NON-NEOPLASTIC SALIVARY GLAND DISEASES

INTRODUCTION

CLASSIFICATION

• A. Infectious
  • 1. Acute bacterial sialadenitis
  • 1. Viral sialadenitis (Mumps/Epidemic parotitis)
  • 1. Granulomatous (Tuberculosis, Actinomycosis, Cat-scratch disease)
• B. Non-infectious
  • 1. Chronic recurrent (obstructive) sialadenitis
  • 1. Chronic sclerosing sialadenitis (Kuttner tumour)
  • 1. Recurrent parotitis of childhood
  • 1. Autoimmune: Sjogren syndrome
  • 1. Sarcoidosis (Heerfordt syndrome)
  • 1. Radioiodine/radiation-induced sialadenitis
  • 1. IgG4-related sialadenitis

• Sialolithiasis (salivary calculi)
• Salivary duct strictures

• Xerostomia (drug-induced, post-radiation, Sjogren)

• Mucoceles (extravasation and retention types)
• Ranula

• Sialosis (sialadenosis)
• Necrotizing sialometaplasia
• Frey syndrome (gustatory sweating)

I. SIALOLITHIASIS (SALIVARY CALCULI)

Definition

Incidence and Distribution

• Submandibular gland: 80-90% (most common) - due to Wharton's duct
• Parotid gland: 10-20% - within Stensen's duct
• Sublingual and minor glands: 1%
• Peak age: fifth to eighth decades; males more commonly affected than females
• Lifetime prevalence of symptomatic calculi: 0.45%

Composition

Why Submandibular Gland is Predominantly Affected

┌─────────────────────────────────────────────────────────┐
│         FACTORS FAVOURING SMG CALCULUS FORMATION        │
├─────────────────────────────────────────────────────────┤
│  Wharton's duct: longer, wider, more tortuous           │
│  Flow against gravity (courses round mylohyoid)         │
│  Saliva: more alkaline, mucoid, viscous                 │
│  Higher calcium and phosphate concentration in saliva  │
│  Slower flow rate → increased stasis                    │
└─────────────────────────────────────────────────────────┘

Pathogenesis

Clinical Features

• Recurrent postprandial pain and swelling of the affected gland (salivary colic)
• Swelling appears at mealtimes (gustatory stimulus) and slowly resolves over hours
• History of multiple episodes of acute suppurative sialadenitis
• On examination: bimanual palpation may reveal a palpable stone in the floor of mouth (Wharton's duct)
• Absence or diminished salivary flow from the duct orifice
• Long-standing cases may show signs of chronic sialadenitis

Radiology Notes

• 90% of submandibular stones are radio-opaque (high calcium content)
• 90% of parotid stones are radiolucent (lower calcium content)
• Up to 15% of all calculi are radiolucent on plain radiographs

Investigations

1. Plain radiograph (Floor of mouth/Occipitomental view/OPG) - for radio-opaque stones
2. Ultrasound - most commonly used; identifies stones >2 mm, shows gland echogenicity and ductal dilatation
3. Computed Tomography - more sensitive; identifies all stone types including radiolucent
4. Sialography - instillation of contrast into duct (4-15% failure rate, risk of provoking acute sialadenitis); demonstrates ductal anatomy, strictures, and filling defects
5. Magnetic resonance sialography - non-invasive; relies on T2-weighted signal from inherent salivary fluid; no cannulation or contrast needed

Management

┌──────────────────────────────────────────────────────────────┐
│              MANAGEMENT OF SIALOLITHIASIS                   │
├──────────────────────────────────────────────────────────────┤
│ CONSERVATIVE (all cases initially)                          │
│  • Adequate hydration, sour candy/lemon to stimulate flow   │
│  • Massage the gland from posterior to anterior             │
│  • Warm compresses                                          │
│  • Analgesics, anti-inflammatory agents                     │
│  • Antibiotics if acute sialadenitis present                │
├──────────────────────────────────────────────────────────────┤
│ MINIMALLY INVASIVE / INTERVENTIONAL                         │
│  • Surgical milking/manual extraction (distal duct stones)  │
│  • Sialoendoscopy (diagnostic and therapeutic)              │
│  • Extracorporeal shock wave lithotripsy (ESWL)             │
│  • Interventional sialography (basket retrieval)            │
├──────────────────────────────────────────────────────────────┤
│ SURGICAL (failed conservative, large/multiple stones)       │
│  • Intraoral incision over duct for anterior floor-of-mouth │
│    stones (submandibular duct stone)                        │
│  • Submandibulectomy - for recurrent/intraglandular stones  │
│  • Parotidectomy - rare, for intraglandular parotid stones  │
└──────────────────────────────────────────────────────────────┘

II. ACUTE BACTERIAL SIALADENITIS

Pathogenesis

• Dehydration (post-operative, elderly, bedridden patients)
• Malnutrition
• Poor oral hygiene
• Medications causing xerostomia (anticholinergics, diuretics, antidepressants)
• Ductal obstruction from a sialolith

┌────────────────────────────────────────────────────────┐
│           PATHOGENESIS OF ACUTE BACTERIAL              │
│              PAROTID SIALADENITIS                      │
│                                                        │
│  Dehydration / Salivary stasis                        │
│           ↓                                           │
│  Reduced salivary flow & antimicrobial activity       │
│           ↓                                           │
│  Retrograde ascent of oral bacteria via Stensen duct  │
│           ↓                                           │
│  Acute suppurative parotitis                          │
│           ↓                                           │
│  If untreated → Abscess formation                     │
└────────────────────────────────────────────────────────┘

Common Organisms

• Staphylococcus aureus - most common (including methicillin-resistant strains)
• Streptococcus viridans
• Haemophilus influenzae
• Anaerobes (Bacteroides, Peptostreptococcus) - in mixed infections

Clinical Features

• Sudden onset tender, firm swelling of the parotid gland
• Trismus may be present (indicating parapharyngeal extension)
• Erythema and oedema of overlying skin
• Pus expressible from Stensen's duct orifice
• Systemic features: fever, malaise, raised white cell count
• Medial tonsillar displacement or trismus suggests deeper parapharyngeal space involvement

Investigations

• Full blood count, blood cultures
• Pus culture and sensitivity from duct orifice
• Ultrasound - confirms parotid involvement, identifies abscess, excludes obstructing calculus
• Computed tomography - for deep space involvement (parapharyngeal abscess)

Management

• Intravenous antibiotics (anti-staphylococcal: flucloxacillin or co-amoxiclav) - adjusted according to culture sensitivities
• Adequate hydration (intravenous fluid replacement)
• Oral hygiene measures
• Gland massage
• Sialogogues
• Surgical drainage for abscess formation (incision with facial nerve preservation)

III. VIRAL SIALADENITIS - MUMPS (EPIDEMIC PAROTITIS)

Epidemiology

Clinical Features

• Prodrome: fever, malaise, anorexia, headache (1-2 days)
• Parotid swelling: painful, bilateral in 75% of cases (may start unilateral, become bilateral within 1-5 days)
• The swelling lifts the ear lobe outwards (pathognomonic appearance)
• Erythema around Stensen's duct orifice
• Trismus may be present
• Clear saliva (not purulent) - differentiates from bacterial sialadenitis

Complications

┌──────────────────────────────────────────────────────────┐
│              COMPLICATIONS OF MUMPS                     │
├──────────────────────────────────────────────────────────┤
│  Orchitis (most common in post-pubertal males - 25%)    │
│  → may cause infertility                                │
│  Oophoritis (in post-pubertal females - 5%)             │
│  Meningoencephalitis (most common complication overall) │
│  Pancreatitis                                           │
│  Deafness (sensorineural - unilateral, permanent)       │
│  Myocarditis                                            │
│  Arthritis                                              │
└──────────────────────────────────────────────────────────┘

Diagnosis

• Raised serum amylase (salivary isoenzyme)
• Complement fixation tests (S and V antibodies)
• Mumps IgM antibody (ELISA)
• Virus isolation from saliva, urine, cerebrospinal fluid

Management

• Supportive: analgesics, adequate hydration, soft diet
• No specific antiviral treatment
• Prevention: MMR vaccination (two-dose schedule)

IV. CHRONIC SIALADENITIS

Chronic Recurrent (Obstructive) Sialadenitis

• Treat acute episodes with antibiotics
• Salivary duct dilation or sialoendoscopy
• Gland excision (submandibulectomy or parotidectomy) for recurrent/refractory cases

Chronic Sclerosing Sialadenitis (Kuttner Tumour)

V. SJOGREN SYNDROME

Definition

Epidemiology

• Estimated prevalence: 1-3% of the population
• Peak onset: fourth to fifth decade of life
• More than 90% of patients are women (strong female preponderance)
• Second most common autoimmune rheumatic disease after rheumatoid arthritis

Classification

┌──────────────────────────────────────────────────────────────┐
│                CLASSIFICATION OF SJOGREN SYNDROME           │
├─────────────────────┬────────────────────────────────────────┤
│  PRIMARY            │  SECONDARY                            │
│  (isolated)         │  (associated with another             │
│                     │   autoimmune disease)                 │
│  Exocrine gland     │  Rheumatoid arthritis                 │
│  involvement only   │  Systemic lupus erythematosus         │
│  (sicca complex)    │  Systemic sclerosis (scleroderma)     │
│                     │  Primary biliary cirrhosis            │
│                     │  Polymyositis                         │
└─────────────────────┴────────────────────────────────────────┘

Pathogenesis

┌────────────────────────────────────────────────────────────┐
│              PATHOGENESIS OF SJOGREN SYNDROME             │
│                                                           │
│  Genetic predisposition (HLA-B8, HLA-DR3 alleles)        │
│           ↓                                              │
│  Environmental trigger (likely viral - Epstein-Barr      │
│  virus, Coxsackie, Hepatitis C)                          │
│           ↓                                              │
│  Aberrant autoimmune activation                          │
│           ↓                                              │
│  B-cell overstimulation → excess immunoglobulins +       │
│  autoantibodies (anti-Ro/SS-A, anti-La/SS-B)            │
│           ↓                                              │
│  Dense lymphocytic (CD4+ T-cell) infiltration of        │
│  exocrine glands                                         │
│           ↓                                              │
│  Formation of germinal centres → autoreactive B-cell    │
│  clones escape tolerance checkpoints                     │
│           ↓                                              │
│  Progressive acinar destruction + ductal obstruction    │
│           ↓                                              │
│  Salivary and lacrimal hypofunction                      │
└────────────────────────────────────────────────────────────┘

Clinical Features

• Difficulty chewing, swallowing, and phonation
• Adherence of food to the buccal mucosa
• Intolerance to acidic and spicy foods
• Multiple dental caries (rampant caries)
• Smooth, fissured tongue with atrophy of filiform papillae
• Absence of pooled saliva in the floor of mouth
• Oral candidiasis (Candida albicans overgrowth)
• Scant/cloudy saliva expressible from ducts

• Foreign body sensation ("gritty" or "sandy" eyes)
• Keratoconjunctivitis sicca

• Bilateral parotid enlargement in 25-66% of patients (recurrent, episodic or chronic, fixed)
• Submandibular gland may also be enlarged

• Arthralgia/arthritis
• Vasculitis
• Peripheral neuropathy
• Renal tubular acidosis
• Thyroid disease
• Lymphoma (5-fold increased risk) - a serious complication; secondary mucosa-associated lymphoid tissue (MALT) lymphoma

Diagnostic Criteria (American-European Consensus Group 2002 - as referenced in standard texts)

┌────────────────────────────────────────────────────────────────┐
│         DIAGNOSTIC CRITERIA FOR SJOGREN SYNDROME             │
├────────────────────────────────────────────────────────────────┤
│  1. Ocular symptoms (dry eye, foreign body sensation)         │
│  2. Oral symptoms (dry mouth, recurrent salivary swelling)    │
│  3. Objective ocular signs: Schirmer test ≤5 mm/5 min OR     │
│     Rose Bengal staining score ≥4                            │
│  4. Salivary gland histopathology: focal lymphocytic         │
│     sialadenitis (focus score ≥1 per 4 mm²)                  │
│  5. Objective evidence of salivary gland involvement:        │
│     - Unstimulated whole saliva flow ≤1.5 mL/15 min, OR     │
│     - Parotid sialography showing punctate/globular/         │
│       cavitary pattern, OR                                   │
│     - Salivary scintigraphy showing delayed uptake/          │
│       reduced concentration                                  │
│  6. Serology: anti-Ro (SS-A) or anti-La (SS-B) antibodies   │
│                                                              │
│  Primary SS: ≥4 criteria; criteria 4 or 6 must be positive  │
│  Secondary SS: criteria 1 or 2 PLUS any 2 of criteria 3-5   │
└────────────────────────────────────────────────────────────────┘

Investigations

• Serology: Raised erythrocyte sedimentation rate, raised immunoglobulins, anti-nuclear antibodies (ANA), anti-Ro (SS-A), anti-La (SS-B) antibodies, rheumatoid factor
• Schirmer test: Filter paper placed under lower eyelid; <5 mm wetting in 5 minutes indicates reduced lacrimal secretion
• Slit-lamp examination: Rose Bengal staining for keratoconjunctivitis sicca
• Salivary flow rate measurement (Lashley cup cannula)
• Lip biopsy (minor salivary gland biopsy): Gold standard histological test - shows focal lymphocytic sialadenitis with focus score >1
• Parotid sialography/scintigraphy
• Ultrasound of salivary glands

Histopathology

• Focal lymphocytic sialadenitis
• Foci (aggregates) of >50 lymphocytes per 4 mm² (focus score)
• Acinar atrophy and replacement by lymphocytes
• Ductal changes with epimyoepithelial islands

Management

┌──────────────────────────────────────────────────────────────┐
│              MANAGEMENT OF SJOGREN SYNDROME                 │
├──────────────────────────────────────────────────────────────┤
│  LOCAL (symptomatic)                                        │
│  • Artificial saliva substitutes / frequent water sips     │
│  • Sugar-free chewing gum (increases salivary flow)        │
│  • Fluoride applications (prevent dental caries)           │
│  • Artificial tears (eye lubricants) for dry eyes          │
│  • Antifungals (nystatin/fluconazole) for oral candidiasis  │
├──────────────────────────────────────────────────────────────┤
│  SYSTEMIC (sialagogues)                                     │
│  • Pilocarpine (muscarinic M1/M3 agonist) 5 mg four times  │
│    daily - licensed for Sjogren syndrome                   │
│  • Cevimeline 30 mg three times daily                      │
│  • Side effects: sweating, flushing, urinary frequency     │
├──────────────────────────────────────────────────────────────┤
│  IMMUNOMODULATORY (systemic disease)                        │
│  • Hydroxychloroquine                                       │
│  • Methotrexate                                             │
│  • Biologics: rituximab (anti-CD20) for systemic disease    │
│  • Corticosteroids (for acute exacerbations)               │
└──────────────────────────────────────────────────────────────┘

VI. RECURRENT PAROTITIS OF CHILDHOOD

Definition

Aetiology

Clinical Features

• Recurrent episodes of unilateral (less commonly bilateral) parotid swelling
• Each episode lasts 3-7 days, resolving spontaneously
• Mild fever and malaise
• Serous (not purulent) saliva from Stensen's duct
• Attacks decrease in frequency and severity as puberty approaches

Diagnosis

• Sialography: punctate sialectasis ("cherry blossom" or "fruit-laden tree" appearance)
• Ultrasound: multiple hypoechoic foci within parotid parenchyma

Management

• Antibiotics during acute episodes
• Analgesics, hydration, massage
• Sialoendoscopy and therapeutic interventional sialography (early intervention may avoid glandular destruction)
• Reassurance: the condition typically resolves at puberty
• Parotidectomy is rarely required

VII. SIALOSIS (SIALADENOSIS)

Definition

Causes

┌──────────────────────────────────────────────────────┐
│              CAUSES OF SIALOSIS                     │
├──────────────────────────────────────────────────────┤
│  Nutritional/Metabolic:                             │
│   • Chronic alcoholism (most common)               │
│   • Malnutrition, kwashiorkor, anorexia nervosa    │
│   • Obesity                                        │
│   • Vitamin deficiency                             │
├──────────────────────────────────────────────────────┤
│  Endocrine:                                         │
│   • Diabetes mellitus                              │
│   • Hypothyroidism, acromegaly                     │
│   • Ovarian and pituitary disorders                │
├──────────────────────────────────────────────────────┤
│  Drug-induced:                                      │
│   • Antihypertensives (guanethidine)               │
│   • Antipsychotics (phenothiazines)                │
│   • Iodine-containing drugs                        │
└──────────────────────────────────────────────────────┘

Pathology

Management

• Treatment of underlying systemic cause
• Surgical parotidectomy is reserved for cosmetically unacceptable bilateral enlargement

VIII. GRANULOMATOUS SIALADENITIS

Sarcoidosis (Heerfordt Syndrome)

1. Bilateral parotid enlargement (parotitis)
2. Anterior uveitis
3. Facial nerve palsy
4. Low-grade fever

Tuberculosis

• Rare; presents as a firm parotid or submandibular mass
• May mimic malignancy
• Caseating granulomas on histopathology; Acid-fast bacilli on Ziehl-Neelsen stain
• Management: standard anti-tuberculosis therapy

IX. MUCOCELES AND RANULA

Mucoceles

1. Extravasation mucocele (most common): Duct rupture causes pooling of mucus in adjacent connective tissue. Not lined by epithelium.
2. Retention mucocele (less common): Partial or complete ductal obstruction causes retention of secretions and ductal dilatation. True cyst lined by epithelium.

• Single, recurrent, fluctuant, painless, bluish swelling
• Lower lip is the most common site (lateral aspect)
• Other sites: floor of mouth, ventral surface of tongue
• Peak age: 10-29 years
• Ruptures easily releasing viscid saliva

• Surgical excision with the associated minor gland
• Marsupialization for recurrence
• Cryotherapy/laser ablation in selected cases

Ranula

┌────────────────────────────────────────────────────────┐
│                   TYPES OF RANULA                     │
├──────────────────────┬─────────────────────────────────┤
│  SIMPLE (oral)       │  PLUNGING (diving/cervical)    │
├──────────────────────┼─────────────────────────────────┤
│  Confined to floor   │  Herniates through or around   │
│  of mouth            │  mylohyoid muscle into neck    │
│  Bluish translucent  │  Presents as neck swelling     │
│  swelling            │  (no floor-of-mouth swelling   │
│                      │  may be present)               │
└──────────────────────┴─────────────────────────────────┘

• Marsupialization (for simple ranula) - wide excision of the roof with sublingual gland removal
• Sublingual gland excision (definitive; reduces recurrence)
• For plunging ranula: sublingual gland excision ± cervical approach

X. XEROSTOMIA (DRY MOUTH)

Definition

Causes

• Drug-induced (most common): Anticholinergics, antidepressants (tricyclics), antihypertensives, antihistamines, diuretics, antipsychotics
• Sjogren syndrome
• Radiation therapy to head and neck (dose-dependent; permanent if >26 Gray to parotid tissue)
• Systemic diseases: Sarcoidosis, amyloidosis, human immunodeficiency virus (diffuse infiltrative lymphocytosis syndrome), graft-versus-host disease
• Dehydration, anxiety

Consequences

• Rampant dental caries
• Oral candidiasis
• Difficulty with mastication, deglutition, and speech
• Mucositis, oral ulcers
• Dysgeusia (altered taste)

Management

• Identify and treat/modify the causative drug or condition
• Artificial saliva substitutes (carboxymethylcellulose-based sprays)
• Frequent sips of water, ice chips
• Sugar-free chewing gum (stimulates residual flow)
• Pilocarpine or cevimeline (sialagogues) for Sjogren syndrome
• Meticulous oral hygiene and fluoride applications
• Acupuncture (some evidence for radiation-induced xerostomia)

XI. FREY SYNDROME (AURICULOTEMPORAL NERVE SYNDROME / GUSTATORY SWEATING)

Definition

Pathogenesis (Aberrant Nerve Regeneration)

┌──────────────────────────────────────────────────────────────┐
│              PATHOGENESIS OF FREY SYNDROME                  │
│                                                              │
│  Parotidectomy/parotid surgery/trauma                       │
│           ↓                                                 │
│  Division of parasympathetic secretomotor fibres of         │
│  auriculotemporal nerve to parotid gland                    │
│           ↓                                                 │
│  Aberrant regeneration of these fibres                      │
│           ↓                                                 │
│  Parasympathetic fibres reinnervate sweat glands and        │
│  blood vessels of the overlying skin (instead of gland)     │
│           ↓                                                 │
│  Gustatory stimulus → sweating and flushing of skin        │
│  (in distribution of auriculotemporal nerve)               │
└──────────────────────────────────────────────────────────────┘

Clinical Features

• Onset: months to years after parotid surgery
• Sweating and flushing over the cheek during eating
• Minor's starch-iodine test (sweating area turns blue-black) is the gold standard for diagnosis

Management

• Minor topical treatments (antiperspirants)
• Botulinum toxin A injection (current most effective treatment) - subcutaneous infiltration; benefit lasts approximately 1.5 years in 60% of patients
• Surgical: sternocleidomastoid muscle flap interposition (limited benefit)

SALIVARY GLAND INVESTIGATIONS - SUMMARY TABLE

CONCLUDING SUMMARY

1. Sialolithiasis - submandibular gland most common (80-90%); postprandial pain and swelling; management is now gland-conservative (sialoendoscopy, lithotripsy) before surgical gland removal.
2. Acute bacterial sialadenitis - parotid, retrograde bacterial migration; Staphylococcus aureus; treat with hydration and appropriate antibiotics.
3. Mumps - paramyxovirus; bilateral parotitis; complications include orchitis and deafness.
4. Sjogren syndrome - chronic autoimmune exocrinopathy; anti-Ro/SS-A and anti-La/SS-B antibodies; minor salivary gland biopsy is gold standard; increased lymphoma risk.
5. Sialosis - bilateral painless parotid enlargement; associated with alcoholism, diabetes, malnutrition.
6. Ranula - sublingual gland mucocele; simple vs. plunging types; treated by sublingual gland excision.
7. Frey syndrome - post-parotidectomy gustatory sweating; managed with botulinum toxin.