermoid carcinoma
Treatment
NS resolves spontaneously.
No treatment is necessary.
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Frequently asked questions
Short Notes on:
1. Mucoepidermoid carcinoma
2. Adenoid cystic carcinoma
3. Polymorphous low grade adenocarcinoma
4. Sjogren’s syndrome.
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Objective type questions:
a) Name the histopathologic patterns seen in adenoid cystic carcinoma.
b) Which is the classic histopathologic pattern seen in adenoid cystic carcinoma
c) Name the tumor-like lesion of salivary gland which mimics malignancy clinically as well as microscopically. Which is the most common site of this lesion?
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REFERENCES
Text book of Oral Pathology. Shafer’s. Eighth edition.
Oral & Maxillofacial Pathology. Neville. Third Edition.
Clinical Pathologic correlations in Oral Pathology. Regezzi. Sixth Edition.
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