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Non-Neoplastic Salivary Gland Diseases

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CLASSIFICATION OF NON-NEOPLASTIC SALIVARY GLAND DISEASES

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1. SIALOLITHIASIS (Salivary Calculi)

Epidemiology

• Most common cause of inflammatory salivary gland disease
• Lifetime symptomatic prevalence: ~0.45%
• Age: 5th to 8th decades most commonly; rare in children (present around age 10)
• Males > Females

Gland Distribution

• Submandibular gland: 80-90% (most common - Wharton duct)
• Parotid (Stensen duct): 10-20%
• Sublingual duct: 1%
• Minor salivary glands: rare

Why Submandibular Gland?

1. Wharton duct is longer, wider, more tortuous, and angulated against gravity as it courses around the mylohyoid
2. Submandibular saliva is more mucoid, alkaline, with higher concentration of calcium and phosphate
3. Retrograde bacterial migration is more likely

Composition

• Predominantly calcium phosphate and carbonate + organic matrix (glycoproteins, mucopolysaccharides)
• Small amounts of Mg, K, NH4

Pathogenesis

• Salivary stasis + inflammatory changes -> alteration of mucoid elements -> organic gel framework -> salt deposition -> calculus formation
• Serum Ca/PO4 levels are not related to stone formation
• In submandibular gland: sialolith is the primary event causing stasis and sialadenitis
• In parotid gland: chronic sialadenitis causes ductal injury which is the inciting event for sialolithiasis

Radiology

• 90% of submandibular stones are radio-opaque (plain X-ray visible)
• 90% of parotid stones are radiolucent (need ultrasound or CT)
• Up to 15% of all calculi are radiolucent on plain film
• Imaging modalities:
  • Ultrasound: first-line, detects stones >2mm, no radiation
  • CT (non-contrast): most sensitive, gold standard for stone detection
  • MR sialography: non-invasive, uses inherent T2-weighted salivary fluid signal, no ductal cannulation needed, good for duct mapping
  • Conventional sialography: invasive, 4-15% failure rate, can provoke acute sialadenitis; largely replaced by CT/MR

Clinical Features

• Mealtime syndrome: pain and swelling of affected gland that occurs during eating (saliva cannot drain past the obstruction), subsides after 1-2 hours
• Tender, enlarged gland
• Purulent discharge from duct orifice (if infected)
• Bimanual palpation of floor of mouth for submandibular stones

Complications

• Acute suppurative sialadenitis
• Ductal stenosis
• Chronic sialadenitis with gland fibrosis
• Abscess formation

Treatment

• Hydration, massage, warm compresses, sialagogues (lemon drops, citric acid), antibiotics if infected
• Many small stones will pass spontaneously

• Diagnostic + therapeutic
• Endoscopic visualization of stenosis or calculi
• Balloon dilatation of stenoses
• Holmium laser fragmentation of large stones
• Wire basket ensnarement and extraction of stones

• Submandibulectomy: for large parenchymal stones, recurrent disease, gland fibrosis
• Parotidectomy: rarely needed

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2. ACUTE SUPPURATIVE SIALADENITIS

Etiology

• Usually bacterial; most common organism: Staphylococcus aureus (60-90% of cases)
• Other organisms: Streptococcus viridans, Haemophilus influenzae, anaerobes
• Predisposing factors:
  • Dehydration, debilitation, post-operative state (the classic "post-op parotitis")
  • Ductal obstruction (sialolithiasis)
  • Immunosuppression
  • Xerostomia (drugs, radiotherapy)
  • Poor oral hygiene

Parotid Gland Predisposition

• Saliva of parotid is serous and low in IgA relative to submandibular
• Less protective against retrograde bacterial migration
• Stensen duct opens at the level of upper 2nd molar (Stensen's papilla)

Clinical Features

• Acute onset painful swelling of the affected gland
• Trismus (due to masseter involvement/spasm if parotid)
• Fever, malaise, leukocytosis
• Pus expressible from duct orifice on palpation
• Overlying skin erythema and tenderness

Management

• Acute: IV antibiotics (anti-staphylococcal: nafcillin, clindamycin, or amoxicillin-clavulanate), aggressive hydration, warm compresses, sialagogues, oral hygiene, massage
• Surgical drainage: indicated for abscess formation - incisions placed to avoid facial nerve branches; for parotid abscess, multiple stab incisions through the parotid fascia

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3. CHRONIC SIALADENITIS

Pathogenesis

• Repeated episodes of acute sialadenitis -> progressive periductal fibrosis, acinar atrophy, ductal dilation
• Most commonly secondary to sialolithiasis

Histology

• Periductal fibrosis, lymphocytic infiltration, acinar loss, ductal ectasia
• "Kuttner tumor" - chronic sclerosing sialadenitis of the submandibular gland; presents as a hard, painless mass that can mimic malignancy; associated with IgG4-related disease

Clinical Features

• Recurrent episodes of gland swelling (especially post-prandially)
• Firm, non-tender gland between episodes
• May have reduced salivary flow

Management

• Conservative: sialendoscopy with ductal dilation
• Gland excision for refractory disease

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4. VIRAL SIALADENITIS

A. Mumps (Epidemic Parotitis)

• Causative agent: Paramyxovirus (RNA virus)
• Most common cause of parotitis worldwide (before vaccination)
• Transmitted by respiratory droplets
• Peak incidence: 4-6 years (but can affect adults)

• Prodrome: fever, malaise, headache, anorexia (1-2 days)
• Acute tender bilateral (or unilateral) parotid swelling
• Earache, difficulty chewing
• Obliteration of the angle of the jaw
• Stensen duct orifice may be erythematous ("Mursu's sign")

• Orchitis (20-35% of post-pubertal males) - most feared; may lead to infertility
• Oophoritis
• Aseptic meningitis (10%)
• Encephalitis
• Sensorineural hearing loss (may be unilateral and permanent)
• Pancreatitis
• Myocarditis

B. HIV-Associated Salivary Gland Disease

• Parotid most commonly affected (has intraparotid lymph nodes)
• Pediatric population: salivary gland lesions in up to 18% of HIV cases

• Most common parotid lesion in HIV (75%)
• Pathogenesis: viral inflammation of intraparotid lymph nodes
• Often bilateral (up to 80%); may appear unilateral clinically
• Cervical lymphadenopathy present in 90%
• May mimic Warthin tumor (both cystic and bilateral)
• Treatment:
  • ART (complete response ~53%)
  • Serial aspiration for cosmesis (33%)
  • Sclerotherapy with doxycycline (56%)
  • High-dose external beam radiotherapy (66%)
  • Parotidectomy: reserved for large disfiguring lesions or suspected malignancy

• Clinically similar to Sjögren syndrome
• CD8+ T-cell infiltration of salivary and lacrimal glands
• Bilateral parotid swelling, xerostomia

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5. GRANULOMATOUS SIALADENITIS

Sarcoidosis

• Bilateral parotid involvement in ~6% of sarcoidosis cases
• Heerfordt syndrome (uveoparotid fever): parotid swelling + uveitis + facial nerve palsy + low-grade fever
• Also called "Heerfordt-Waldenström syndrome"
• Elevated serum ACE, calcium
• Non-caseating granulomas on biopsy
• Treatment: systemic corticosteroids

Actinomycosis

• Caused by Actinomyces israelii (anaerobic Gram-positive filamentous bacterium - normal oral flora)
• Affects parotid and cervicofacial region
• Hard, indurated, "woody" swelling with multiple sinus tracts discharging sulfur granules
• Treatment: prolonged penicillin (6-12 months)

Cat-Scratch Disease

• Caused by Bartonella henselae
• Unilateral parotid or submandibular swelling after cat scratch
• Diagnosis: Warthin-Starry stain, serology, FNA showing stellate microabscesses
• Usually self-limited; doxycycline or azithromycin for severe disease

Tuberculosis

• Primary or secondary TB of salivary glands is rare
• Cold abscess, sinus formation
• AFB smear, culture, PCR; caseating granulomas on biopsy
• Anti-TB treatment

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6. SJÖGREN SYNDROME

Definition

Epidemiology

• Female predominance (9:1 female to male ratio)
• Peak onset: 4th-5th decade
• Primary Sjögren: isolated gland involvement
• Secondary Sjögren: occurs with another connective tissue disease (RA most common, also SLE, scleroderma, polymyositis)

Pathogenesis

• Autoimmune T-cell (CD4+) and B-cell infiltration of salivary and lacrimal glands
• Characteristic autoantibodies: anti-SSA (anti-Ro) and anti-SSB (anti-La)
• Also ANA positive, RF positive

Clinical Features

• Bilateral parotid enlargement (diffuse, non-tender)
• Xerostomia (dry mouth): difficulty swallowing dry food, altered taste, burning mouth
• Keratoconjunctivitis sicca: dry, gritty eyes, photophobia

• Arthralgias/arthritis
• Raynaud phenomenon
• Skin: purpura, vasculitis
• Pulmonary: interstitial lung disease
• Renal: tubulointerstitial nephritis
• Peripheral neuropathy
• Increased risk of lymphoma (40-fold increase): MALT lymphoma of salivary gland

Diagnosis

• Schirmer test: < 5 mm wetting in 5 min (lacrimal gland dysfunction)
• Rose Bengal test: corneal staining with dye
• Minor salivary gland biopsy (lip biopsy): lymphocytic infiltration with focal aggregates, focus score >1 (>50 lymphocytes per 4mm² area) - gold standard
• Serology: anti-SSA/Ro, anti-SSB/La, ANA, RF
• Sialometry: reduced salivary flow rate
• MR sialography / Sialography: "cherry blossom" pattern (multiple small cavities/sialectasis)
• Salivary scintigraphy (Tc-99m pertechnetate): reduced uptake and delayed excretion

Treatment

• Artificial saliva substitutes, frequent sips of water
• Pilocarpine (muscarinic agonist) or cevimeline: oral sialagogues to stimulate residual function
• Frequent dental examinations (xerostomia -> caries risk)
• Eye drops (artificial tears), lubricants

• Hydroxychloroquine
• Corticosteroids for severe systemic manifestations
• Rituximab (anti-CD20) for lymphoma or severe disease

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7. SIALADENOSIS (SIALOSIS)

Definition

Causes (Mnemonic: DALE)

• Diabetes mellitus
• Alcohol-related liver disease / malnutrition
• Liver cirrhosis
• Endocrine: hypothyroidism, acromegaly, Cushing disease
• Also: bulimia nervosa (classic presentation of bilateral painless parotid enlargement in young females with self-induced vomiting), pregnancy

Pathology

• Hypertrophy of acinar cells, especially serous cells
• No inflammation or malignancy
• Exact mechanism unclear - may involve autonomic neuropathy

Clinical Features

• Bilateral, painless, diffuse parotid enlargement
• Normal salivary flow
• Often an incidental finding

Management

• Treatment of the underlying systemic disorder

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8. XEROSTOMIA (Dry Mouth)

Causes

• Drugs (most common cause): anticholinergics, antihistamines, antidepressants (TCAs, SSRIs), antihypertensives (diuretics, beta-blockers), opioids
• Sjögren syndrome
• Radiation therapy to head and neck: most common short- and long-term adverse effect of radiotherapy for head/neck cancers; the high turnover of salivary duct unit cells makes them extremely vulnerable to ionizing radiation
• Aging (reduced gland function)
• Dehydration, mouth breathing

Consequences

• Dental caries (rampant)
• Oral candidiasis
• Dysphagia
• Altered taste (dysgeusia)
• Halitosis
• Difficulty speaking

Management

• Pilocarpine / cevimeline
• Artificial saliva
• Sugar-free gum/candy
• Amifostine (radio-protective agent used prophylactically before radiotherapy)
• Submandibular gland transfer outside radiation field (surgical option to preserve salivary function in patients undergoing H&N radiotherapy)

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9. MUCOCELE AND RANULA

Mucocele

• Most common lesion of minor salivary glands
• Due to: mucous extravasation (ruptured duct causing mucin spillage into connective tissue - no epithelial lining) or mucous retention (duct obstruction causing cystic dilation lined by epithelium)
• Extravasation type: more common, lower lip most common site, seen in children and young adults after lip trauma/biting
• Retention type: older patients, any minor gland location

• Soft, fluctuant, translucent/bluish swelling
• Usually 0.5-1 cm, on lower lip most commonly
• May rupture spontaneously

Ranula

• Mucocele arising from the sublingual gland (or minor salivary glands in the floor of mouth)
• Name derives from rana (frog) - resembles the underbelly of a frog

• Simple ranula: within the floor of mouth, above the mylohyoid muscle
• Plunging (diving) ranula: extends through or around the mylohyoid muscle into the submandibular or parapharyngeal space; presents as a neck swelling

• Soft, bluish, dome-shaped swelling in floor of mouth
• Usually unilateral
• Plunging ranula appears as a soft neck mass without overlying skin changes

• Marsupialization: opening and suturing cyst wall to floor of mouth mucosa (for simple ranula)
• Sublingual gland excision: definitive treatment; removes the source gland to prevent recurrence
• Intralesional OK-432 (picibanil) injection: sclerotherapy, useful especially for plunging ranula - causes fibrosis
• For plunging ranula: transoral sublingual gland excision is preferred over transcervical approach

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10. RADIATION-INDUCED SALIVARY GLAND DAMAGE

• Due to high cellular turnover, salivary duct and acinar cells are extremely radiosensitive
• Xerostomia is the most common and debilitating short- and long-term side effect of head and neck radiotherapy
• Affects quality of life, swallowing, dental health
• Severity depends on total radiation dose, fractionation, and volume of salivary glands included in the radiation field
• IMRT (Intensity-Modulated Radiation Therapy): reduces dose to contralateral parotid to minimize xerostomia
• Amifostine: radioprotective agent given IV before each radiotherapy fraction

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SUMMARY TABLE FOR QUICK REVISION

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IMPORTANT EXAM POINTS

1. Submandibular stones are radio-opaque (90%); Parotid stones are radiolucent (90%) - classic viva question
2. S. aureus is the most common organism in acute suppurative parotitis
3. Mumps complication most feared in post-pubertal males: orchitis (may cause infertility)
4. Anti-Ro (SSA) and Anti-La (SSB) antibodies in Sjögren syndrome
5. Minor salivary gland (lip) biopsy with focus score >1 is the gold standard for Sjögren diagnosis
6. Heerfordt syndrome = parotid + uveitis + facial palsy (Sarcoidosis)
7. Kuttner tumor = chronic sclerosing sialadenitis of submandibular gland (IgG4-related)
8. Plunging ranula - extends through mylohyoid; treatment = sublingual gland excision
9. Mucocele of lower lip = most common minor salivary gland lesion
10. Sialadenosis in young females with parotid enlargement = think bulimia nervosa
11. Pilocarpine (muscarinic agonist) is the pharmacological sialagogue of choice in Sjögren/xerostomia
12. IMRT + amifostine minimize radiation-induced xerostomia

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