3.

2020

Salivary Gland Diseases

Nguyen Thi Hong, DDS, PhD

Hong Bang International University
 Learning objectives

1. Describe etiology, clinical features, diagnostic procedure

& treatment of salivary gland cysts.
2. Describe etiology, clinical features, diagnostic procedure
& treatment of common sialadenitis.
3. Describe clinical features, diagnostic procedure &
treatment of common benign and malignant salivary
gland tumors.
2
 CONTENTS

1. Anatomy and histology of SG

2. Reactive lesions
3. Sialadenitis
4. Benign SG tumors
5. Malignant SG tumors
 ANATOMY
Major salivary glands:
Parotid glands
Submandibular glands
Sublingual glands

Minor salivary glands:

Labial & buccal glands
Palatine glands
Lingual glands
Pharyngeal glands
 Parotid glands
 Gland: In parotid space
Superficial part - Facial nerve - Deeper part.
 Stenon’s duct: 5 cm -> buccal mucosa opposite to
the 2nd maxillary molar.
 Submandibular glands

• Gland in submandibular space, esp. facial vessels, XII

• Wharton’s duct: 5 cm
Submandibular gland or lymph node ?
 Sublingual glands
 B/t floor of mouth & mylohyoid muscle.
 Large main part & small numerous glands.
 5-15 Rivinus ducts
 Bartholin’s duct: opens with in or adjacent to the
wharton’s duct.

Sublingual glands
 Minor salivary glands
1. Labial & Buccal glands

2. Palatine glands: hundreds;

in the lamina propria of the posto-lateral region of
hard palate & in submucosa of soft palate & uvula.
3. Lingual glands:
ducts -> ventral surface of tongue
near lingual frenum
4. Pharyngeal glands
 HISTOLOGY

1. Serous glands: Parotid glands

2. Mucous glands: Minor SG
• Palatine glands
• Lingual glands: borders & base
of tongue
• Pharyngeal glands
3. Mixed glands:
• Submandibular glands: serous >
• Sublingual glands: mucous >
• Labial and buccal glands
Anterior lingual glands
Structural elements of the salivary gland unit
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Pathology of the Salivary Glands (SG)

1. Anatomy and histology of SG

2. Reactive lesions:
- Cyst
- Necrotizing sialometaplasia
3. Sialadenitis
4. Benign SG tumors
5. Malignant SG tumors
 Salivary Gland Cysts (sialocysts)

1. Minor salivary glands: Mucocele (1st)

2. Sublingual glands: Ranula
3. Parotid glands: cyst, Warthin’s tumor
4. Submandibular glands: cyst
caused by trauma most caused by sialolith

Mucocele is a clinical term that includes

mucus extravasation phenomenon
and mucus retention cyst.
Extravasation cyst Retention cyst
Minor SG • Submandibular gland 80%,
Sublingual gland: parotid 20%, others 1-15%
esp lower lip (esp. upper lip)
• Sialolith  X ray
Extravasation mucocele

Labial glands
Ranula

Plunging or cervical ranula

 Salivary gland cysts

No Superficial mucocele
Treatment

Cyst of major SGs

Excision
Mucocele & associated SG

Marsupialization Ranula

Prognosis: ± recurrent retention cyst

due to duct scarring or reformation of stone
Necrotizing sialometaplasia
- Etiology -

Local
anesthesis injury

spontanous

ischaemia

SG necrosis
 Necrotizing sialometaplasia
- Clinical features -
 Hard palate
 Painful red nodule
central necrosis, ulcer, moderate pain
± extend to deep soft tissue & palatal bone
 6-8 weeks: self-limiting
Necrotizing sialometaplasia

 Microscopical features:
1. Lobular inflammation & necrosis
2. Ductal squamous metaplasia

 Treatment:
• incisional biopsy → diagnosis
• Follow-up only
• Self limiting & heal spontaneously in 6 - 10 weeks.

 Prognosis: Good
Pathology of the Salivary Glands (SG)

1. Anatomy and histology of SG

2. Reactive lesions:
3. Sialadenitis
– Viral infection (Mumps)
– Bacterial infection
– Sialolithiasis
– Allergic, Irradiation
– Immune-related
4. Benign SG tumors
5. Malignant SG tumors
 Viral parotitis (mumps)

 Mumps virus (Paramyxoviridae family)

→ Airborne droplets
→ Epidemic
 Age: esp. 5-18
 Parotid glands, ± submandibular glands
 Rapid bilateral swelling of parotid gland with
acute pain, esp. during salivation, exudate clear
→ persists for 7 - 10 days
→ most cases are uncomplicated
± testis or encephalitis.
 Mumps

• serum level of salivary amylase

• complement-fixing antibodies to the mumps “S”
and “V” antigens
 Diagnosis:
- History + Clinical findings
- Sialolograhy: contraindication
 Treatment:
- Symptom treatment

 Vaccin against mumps

 Bacterial sialadenitis

 Etiology:
- Staphylococcus aureus, Streptococcus pyogenes
- Predisposing factors:
– Reduction in salivary flow
due to localized (calculus)
or systemic factor (Sjögren)
– Low immunity

Suppurative parotitis
 Bacterial sialadenitis
 Clinical features:
– Sudden onset (acute) / Chronic
– Gland: usually unilateral, painful, swollen &
indurated, erythematous overlying skin
– Purulent discharge from orifice

Suppurative parotitis
Bacterial sialadenitis

 Diagnosis:
– History
– Clinical findings
– Sialography
– Ultrasonic
– Bacterial culture
& Antibiogram
– ± FNA or biopsy
(if necessary)
 Bacterial sialadenitis

 Antibiotics after culture &

sensitivity, if not possible →
Antibiotics Flucloxacillin or Spiramycin
Treatment

 Milk the gland several times/day

(not during acute phase)
 hydration & sialogogue
 ± tuberculous sialadenitis

 Remove obstruction (calculus)

Surgery
Surgery  Excision of severely damaged
gland (chronic or recurrent)
→ histopathology
 Sialolithiasis

• Etiology: unknown
(→ Recurrence rate # 20%)

• Contributing factors:
– Chronic sialadenitis
– Irregular duct system
– Local irritants
– Anticholinergic medication
– saliva pH
– saliva viscosity
 Sialolith
salivary stone

White to yellowish to tan with a smooth or rough surface, ± friable.

In cross section: stones show concentric laminations
 Sialolith
(salivary stone)
+ Calcium phosphate
+ Calcium carbonate
+ trace amounts of Mg, KCl, Al

concentrically arranged
layers of the calculus matrix

deposition of calcium salts

a nidus of debris
(include mucus, bacteria, ductal
epithelial cells, foreign bodies)
 Sialolith
80 – 90%
80 – 90 % in submandibular glands

 Most frequent at the duct's bend around the posterior edge

of mylohyoid muscle.
 Sialolithiasis

Clinical features:
 M=2F
 Pain and swelling upon eating, ceases and output
decreases.
 Secondary infection (suppurative exudate from the duct,
fever,…), fibrosis and gland atrophy
 Diagnosis of sialolithiasis

1. History
2. Clinical findings
3. Radiograph:
- Occlusal / Submandibular stone
- Face / Parotid stone
50% parotid & 20% submandibular
sialoliths are poorly calcified
- CT scan (sensitivity = 10 plain-film radiography)
- Sialography (differential diagnosis of phlebolith)
4. Ultrasonography
6. ± FNA (if necessary)
6. ± Sialoendoscopy
 Sialolithiasis

 Acute phrase: antibiotics, antipyrics, analgesics,

hydration
Treatment

 Milking the gland (stone near the orifice of duct)

Remove  Surgery
stone  Sialendoscopy (sialolith < 4 mm)
 Lithotripsy (sialolith 5 - 7 mm)

Remove Surgery (intraglandular stones

gland or chronic sialadenitis)
Sialolithiasis

Prognosis
• If the sialolith has been present for a short time,
the gland may recover after sialolith removal.
• If the sialolith is of long standing, the gland may
harbor irreversible inflammation and fibrosis, so
that it cannot recover even if the sialolith is
removed.
Immune - mediated diseases
 Sarcoidosis

• Chronic granulomatous disorder in several organs

(lungs, skin, eyes, parotid glands,…)

• Heerfordt syndrome:
Painless bilateral parotid gland enlargement
+ facial palsy + uveitis + fever
 Mikulicz’s disease

Simultaneous enlargement
of the lacrimal glands + parotid glands

twitter.com/hashtag/mikulicz
 Sjögren’s syndrome (SS)

• 0,5- 1%
• Female (90%): middle-aged or elderly women
• CD4 lymphocytic infiltration + Acinar destruction
• Mutiple autoantibodies, esp. Ro (SS-A) and La (SS-B)

• Primary SS = lacrimal glands (xerophthalmia)

& salivary glands (xerostomia)
Secondary SS = 1SS + other autoimmune conditions
(usually rheumatoid arthritis, less often lupus
erythematosus, systemic sclerosis, …)
Sjögren’s syndrome

snow-storm appearance
1. Ocular symptoms (at least one): Dry eyes >3 months
Foreign body sensation in the eyes
2. Oral symptoms (at least one)
 Dry mouth >3 months
 Recurrent or persistently swollen salivary glands
 Need liquids to swallow dry foods
3. Ocular signs (Schirmer's test < 5 mm / 5 mins)
4. Oral signs (at least one)
 Unstimulated salivary flow ≤ 0.1 ml/ 1 mins
 Abnormal parotid sialography
5. Histopathology (Lip biopsy):
Focal lymphocytic sialoadenitis
6. Autoantibodies (at least one):
Anti-SSA (Ro), Anti-SSB (La)
Salivary Gland Tumors
 Benign Malignant
SG tumors

Tumor cells Adenoma Adeno- Carcinoma

Stroma - oma Sarcoma

Rare
Metastasizing SG - Carcinoma
Sarcoma
 2017 WHO classification of epithelial SGTs
Benign Epithelial Tumors
 Pleomorphic Adenoma (PA)
 Warthin’s tumor
 Myoepithelioma
 Basal cell adenoma
 Oncocytoma
 …
Malignant Epithelial Tumors
- Mucoepidermoid Carcinoma (MEC)
- Adenoid cystic carcinoma (AdCC)
- Acinic cell carcinoma (ACC)
- Polymorphous low-grade
adenocarcinoma (PLGA)
- Epithelial-myoepithelial carcinoma
- Clear cell carcinoma
- Basal cell adenocarcinoma
- …..
Phân loại U Tuyến Nước Bọt (WHO, 2017)
U biểu mô lành tính Ung thư biểu mô

U tuyến đa dạng Carcinôm nhầy - bì

U Warthin Carcinôm tuyến dạng nang
U cơ biểu mô Carcinôm tế bào túi tuyến
U tuyến tế bào đáy Carcinôm tuyến grad thấp đa dạng
U phồng bào …………
………..
 Salivary Gland Tumors

• 80%: Parotid glands

• 10%: Submandibular glands

• 9% : Minor SG (50% in palate)
• 1% : Sublingual glands
 Salivary Gland Tumors
Benign
Parotid glands

Submandibular glands

Minor SG
Sublingual glands
Malignant
Acinic Cell Caricnoma (ACC)
Mucoepidermoid carcinoma (MEC)
Squamous Cell Carcicnoma (SCC)

Excretory duct

Intercalated duct Striated duct

Myoepithelial cell
Oncocytoma

Pleomorphic Adenoma (PA)

Ultrasonography
CT scan
MRI
 Fine Needle Aspiration (FNA)

 Efficacy:
- Sensitivity: 54 - 95%
- Specificity: 86 -100% => distinguish
benign vs. malignant nature of neoplasm
- Accuracy: 84 - 97%

 Safe, well tolerated

 FNA Cắt lạnh FNA + Cắt lạnh
Giá trị chẩn đoán
n =408 n =67 n = 54
Độ nhạy (%) 50,6 83,3 93,8
Độ đặc hiệu (%) 98,1 97,7 97,4
Độ chính xác (%) 87,7 92,5 96,3
Giá trị tiên đoán dương (%) 88,2 95,2 93,8
Giá trị tiên đoán âm (%) 87,7 91,3 97,4

Oncology Hospital HCM city, 2009-2010

Pleomorphic Adenoma
Mixed tumor

Heterogeneous pattern
 Pleomorphic Adenoma
1. Epithelial components: Myoepithelial cells
2. Mesenchymal components:
– Fibrous connective tissue
– Myxoid tissue
– Chondroid & even osseous tissue metasplasia
 Pleomorphic Adenoma

Benign tumor
± Nelaton sign (+)

Ultrasound
FNA
 Tế bào cơ biểu mô
Màng đáy Myoepithelial cells

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•Immnunohischemical staining:

Böôùu hoãn hôïp

Epithelial Markers: CK, EMA, CEA (+)

Mesothelial Markers: S-100, Vimentin, GFAP, SMA, Calponin (+)

 Pleomorphic Adenoma
- Treatment -

• Do not enucleation
• Parotidectomy:
- Partial
- Superficial parotidectomy
- Redon surgery
• Resection of submandibular gland
• Malignant transformation: 3%
(esp. recurrent or untreated 25%)
 Warthin's tumor
Papillary cystadenoma lymphomatosum

 7% of SGTs
 2nd common benign tumor (10%)
 90% in parotid gland
 Bilateral 10%
 Arise from SG inclusions within
lymph nodes
 Average age: 50 – 60 (older)
 M:F = 3-5 : 1
 Doughy to cystic mass in the
inferior pole of the gland
 Mucoid brown fluid in FNA
 Warthin’s Tumor
Papillary cystadenoma lymphomatosum

• Gross pathology:
– Encapsulated
– Smooth or lobulated surface
– Cystic spaces of variable size, with viscous
fluid, shaggy epithelium
– Solid areas with white nodules representing
lymphoid follicles
Epithelium: tubular gland
follicle formation (yellow arrow) 2-layered epithelial cells:
High columnar cells (white
 Mature lymphoid tissue
arrow) & (cuboidal) basal cells
stroma with germinal centers (yellow arrows)
(white arrow) (50% cases)
 Malignant
Salivary Gland Tumors
 MALIGNANT SALIVARY GLAND TUMORS
1. Mucoepidermoid carcinoma (MEC)
2. Adenoid cystic carcinoma (AdCC)
3. Acinic cell carcinoma (ACC)
4. Adenocarcinoma, NOS
5. Polymorphous low-grade adenocarcinoma (PLGA)
6. Carcinoma ex-PA
7. Epimyoepithelial carcinoma
8. Salivary duct carcinoma
9. Basal cell adenocarcinoma
10. Oncocytic adenocarcinoma
11. Clear cell carcinoma
12. Sebaceous carcinoma
13. Squamous cell carcinoma (SCC)
MALIGNANT SALIVARY GLAND TUMORS
- Biologic classification –
Low-grade malignancies
1. MEC (low grade)
2. ACC
3. PLGA
4. Clear cell carcinoma
5. Basal cell adenocarcinoma (BCAC)

Intermediate-grade malignancies
1. MEC (intermediate grade)
2. AdCC (cribri/tubular)
3. Epimyoepithelial carcinoma
4. Sebaceous carcinoma
 MALIGNANT SALIVARY GLAND TUMORS
- Biologic classification –

High-grade malignancies
1. MEC (high grade)
2. AdCC (solid)
3. Carcinoma ex-PA
4. Adenocarcinoma, NOS
5. Salivary duct carcinoma
6. Squamous cell carcinoma SCC
7. Oncocytic adenocarcinoma
 Malignant Salivary Gland Tumors
CLINICAL FEATURES
Adults, M = F
Mass / ulcer, asymptomatic in early stages
Oral sites: Palate > BM > Retromolar pad> upper lip >
tongue
Low-grade MEC > AdCC > ACC

HISTOPATHOLOGY
Highly variable but characteristic patterns
Infiltrative margins
Rare mitoses
Little polymorphism
Low-to high-grade
 Mucoepidermoid Carcinoma (MEC)

• Most common salivary gland malignancy (35%)

• 13% of SG tumors (2nd after pleomorphic adenoma)
• Parotid glanf (80 - 90%), palate (18%)
• Most common malignant tumor of parotid gland and the
2nd malignancy (after adenoid cystic carcinoma) MEC
of submandibular & minor SGs.
• 3rd-8th decades, peak 50s
• F>M
 MEC
 From cells in the interlobular & intralobular duct system.

 Low-, intermediate- & high-grade lesions

Majority (80%): low-grade
 Radical excision, ± neck dissection, ± radiotherapy
 5-year survival: low-grade 95%, high-grade 40%
 MEC
Gross pathology:
– Well-circumscribed to partially
encapsulated to unencapsulated.
– Solid tumor with cystic spaces.

Microscopic features:
- Numerous cystic spaces lined
by epithelium, containing a
mixture of mucin &
desquamation keratin.
 MEC
 mucus cells (finely granular cells) (arrow)
 squamous cells
 Adenoid Cystic Carcinoma (AdCC)
 Cylindroma (previously)

 2nd most common SG malignancy

 Most common in submandibular, sublingual & minor SG
 5-10% SGTs, 23% SG carcinomas
 55-70% in minor SG, esp.palate
 AdCC

 Age > 50. F:M = 2:1

 Firm mass, ± ulcerated, ± pain,
± facial nerve paralysis
 Perineural invasion: often ***
 Bone invasion: often
 Slow growth, but high grade of malignancy, high
recurrence, metastasis (40%) (Lung > Nodes)
 Gross pathology:
Well-circumscribed, solid, rarely with cystic spaces
 AdCC
3 histopathologic patterns:

Solid pattern
Cribiform pattern Tubular pattern
(most frequent) (least frequent)
(best-recognized pattern)
 Adenoid cystic carcinoma
Perineural invasion >> pain (common feature)
Invasion of internal growth to (yellow arrow) of
peripheral nerve tumor cells (N) & around (white arrow)
 Adenoid Cystic Carcinoma
Grading:
Cribiform or Tubular : intermediate grade
Solid : high grade
Treatment: Radical excision (perineural invasion) +
Postoperative radiotherapy (radiosensitive)
Prognosis: Local recurrence 42%, (M): lung
Survival: 5-year survival 70%, 15-year survival 10%
5 year 15 -year survival
Cribiform/Tubular 90% 40%
Solid 35% 5%
 Acinic Cell Carcinoma (ACC)

 3% of SG tumors, 3rd SG malignancies

 Primarily in parotid gland (2nd after MEC)
 Low-grad malignancy, but tendency for local recurrence.
 Female:Male = 2:1, average age: 44
 Most tumors < 3 cm, firm, well-defined, rarely VII palsy
 Gross pathology:
Well-demarcated, most often homogeneous
 Acinic Cell Carcinoma (ACC)
 Treatment: Lobectomy or total parotidectomy,
± Neck dissection.
Radioresistant.
 Prognosis: 5-year survival 80% -> < 65% at 10 years
 References
1. Neville BW, Damm DD, Allen CM, Bouquot JE (2015),
Oral and maxillofacial pathology, 4th edition, Saunders,
Elsevier.
2. Odell EW (2017), Cawson’s essentials of oral pathology
and oral medicine, 9th edition, Elsevier.
3. Regezi JA, Sciubba JJ, Jordan RCK (2015), Oral
pathology: Clinical pathologic correlations, 7th edition,
Saunders.
4. Sapp JP, Eversole LR, Wysocki GP (2004), Contemporary
oral and maxillofacial pathology, 2nd edition, Mosby.
5. Scully C, et al (2013), Oral and maxillofacial: the basis of
diagnosis and treatment, 3rd edition, Churchill Livingstone,
Elsevier.