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Salivary Glands [Bailey]

Disorders of the Salivary Glands

Introduction

  • Major salivary glands: Parotid, submandibular, and sublingual (three pairs).
  • Minor salivary glands: Numerous[800-1000]; located mainly in lips, buccal mucosa, tongue, and palate; can be anywhere along the aerodigestive tract.
  • Saliva functions:
    • Clears substances from the mouth.
    • Maintains pH and tooth mineralization.
    • Influences the oral microbiome.
    • Neutralizes harmful dietary components.
    • Lubricates and hydrates oral mucosal surfaces.

Clinical Anatomy and Embryology

Parotid Gland

  • Largest salivary gland; situated in front of the external acoustic meatus.
  • Ectodermal origin; develops in the sixth week of gestation.
  • Structure:
    • Encapsulated; composed of fat and serous fluid-secreting cells.
    • Stensen’s duct: Main duct opening opposite the upper second molar tooth.
  • Facial nerve:
    • Enveloped within the gland substance.
    • Divides the gland into superficial and deep lobes.
  • Accessory parotid gland:
    • Located along Stensen’s duct.
    • Present in 21–61% of individuals.
    • Might require removal during Parotidectomy
    • If not removed, Sialocele can develop
    • It can lead to Fistula formation.

Parotid Innervation and Frey's Syndrome

  • Innervation:
    • Parasympathetic fibers from the glossopharyngeal nerve (cranial nerve IX).
    • Lesser petrosal nerve synapses in the otic ganglion.
    • Postganglionic fibers join the auriculotemporal nerve to reach the gland.
  • Frey's syndrome:
    • Gustatory sweating: Sweating and flushing over the parotid region while eating.
    • Caused by aberrant regeneration of parasympathetic fibers to sweat glands.
    • Involves acetylcholine acting on both sympathetic and parasympathetic fibers.

Submandibular Gland

  • Endodermal origin; develops between the 18th and 25th embryonic weeks.
  • Location:
    • In the submandibular space between the digastric muscles.
    • Larger superficial lobe and smaller deep lobe.
  • Wharton's duct:
    • Arises from the deep lobe.
    • Opens into the floor of the mouth near the frenulum.
  • Innervation:
    • Postganglionic parasympathetic fibers from the submandibular ganglion.
    • Fibers originate from the superior salivatory nucleus via the chorda tympani and lingual nerve.

Sublingual Gland

  • Smallest major salivary gland; contributes ~5% of saliva production.
  • Location:
    • Above the mylohyoid muscle, below the oral mucosa.
    • Bordered by the mandible and genioglossus muscle.
  • Ducts:
    • Rivinus’s ducts: Multiple small ducts along the sublingual fold.
    • Bartholin’s duct: Common duct formed by anterior ducts; empties near the sublingual caruncle.
  • Pathology:
    • Prone to mucous retention cysts (ranulas).
    • Nearly all tumors here are malignant.

Minor Salivary Glands

  • Development:
    • Appear around the 12th week of gestation.
    • Originate from ectoderm.
  • Characteristics:
    • Lack a distinct capsule.
    • Merge with surrounding connective tissue.
    • Widely distributed in the head and neck region.
  • Function:
    • Contribute 8–10% of saliva.
    • Play a major role during sleep.

Common Disorders

Mucoceles

  • Definition: Mucous extravasation phenomena due to trauma or obstruction.
  • Types:
    • Extravasation mucocele:
      • Caused by trauma to minor salivary gland ducts.
      • Saliva accumulates in connective tissue, triggering inflammation.
      • Common in children and adolescents; often on the lower lip.
      • Ranula: A type of extravasation mucocele in the floor of the mouth.
    • Retention cyst:
      • Results from duct obstruction (e.g., sialolithiasis).
      • Contains mucous material or sialolith fragments.

Ranula (Little Frog)

  • Appearance: Bluish swelling in the anterior floor of the mouth, resembling a frog's belly.
  • Cause:
    • Rupture of the main duct or obstructed acini of the sublingual gland.
  • Types:
    • Simple ranula: Localized to the floor of the mouth.
    • Plunging ranula: Extends through the mylohyoid muscle into the neck.
  • Diagnosis:
    • Clinical examination and imaging.
    • Aspiration yields thick, sticky saliva.
  • Treatment:
    • Removal of the sublingual gland to prevent recurrence.
      • Most Common Structure injured = Sub Mandibular Gland duct
      • Most Common nerve injured = Lingual Nerve
    • Marsupialization has low success rates.
    • OK-432 injection or botulinum toxin may be used.

Acute Necrotising Sialometaplasia

  • Location: Primarily on the palate.
  • Presentation:
    • Swelling that ulcerates with rolled margins.
    • Mimics a malignant ulcer.
  • Diagnosis:
    • Biopsy shows necrosis and hyperplasia but preserves lobular architecture.
  • Outcome:
    • Lesion heals spontaneously within a few weeks.

Immunological Conditions

Sjögren's Syndrome (SjS)

  • Definition: Chronic autoimmune disease affecting salivary and lacrimal glands.
  • Symptoms:
    • Xerostomia (dry mouth).
    • Dry eyes.
    • Salivary gland enlargement, especially the parotid.
  • Types:
    • Primary SjS: Occurs alone.
    • Secondary SjS: Associated with other autoimmune diseases (e.g., lupus, rheumatoid arthritis).
  • Diagnosis:
    • Based on EULAR criteria.
    • Biopsy: Focal lymphocytic sialadenitis with focus score >50 lymphocytes per 4 mm².
    • Serology: Anti-SSA/Ro or anti-SSB/La antibodies; may be seronegative.
  • Treatment:
    • Symptomatic: Tear substitutes, saliva stimulants.
    • Severe cases: Glucocorticoids, immunosuppressants.

Scleroderma

  • Definition: Autoimmune disease with excessive collagen deposition.
  • Affected Organs:
    • Skin, heart, lungs, kidneys, gastrointestinal tract.
    • Salivary glands: Parenchyma replaced by collagen, leading to xerostomia.
  • Diagnosis:
    • Clinical features.
    • Minor salivary gland biopsy.

Sarcoidosis

  • Definition: Inflammatory disorder with non-caseating granulomas in multiple systems.
  • Symptoms:
    • Dry cough, fatigue, shortness of breath.
    • Chest radiograph: Bilateral hilar lymphadenopathy.
  • Salivary Gland Involvement:
    • Sarcoid pseudotumor: Localized parotid swelling.
    • Heerfordt’s syndrome: Parotid swelling, anterior uveitis, facial palsy, fever.
  • Diagnosis:
    • Clinical and radiological findings.
    • Biopsy confirming granulomas.

Ectopic/Aberrant Salivary Gland Tissue

  • Stafne Bone Cyst:
    • Radiolucent lesion in the mandible due to ectopic salivary tissue.
    • Size ranges from 0.5 to 2 cm.
    • Located between the first molar and the angle of the mandible.
  • Other Ectopic Sites:
    • Cervical lymph nodes, middle ear, thyroid gland, and others.

Sialadenitis

  • Definition: Inflammation of a salivary gland.
  • Types:
    • Acute: Viral or bacterial infection.
    • Chronic: Due to obstruction or autoimmune conditions.
  • Acute Viral Sialadenitis:
    • Causes: Mumps (paramyxovirus), cytomegalovirus, HIV.
    • Presentation: Painful gland swelling; often self-limiting.
  • Acute Bacterial Sialadenitis:
    • Cause: Staphylococcus aureus.
    • Predisposing Factors: Duct obstruction, xerostomia.
    • Treatment: Antibiotics.

Human Immunodeficiency Virus Sialadenitis

  • Presentation:
    • Bilateral parotid enlargement.
    • Xerostomia.
  • Associated with:
    • HAART therapy, especially protease inhibitors.
  • Pathology:
    • Benign lymphoepithelial cysts in parotid glands.
    • CD8 lymphocytic infiltration.
  • Differentiation:
    • Mimics Sjögren's syndrome but lacks specific antibodies.
  • Management:
    • Symptomatic treatment.
    • Monitor for potential lymphoma transformation.

Recurrent Parotitis of Childhood

  • Characteristics:
    • Rapid, recurrent swelling of one or both parotid glands.
    • Aggravated by chewing and eating.
  • Age Group:
    • Mainly affects children aged 3 to 6 years.
  • Cause:
    • Possibly due to an incompetent parotid duct leading to contamination.
  • Diagnosis:
    • Sialography shows punctate sialectasis ("snowstorm" appearance).
  • Treatment:
    • Long-term antibiotics.
    • Endoscopic duct washouts.

Sialadenosis

  • Definition: Non-inflammatory, bilateral enlargement of the parotid glands.
  • Associations:
    • Chronic malnutrition, obesity, alcoholism, liver disease, diabetes.
    • Certain medications (e.g., guanethidine).
  • Symptoms:
    • Painless swelling.
    • Reduced saliva production.
  • Management:
    • Address underlying systemic condition.

Sialolithiasis

  • Definition: Formation of salivary stones within the ducts.
  • Most Common Site: Submandibular gland (85%).
  • Predisposing Factors:
    • Ascending duct course.
    • Viscous, alkaline saliva.
  • Symptoms:
    • Postprandial swelling and pain.
    • Possible palpable stone.
  • Diagnosis:
    • Radiographs: Initial test; 80% of stones are radio-opaque.
    • NCCT scan, Ultrasonography, MRI sialography: For non-opaque stones.
  • Treatment:
    • Small stones (<5 mm): Endoscopic removal.
    • Larger stones (>5 mm): Duct slitting or transoral approach.
    • ESWL: For stones not amenable to endoscopic removal.
    • Gland excision: Last resort.

Xerostomia

  • Definition: Dry mouth due to decreased salivary flow.
  • Common Causes:
    • Aging, medications (anticholinergics, antidepressants).
    • Systemic diseases (e.g., Sjögren's syndrome).
    • Radiotherapy to the head and neck.
  • Symptoms:
    • Difficulty swallowing and speaking.
    • Altered taste.
    • Oral discomfort.
  • Management:
    • Hydration and humidification.
    • Saliva substitutes and stimulants.
    • Avoid irritants and dry foods.

Sialorrhoea

  • Definition: Excessive salivation leading to drooling.
  • Common in:
    • Children with neurological disorders (e.g., cerebral palsy).
  • Management:
    • Antisialogogues: Medications that reduce saliva production.
    • Botulinum toxin injections: Into salivary glands.
    • Surgical interventions: Duct repositioning or gland excision.

Trauma

  • Causes:
    • Penetrating injuries, blasts, vehicular accidents.
  • Potential Injuries:
    • Damage to salivary gland tissue and ducts.
    • Injury to surrounding nerves (facial and hypoglossal nerves).
  • Complications:
    • Salivary fistula.
    • Sialocele (saliva-filled cyst).
    • Nerve palsy.
  • Management:
    • Wound care: Debridement and tension-free closure.
    • Duct repair:
      • Within 72 hours over a cannula.
      • For significant duct loss, consider marsupialization or rerouting.
    • Nerve repair:
      • Direct repair or grafting if injury is posterior to the lateral canthus line.
      • Tagging nerve endings for future repair if immediate repair is not feasible.
    • Gland excision:
      • Considered if there is severe parenchymal damage.

Neoplasms of the Salivary Gland

Introduction

  • Incidence:
    • Benign neoplasms: 0.4–13.5 cases per 100,000.
    • Malignant tumours: 0.4–2.6 per 100,000.
    • Account for less than 3% of head and neck malignancies.
  • Age and Gender:
    • Typically present after the fourth decade.
    • Both sexes are equally affected.
    • Warthin's tumours: More common in older men.
    • Pleomorphic adenomas: Slightly more common in women.
  • Gland Involvement:
    • Major salivary glands: >80% of tumours; majority are benign.
    • Minor salivary glands: >50% of tumours are malignant.
  • Common Tumours:
    • Benign:
      • Pleomorphic adenoma (most common).
      • Warthin's tumour.
    • Malignant:
      • Mucoepidermoid carcinoma (most common).
  • Risk Factors:
    • Radiation exposure: Linked to both benign and malignant tumours.
    • Smoking: Strongly associated with Warthin's tumour.
    • Others: Viral infections, environmental and industrial exposures (e.g., rubber manufacturing, nickel compounds, hair dyes).

Benign Tumours

Pleomorphic Adenoma

  • Most common benign salivary gland tumour.
  • Epidemiology:
    • Occurs in all ages; most common between 30–60 years.
    • Slightly more frequent in women.
  • Locations:
    • Parotid gland (>80%).
    • Also in submandibular gland and hard palate.
  • Clinical Features:
    • Painless, well-defined, mobile mass.
    • Gradual progression over years; can become very large.
    • Deep lobe involvement: May present as a paratonsillar bulge.
    • Malignant transformation: Indicated by sudden increase in size or facial nerve palsy (rare).
  • Treatment:
    • Surgical excision with a cuff of normal tissue.
    • Avoid enucleation to prevent recurrence due to capsular breach.

Histopathology

  • Gross Appearance:
    • Well-circumscribed, nodular, firm mass.
    • White to tan cut surface; may have cartilaginous areas.
  • Microscopic Features:
    • Mixed components: Epithelial, myoepithelial, and stromal.
    • Cellular diversity: Oval, spindle-shaped, plasmacytoid, clear cells.
    • Stroma: Myxoid to chondroid and hyalinized.
  • Immunohistochemistry:
    • Luminal cells: CK7 positive.
    • Myoepithelial cells: p63, S-100, SOX10, SMA positive.

Warthin's Tumour

  • Also known as adenolymphoma or cystadenoma lymphomatosum.
  • Second most common benign salivary gland tumour (5–15%).
  • Epidemiology:
    • Predominantly affects older men (after sixth decade).
    • Associated with cigarette smoking and radiation exposure.
  • Location:
    • Almost exclusively in the parotid gland, especially the inferior pole.
    • May occur bilaterally or synchronously/metachronously.
  • Clinical Features:
    • Painless, slow-growing swelling.
    • Facial palsy is rare.
    • Malignant transformation is extremely rare (<1%).
  • Treatment:
    • Complete surgical excision with adequate margin.
    • Recurrences are rare; may be due to multifocality.

Histopathology

  • Gross Appearance:
    • Well-circumscribed, ovoid to spherical mass.
    • Cut surface shows solid and cystic areas with mucoid to brownish fluid.
  • Microscopic Features:
    • Papillary and cystic structures lined by bilayered oncocytic epithelial cells.
    • Lymphoid stroma with germinal centers.
    • Possible metaplastic changes: Squamous, sebaceous, ciliated, mucous cells.

Malignant Tumours

Mucoepidermoid Carcinoma

  • Most common malignant salivary gland tumour.
  • Epidemiology:
    • Affects children and young adults; peak in the second decade.
    • Can occur post-radiation or chemotherapy in childhood.
  • Locations:
    • Both major and minor salivary glands.
    • Parotid gland is the most frequent site.
  • Clinical Features:
    • Soft to firm, painless mass with gradual growth.
    • Classified as low, intermediate, or high grade based on histology.
    • High-grade tumours: Locally aggressive, possible bone/skin involvement, nodal metastases.
    • Distant metastases: Mainly to the lungs.
  • Treatment:
    • Complete surgical excision with wide margins.
    • Adjuvant radiotherapy for intermediate/high-grade tumours.

Histopathology

  • Cell Types:
    • Mucinous, intermediate, and squamoid cells.
  • Patterns:
    • Low-grade: Cystic, well-circumscribed, rich in mucous cells.
    • High-grade: Solid, infiltrative, with nuclear atypia, mitoses, necrosis.
  • Essential Feature:
    • Intracellular mucin is key for diagnosis.

Adenoid Cystic Carcinoma

  • Slow-growing malignancy with high perineural invasion propensity.
  • Epidemiology:
    • Occurs in 5th–6th decades.
    • Slight female predilection (1.5:1).
  • Locations:
    • Most Common malignant tumor of Mandibular gland.
    • Major and minor salivary glands.
    • Can also occur in paranasal sinuses, tracheobronchial tree.
  • Clinical Features:
    • Slow-growing mass, may have numbness, pain.
    • Possible facial nerve palsy.
    • Distant metastases: Lungs (common), bone, liver, brain.
  • Treatment:
    • Radical surgical excision with/without adjuvant radiotherapy.
    • Proton/carbon ion therapy for unresectable/metastatic cases.
  • Prognosis:
    • Good 5-year control, poor 10-year survival due to delayed metastases.

Histopathology

  • Patterns:
    • Cribriform (most characteristic), tubular, and solid.
  • Cell Features:
    • Small, angulated, hyperchromatic nuclei with scant cytoplasm.
  • Perineural invasion:
    • Common and significant for prognosis.
  • Immunohistochemistry:
    • Ductal cells: c-KIT positive.
    • Myoepithelial cells: p63, SMA positive.

Acinic Cell Carcinoma

  • Low to intermediate-grade malignancy composed of neoplastic acinar cells.
  • Epidemiology:
    • Mostly affects the parotid gland (90%).
    • Occurs in the 5th decade.
    • Slight female predilection (1.5:1).
  • Clinical Features:
    • Slow-growing, painless, mobile mass.
    • Rare facial palsy.
  • Treatment:
    • Complete surgical excision with adequate margins.
    • Recurrence possible with incomplete resection.

Histopathology

  • Cell Types:
    • Serous acinar cells, clear, vacuolated, oncocytic, hobnail features.
  • Patterns:
    • Solid (most common), follicular, microcystic.
  • Immunohistochemistry:
    • Positive: DOG1, SOX10.
    • Negative: Mammaglobin (distinguishes from secretory carcinoma).

Carcinoma ex Pleomorphic Adenoma

  • Definition: Malignancy arising within a pleomorphic adenoma.
  • Epidemiology:
    • Occurs mainly in the parotid gland.
    • More common in women.
    • Presents in the sixth decade.
  • Clinical Features:
    • Rapidly growing mass within a longstanding swelling.
    • Associated with pain and facial nerve palsy.
  • Treatment:
    • Radical surgical excision with/without adjuvant radiotherapy.
  • Prognosis:
    • Poor 5-year survival (25–65%).
    • High incidence of local and distant metastases (70%).

Histopathology

  • Components:
    • Both benign pleomorphic adenoma and malignant adenocarcinoma.
  • Invasion Levels:
    • Non-invasive (intracapsular).
    • Minimally invasive.
    • Widely invasive.
  • Genetic Alterations:
    • TP53 mutations, HER2 amplification.

Salivary Duct Carcinoma

  • High-grade adenocarcinoma resembling mammary ductal carcinoma.
  • Epidemiology:
    • Mostly in elderly men (6th–7th decade).
    • Arises in the parotid gland.
  • Clinical Features:
    • Rapidly growing mass with facial palsy, pain, cervical lymphadenopathy.
  • Treatment:
    • Total parotidectomy with neck dissection.
  • Prognosis:
    • High risk of recurrence and metastasis.
    • Poor overall survival.

Histopathology

  • Features:
    • Large duct-like structures with comedo necrosis, cribriform patterns.
    • Vascular and perineural invasion.
  • Immunohistochemistry:
    • Androgen receptor positive.
    • HER2 receptor positive.

Investigations

Imaging

  • Ultrasonography:
    • Useful for major salivary gland lesions.
    • Benign tumours: Well-lobulated, hypoechoic.
    • Malignant tumours: Irregular, hypoechoic, blurred margins.
  • Computed Tomography (CT):
    • Assesses tumour extent, bone erosion, extraglandular involvement.
  • Magnetic Resonance Imaging (MRI):
    • Superior soft tissue contrast.
    • Diffusion-weighted MRI: Differentiates benign from malignant based on ADC values.
  • Positron Emission Tomography (PET-CT):
    • Detects distant metastases.

Cytology

  • Fine-Needle Aspiration Cytology (FNAC):

    • First-line diagnostic tool.
    • High sensitivity (80%) and specificity (97%).
    • Reported using the Milan system (assesses risk of malignancy).

    image.png

  • Core Needle Biopsy:

    • Provides more tissue for definitive diagnosis.
    • Useful when FNAC is inconclusive.

Staging of Salivary Gland Malignancies

  • Staged using the 8th edition of the AJCC.

  • Primary Tumour (T) Classification:

    • T1: ≤2 cm, no extraparenchymal extension.
    • T2: >2 cm but ≤4 cm, no extraparenchymal extension.
    • T3: >4 cm and/or extraparenchymal extension.
    • T4a: Moderately advanced; invades skin, mandible, ear canal, facial nerve.
    • T4b: Very advanced; invades skull base, pterygoid plates, encases carotid artery.

    image.png

  • Nodal (N) and Metastasis (M) staging similar to other head and neck cancers.

Treatment of Salivary Gland Malignancies

  • Surgery:
    • Mainstay of treatment.
    • Aim for complete excision with microscopic margins (≥0.5 cm).
    • Facial nerve preservation if oncologically safe.
  • Neck Dissection:
    • Elective for T3/T4 tumours and high-grade histology.
    • Comprehensive neck dissection for node-positive disease.
  • Adjuvant Radiotherapy:
    • Indicated for stage III/IV tumours, high-grade histology, or high-risk features (e.g., positive margins, perineural invasion).
  • Chemoradiation:
    • Role under investigation.
  • Palliative Therapy:
    • Chemotherapy and targeted therapy for unresectable or metastatic disease.

Surgery and Complications

Submandibular Gland Resection

  • Important Anatomical Relations:
    • Lingual nerve.
    • Hypoglossal nerve.
    • Marginal mandibular branch of the facial nerve.
    • Facial artery and vein.
  • Surgical Approach:
    • Incision: Horizontal, two finger breadths below the mandible.
    • Flap Elevation: In subplatysmal plane.
    • Nerve Identification: Preserve the marginal mandibular nerve.
    • Gland Mobilization:
      • Ligate facial vessels below the nerve.
      • Dissect gland from surrounding structures.
      • Wharton's duct: Clamped, divided, and ligated.
  • Complications:
    • Nerve Palsy: Marginal mandibular, lingual, hypoglossal nerves.
    • Hemorrhage: From facial artery or ranine veins.

Parotidectomy

  • Types of Surgery:
    • Extracapsular Dissection.
    • Adequate Parotidectomy.
    • Superficial Parotidectomy.
    • Total Conservative Parotidectomy.
    • Radical Parotidectomy.
  • Surgical Technique:
    • Incision: Modified Blair or facelift incision.
    • Flap Elevation: Preserve facial nerve branches.
    • Facial Nerve Identification:
      • Landmarks: Tragal pointer, digastric muscle, tympanomastoid suture.
      • Antegrade Technique: From trunk to branches.
    • Gland Removal:
      • Superficial Lobe: Dissected off facial nerve branches.
      • Deep Lobe: Removed if tumour extends deep.
  • Complications:
    • Facial Nerve Weakness: Temporary or permanent.
    • Hematoma.
    • Infection.
    • Sialocele.
    • Frey's Syndrome: Gustatory sweating.

Frey's Syndrome

  • Cause: Aberrant reinnervation of sweat glands by auriculotemporal nerve.
  • Symptoms: Sweating and flushing over parotid region while eating.
  • Prevention:
    • Use of thick skin flaps.
    • Interposition of tissue (e.g., sternocleidomastoid flap) between skin and parotid bed.
  • Management:
    • Antiperspirants containing aluminium chlorohydrate.
    • Botulinum toxin injections into affected skin.
    • Tympanic neurectomy (less common).

Complications of Parotid Gland Surgery

  • Immediate:
    • Hematoma Formation.
    • Infection.
  • Functional:
    • Facial Nerve Weakness: Temporary or permanent.
    • Great Auricular Nerve Injury: Numbness of the ear lobe. or anesthesia over beard region
  • Aesthetic:
    • Unsightly Scar.
    • Retromandibular Hollowing.
  • Others:
    • Sialocele.
    • Facial Numbness.
    • Frey's Syndrome.

Note: Proper surgical planning and technique are crucial to minimize complications and ensure optimal outcomes in the management of salivary gland neoplasms.