Quartz 4

13. Salivary Gland Diseases

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Oral Pathology module1

Salivary gland diseases

CLASSIFICATION OF SALIVARY GLAND DISEASES2

A. DEVELOPMENTAL

  • Congenital aplasia/agenesis
  • Congenital hypoplasia
  • Atresia
  • Aberrance / ectopic gland
  • Diverticuli
  • Accessory duct
  • Congenital fistula

Anatomical Reminder

The lecture emphasizes the importance of understanding the anatomy and histology of both major salivary glands (Parotid, Submandibular, Sublingual) and minor salivary glands (600-1,000 distributed throughout the oral cavity).

B. INFLAMMATORY3

  • ACUTE OR CHRONIC
    • STAPHYLOCOCCAL
    • STREPTOCOCCAL
    • ACTINOMYCOSIS
    • TUBERCULOSIS
  • VIRAL INFECTION
    • MUMPS
    • CYTOMEGALO VIRUS INFECTION
    • PARAINFLUENZA
  • SARCOIDOSIS
  • MELKERSON-ROSENTHAL SYNDROME
  • ALLERGY
  • SALIVARY FISTULA
  • **POST IRRADIATION TO ORAL TUMOUR

Post-Radiation Sialadenitis

Radiation therapy for head and neck cancer causes significant salivary gland damage, leading to severe dysfunction and xerostomia.

**

C. SIALOLITHIASIS4

  • DUE TO STRICTURE OF DUCT
  • DUE TO TRAUMA OR INFECTION
  • DUE TO SALIVARY STONE
  • MUCOUS PLUG

D. CYSTS

  • MUCOCELE
  • RANULA
  • LYMPHO EPITHELIAL CYST
    • Commonly seen on the posterior side of the tongue.
  • BRANCHIAL CYST

E. F. SIALADENOSIS

G. SJOGRENS SYNDROME5

**I. NEOPLASMS

Note

Salivary gland tumors are relatively uncommon but are challenging to diagnose and manage. The WHO classification is extensive, with the 2022 version listing 38 different entities.

**

BENIGN EPITHELIAL

  • ADENOMA
  • ONCOCYTOMA
  • WARTHINS TUMOUR
  • PLEOMORPHIC ADENOMA

MALIGNANT EPITHELIAL

  • ADENOCARCINOMA
  • MUCOEPIDERMOID CARCINOMA
  • ADENOCYSTIC CARCINOMA
  • ACINIC CELL CARCINOMA
  • MALIGNANT PLEOMORPHIC ADENOMA

BENIGN MESENCHYMAL6

  • HEMANGIOMA
  • LYMPHANGIOMA
  • NEUROFIBROMA
  • SCHWANNOMA
  • LIPOMA

MALIGNANT MESENCHYMAL

  • RHABDOMYOSARCOMA
  • HEMANGIOENDOTHELIOMA

OTHERS

  • LYMPHOMA-HODGKINS & NON HODGKINS
  • METASTATIC

Sialolithiasis (Salivary Stones)7

  • Sialoliths are calcified and organic matter that form within the secretory system of the major salivary glands. The etiology of sialolith formation is still unknown;
  • however, several factors contribute to stone formation. Inflammation, irregularities in the duct system, local irritants, and anti-cholinergic medications may cause pooling of saliva within the duct, which is thought to promote stone formation.

Etiology

Formation requires a central nidus or core (e.g., a cell or mucus plug) around which calcium salts can deposit in layers. Systemic conditions can contribute to their formation.

  • It is believed that a nidus of salivary organic material becomes calcified and gradually forms a sialolith.

  • The submandibular gland is the most common site of involvement, and 80 to 90% of sialoliths occur in this gland.

  • Diagnosis: ==Imaging, such as a sialogram, is used to visualize the gland’s ductal system and identify blockages.==

  • Clinical Presentation: Can sometimes be palpated as a yellowish, firm, hard swelling within the duct.

  • Histopathology: ==The ductal epithelium may undergo metaplasia as an adaptive response to the chronic irritation and blockage.==

  • Treatment: ==Small, accessible stones can be removed with a simple incision. Deeper stones or extensive gland damage often require surgical removal of the entire gland (sialadenectomy).==

  • A) Lamellated calculi were found within the lumen of a dilated minor salivary duct

  • B) Squamous metaplasia of the excretory ductal epithelium and exfoliated epithelium were observed in the minor salivary glands

Mucocele8910

“Mucocele” is a clinical term that describes swelling caused by obstructed minor salivary gland duct.

Mucoceles are classified as

  1. Extravasation
  2. Retention types.
  3. A large form of mucocele located in the floor of the mouth is known as a RANULA.

Clinical Presentation

Extravasation mucoceles most frequently occur on the lower lip, where trauma is common. Buccal mucosa, tongue, floor of the mouth, and retro molar region are other commonly traumatized areas where mucous extravasation may be found. Mucous retention cysts are more commonly located on the palate or the floor of the mouth.

  • Appears as a soft, bluish, dome-shaped swelling.
  • The size can fluctuate; it may shrink as the body's inflammatory cells process the pooled mucin and then enlarge again as more saliva accumulates.
  • If it ruptures, a clear, viscous fluid (saliva) is released.

Mucous extravasation cyst11

Epithelioid macrophages forming a pseudocyst around the extravasated mucin, no true epithelium is present.

Pathogenesis of Extravasation Cysts

  • Cause: Trauma (e.g., lip or cheek biting) ruptures a salivary duct, causing saliva to spill into the surrounding connective tissue.
  • Response: The spilled mucin acts as a foreign material, triggering an inflammatory response. A wall of granulation tissue containing phagocytes (macrophages) forms around the mucin.
  • Histopathology: It is a pseudocyst because it lacks a true epithelial lining. Instead, it is lined by granulation tissue and inflammatory cells.
  • Treatment: Surgical excision is required. It is crucial to remove the associated, damaged minor salivary glands to prevent recurrence.

Mucous Retention Cyst

This is a less common type where the cyst forms within the duct itself due to an obstruction, leading to ductal dilation. It is a true cyst with an epithelial lining.

XEROSTOMIA12

CAUSES OF XEROSTOMIA-

  1. TEMPORARY-psychological (anxiety), duct calculi, sialoadenitis, drug therapy( anticholinergic, sympathomimetic, etc.)
  2. PERMANENT-
    • Salivary gland aplasia, sjogrens syndrome, following radio therapy, surgical desalivation

Info

Permanent xerostomia is caused by irreversible destruction of the salivary gland parenchyma (the saliva-producing tissue), which is replaced by fibrous or adipose tissue.

  • Common
  • Especially in middle to late life
  • USA: 17% of 65-84 year olds had symptoms of oral dryness
  • Europe: 29% of persons in a may have symptoms of dry mouth

BUT little correlation with objective measurements

Note

In Australia, it is estimated to affect around 20% of the population, with rates as high as 80% in patients over 65.

Causes1314

Common

  • Drugs
  • Radiotherapy to head and neck
  • Sjogren’s syndrome
  • Psychogenic?
  • HCV disease?
  • HIV disease?

Uncommon

  • Chronic graft versus host disease
  • Sarcoidosis
  • Cystic fibrosis
  • Diabetes mellitus
  • Amyloidosis
  • Haemochromatosis
  • Wegener’s disease
  • Salivary gland agenesis
  • Triple A syndrome
  • Cholinergic dysautonomia
  • Others

Clinical Features15

  • Dysarthria

  • Dysphagia

  • Mucosal adhesion

  • “Stringy saliva”

  • Caries

  • ==A glossy, atrophic appearance of the tongue.==

  • The dental mirror sticking to the buccal mucosa is a classic sign.

  • ==Increased risk of dental caries, particularly cervical caries.==

  • ==Increased susceptibility to oral infections, especially candidiasis.==

Discrete swelling in gland16

  • Define location – clinical, imaging MRI – is it in the gland?
  • Exclude infectious causes
  • Fine needle aspiration
  • Excisional biopsy if thought benign
  • Incisional biopsy if thought malignant

Classification of salivary tumours1718

Benign:

  • Pleomorphic adenoma
  • Warthin’s tumour

Malignant:

  • Mucoepidermoid carcinoma
  • Polymorphous low-grade adenocarcinoma
  • Adenoid cystic carcinoma
  • Carcinoma ex pleomorphic adenoma

Site prevalence of salivary neoplasms19

  • Parotid
    • probably benign (85%)
  • Submandibular
    • probably benign (70%)
  • Minor glands
    • palate 45% malignant
  • sublingual
    • almost certainly malignant

Clinical Rule of Thumb

Any lump in a minor salivary gland, especially in the upper lip, should be considered suspicious for malignancy until proven otherwise.

Distinguishing Benign vs. Malignant Tumours2021

BenignMalignant
CircumscribedPoorly circumscribed
MobileFixed
Slow-growingInduration (difficult)
PainlessUlceration
Symptoms only cosmetic or pressurePain
Metastasis
Nerve signs
Sometimes rapid growth

Key Distinctions

  • Nerve Signs: The presence of numbness, paresthesia, or facial nerve palsy is a strong indicator of malignancy.
  • Fixation: Malignant tumors are often fixed to adjacent structures, whereas benign tumors are mobile.
  • Capsule: Benign tumors are typically encapsulated, while malignant ones are not.

Pleomorphic (salivary) adenoma22

  • So-called ‘mixed tumour”
  • Commonest salivary neoplasm
  • Most in major glands but common in minor
  • Benign (but may transform to malignancy)
  • Encapsulated (but must not be enucleated)
  • Painless, slow-growing

Malignant Transformation

While benign, if left untreated for many years (e.g., >10 years), it can transform into a highly aggressive Carcinoma ex Pleomorphic Adenoma, which has a very poor prognosis (patients often die within 18 months).

Cellular Origin

Arises from two cell types: intercalated duct cells and myoepithelial cells. The term “mixed tumour” is now obsolete.

Clinical features232425262728

  • †Mean age – 40 yrs
  • †Slight female predilection; 2:1
  • Incidence in major and minor salivary glands is 10:1,
  • Appears as a painless, slowly growing, smooth surfaced, dome shaped, firm mass

Histopathology Summary

The tumor is encapsulated and shows a pleomorphic (mixed) appearance with three main components:

  1. Epithelial Component: Duct-like or sheet-like structures formed by cuboidal cells.
  2. Myoepithelial Component: Cells can be spindle-shaped or have a distinct plasmacytoid (plasma cell-like) appearance.
  3. Stromal Component: The supporting connective tissue is highly variable and can be hyalinized (glassy), myxoid (mucoid), or even form cartilage (chondroid stroma).

Warthin’s tumour29303132

  • ‘Adenolymphoma’ not a lymphoma!!

  • Almost all in parotid gland

  • Elderly patients

  • Benign, mobile, firm to fluctuant

  • Sometimes multiple

  • Encapsulated neoplasm

  • Synonym: Papillary cystadenoma lymphomatosum

  • Site: Tail of parotid

  • Bilateral occurrence

  • Age: 6th –7th decade

  • Male predominance

  • Associated with smoking

Macroscopic Appearance

The cystic fluid is often thick, brown, and described as ‘chocolate-like.’

  • Varying proportions of papillary cystic structures lined by bilayered oncocytic epithelial cells and surrounded by a lymphoid stroma including germinal centers

Histopathology Summary

The name Papillary Cystadenoma Lymphomatosum describes its key features:

  • Cystic Spaces: Contains multiple cysts with papillary projections.
  • Epithelial Lining: A characteristic double layer of oncocytic epithelial cells.
  • Lymphoid Stroma: The stroma is densely packed with lymphoid tissue, often forming germinal centers.

High power view showing papillary structures lined by bilayered oncocytic epithelial cells, surrounded by a lymphoid stroma

Mucoepidermoid carcinoma3334

  • Most common
  • Site: Major & minor salivary glands
  • 2nd to 7th decade
  • Female predilection
  • Site:
    • Palate
    • Tuberosity
    • Retromolar region
    • Tongue
    • Floor of the mouth
  • Asymptomatic swelling + pain + facial nerve palsy

Histopathology

The name reflects its three cellular components:

  1. Muco- (Mucous cells): Cells with cloudy, pale cytoplasm that produce mucin.
  2. -epidermoid (Squamous cells): Islands of cells resembling stratified squamous epithelium.
  3. Intermediate cells: Smaller, basaloid-type cells. The tumor grows in a combination of solid sheets and cystic spaces.

1112/02 Mucoepidermoid carcinoma, low-grade

Adenoid cystic carcinoma353637

  • Infrequent but very important
  • May arise in any salivary gland
  • Vague presenting symptoms (eg ‘funny feeling’)
  • Slow-growing but highly infiltrative
  • Late diagnosis common
  • Good 5-year prognosis, very poor 15-year

Hallmark Feature: Perineural Invasion

This tumor has a strong tendency for perineural invasion (invading along nerve sheaths), which explains the common symptoms of pain and paresthesia (numbness) and is associated with a poorer prognosis.

  • Synonym: Cylindroma
  • Site: Minor salivary gland
  • Age: Mid aged adults, 5th –7th decade
  • Slow growing swelling
  • Swelling + dull ache + facial nerve paralysis
  • Late metastasis
  • Prognosis: Worse
  • Complications:
    • CNS involvement

Adenoid cystic carcinoma

Questions38394041

  • Slow growing swelling
  • Swelling + dull ache + facial nerve paralysis
  • Late metastasis
  • Prognosis : Worse
  • Complications :
    • CNS involvement

Adenoid cystic carcinoma353637

Histopathology

  • Composed of small, dark-staining basaloid cells.
  • The cells arrange in various patterns, with the most classic being the cribriform (‘Swiss cheese’) pattern, featuring multiple small, punched-out cystic spaces.
  • Perineural Invasion: Tumor cells can be seen surrounding and infiltrating nerve bundles, which is a key diagnostic feature.

38394041

Footnotes

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