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Salivary Gland Tumors Dr. Arsalan Malik Assistant Professor (Oral Pathology) ِ م يِ حَ ّ ر ل اِ ن مْ حَ ّ ر ل اِ له ل اِ مْ سِ ب1

Salivary gland pathology

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Page 1: Salivary gland pathology

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Salivary Gland Tumors

Dr. Arsalan MalikAssistant Professor (Oral Pathology)

حيم الر حمن الر الله بسم

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Anatomy of Salivary Glands

Three major salivary glands

• Parotid gland (Stensen’s duct)

• Submandibular gland (warthin’s duct)

• Sublingual gland (Bartholin’s duct)

• Innumerable minor salivary glands in mucosa and oral cavity

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Functions of Saliva• Protection• Lubrication• Buffering• Digestion• Taste• Antimicrobial • Tooth integrity

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Normal histology of salivary gland

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Acinar cells of Salivary Glands

Classified as either:

• Serous cells: produce a thin watery secretion

• Mucous cells: produce a more viscous secretion

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Salivary gland secretory unit

• Composed of terminal acini

• Intercalated, striated and excretory ducts

• Myoepithelial cells

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Major Glands/Secretions

• Major SG are paired structures and include the parotid, submandibular and

sublingual

• Parotid: serous

• Submandibular: mucous & serous

• Sublingual: mucous

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Diseases of Salivary Glands

• Neoplastic

• Developmental

• Infectious

• Inflammatory

• Autoimmune

• Ischemic

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Salivary Gland Tumors

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Etiologic Factors

• Radiation exposure

• Genetic predisposition

• Tobacco

• Chemical carcinogens

• Viruses

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Salivary Gland Tumors• Incidence: • 6 % of head & neck neoplasms

• Age: 6 – 7th decades - peak incidence• Gender: female predilection• Site: • Parotid: 64 - 80% • Minor glands (palate): 9 -23%• Submandibular gland: 8 - 11% • Sublingual gland: < 1%

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Tumors of the salivary gland may arise from -- the salivary epithelium (the parenchyma) --or the supportive stroma (mesenchymal)

Benign parenchymal tumors are known as Adenomas Malignant tumors are known as adenocarcinomas .

Salivary gland tumors may arise form any cellular component including the basal cells ductal, striated intercalated ducts, acini and the myoepithelial cells.

Salivary gland Tumors

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Salivary Gland Tumors• Benign• Malignant

Relative proportion of malignancy increasing in the smaller glands (rule of thumb is the 25/50/75 rule)

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Salivary Gland TumorsBenign

► Pleomorphic adenoma► Warthin`s tumor ► Oncocytoma► Myoepithelioma ► Ductal papilomas► Monomorphic adenoma1. Basal cell adenoma 2. Canalicular adenoma

Malignant ►Mucoeidermoid carcinoma►Acinic cell carcinoma►Adenoid cystic carcinoma►Polymorphous low grade adenocarcinoma►Carcinoma arising in pleomorphic adenoma

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BENIGN SAIVARY GLAND TUMORS

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General Characteristics• Grow slowly,

• Asymptomatic,

• Do not fluctuate in size

• Usually of long duration

• Present a single nodule

• Not fixed to overlying skin or mucous membrane

• Recurrent lesion may be multi- nodular

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Salivary Gland TumorsBenign

► Pleomorphic adenoma► Warthin`s tumor ► Oncocytoma► Myoepithelioma ► Ductal papilomas► Monomorphic adenoma1. Basal cell adenoma 2. Canalicular adenoma

Malignant ►Mucoeidermoid carcinoma►Acinic cell carcinoma►Adenoid cystic carcinoma►Polymorphous low grade adenocarcinoma►Carcinoma arising in pleomorphic adenoma

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Pleomorphic Adenoma• Benign glandular neoplasm

• Incidence: common

• 70% of salivary tumors

• Gender: female > male

• Age: 3-6th decades

• Site: parotid, palate, upper lip, buccal mucosa

• Symptoms: slow growing painless mass

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Pleomorphic Adenoma Gross Pathology:

- well circumscribed firm tan white solid or partially cystic mass

Histology: - ductal epithelial cells - myoepithelial cells - stroma: myxoid, chondroid, fibrohyaline

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Pleomorphic Adenoma

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Pleomorphic AdenomaTreatment:

• Surgical excision

• Superficial parotidectomy

• Prognosis: excellent

• Complications:

• recurrence – multifocal

• malignant transformation (5%)

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Salivary Gland TumorsBenign

► Pleomorphic adenoma► Warthin`s tumor ► Oncocytoma► Myoepithelioma ► Ductal papilomas► Monomorphic adenoma1. Basal cell adenoma 2. Canalicular adenoma

Malignant ►Mucoeidermoid carcinoma►Acinic cell carcinoma►Adenoid cystic carcinoma►Polymorphous low grade adenocarcinoma►Carcinoma arising in pleomorphic adenoma

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Warthin’s Tumor (Papillary Cystadenoma Lymphomatosum)• Benign salivary gland tumor

• Incidence: common

• Gender: male > female

• Age: 5-7th decades

• Symptoms: painless mass

• Site: parotid, multi-focal/bilateral (14%)

• Etiology: smoking (8 fold risk)

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Warthin’s Tumor• Gross Pathology:• Well circumscribed cystic mass• Papillations • “machine oil fluid”

Histology: • Encapsulated cystic lesion• Papillary fronds• Oncocytic columnar cells• Lymphoid stroma

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Warthin’s Tumor

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Warthin’s TumorTreatment:• Surgical excision• Superficial parotidectomy• Prognosis: excellentComplications: • Recurrence – 6-12% (multicentric)• Association with other salivary tumors • Malignant transformation – extremely rare

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Salivary Gland TumorsBenign

► Pleomorphic adenoma► Warthin`s tumor ► Oncocytoma► Myoepithelioma ► Ductal papilomas► Monomorphic adenoma1. Basal cell adenoma 2. Canalicular adenoma

Malignant ►Mucoeidermoid carcinoma►Acinic cell carcinoma►Adenoid cystic carcinoma►Polymorphous low grade adenocarcinoma►Carcinoma arising in pleomorphic adenoma

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Oncocytoma

• Benign salivary gland neoplasm• Incidence: rare (1% of salivary tumors)• Site: parotid gland (85-90%)• Age: 6-8th decades• No gender predilection• Symptoms: painless mass (<4 cm)• Multifocal/bilateral

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Oncocytoma

• Encapsulated

• Trabecular-organoid

• Oncocytic epithelial cells

• Fibrous septae

• Clear cells

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OncocytomaTreatment

• Surgical excision

Prognosis

• Excellent

• Recurrence uncommon

• Oncocytic Adenocarcinoma - sinonasal tract

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Oncocytoma• Electron Microscopy:

-Mitochondrial hyperplasia

-60% of cell volume

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Ductal Papillomas

Present in three forms

• 1-Simple ductal papilloma

• 2-Inverted ductal papilloma

• 3-Sialadenoma papilliferum

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Simple ductal papilloma

-Exophytic lesion, papillary surface and pedunculated base

-Reddish in color present on palate or buccal mucosa

-It consist of non-keratinized epithelium, columnar, supported by a core of vascular fibrous connective tissue

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Inverted ductal papilloma

-Present as a nodule of oral mucosa of adults. No

distinctive clinical features

-Histologically it consist of squamous, cuboidal,or

columnar cells which proliferate into duct to form a

bulbous masses.

Mucous cells and micro cyst with mucous may be

seen

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Sialadenoma Papilliferum

-The lesion occurs in adults

-Exophitic papillary lesion of hard palate

-Luminal layer of columnar cells on cuboidal

basal layer.

-Connective tissue papillae contain plasma

cells

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Salivary Gland TumorsBenign

► Pleomorphic adenoma► Warthin`s tumor ► Oncocytoma► Myoepithelioma ► Ductal papilomas► Monomorphic adenoma1. Basal cell adenoma 2. Canalicular adenoma

Malignant ►Mucoeidermoid carcinoma►Acinic cell carcinoma►Adenoid cystic carcinoma►Polymorphous low grade adenocarcinoma►Carcinoma arising in pleomorphic adenoma

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Monomorphic adenoma

• Consists of single epithelial cells type

• Basal cell, canalicular, sebaceous, glycogen-rich, clear cell

• Most common types are

- Basal Cell Adenoma

- Canalicular Adenoma

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Canalicular Adenoma

• Benign salivary gland neoplasm

• Monomorphic adenoma

• Site: upper lip (75%)

• Age: 7th decade

• Gender: female predilection

• Symptoms: slow growing mass

• Multifocal

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Canalicular Adenoma

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Canalicular AdenomaTreatment

• Conservative surgical excision

• Enucleation not recommended

Prognosis

• Excellent

• Rare recurrence

• Can be misdiagnosed as a malignancy

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Basal Cell Adenoma• Benign salivary gland neoplasm

• Monomorphic adenoma

• Incidence: 2% of salivary gland tumors

• Site: parotid gland (75%)

• Age: 4-9th decades

• Gender: female predilection (2:1)

• Symptoms: slow growing mass (< 3cm)

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Basal Cell Adenoma

• Solid

• Most common

• Solid nests of tumor cells

• Uniform, hyperchromatic, round nuclei,

indistinct cytoplasm

• Peripheral nuclear palisading

• Scant stroma

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Basal Cell Adenoma

Trabecular pattern `Elongated anastomosing cords of basal

cells, surrounded by connective tissue stroma.

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Basal Cell Adenoma

Tubular Pattern `Basaloid cells surrounds the duct like

structure.

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Basal Cell Adenoma

Membranous or dermal analogue adenoma

`Tumor islands moulded in jig saw

puzzle fashion surrounded by

hylinized basal lamina

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Basal Cell AdenomaTreatment• Complete surgical excision

Prognosis• Excellent• Recurrences may occur• Malignant transformation is rare • Hybrid tumor

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Malignant Epithelial Tumors

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Malignant Epithelial Tumors Mucoepidermoid carcinoma – 29% Adenocarcinoma, NOS –

27% Acinic cell carcinoma –

17% Polymorphous low grade

carcinoma – 19.6% Adenoid cystic carcinoma – 7.5%

Basal cell adenocarcinoma – 2.9%

Epithelial myoepithelial carcinoma – 1%

Clear cell carcinoma – 1%

Salivary duct carcinoma – 0.5%

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Malignant salivary gland tumors

• Shorter duration than benign

• Grow rapidly or history of slow growth with sudden rapid activity

• Fixed to surrounding tissues

• Overlying skin or mucous membrane may be ulcerated or inflamed

• Surface talengectasia

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Malignant salivary gland tumors

• Parotid gland tumors associated with facial nerve paralysis or neurological

symptoms

• Regional lymph nodes may be enlarged

• Palate and retromolar gland tumors infiltrate bone,produce radiolucencies and

loosening of teeth

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Salivary Gland Tumor Staging

• T1: tumor < 2 cm

• T2: tumor 2 - 4cm

• T3: tumor > 4 cm or extraparenchymal

• T4a: invades skin, mandible, ear canal or facial nerve

• T4b: tumor invades skull base, pterygoid plates or encases carotid artery

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Salivary Gland TumorsBenign

► Pleomorphic adenoma► Warthin`s tumor ► Oncocytoma► Myoepithelioma ► Ductal papilomas► Monomorphic adenoma1. Basal cell adenoma 2. Canalicular adenoma

Malignant ►Mucoeidermoid carcinoma►Acinic cell carcinoma►Adenoid cystic carcinoma►Polymorphous low grade adenocarcinoma►Carcinoma arising in pleomorphic adenoma

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Mucoepidermoid Carcinoma• Malignant epithelial salivary gland tumor• 2nd most common salivary gland tumor • 30% of malignant salivary gland tumors• Age: 2nd – 7th decades• Gender: slight female predilection• Site: parotid gland, palate• Etiology: radiation exposure• Asymptomatic swelling

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Mucoepidermoid Carcinoma• Gross pathology

• Well-circumscribed to partially encapsulated to unencapsulated

• Solid tumor with cystic spaces

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Mucoepidermoid Carcinoma

• Histology—Low-grade

• Mucus cell > epidermoid cells

• Prominent cysts

• Mature cellular elements

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Mucoepidermoid Carcinoma

• Histology—Intermediate- grade

• Mucus = epidermoid

• Fewer and smaller cysts

• Increasing pleomorphism and

mitotic figures

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Mucoepidermoid Carcinoma

• Histology—High-grade

• Epidermoid > mucus

• Solid tumor cell proliferation

• Mistaken for SCCA

• Mucin staining

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Mucoepidermoid Carcinoma

• Histology—High-grade

• Epidermoid > mucus

• Solid tumor cell proliferation

• Mistaken for SCCA

• Mucin staining

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Mucoepidermoid CarcinomaTreatment

Influenced by site, stage, grade

Stage I & II

Wide local excision

Stage III & IV

Radical excision

+/- neck dissection

+/- postoperative radiation therapy

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Prognosis• Recurrence

• Metastasis – lymph nodes, lung, bone, skin

• Low to intermediate grades

• – good prognosis ( 90% 5 year survival )

• High grade

• – poor prognosis (40% 5 year survival)

• Site: submandibular, floor of mouth, tongue

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Salivary Gland TumorsBenign

► Pleomorphic adenoma► Warthin`s tumor ► Oncocytoma► Myoepithelioma ► Ductal papilomas► Monomorphic adenoma1. Basal cell adenoma 2. Canalicular adenoma

Malignant ►Mucoeidermoid carcinoma►Acinic cell carcinoma►Adenoid cystic carcinoma►Polymorphous low grade adenocarcinoma►Carcinoma arising in pleomorphic adenoma

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Acinic Cell Carcinoma

• 2nd most common parotid and pediatric malignancy

• 5th decade

• F>M

• Bilateral parotid disease in 3%

• Presentation

• Solitary, slow-growing, often painless mass

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Acinic Cell Carcinoma

• Gross pathology

• Well-demarcated

• Most often homogeneous

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Histopathology

• Circumscribed

• Variable growth patterns

• Variable cytology

• Low grade tumor

• Scant stroma

• Lymphoid infiltrate

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Histopathology

• Histology

• Solid and microcystic patterns

• Most common

• Solid sheets

• Numerous small cysts

• Polyhedral cells

• Small, dark, eccentric nuclei

• Basophilic granular cytoplasm

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Acinic Cell Carcinoma Treatment:

- surgical excision Prognosis: - low-grade malignancy

- 12% recur - 8% metastasize - 6% mortality - prognosis is better for minor gland tumors Undifferentiated carcinoma component (rare) Difficult diagnosis for pathologist

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Adenoid Cystic Carcinoma• Overall 2nd most common malignancy

• Most common in submandibular, sublingual and minor salivary glands

• M = F

• 5th decade

• Presentation

• Asymptomatic enlarging mass

• Pain, paresthesias, facial weakness/paralysis

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Adenoid Cystic Carcinoma• Gross Pathology:

• - uncapsulated firm solid tan mass

• Histology:

highly infiltrative

small hyperchromatic cells

cribriform (“Swiss cheese”), tubular, solid

mucohyaline stroma

Perineural invasion

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Adenoid Cystic Carcinoma• Gross pathology

• Well-circumscribed

• Solid, rarely with cystic spaces

• infiltrative

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Adenoid Cystic Carcinoma• Histology—

• cribriform pattern

• Most common

• “swiss cheese” appearance

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Adenoid Cystic Carcinoma• Histology—tubular pattern• Layered cells forming duct-

like structures• Basophilic mucinous

substance

• Histology—solid pattern• Solid nests of cells without

cystic or tubular spaces

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Adenoid Cystic CarcinomaTreatment

Complete local excision

Tendency for perineural invasion: facial nerve sacrifice

Postoperative Radiations

Prognosis

Local recurrence: 42%

Distant metastasis: lung

Indolent course: 5-year survival 75%, 20-year survival 13%

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Salivary Gland TumorsBenign

► Pleomorphic adenoma► Warthin`s tumor ► Oncocytoma► Myoepithelioma ► Ductal papilomas► Monomorphic adenoma1. Basal cell adenoma 2. Canalicular adenoma

Malignant ►Mucoeidermoid carcinoma►Acinic cell carcinoma►Adenoid cystic carcinoma►Polymorphous low grade adenocarcinoma►Carcinoma arising in pleomorphic adenoma

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Polymorphous low grade adenocarcinoma• Malignant epithelial neoplasm

• Oral cavity - minor glands

• Age: wide range – 6-8th decades

• Female gender predilection

• Site: palate (65%), lip, buccal mucosa

• Symptoms: painless swelling

• Duration: weeks to years

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Polymorphous low grade adenocarcinoma• Malignant epithelial neoplasm

• Oral cavity - minor glands

• Age: wide range – 6-8th decades

• Female gender predilection

• Site: palate (65%), lip, buccal mucosa

• Symptoms: painless swelling

• Duration: weeks to years

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Polymorphous low grade adenocarcinoma• 2nd most common malignancy in

minor salivary glands• 7th decade• F > M• Painless, submucosal mass• Morphologic diversity

• Solid, glandular, cribriform, ductular, tubular, trabecular, cystic

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Polymorphous low grade adenocarcinoma• Histology• Isomorphic cells, indistinct borders,

uniform nuclei• Peripheral “Indian-file” pattern

• Treatment• Complete yet conservative excision

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Lymphoepithelial Carcinoma• Rare• High grade/poorly differentiated carcinoma• Lymphoid stroma• Asians, Greenlanders• Epstein-Barr virus• Prognosis - guarded

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Lymphoepithelial Carcinoma• undifferentiated tumor associated with

a dense lymphoid stroma

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Salivary Adenocarcinoma NOS• Some tumours still defy the current classification of salivary gland

tumours• These are labelled as Salivary Adenocarcinoma Not Otherwise

Specified (NOS)

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Treatment & Prognosis

• Early stage, well differentiated tumours appear to have a better

prognosis

• The survival rate is better for tumours of oral cavity as compared to

tumours of major salivary gland.