• Salivary gland tumours are relatively uncommon, representing approximately 2% of all head and neck neoplasms ^[1] (some sources quote 6–8% of all H&N cancers ^[2])
• Annual incidence: approximately 0.4–13.5 per 100,000 population globally, with geographic variation
• Male preponderance overall for malignant salivary gland tumours ^[2], though specific subtypes vary:
  • Pleomorphic adenoma: F:M = 2:1 ^[1]
  • Mucoepidermoid carcinoma: F > M ^[1]
  • Adenoid cystic carcinoma: M = F ^[1]
  • Squamous cell carcinoma: M:F = 2:1 ^[1]
• Predominantly a disease of the elderly (age > 60) for malignant tumours ^[2], though benign tumours peak in the 4th–6th decades ^[1]
• Age distribution varies by subtype:
  • Pleomorphic adenoma: 4th–6th decades ^[1]
  • Mucoepidermoid carcinoma: 3rd–8th decades, peak in 5th decade ^[1]
  • Adenoid cystic carcinoma: 5th decade ^[1]
  • Squamous cell carcinoma: 7th–8th decades ^[1]

This is a critical table to memorise — it defines the clinical approach:

^[1][2]

High Yield: 80-80-80 rule for the parotid — 80% of salivary gland tumours occur in the parotid, 80% of parotid tumours are benign, 80% of benign parotid tumours are pleomorphic adenomas ^[1]. This is the single most tested fact.

• In Hong Kong and Southern China, there is a relatively higher prevalence of EBV-associated lymphoepithelial carcinoma of the salivary glands due to the endemic nature of EBV in this population
• Nasopharyngeal carcinoma (NPC), which is EBV-driven and highly prevalent in Southern China, can metastasise to or be confused with primary salivary gland lesions
• Betel nut chewing, while primarily associated with oral cavity carcinoma, is less common in HK compared to Southeast Asia but still relevant in immigrant populations

• 600–1000 small glands distributed throughout the submucosa of the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, trachea, and paranasal sinuses ^[2]
• Most common sites: hard palate, lips, tonsils ^[2]
• Produce predominantly mucous saliva
• No capsule → tumours here tend to be less well-defined and have a higher malignancy rate (50–75%) ^[2]

Understanding saliva function explains why salivary gland surgery/radiotherapy causes morbidity:

• Lubrication and protection of oral mucosa
• Digestion (amylase, lipase)
• Antimicrobial (IgA, lysozyme, lactoferrin)
• Buffering (bicarbonate maintains oral pH)
• Remineralisation of teeth (calcium, phosphate)
• Total daily production: ~1–1.5 L/day; 60–65% from submandibular, 20–25% from parotid, 7–8% from sublingual, remainder from minor glands

• Increased risk in long-term cancer survivors who received radiotherapy as part of their treatment, particularly for Hodgkin lymphoma ^[2]
• Increased risk in individuals who received radiation to the H&N region for childhood cancer or other benign conditions ^[2]
• Pathophysiology: Ionising radiation causes DNA double-strand breaks → if misrepaired, leads to chromosomal translocations and oncogene activation. There is typically a long latency period (10–30 years)
• Previous irradiation/malignancy is also listed as a general risk factor for H&N cancers ^[4]

• Warthin's tumour is STRONGLY associated with smoking, in contrast to other salivary gland tumours for which there is no clear relationship ^[2]
• The mechanism is not entirely understood, but hypotheses include:
  • Smoking causes chronic irritation and metaplasia of salivary duct epithelium
  • Smoking promotes lymphoid hyperplasia within the parotid (Warthin's tumour characteristically has a prominent lymphoid stroma)
  • Smokers have an 8-fold increased risk of developing Warthin's tumour
• Note: Unlike most other H&N cancers, smoking is NOT a major risk factor for most salivary gland tumours — this is a commonly tested distinction

• Nickel, silica dust, and rubber manufacturing have been linked in some studies
• UV light exposure — relevant for skin SCC that metastasises to parotid intraglandular lymph nodes

• Specific chromosomal translocations are identified in certain subtypes:
  • Pleomorphic adenoma: rearrangements involving PLAG1 (8q12) or HMGA2 (12q14-15) — these transcription factors drive the mixed epithelial-mesenchymal differentiation pattern
  • Mucoepidermoid carcinoma: MAML2 rearrangement (t(11;19)(q21;p13)) creating CRTC1-MAML2 fusion — activates Notch signalling. Present in ~55% of cases and associated with favourable prognosis
  • Adenoid cystic carcinoma: MYB-NFIB fusion (t(6;9)(q22-23;p23-24)) — MYB is a transcription factor driving cell proliferation. This fusion is found in ~60–80% of cases and is considered a hallmark
  • Secretory carcinoma (previously mammary analogue secretory carcinoma): ETV6-NTRK3 fusion — identical to the translocation seen in secretory carcinoma of the breast

Salivary gland tumours arise from the intercalated duct reserve cells (stem/progenitor cells) that have the capacity to differentiate into both luminal (ductal/acinar) and abluminal (myoepithelial/basal) cell types. This explains the remarkable histological diversity:

• Tumours differentiating towards luminal cells → acinic cell carcinoma, salivary duct carcinoma
• Tumours differentiating towards myoepithelial cells → myoepithelioma
• Tumours differentiating towards both → pleomorphic adenoma (hence "pleomorphic" = many forms — it contains epithelial and mesenchymal-like elements, including myxoid, chondroid, and osseous stroma)

Simply because it is the largest salivary gland with the most tissue mass → more cells → more opportunity for neoplastic transformation. Additionally, it contains intraglandular lymph nodes that can harbour metastatic disease.

This is not entirely understood but likely reflects:

1. Selection bias: benign tumours in small glands may be too small to present clinically → the ones that do present are more likely to be malignant (growing faster)
2. Microenvironment differences: minor salivary glands lack a capsule → less physical constraint on growth → malignant behaviour may be more easily established
3. Different stem cell populations: the progenitor cell pool in minor glands may have different susceptibility to malignant transformation

Understanding how salivary gland cancers spread explains staging and surgical approach:

1. Local invasion:

   • Through the gland capsule (or pseudocapsule in pleomorphic adenoma)
   • Into adjacent structures: skin, mandible, masseter, pterygoid muscles, external auditory canal, temporal bone
   • Perineural invasion — particularly characteristic of adenoid cystic carcinoma ^[1][2] — tumour cells track along nerve sheaths, sometimes far from the primary tumour. This causes pain, paraesthesia, and facial nerve palsy and is the main reason adenoid cystic carcinoma has such high local recurrence rates

2. Lymph node metastasis ^[2]:

   Primary Site	First Echelon Nodes
   Parotid gland	Intraparotid nodes → Level I & II cervical nodes
   Submandibular gland	Adjacent perivascular nodes → Cervical nodes
   Sublingual gland	Submental and submandibular nodes
   Minor salivary glands	Retropharyngeal nodes

3. Distant metastasis ^[2]:

   • Lung (most common site)
   • Bone
   • Liver
   • Adenoid cystic carcinoma is particularly notorious for haematogenous distant metastasis (especially to lungs), even in the absence of lymph node involvement — this is because it preferentially invades blood vessels and perineural spaces rather than lymphatics

Salivary gland tumour grading is subtype-dependent:

• Mucoepidermoid carcinoma: graded as low, intermediate, or high grade (based on proportion of cystic vs solid component, mitotic rate, necrosis, neural invasion, anaplasia)
• Adenoid cystic carcinoma: graded by histological pattern — tubular (best prognosis) → cribriform → solid (worst prognosis)
• Many other subtypes are considered inherently low-grade or high-grade (e.g., acinic cell = low-grade; salivary duct carcinoma = high-grade)

• Why it mimics a tumour: A stone obstructing Wharton's or Stensen's duct causes episodic swelling of the gland that can become chronically enlarged and firm, mimicking a tumour
• How to differentiate: The hallmark is pain and swelling aggravated by eating (or even anticipation of eating) — because meals stimulate saliva production, increasing pressure behind the obstruction ^[6]. This waxing-and-waning pattern is not seen in tumours, which enlarge progressively
• 80% occur in the submandibular gland ^[6] — because Wharton's duct is longer, runs against gravity, and submandibular saliva is more viscous (higher mucin content, higher calcium concentration)
• On examination, palpate the ducts for stones and express pus if infected ^[1]
• Chronic obstruction will eventually cause the gland to cease producing saliva, and the gland will feel firm and may be mistaken for a focal mass with the patient being asymptomatic ^[6]

• Typically affects older adults, malnourished or post-operative patients ^[3] — reduced oral intake → reduced salivary flow → stasis → ascending bacterial infection via the duct
• Commonly caused by S. aureus ^[3]
• Characterized by sudden onset of a very firm and tender swelling with fever, chills and fairly marked systemic toxicity ^[3]
• Purulent discharge can be expressed from the affected duct orifice ^[3] — this is the key distinguishing sign from a tumour (tumours don't produce pus from the duct)
• Why it mimics a tumour: The acutely inflamed gland can be rock-hard due to oedema and cellulitis, mimicking a malignant mass. However, the acute onset, tenderness, fever, and pus from the duct all point to infection

• Low-grade chronic infection that eventually leads to destruction of the salivary gland ^[3]
• Occurs more commonly in patients with decreased salivary secretion and increased mucus content in the saliva ^[3]
• Predisposing factors include stones, strictures and trauma ^[3]
• Results in a chronically enlarged, firm gland that can be very difficult to distinguish from a low-grade tumour on examination alone → imaging (USS/CT) and FNA are essential

• A specific form of chronic sialadenitis characterised by dense fibrosis and lymphocytic infiltration of the submandibular gland
• The name "Kuttner's tumour" itself tells you it mimics a neoplasm — it presents as a hard, painless submandibular mass
• Now increasingly recognised as part of the IgG4-related disease spectrum — check serum IgG4 levels
• Why it mimics a tumour: The fibrotic replacement makes the gland hard and irregular, essentially indistinguishable from submandibular gland carcinoma on palpation. FNA or biopsy is needed to make the distinction

• Commonly caused by mumps virus leading to acute pain and swelling of one or both parotid glands ^[3]
• Associated with non-specific prodrome consisting of low-grade fever, malaise, headache, myalgia and anorexia ^[3]
• Why it's usually not confused with a tumour: Bilateral involvement, acute onset, systemic symptoms, and self-limiting course (7–10 days) make this clinically distinct. However, unilateral viral parotitis in the early stages can briefly mimic a rapidly growing tumour
• Other viral causes: influenza, parainfluenza, coxsackievirus, EBV, CMV, HIV ^[7]

• Chronic inflammatory disorder characterized primarily by diminished lacrimal and salivary gland secretions resulting in symptoms of dry eyes and mouth (sicca complex) ^[3]
• Presents with a gradual swelling of parotid or submandibular glands, typically bilaterally ^[3]
• Autoimmune sialadenitis causes parenchymal destruction and dilation of intraglandular ducts ^[3]
• Why it matters in the DDx of salivary gland tumour: Sjögren's patients have a 15–20× increased risk of developing lymphoma (MALT lymphoma) of the salivary gland. A unilateral, progressive enlargement of one gland in a known Sjögren's patient should raise suspicion for lymphomatous transformation
• Also associated with increased risk of other salivary gland tumours

• Include mucoceles (from minor salivary glands), ranulas (sublingual gland retention cysts), and simple cysts of the major glands
• Mucoceles: painless, bluish, dome-shaped swellings on the lower lip (most common location) — caused by trauma to a minor salivary gland duct → extravasation of mucus into surrounding tissue
• Ranulas: translucent, bluish swelling in the floor of the mouth; a "plunging ranula" extends through the mylohyoid into the neck and can mimic a submandibular mass
• Usually soft/fluctuant on palpation, distinguishing them from solid tumours

• Benign cystic lesions of the parotid, particularly associated with HIV infection
• Bilateral parotid cystic enlargement in a young patient → think HIV-associated lymphoepithelial cysts
• Pathophysiology: HIV-driven reactive lymphoid hyperplasia within intraglandular lymph nodes leads to ductal obstruction → cyst formation
• On imaging, these appear as multiple bilateral parotid cysts — quite characteristic

• This is the single most common mimic of a salivary gland tumour, particularly in the submandibular and parotid regions
• It can be difficult to ascertain whether a mass is a parotid tumour versus parotid region lymph node ^[1]
• Cannot really differentiate between submandibular lymph nodes or submandibular gland tumour on palpation alone ^[1]
• Causes of lymphadenopathy:
  • Reactive: dental infections, pharyngitis, skin infections of the scalp/face
  • Granulomatous: tuberculosis (important in Hong Kong), sarcoidosis, cat-scratch disease
  • Malignant: lymphoma, metastatic SCC (from scalp/face/oral cavity), metastatic NPC (level II nodes mimicking parotid tail mass)

• Metastatic SCC to intraglandular lymph nodes, usually from scalp SCC ^[1] — this is extremely important because the parotid contains intraglandular lymph nodes that drain the scalp, forehead, temple, and ear skin
• Cutaneous melanoma of the scalp/face can also metastasise to parotid nodes
• Metastatic H&N carcinoma is predominantly related to metastatic squamous cell carcinoma arising from the aerodigestive tract ^[5]
• Always examine the scalp, face, ears and oral cavity carefully in any patient with a parotid mass

• Tonsils and tongue base may be the presenting site for a lymphoma ^[5]
• Lymphoma can present as a parotid mass (arising from intraglandular lymph nodes) or as a submucosal oropharyngeal mass mimicking a minor salivary gland tumour
• Tissue diagnosis is required to make the diagnosis of a salivary gland tumour prior to definitive treatment whenever possible to avoid major surgery for a benign tumour or a lymphoma ^[2] — this point is critical because lymphoma is treated with chemotherapy/radiotherapy, NOT surgery. Performing a parotidectomy for what turns out to be lymphoma would be unnecessary morbidity
• MALT lymphoma of salivary glands is particularly associated with Sjögren's syndrome

• Incidental finding; present during URTI; no trismus; 80% benign ^[8]
• These present as a medial bulge of the tonsillar pillar/soft palate on intraoral examination and can mimic a deep-lobe parotid tumour
• Include: deep lobe pleomorphic adenoma (most common), paragangliomas, schwannomas, neuromas
• The key distinguishing feature from a mucosal (minor salivary gland) tumour is that the overlying mucosa is normal (smooth) because the tumour is deep to the mucosa ^[8]

• Neoplasm arising from extra-adrenal chromaffin cells of the parasympathetic paraganglia ^[5]
• Pulsatile mass with a bruit on auscultation ^[5]
• Mobile in a side-to-side but not up-and-down direction (Fontaine's sign) ^[5] — because the carotid sheath allows lateral displacement but is tethered superiorly and inferiorly
• Located at the carotid bifurcation → can mimic a parotid tail or upper cervical mass
• Highly vascular and typically benign ^[5]

• Neoplastic proliferation of Schwann cells; arise from any peripheral nerve and commonly from the vagus nerve or superior cervical sympathetic chain in the neck ^[5]
• Vagal schwannoma may cause hoarseness or aspiration ^[5]
• Sympathetic chain schwannoma may cause Horner's syndrome ^[5]
• Can present as a parapharyngeal or upper neck mass mimicking a salivary gland tumour

• Accounts for 20% of paediatric neck masses ^[5]
• 1st branchial cleft cyst passes through the parotid gland in close proximity to the facial nerve — directly mimics a parotid tumour ^[5]
• 2nd branchial cleft cyst (most common) presents inferior to the angle of the mandible, anterior to SCM ^[5]
• Present in late childhood or early adulthood when a previously unrecognised cyst becomes infected ^[5]
• The key clue is the age (young patient), location (anterior to SCM), and recurrent infections

• Lipoma: benign neoplasm comprised of fat; typically asymptomatic and presents as soft, ill-defined, slowly enlarging mass ^[5] — easily distinguished from a salivary gland tumour by its soft consistency and superficial location
• Epidermoid inclusion cyst, dermoids, or pilomatrixoma can also present as masses in the salivary gland region ^[5]
• Confirm the lesion is not arising from the skin on palpation ^[1] — if the mass moves with the skin, it's a skin/subcutaneous lesion, not a salivary gland tumour

• Bruxism (excess teeth grinding or jaw clenching) ^[2] and masseter hypertrophy ^[2] can cause bilateral parotid-region fullness
• Distinguished by: bilateral, no discrete mass, hypertrophied masseter palpable as a firm muscle bulk (ask the patient to clench their jaw), no abnormality on imaging of the parotid gland itself

• Previous skin cancer (e.g., SCC) ^[2] — metastatic cutaneous SCC to intraglandular parotid lymph nodes is a critical differential; must rule out metastatic SCC to intraglandular lymph nodes, usually from scalp SCC ^[1]
• Melanoma of scalp or facial region ^[2] — same mechanism as above
• Sjögren's syndrome — increased risk of MALT lymphoma and other salivary gland tumours
• HIV status — lymphoepithelial cysts, lymphoepithelial carcinoma

• Radiotherapy ^[2] — prior radiation to H&N region increases risk of salivary gland malignancy (10–30 year latency)
• Phenytoin, thiouracil — can cause bilateral parotid swelling (sialadenosis), not tumour

• Smoking ^[2] — Warthin's tumour is strongly associated with smoking; also relevant for concurrent H&N SCC risk
• Alcohol — associated with sialadenosis (alcoholic cirrhosis) and synergistic risk for H&N SCC
• Betel nut chewing — oral cavity SCC risk

Ultrasound is the first-line investigation ^[1] for any salivary gland mass. It is the logical starting point because it is non-invasive, radiation-free, inexpensive, widely available, and can be performed at the bedside.

What USS tells you:

Why USS cannot be the final investigation: USS cannot assess deep lobe extension, parapharyngeal space, skull base, or bone invasion. It also cannot reliably determine the histological subtype. Hence, cross-sectional imaging (CT/MRI) and tissue diagnosis are always needed for surgical planning.

USS also facilitates fine needle aspiration (FNA) and core needle biopsy ^[2] — ultrasound-guided sampling is more accurate than blind FNA, particularly for small or deep lesions.

FNA for cytology can usually discriminate benign tumours from malignant tumours and metastasis but is less specific in the exact type of tumour ^[2].

Why FNA is the preferred tissue sampling method for major salivary glands:

1. Safety: Uses a 21–25 gauge needle — minimal risk of damaging the facial nerve (compared to larger core needles or incisional biopsy)
2. No tumour spillage: The fine needle creates a tiny puncture track with negligible risk of seeding tumour cells (a critical concern for pleomorphic adenoma, which recurs if there is capsular disruption)
3. Quick and cheap: Can be done in the outpatient clinic, often at the same time as USS
4. Guides management: The main clinical question FNA answers is: Is this benign, malignant, or lymphoma? This determines whether the patient needs:
   • Simple parotidectomy (benign)
   • Extended surgery + neck dissection + possible adjuvant radiotherapy (malignant)
   • Chemotherapy/radiotherapy without surgery (lymphoma)

Tissue diagnosis is required to make the diagnosis of a salivary gland tumour prior to definitive treatment whenever possible to avoid major surgery for a benign tumour or a lymphoma ^[2]

Limitations of FNA:

• Sensitivity: ~85–95% for distinguishing benign vs malignant
• Specificity for exact histological subtype is lower (~60–75%) — e.g., low-grade mucoepidermoid carcinoma can look like a mucocele on FNA; adenoid cystic carcinoma can look like pleomorphic adenoma
• Non-diagnostic rate: ~5–15% — insufficient cells, blood-contaminated, or non-representative sampling
• Uses the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) (2018) for standardised reporting:

Trucut (core needle biopsy) ^[1] provides a core of tissue with preserved architecture, allowing histological (not just cytological) analysis. This gives more information about the subtype and grade.

Core needle biopsy has risks of bleeding, nerve injury and tumour seeding ^[2]

When to use core biopsy instead of FNA:

• Non-diagnostic FNA (repeated)
• Suspicion of lymphoma (FNA cannot provide the architectural information needed for lymphoma subtyping — need tissue for flow cytometry, immunohistochemistry)
• Need to distinguish high-grade subtypes where FNA is ambiguous

Risks (why it's not first-line for all cases):

• Nerve injury: The larger-bore needle (14–18 gauge) has a small but real risk of damaging the facial nerve or its branches within the parotid
• Bleeding: More tissue disruption → haematoma risk
• Tumour seeding: Larger track → theoretical risk of implanting tumour cells along the needle path; particularly concerning for pleomorphic adenoma

Incisional biopsy — tumour spillage; for minor salivary glands only ^[1]

Why incisional biopsy is generally AVOIDED for major salivary glands:

• Risk of tumour spillage — particularly for pleomorphic adenoma, where capsular disruption leads to multifocal recurrence
• Risk of facial nerve injury in the parotid
• Risk of fistula formation
• Creates tissue planes that make subsequent definitive surgery more difficult

When it IS appropriate:

• For minor salivary glands only ^[1] — e.g., a submucosal hard palate mass can be biopsied transorally because:
  • No facial nerve is at risk
  • The biopsy site will be included in the definitive surgical resection specimen
  • The clinical situation demands tissue diagnosis before committing to potentially disfiguring palatal surgery

Excisional biopsy: Parotidectomy, Submandibulectomy ^[1]

In many cases, the definitive diagnosis is only obtained when the entire tumour is excised. This is particularly true when:

• FNA is repeatedly non-diagnostic
• There is high clinical suspicion of neoplasm despite equivocal FNA
• The tumour is small and the definitive surgery (superficial parotidectomy or submandibulectomy) serves as both diagnostic and therapeutic

The concept: you are performing a therapeutic excision that simultaneously provides the definitive histological diagnosis. This is the standard approach for most parotid tumours — you don't wait for a confirmed histological diagnosis before offering parotidectomy if the clinical and imaging picture is consistent with a benign neoplasm (e.g., pleomorphic adenoma on FNA + typical USS/MRI features).

CT scan/CT sialogram ^[1] provides cross-sectional anatomical detail:

Why CT and not just USS?

• USS cannot see deep to bone (temporal bone, skull base, mandible)
• USS cannot evaluate the parapharyngeal space adequately
• CT provides the 3D anatomical roadmap needed for surgical planning
• CT is superior to MRI in terms of providing greater spatial resolution, faster acquisition time and better for evaluation of bony destruction ^[11]

CT sialogram: CT performed after injection of contrast medium into the salivary duct — demonstrates ductal anatomy, strictures, filling defects (stones), and the relationship of a mass to the ductal system. Less commonly used now that MRI sialography is available.

MRI is the gold standard imaging modality for salivary gland tumours, particularly for the parotid gland. It provides:

MRI signal characteristics of common tumours:

PET-CT: Workup for distant metastasis ^[1]

• Principle: FDG-PET detects metabolically active cells (cancer cells with high glucose uptake). Combined with CT, it provides both functional and anatomical information
• Role in salivary gland tumours:
  • Evaluate for lymph node and distant metastasis ^[2] — lungs, bone, liver
  • PET scan is superior to both CT and MRI for detecting regional nodal metastasis as well as distant metastasis and second primary tumours ^[11]
  • Particularly important for adenoid cystic carcinoma (propensity for distant haematogenous metastasis, especially lungs)
  • Can detect synchronous primary tumours in the rest of the aerodigestive tract (field cancerisation concept)
• Limitations:
  • Low-grade tumours (e.g., low-grade mucoepidermoid, acinic cell carcinoma) may not be FDG-avid → false negatives
  • Warthin's tumour and pleomorphic adenoma can be FDG-avid → false positives
  • Not routinely used for clearly benign tumours

Chest X-ray (CXR)

• CXR ^[12] — baseline screening for pulmonary metastases, particularly relevant for adenoid cystic carcinoma
• Quick, cheap, and available everywhere; if suspicious, follow up with CT chest

Panendoscopy

• Panendoscopy + biopsy ^[12] — direct laryngoscopy + bronchoscopy + oesophagoscopy (OGD)
• Required when: (a) 10% risk of synchronous/metachronous tumour (field cancerisation) ^[12] in patients with H&N malignancy, (b) looking for a primary in patients presenting with metastatic cervical LN of unknown primary
• Panendoscopy may identify synchronous primaries that are too small to be identified with PET scan ^[11]

Blood Tests

• Routine bloods (FBC, RFT, LFT) — baseline for surgical fitness
• Serum IgG4 — if chronic sclerosing sialadenitis (IgG4-related disease / Kuttner's tumour) is suspected
• Anti-Ro/Anti-La, ANA — if Sjögren's syndrome is in the differential
• EBV serology/DNA — if lymphoepithelial carcinoma is suspected (particularly relevant in Hong Kong)
• HIV test — if bilateral cystic parotid enlargement in a young patient

Tc-99m Pertechnetate Scintigraphy (Technetium Scan)

• Largely historical but worth knowing: Warthin's tumour and oncocytoma appear as "hot" (warm) nodules because their oncocytic cells actively concentrate technetium. Most other salivary gland tumours appear "cold"
• Rarely used in current practice (replaced by USS, MRI, and PET-CT)

Submandibular sialoadenectomy — resection of the submandibular gland ^[2]

This is the standard operation for both benign and malignant submandibular gland tumours. Remember that ~50% of submandibular tumours are malignant ^[1], so a high index of suspicion is warranted.

Anatomical considerations include close proximity to: ^[2]

• Facial artery and vein — these are ligated during the procedure
• Marginal mandibular branch of the facial nerve — runs superficial to the gland; injury causes inability to depress the lower lip (asymmetric smile). The Hayes-Martin manoeuvre (reflecting the marginal mandibular branch superiorly with the facial vein) protects the nerve
• Hypoglossal nerve (CN XII) — runs deep to the gland; injury causes ipsilateral tongue deviation and difficulty with speech/swallowing
• Lingual nerve — loops under Wharton's duct; injury causes loss of taste and sensation to the anterior 2/3 of the ipsilateral tongue
• Wharton's duct — must be ligated and divided

For malignant submandibular tumours: the excision may need to be extended to include:

• Adjacent floor of mouth mucosa
• Mandible (marginal or segmental mandibulectomy if bone is invaded)
• Neck dissection (supraomohyoid — levels I–III)

Resection of floor of mouth and involved sublingual gland and ipsilateral submandibular gland ^[2]

Because sublingual tumours have a very high malignancy rate (60–90%), surgery is often extensive:

• En bloc resection for large tumours may entail a marginal or segmental mandibulectomy and resection of lingual nerve with reconstruction with microvascular free-flaps ^[2]
• The ipsilateral submandibular gland is included because of shared lymphatic drainage and the need for adequate margins

Surgical resection of involved minor salivary gland according to the anatomical site they arise ^[2]

The approach is dictated by the tumour location:

For minor salivary gland tumours, wide local excision ^[1] is the standard — unlike major gland tumours where you remove the entire gland, here you excise the tumour with a margin of normal tissue from the surrounding soft tissue/bone.

Treatment: complete surgical excision ^[1]

• Parotidectomy with facial nerve preservation ^[1]
• Submandibular gland excision ^[1]
• Wide local excision of minor salivary gland ^[1]
• Avoid enucleation and tumour spillage ^[1]
• Consider radiotherapy for recurrent tumour or prevention of recurrence in case of spillage ^[1]

Why long-term follow-up is essential: Malignant degeneration 10–15% risk in 10 years ^[1]. Even after complete excision, patients need surveillance for:

1. Local recurrence (especially if initial surgery was inadequate)
2. Malignant transformation in any residual/recurrent tumour

Treatment is influenced by site, stage, grade ^[1]:

Why does grade matter so much?

• Low-grade mucoepidermoid carcinoma behaves almost like a benign tumour: 5-year survival > 95%; surgery alone is usually curative
• High-grade mucoepidermoid carcinoma is aggressive with higher rates of nodal and distant metastasis: 5-year survival ~50%; needs multimodality treatment (surgery + adjuvant RT ± chemotherapy)

Treatment follows the general principles of radical surgery + adjuvant radiotherapy, but with special considerations:

• Perineural invasion is the hallmark → surgery must aim for negative perineural margins, which can mean tracing nerves back to the skull base. Even then, microscopic perineural disease often persists
• Adjuvant radiotherapy is almost always indicated because of the high rate of microscopic positive margins and perineural invasion
• Neck dissection only if clinically/radiologically N+ (adenoid cystic carcinoma metastasises haematogenously more than via lymphatics)
• Role of neutron/proton/carbon ion therapy: Adenoid cystic carcinoma is relatively radioresistant to conventional photon radiotherapy. Particle beam therapies (neutrons, protons, carbon ions) have shown improved local control rates and are increasingly used, particularly for skull base extension or unresectable disease

Treatment: Complete local excision +/- postoperative XRT ^[1]

Prognosis — good ^[1]:

• 5-year survival: 82% ^[1]
• 10-year survival: 68% ^[1]
• 25-year survival: 50% ^[1]

Note the slow decline in survival over decades — this reflects the indolent but persistent nature of the tumour. Late recurrences (10+ years) can occur, similar to adenoid cystic carcinoma.

Treatment ^[1]:

• Radical excision ^[1]
• Neck dissection (25% with lymph node involvement at presentation) ^[1]
• Postoperative XRT ^[1]

Prognosis ^[1]:

• Dependent upon stage and histology ^[1]
• Usually not very good ^[1]

Why is the prognosis poor? Because by the time a carcinoma ex pleomorphic adenoma presents (sudden growth of a long-standing mass), the malignant component has often already invaded beyond the original pseudocapsule, and the long-standing nature means the tumour has had time to develop aggressive biology.

• Must rule out: high-grade mucoepidermoid carcinoma, metastatic SCC to intraglandular lymph nodes from scalp SCC, direct extension of skin SCC ^[1]
• If truly primary: radical excision + neck dissection + adjuvant radiotherapy
• If metastatic from cutaneous primary: treatment of primary cutaneous SCC + parotidectomy + neck dissection + adjuvant RT to parotid bed and neck

Adjuvant RT is indicated when there are high-risk features that predict a high probability of local recurrence or regional failure:

Consider radiotherapy for recurrent tumour or prevention of recurrence in case of spillage ^[1]

• Conventional external beam radiotherapy (EBRT) — standard photon-based RT; 60–70 Gy in 30–35 fractions
• Intensity-modulated radiotherapy (IMRT) — allows precise dose shaping to spare adjacent critical structures (contralateral parotid, oral cavity, brainstem, spinal cord) while maximising dose to the tumour bed
• Particle beam therapy (proton/carbon ion) — particularly considered for adenoid cystic carcinoma (radioresistant) and skull base tumours. Carbon ion therapy delivers higher relative biological effectiveness (RBE) than photons
• Brachytherapy — rarely used; sometimes for boost dose in minor salivary gland tumours of the oral cavity

• Recurrent/metastatic disease not amenable to surgery or RT
• Concurrent chemo-radiation for unresectable locally advanced disease
• Palliative setting — symptom control in distant metastatic disease

• Cisplatin-based regimens — most commonly used (cisplatin + doxorubicin, or cisplatin + 5-FU)
• Targeted therapy (emerging):
  • Trastuzumab (anti-HER2) — salivary duct carcinoma frequently overexpresses HER2 (~30%); trastuzumab + docetaxel has shown benefit
  • Androgen receptor (AR) antagonists — salivary duct carcinoma often expresses AR; enzalutamide or bicalutamide can be used
  • NTRK inhibitors (larotrectinib, entrectinib) — for secretory carcinoma with ETV6-NTRK3 fusion; these are "tumour-agnostic" therapies approved based on the molecular target regardless of tumour type
  • Lenvatinib (multi-kinase inhibitor) — showing activity in adenoid cystic carcinoma
• Immunotherapy (pembrolizumab, nivolumab) — checkpoint inhibitors are being studied; some benefit in PD-L1 positive salivary gland cancers, but evidence is still evolving

The most feared complication. Can be:

• Temporary (neuropraxia): occurs in 10–30% of parotidectomies due to nerve stretching, heat from diathermy, or oedema. Recovers within weeks to months
• Permanent: occurs in ~1–3% of superficial parotidectomies; higher in revision surgery or malignant cases requiring nerve sacrifice

Clinical consequences by branch:

The zygomatic branch injury is the most dangerous — inability to close the eye → corneal desiccation → ulceration → potentially blindness. Requires urgent eye protection (artificial tears, taping the eye shut, gold weight implant).

Also known as auriculotemporal syndrome or gustatory sweating ^[2]

Characterised by sweating and flushing of facial skin over parotid bed and neck during mastication ^[2]

Result of aberrant regeneration of cut parasympathetic fibres between the otic ganglion and salivary tissues which leads to innervation of sweat glands and subcutaneous vessels ^[2]

Why does this happen? During parotidectomy, the auriculotemporal nerve (which carries parasympathetic secretomotor fibres from the otic ganglion to the parotid) is divided. During nerve regeneration, the parasympathetic fibres meant for salivary glands aberrantly regenerate into the sympathetic pathways that innervate dermal sweat glands and blood vessels. So when the patient eats (which should stimulate saliva production), the misdirected parasympathetic impulses instead cause sweating and flushing of the skin overlying the parotid bed.

• Incidence: 30–60% of patients (subclinical in many; symptomatic in ~10–15%)
• Diagnosis: Minor's starch-iodine test — apply iodine to the affected skin, dust with starch, then give the patient something to eat. Sweating produces moisture → starch + iodine = blue-black colour change
• Treatment:
  • Antiperspirants (aluminium chloride) — first-line
  • Botulinum toxin injection — blocks acetylcholine release at the aberrant nerve endings → highly effective, lasts 6–12 months, can be repeated
  • Interposition of tissue (e.g., sternocleidomastoid muscle flap, acellular dermal matrix) between the skin and the parotid bed during surgery — preventive measure

• The most devastating consequence of an untreated parotid malignancy
• Why it happens: Malignant tumours (especially adenoid cystic carcinoma) invade the facial nerve directly as it traverses the parotid gland. The tumour cells physically infiltrate the nerve sheath, compress and destroy axons, and cause progressive denervation of the facial muscles
• Clinical consequences:
  • Eye: Inability to close the eye (zygomatic branch) → lagophthalmos → corneal exposure → keratitis → corneal ulceration → potentially permanent visual loss if untreated. This is an ophthalmic emergency
  • Mouth: Oral incompetence (buccal and marginal mandibular branches) → drooling, food pocketing in the buccal sulcus, difficulty eating and speaking
  • Cosmesis and psychosocial impact: Facial asymmetry is profoundly distressing; affects social interaction, self-esteem, and quality of life

• Adenoid cystic carcinoma has a propensity for perineural invasion ^[2] — tumour cells track along the facial nerve proximally towards the stylomastoid foramen and into the temporal bone, and can reach the brainstem
• Can also track along trigeminal nerve branches (V2, V3) into the skull base via the foramen rotundum or foramen ovale
• Results in: intractable neuropathic pain, multiple cranial nerve palsies (CN V, VII, IX, X, XI, XII), and potentially intracranial disease that is essentially inoperable

• Pleomorphic adenoma has a malignant degeneration risk of 10–15% in 10 years ^[1]
• Carcinoma ex pleomorphic adenoma is manifested by sudden growth of a previously stable mass ^[2]
• Long-standing pleomorphic adenomas that are observed rather than excised carry increasing risk over time (up to 25% at 15–20 years)
• This is a preventable complication — the reason we excise all pleomorphic adenomas rather than "watching and waiting"

• Malignant salivary gland tumours metastasise to regional lymph nodes and distant sites (lung, bone, liver) ^[2]
• Adenoid cystic carcinoma: distant metastasis common, especially lung ^[1]. Uniquely, patients may survive with pulmonary metastases for years due to the indolent growth rate, but the disease is ultimately fatal — 5-year survival 75%, 20-year survival 13% ^[1]
• Local recurrence of adenoid cystic carcinoma: 40% ^[1] — even after complete excision, reflecting the microscopic perineural disease that escapes the surgical field

• Recurrence ^[1] is a complication of both the disease and its treatment
• Pleomorphic adenoma: recurrence after enucleation is 20–45%; after formal parotidectomy < 5%
• Adenoid cystic carcinoma: local recurrence 40% ^[1], often many years (even 10–20 years) after initial treatment, due to perineural invasion
• Recurrent tumours are harder to treat because:
  • Tissue planes are scarred from prior surgery
  • The facial nerve is at higher risk of injury during re-operation
  • Multiple recurrent nodules may be scattered throughout the parotid bed (especially recurrent pleomorphic adenoma after enucleation)

The lecture slides explicitly divide these into Early and Late complications:

Early Complications [1]

• Why it happens: The parotid bed is highly vascular (external carotid artery and its branches — superficial temporal artery, maxillary artery, transverse facial artery — run through or adjacent to the gland). Post-operative reactionary or secondary bleeding can accumulate in the surgical dead space
• Clinical significance: A rapidly expanding haematoma in the neck is a surgical emergency because:
  • Compression of the airway → stridor → asphyxiation
  • Compression of the vascular pedicle of the facial nerve → ischaemic nerve injury
• Management:
  • Prevention: meticulous intraoperative haemostasis; suction drain placement (closed suction drain left for 24–48 hours post-operatively)
  • If expanding haematoma: immediate return to operating theatre — open the wound, evacuate the haematoma, secure the bleeding point
  • If airway compromise is imminent before theatre is available: open the wound at the bedside (remove skin staples/sutures) to decompress

Transient ~5%; Permanent ~1% ^[1]

• Transient palsy (neuropraxia): The nerve is anatomically intact but functionally impaired due to:
  • Stretching during dissection (traction injury)
  • Thermal injury from diathermy/cautery used near the nerve
  • Oedema compressing the nerve within its sheath
  • Expected to recover within 6 weeks to 6 months as the nerve heals and oedema resolves
• Permanent palsy: Due to actual nerve transection, avulsion, or irreversible thermal injury. More common with:
  • Total parotidectomy (more extensive dissection)
  • Revision/re-do surgery (scarred tissue planes from previous operation)
  • Malignant tumours requiring deliberate nerve sacrifice

Branch-specific deficits (worth knowing for exams):

Management of facial nerve palsy post-parotidectomy:

• Immediate (if nerve was sacrificed intraoperatively): nerve graft reconstruction at the same procedure (sural nerve or great auricular nerve interposition graft) + static procedures (gold weight, fascia lata sling) ^[2]
• If transient palsy: observe, protect the eye (lubricating eye drops, eye taping at night, moisture chamber), physiotherapy
• If not recovering by 6 months: consider dynamic reanimation procedures (hypoglossal-facial nerve anastomosis, cross-facial nerve graft, free gracilis muscle transfer)

• Relatively uncommon (clean surgical field)
• Risk factors: diabetes, immunosuppression, haematoma (blood is a culture medium), prolonged surgery
• Presents with erythema, warmth, swelling, discharge from the wound, ± fever
• Management: wound swab for culture, antibiotics (empirical then targeted), drainage if abscess forms

• Why it happens: If residual functional salivary gland tissue remains after partial parotidectomy, it continues to produce saliva. If the saliva cannot drain normally into the mouth (because the duct has been disrupted), it leaks through the surgical wound
• Also called a sialocele when saliva collects as a subcutaneous fluid collection rather than draining externally
• Incidence: ~5–15% after superficial parotidectomy
• Management:
  • Usually self-limiting — the residual gland tissue eventually atrophies due to disrupted ductal drainage
  • Pressure dressing to the parotid bed
  • Anti-sialagogues (glycopyrrolate — an anticholinergic that reduces salivary secretion)
  • Botulinum toxin injection into the residual gland (blocks acetylcholine release at parasympathetic nerve terminals → reduces salivary output)
  • Repeated aspiration of sialoceles if they accumulate

Late Complications [1]

• Recurrence is listed as a late complication of parotidectomy ^[1]
• Most relevant for pleomorphic adenoma (if initial excision was inadequate — enucleation or positive margins) and adenoid cystic carcinoma (perineural invasion leading to late recurrence even after adequate surgery)
• Avoid enucleation and tumour spillage ^[1] — this is the single most important preventive measure against pleomorphic adenoma recurrence
• Consider radiotherapy for recurrent tumour or prevention of recurrence in case of spillage ^[1]
• Recurrent pleomorphic adenoma management is challenging:
  • Often multinodular (seeded along the previous surgical bed)
  • Higher risk of facial nerve injury during re-operation (scarred tissue)
  • Higher risk of further recurrence
  • Adjuvant radiotherapy is often recommended after re-excision

Also known as auriculotemporal syndrome or gustatory sweating ^[2]

Characterised by sweating and flushing of facial skin over parotid bed and neck during mastication ^[2]

Result of aberrant regeneration of cut parasympathetic fibres between the otic ganglion and salivary tissues which leads to innervation of sweat glands and subcutaneous vessels ^[2]

Detailed pathophysiology (from first principles):

1. Normal anatomy: The auriculotemporal nerve (a branch of V3, the mandibular division of the trigeminal nerve) carries postganglionic parasympathetic fibres from the otic ganglion to the parotid gland. These fibres are secretomotor — they stimulate salivary secretion when you eat
2. During parotidectomy: The auriculotemporal nerve is inevitably divided or damaged when the parotid gland is removed. The skin flap is raised, disconnecting the nerve endings from the gland
3. During healing: The severed parasympathetic nerve fibres attempt to regenerate. However, instead of finding salivary gland tissue (which has been removed), they aberrantly regenerate into the sympathetic nerve pathways that innervate:
   • Sweat glands (eccrine glands in the skin overlying the parotid bed)
   • Subcutaneous blood vessels
4. Result: When the patient eats, the parasympathetic stimulation meant for the (now absent) parotid gland instead travels down these misdirected fibres to sweat glands and blood vessels → sweating (gustatory sweating) and flushing (vasodilation) of the skin over the parotid bed

Clinical features:

• Onset: typically 6–18 months post-parotidectomy (time needed for nerve regeneration)
• Triggered by eating, especially sour or strongly flavoured foods (which are the strongest parasympathetic stimulators of salivation)
• Subclinical in up to 60% of patients (detectable only on starch-iodine test); symptomatic in ~10–15%

Diagnosis: Minor's starch-iodine test

1. Paint iodine solution on the skin over the parotid bed
2. Allow to dry, then dust with starch powder
3. Ask the patient to eat a lemon wedge (strong parasympathetic stimulus)
4. Sweating produces moisture → starch + iodine = blue-black colour change in the affected area

Treatment:

• Topical antiperspirants (aluminium chloride hexahydrate 20%) — blocks sweat gland ducts; first-line
• Botulinum toxin (Botox) injection — intradermal injection into the affected area; blocks acetylcholine release at the aberrant parasympathetic nerve endings; highly effective; lasts 6–12 months; can be repeated
• Surgical interposition (preventive) — placing a tissue barrier between the skin flap and the parotid bed during the initial parotidectomy prevents the aberrant nerve regeneration. Options include:
  • Sternocleidomastoid (SCM) muscle flap
  • Superficial musculoaponeurotic system (SMAS) flap
  • Acellular dermal matrix (AlloDerm)
  • Temporoparietal fascia flap
• Tympanic neurectomy (Jacobson's nerve section) — divides the preganglionic parasympathetic fibres proximal to the otic ganglion; effective but invasive, rarely used

• The Modified Blair's incision ^[1] is generally well-concealed (pre-auricular, retro-auricular, upper neck), but some patients are prone to hypertrophic or keloid scarring
• More common in patients with darker skin types (Fitzpatrick IV–VI)
• Management: silicone gel sheets, intralesional corticosteroid injection (triamcinolone), pressure therapy, laser therapy

• Sunken parotid area, cosmetic problem ^[1] — after removal of the superficial or total parotid gland, there is a visible concavity (hollow) at the angle of the jaw ("parotidectomy defect")
• This is particularly noticeable in thin patients and after total parotidectomy
• Why it happens: Loss of parotid gland tissue volume leaves a depression between the mandible, mastoid process, and SCM
• Management:
  • SCM muscle flap — rotating the anterior border of SCM into the defect during wound closure (most commonly done at the time of parotidectomy)
  • Fat grafting — autologous fat injection into the defect
  • Acellular dermal matrix placement
  • Free fat flap — for larger defects, particularly after total parotidectomy

Anatomical considerations include close proximity to facial artery and vein, marginal mandibular branch of facial nerve, hypoglossal nerve, lingual nerve and Wharton's duct ^[2]

Radiotherapy (whether adjuvant or definitive) to the salivary gland region carries specific side effects related to the radiation field:

When neck dissection is performed for nodal metastasis: