Oral Pathology Made Easy ….!!!

Salivary Gland Neoplasm

Salivary Gland
Neoplasm

Dr. Ahmed ElNashar

2023
• Incidence: 2% of head and neck neoplasm & 2nd most common tumors affecting oral cavity (after SCC).
• Etiology: Unknown, but radiotherapy to head and neck considered as an etiological factor.
• Differentiated cells of all cell types of salivary gland tissue are capable of
Multicellular theory producing a neoplasm.
• De-differntiatted theory ) not accepted)
• Stem cell present in (intercalated ducts ) or ( excxretory duct)
• These cell will be differentiated into …….
Bicellular theory (1) epithelial cell that forming the tumor
OR .. (2) myoepithelial cell w is multipotent can differentiate into
multiple & variable cell

Dr Ahmed ElNashar 2023

Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
CLASSIFICATION

Epithelial Salivary Gland Neoplasm

• Plemorphic adenoma • Mucoepidermoid carcinoma
• Papillary cystic adenoma lymphatosum • Acinic cell carcinoma.
= warthin's tumor • Adenoid cystic carcinoma.
• Oncocytoma = oxyphilic adenoma • Polymorphous adenocarcinoma.
• basal cell adenoma. • Carcinoma Ex pleomorphic adenoma
• Myo-epithelioma • Carcinosarcoma
Malignant
Benign • Canalicular adenoma • metastasizing mixed tumor.
=
= • sebaceous lymphadenoma • Basal cell adenocarcinoma.
Adeno-
adenoma • cystadenoma.
carcinoma • Epithelial Myopepithelial Carcinoma
• Sialadenoma. • Clear cell adenocarcinoma
• Ductal papillomas • Sebaceous adenocarcinoma.
• Sialadeno papilliferum • Lympghoadenocarcinoma.
• Inverted ductal papilloma • Polymorphusadenocarcinoma
• Lymphoadenoma • Squamous cell carcinoma.
• Intraductal papilloma • Adenosquamous cell carcinoma
Other MESENCHYMAL TUMORS
Hemangioma , lipoma , hematolymphoid tumors , lymphoma , metastatic tumors.

DISTRIBUTION
Major (Extra-Oral )(91%)
Minor SG (10%)
Parotid Sub-mand. Sub-lingual Benign Malignant
(70-80%) (12%) (0.3%) 55% 45%
Benign Benign Benign Malignant Malignant
75% 70% 70% 30% 90%

(THE SMALLER THE GLAND. THE GREATER THE LIKELIHOOD OF MALIGNANCY)

-most common S.G.T  Pleomorphic adenoma
- most common benign S.G.T.  Pleomorphic adenoma
- most common malignant S.G.T.  mucoepidermoid carcinoma
- most common malignant S.G.T.in childern  mucoepidermoid carcinoma
- most common malignant S.G.T in sublingual SG or minor SG  adenoid cystic carcinoma.
- most common tumor of parotid gland in infancy  hemangioma (no epithelial SGT).

General Clinical features of SGT

Benign salivary gland tumor
Site • 75%of parotid tumors are benign
• outer surface is smooth (=not ulcerated)
• Slowly growing
• Painless =- asymptomatic
S&S • No facial nerve involvement
• No enlarged L.N.
• Soft or rubbery consistency
• No-local bone destruction
• Capsulated.
Metastasis
• No distant metastasis
Prognosis • Prognosis is good
Malignant Salivary Gland tumor
• 45%of minor gland tumors are malignant
• ulcerated, especially intra oral lesions.
• Rapidly growing or slow e sudden rapid growth.
• painful.
• Facial nerve paralysis is common
• Enlarged L.N.
• Sometimes hard consistency
• Bone destruction is usually present
• Not capsulated.
• Metastasize.
• according to the condition.

Dr Ahmed ElNashar 2023

 Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
Benign Salivary Gland Neoplasm
1.Pleomorphic Adenoma
= Benign Mixed tumor
Introduction
• Most common SGT.
80 % of parotid tumor rte begin
• Role of 80 80% of parotid tumor are pleomorphic adenoma
80% of parotid pleomorphic are in superficial lobe
80 % of untreated pleomorphic adenoma remain bengin.
Histogenesis (origin) :
• Pure epithelial tumor arises from intercalated duct stem cell.
• Stem cell can differentiated giving epiuthelial and myoepithelial cells forming the tumors.
Terminology
• Means arises from more than one germ layer, Not completely accurate??? Pure epithelial tumor
Mixed
• Used here bcoz tumor show variable histological changes ( epith.& stromal component)
Clinical features

Age • 30 - 60.
Sex • Slight ♀> ♂.
• common site extraoral is parotid gland(80%)(superficial lobe & tail) 1st site
Site
• common site intraoral, palate. 2nd site
• Long standing parotid lesions may reach giant size (=grotesque).
size
.‫ ف الترم االول‬ameloblastoma ‫• تسند على كتف العيان زي ال‬
• ‫ الكالم العام‬painless. slowly growing, mobile, soft or slightly firm mass.
• overlying skin is intact.
• On palpation: nodular or globular mass.
S&S • Occur . in post lateral part of palate & junction bn hard and soft.
• Non-mobile ???!! bcoz mucosa is tightly bounded to bone.
palate
• Ulcerated ???!! palate has thin stretched over bone so any swelling may
cause mucosal ulceration.
Gross Pathology ‫تستطيع ان تالحظ مزي ج من االنسجة السوفت و الهارد‬

• typically lobulated and show various consistencies and structure.

• Incomplete capsule.
Histopathology
- tumor characterized by : (1) multimodal nature. (2) morphologic diversity. (3) partially capsulated
- tumor is capsulated & composed of epithelial element + mesenchyme –like background

Dr Ahmed ElNashar 2023

 Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
• Tumor composed of………. EPITHELIAL COMPONENT + CT COMPONENT

From Myoepithelial cells or Ductal epithelium

• Epithelial component form (DUCTS, TUBULES) , or (NESTS, SHEET)
Epithelial ▪ Duct structure and tubules from ductal epithelium
▪ Squamous metaplasia of ductal epithelium with keratin formation. lar
▪ Sheets of myoepithelial cells (angular cells
• Myxamtous like (=mucoid like), chondroid like , bone or osteoid tissue.
Stroma • believed to be produced by myoepithelial cells?!!! ‫ازاي‬
=
▪ CHONDROID ??! MUCOID ??!
Intercellular
material ▪ oid mean resemble cartilage tissue…………(not a real cartilage)
• Some cases show bone or osteoid giving calcification.
• capsule may be INCOMPLETE or INFILTRATED WITH tumor cells.
Capsule
• Bcoz of this fact tumor ch. ch. by high rate of recurrence & treated by wide surgical excision.
Tumors composed of myoepith. cells e no ductal elements are called "myoepitheliomas"
- Melting Phenomena myoepithelial cell melt in sea of stroma they produce.
TTT & prognosis
• prognosis is excellent with wide surgical excision. ( i.e with safety margin)
• Best treated by surgical excision e preservation of facial nerve.
• Malignant transformation (5%-10%) to carcinoma EX pleomorphic adenoma.
Lecture notes
• Causes of high rate of recurrence (20%) in pleomorphic??!!
1. incomplete CT capsule. 2. Multi-nodal nature. 3. chondromyxoid material.
2. Warthin’s Tumor
= Papillary cystadenoma lymphomatosum
Introduction
• the 2nd most common benign SGT.
• Heterotropic SGT composed of both epithelial and lymphoid elements.
Histogenesis: ductal cells.
pathogenesis
1st • tumor arise from embryonic Entrapment of SG tissue ein parotid (para or intra parotid) L.N.
(accepted) • ectopic (heterotopic = choristoma)
• reactive lymphoid hyperplasia secondery to chronic irritation.
2nd
• ‫ عكس اللي فاتت‬Proliferation of lymphocytes around salivary gland duct.
• there is a strong association e cigarette smoking.
• EBV implicated in pathogenies.

Dr Ahmed ElNashar 2023

 Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
Clinical features
Age • 5th to 8th decade of live
• Early studies ………. ♂ =♀.(5:1)
Sex
• Recent studies…….. ♀= ♂.e slight male predilection
Race • white > black.
• Extraoral : parotid (mostly) , subman d. (occasionally)
Site
• Intraoral : Rare.
• ‫الكالم العام‬
S&S • Tend to occur bilaterally (2-6%( →mostly metachronous ?!
occurring at different times
Gross Pathology ‫تستطيع ان تالحظ مزي ج من االنسجة السوفت و الهارد‬

(1) smooth or lobulated. (2)encapsulated (well-demarcated).

(3) solid, with white nodule. (4)cystic spaces with viscous fluid and papillary projection.
Histopathological Features

• Composed of … Mix of epithelium + lymphoid stroma.

• cystic spaces lined e 2raws of epith. Cells
▪ lumina = Inner Layer: eosinophilic columnar cells (oncocyte)
Esinophilc granules are mitochondria detected by EM
Epithelial ▪ basal = outer Layer: cuboidal e central & vesicular nuclei.
• Mucous secreting cells (goblet cells ) scattered bn e[pith lining cells.
• multiple papillary in folding protrude into cystic spaces.
• Focal areas of sq. metaplasia.
Lymphoid • Normal lymphoid stroma shows germinal center (B-lymphocytes) + sinusoidal spaces
Treatment & prognosis
• Conservative surgical removal (= enucleation). Very good prognosis.
• In case of parotid : preservation of facial nerve is recommended.
• (6% - 12%) recurrence rate has been reported, mostly pseudo-recurrence. Bcoz , tumor is multicentric.
3. Oncocytoma
= Oxyphilic adenoma
Introduction
• Rare benign SGT (2.3%). ●common in parotid gland. ●Common in elder.
Origin : Acinic cell (= oncocytes).
Clinical features
Age • 6th decade
Sex • ♀= ♂.
• parotid gland (majority) then submandibular.
Site
• Intraoral : upper lip
• unilateral or bilateral
S&S
• Typical clinical features of benign salivary gland tumor.
Histological features
• oncocytoma is usually a well-circumscribed tumor
• composed of sheets of oncocytes , Sometimes these cells form an alveolar or glandular pattern .
Oncocytes
▪ large polyhedral cells + granular eosinophilic cytoplasm + Central small hyperchromatic or large and vesicular nuclei.
▪ granularity of cytoplasm created by large no of mitochondria, demonstrated by E/M & L/M (PTAH) stain.
▪ My contain glycogen, evidenced by +ve (PAS).
• thin fibrovascular septa + lymphocytic infiltrate may be noted + may contain variable no. of clear cell.
TTT: surgical excision.
Dr Ahmed ElNashar 2023
 Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
4. Basal Cell Adenoma
Introduction
• Rare benign SGT (1-2%).
Origin: ductal cells.
Clinical features
Age • 60 years old.
Sex • ♀>♂.
• extraoral  70 % parotid gland then submandibular SG
Site
• intraoral  in upper lip then buccal mucosa then lower lip.
Size • < 3 cm
• Typical clinical features of benign salivary gland tumor.
S&S
• May be mulinodular.
Histological features
• well-defined connective tissue capsule.
• proliferating epithelial cells arranged in 1 of the following manner…..
(1) Solid, sheets of cells resembles bsasal cell carcinoma.
(2) Trabecular- Tubular.
(3) Membranous, thick double membrane (+ve PAS)
TTT: surgical excision.
N.B. Canalicular adenoma (clinically resembles basal cell adenoma) ( upper lip then buccal)

5. Canalicular adenoma
Clinical features
Age • 50 years old (30-60)
Sex • ♀>♂.
Site • 81% of lesion intraoral in upper lip
S&S • Typical clinical features of benign salivary gland tumor.
Histological features
• May be not totally capsulated
• Formed of cords of basaloid cells rembles solid or cystic types of basal cell adenoma.
TTT: surgical excision.
5. Myoepithelioma
Introduction : benign SGT (15%).
Origin : Myoepithelial cells
Clinical features
Age • Adults (53)
Sex • ♀=♂.
• Extraoral  parotid gland.
Site
• Intraoral  palate.
S&S • Typical clinical features of benign salivary gland tumor.
Histological features
• sheets of myoepithelial cells ( spindle or plasmacytoid or epithelioid or clear cell).
• IHC : P63 , S100, SMA , calponin, CD10, smooth ms. actin.
TTT: surgical excision.

Dr Ahmed ElNashar 2023

 Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
2. Malignant epithelial salivary gland Tumor
Risk Factors
radiation •  risk for (pleomorphic adenoma) ( mucoepidermoid carcinoma)
Smoking •  risk for (Warthin’s tumor)
Wood, asbestos, rubber, shoes •  risk for (Adenocarcinoma)
How to differentiate malignant from benign tumors
1. neural manifestation. 2. Warmer ( d.t. angiogenesis)
3. pigmentation. 4. Fixation ( to overlying skin & underlying CT)
5. rough polypoid surface. 6. Highly vascularized.
7. perineural invasion. 8. Early invasion to bone. Important criteria of palatal SGT
Parameters highly suspect malignancy (suggestive features of malignancy)
1. induration of margins and floor. 2. fixation to underlying CT and overlying skin.
3. ulceration (not respond to TTT). 4. rapid growth.
5. discoloration. 6. pain & neural manifestation.
7. fixed regional lymphadenopathy.
1.Muco-epidermoid carcinoma
Epithelial and mucin producing tumors = Mix of mucous-producing cells and epidermoid
Introduction
• Most common malignant SGT extraoral and in childhood.
• accounting for only (10%) of malignant SGT in major SG. & (15-23) % of malignant SGT in minor SG.
N.B. most common unilateral parotid swelling in children While most common bilateral is mumps.
Histogenesis : reserve cell in ductal syst. (intra or inter lobular)
Clinical features
Age • 5th decade of life.
Sex • ♀>♂.
• extraoral: parotid gland (1st common site)
Site • intraoral : palate (2nd common site)
• it is the most common malignant SGT in submandibular SG.
• CF of benign → Slowly growing, fluctuant painless mass , covered e intact mucosa.
low grade
• In lip : Similar to mucocele. In palate : similar to periapical abscess or cysts.
S&S
• CF of malignant → Rapidly growing mass ±pain, covered e ulcerated mucosa.
High grade
• Similar to sq cell carcinoma.
Gross Pathology
Low grade • Lesion with multiple cystic spaces
High grade • Solid mass with few or no cystic spaces.
Histopathological features
• Composed of a mixture of mucus-producing cells and squamous (epidermoid) cells.
Mucous • Round cells , contain foamy cytoplasm → +ve to mucin stains PAS & (mucicarmine)
• resembles epidermis cells.  Reserve cell in origin.
Epidermoid
• squamous or polygonal cell with intercellular bridges & rarely keratinization.
Intermediate • stem cell or reserve cell . ‫ممكن تدي اي واحدة من الخليتين‬
Clear cell • -------------------------------------------

Dr Ahmed ElNashar 2023

 Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
• Tumor classified into 3 Histopathological grades based on ……
1. Amount of cyst formation. 2. Degree of cytologic atypia
3. No. of mucous, epidermoid& intermediate cells
Low grade Intermediate grade High grade
•  cystic spaces • Fewer and smaller cysts. •  cystic spaces
•  mucous cells • Intermediate & epidermoid = mucous •  mucous cells
•  epidermoid cell cells •  epidermoid cell
•  intermediate cells •  intermediate cells
• Well differentiated • ------------------------ • poorly differentiated
•  atypia. •  pleomorphism &mitotic figures •  atypia.
More mucous cell , more well differentiated, and more low grade
• Ch.ch by perineural invasion.
Treatment: wide surgical excision + radiation therapy.
Prognosis: Submandibular poorer than parotid + Minor SGT generally good prognosis .
Central muco-epidermoid carcinoma
Most common intrabony SGT
Pathogenesis
• embryonic entrapment of salivary gland tissue entrapped within jaw. (stafen defect= latent bone cyst)
mandible
• mucous cells in wall of dentigerous cysts (95% of cases)
maxilla • mucous cells in lining of maxillary sinus.
Clinical features
• mand.> max. (3:1).  most often seen in molar ramus area.
Radiographic features:
• well defined multilocular radiolucency related to unerupted tooth
• DDX : ameloblastoma , Odont.myxoma, OKC , centeral mucoepidermoid carcinoma ‫ركز اربعة بس‬
Histopathological Features: similar to that of its soft tissue counterpart (mainly low grade)
TTT : Surgical excision is the treatment of choice, followed by radiation therapy.
2. Adenoid cystic carcinoma = cylindroma
Introduction
• Most common malignant SGT of minor SG (any site intraoral) ‫حضات‬
‫ركزوا يا ر‬
• Most common malignant SGT of sublingual SG.
Histogenesis: Ductal & myoepithelial cells.
Clinical features
Age • Middle age.
Sex • ♀=♂.
• major SG (extra-oral) → parotid.
Site
• major SG (intra-oral)→ minor SG & sublingual SG (60%) & sinonasal glands.
• 1st sign → neural manifestation.
• Pain is a common finding??!! Bcoz of perineural invasion.
S&S • Pain starts as a constant dull pain & gradually increase.
• slowly growing but aggressive?!! bcoz it is a hidden lesion so mass present for years prior patient seeking for TTT.
• May present as an ulceration ‫ و متعالجش قرحة اكتر من اسبوعين‬، ‫فخلى بالك‬، ‫ قرحة او الم‬، ‫اول حاجة ممكن تظهر كلينيكال‬
Histological features
Cells are small cuboidal,+ large hyper chromtic nuclei + little cytoplasm

Dr Ahmed ElNashar 2023

 Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
• composed of mix of myoepithelial cells & ductal cells , arranged in one of 3 major patterns …..
• Consist of islands of epith. cells that contain multiple cyst like spaces.
cribriform pattern
• Cysts contain basophilic or eosinophilic product or combination.
=
Swiss cheese • most common patterns (classic form) & best to be recognized.
• Cells: well defined with hyperchromatic neucli
Tubular pattern • consists of multiple small ducts or tubules of epith. Cells.
• Consists of larger islands or sheets of tumor cells.
Solid pattern
• Most aggressive pattern e poorest prognosis.
Usually a combination of these 3 patterns is seen, and the tumor is classified based on the predominant pattern .
Ch. ch. by: (1) perineural invasion. (2) early metastasis. (3) bone invasion.
Prognosis
• poor prognosis…..why??
(1) local recurrence :42%. (2) Metastatic spread : lungs and bones.
(3) perinerural invasion. (4) inrabony invasion.
• Solid pattern poorest prognosis (present in max sinus, palate , sublingual & submandibular SG)
TTT :
• Radical surgical excision + radiation therapy.
• d.t. perineural invasion we usually sacrifices by facial nerve.

3. POLYMORPHUS LOW GRADE ADENOCARCINOMA

Introduction
• 1st described in 1983 by
• WHO classification 2017: polymorphous adenocarcinoma (low grade removed).
Histogenesis: Ductal cells.
Clinical features
Age • 6th-8th decade
Sex • ♀>♂.
• major SG (extra-oral) → parotid.
Site
• major SG (intra-oral)→ palate >buccal > upper lip
• slowly growing painless lesion.
S&S • Associated with bleeding & ulceration.
• Invade bone.
Gross pathology:
• uncapsulated , Firm, well circumscribed, lobulated nodule.
Histopathological features :
Cells are small cuboidal,+ large hyper chromtic nuclei + little cytoplasm
• CHARACTERIZED BY
1. morphologic diversity.
2. malignant cells has ovoid vesicular nuclei & lightly eosinophilic cytoplasm
3. cells has indefinite out line.
4. cells arranges in single file pattern (Indian file)
5. perineural invasion ( targetoid lesion) cells invade neurovascular bundles.

DDX : adenoid cystic ?!

TTT : wide surgical excision.
Prognosis: better prognosis than adenoid cystic carcinoma & less metastatic spread.

Dr Ahmed ElNashar 2023

 Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
4. ACINIC CELL CARCINOMA
Incidence
• 6% of all salivary gland & 17% of malignant salivary gland.
• 2nd most common parotid malignancy
Histogenesis: (1) intercalated duct reserve cells. (2) terminal acinar intercalated duct unit.
Clinical features
Age • 5th- 6thdecade
Sex • ♀>♂.
• major SG (extra-oral) → parotid (bilateral).
Site
• major SG (intra-oral)→ palate >buccal.
S&S • 50% resembles benign/ SG.
Gross pathology:
• well circumscribed, homogenous , firm to soft, Solid Or Cystic, Grayish or reddish mass.
Histopathological features:
• well circumscribed tumor
• CHARACTERIZED by proliferation of serous acinar cell in 4 different pattern
1) CELLs : plyhydral cells with abundant basophilic cytoplasm & round darkly stained eccentric nuclei
2) PATTERNs : solid OR microcystic OR papillary cystic OR follicular pattern
solid & mictocystic pattern most commn
Prognosis: better prognosis than adenoid cystic carcinoma.
5. malignancy In Mixed tumors
= Malignancy in pleomorphic adenoma
• malignant transformation of epithelial component of a preexist benign
pleomorphic adenoma.
• Incidence:
▪ 2-4 % of all salivary gland.
▪ Parotid > submandibular > palate.
▪ (1.5 % in 1st 5 year) (9.5 % after 15 years).
Carcinoma ex
pleomorphic adenoma • C/F:
▪ 6th – 8th decade
▪ Longstanding painless mass undergoes ….
▪ sudden enlargement + neural manifestation + changes in color + fixation + ulceration
• H/P:
▪ Pleomorphic adenoma that is show….
▪ Infiltration + cancer malignant cells + hemorrhage + necrosis
• Malignant transformation of epithelial (carcinomatous) & mesenchymal
component (sarcomatous) of gland.
• Incidence:
▪ Rare (>0.5 of all salivary gland)
▪ Parotid > submandibular > palate.
▪ (1.5 % in 1st 5 year) (9.5 % after 15 years).
• C/F:
Carcino-sarcoma ▪ 6thdecade.  ♀=♂.
▪ History of : recurrence or previous excision of pleomorphic adenoma
▪ Longstanding painless mass undergoes ….
▪ sudden enlargement + neural manifestation + changes in color + fixation + ulceration
• H/P:
▪ Pleomorphic adenoma that is show, biphasic apperance….
▪ Carcinomatous component (moderate or poorly diffrentiatted ductal epith)
▪ Sarcomatous component (chondrosarcoma)
• Histologically tumor are identical to benign pleomorphic (mixed) tumor.
Metastasizing mixed
• Although this benign appearance , lesion metastasize to 2ry sites.
tumors
• Tumor in 2ry site (metastatic tumor) also has the benign microscopic appearance.

Dr Ahmed ElNashar 2023

Oral Pathology Made Easy ….!!! Salivary Gland Neoplasm
6. BASAL CELL ADENO-CARCINOMA

7.EPITHELIAL-MYOEPITHELAIL CARCINOMA

Def ‫ يا دوب ال‬، ‫ كده يعين انت مش مهم بالنسبة ليك قوي اخر اتنني دول‬: ‫ قالت ف اخر الفيديو‬، ‫استاذتنا دكتورة اميان الشامي‬

Dr Ahmed ElNashar 2023