32.4 Salivary Gland Neoplasms

Salivary Gland Neoplasms

                                 Neoplasms of the Salivary Glands
                                                │
     ┌──────────────────────────────────────────┴──────────────────────────────────────────┐
     ▼                                                                                     ▼
Benign Salivary Tumours                                                               Malignant Salivary Tumours
• Pleomorphic Adenoma (most common)                                                   • Mucoepidermoid Carcinoma
  - Parotid tail, mixed stroma, pseudopodia                                             - Most common salivary cancer
• Warthin Tumour (Papillary cystadenoma)                                                - Mucous + epidermoid cells
  - Older smoking males, bilateral/multifocal,                                         • Adenoid Cystic Carcinoma
    oncocytes + lymphoid stroma                                                         - Cribriform 'Swiss cheese'
                                                                                        - Perineural invasion (pain/palsy)
                                                                                        - Late distant lung metastasis

The "Rules of Proportion" in Salivary Oncology

Understanding the distribution of benign vs malignant tumours is fundamental for clinical triage and exam questions:

1. Gland Size vs Malignancy Inversion: As the anatomical size of the salivary gland decreases, the probability that a primary tumour is malignant increases dramatically:
   • Parotid Gland: Accounts for ~80% of all salivary neoplasms; ~75–80% are BENIGN, ~20–25% are malignant.
   • Submandibular Gland: Accounts for ~10–15% of all neoplasms; ~50% are BENIGN, 50% are MALIGNANT.
   • Sublingual Gland: Accounts for <1% of neoplasms; ~80–90% are MALIGNANT.
   • Minor Salivary Glands (Palate): Account for ~5–10% of neoplasms; ~50% are BENIGN, 50% are MALIGNANT.
2. The most common site for a minor salivary gland neoplasm is the junction of the hard and soft palate.

1. Benign Salivary Neoplasms

Pleomorphic Adenoma (Benign Mixed Tumour)

• Epidemiology: The most common salivary neoplasm, accounting for ~65% of all parotid tumours and ~50% of minor gland tumours.
• Clinical Presentation: Slow-growing, painless, firm, lobulated, mobile mass, classically situated in the tail (superficial lobe) of the parotid gland overlying the mandibular angle, or as a firm, non-ulcerated swelling in the posterior lateral hard palate. Overlying skin/mucosa is intact. Facial nerve function is entirely normal (the presence of facial nerve palsy indicates malignancy!).
• Histopathology: Highly variable ("pleomorphic") architectural pattern featuring an intimate mixture of ductal epithelial cells and myoepithelial cells embedded within a variable mesenchyme-like stroma (chondroid, myxoid, hyaline, or mucoid).
• Surgical Danger — Pseudopodia & Enucleation: Pleomorphic adenomas possess a delicate fibrous pseudocapsule that is incomplete in areas. Microscopic tumour projections or pseudopodia penetrate into and through the capsule into the surrounding normal gland parenchyma. Simple enucleation is strictly contraindicated, as enucleation ruptures these pseudopodia and spills tumour cells, resulting in extensive, multifocal, incurable recurrences. The surgical standard is superficial parotidectomy with identification and anatomical preservation of the facial nerve (CN VII).
• Malignant Transformation: Long-standing, untreated pleomorphic adenomas carry an estimated 5% to 10% lifetime risk of undergoing malignant transformation into a highly aggressive, destructive cancer termed Carcinoma ex-Pleomorphic Adenoma (signaled by rapid sudden growth, ulceration, pain, and facial nerve paralysis in a long-standing dormant mass).

Warthin Tumour (Papillary Cystadenoma Lymphomatosum / Adenolymphoma)

• Epidemiology: The second most common benign parotid tumour (~10% of parotid tumours). Almost exclusively restricted to the parotid gland (usually the inferior pole).
• Risk Factors: Strong, direct epidemiological link with older males who have a history of heavy cigarette smoking.
• Diagnostic Hallmark: Characterized by being bilateral (5–10%) or multifocal within the same gland.
• Histopathology: A distinct biphasic pattern:
  1. Double layer of oncocytic epithelial cells (tall columnar luminal cells with intensely eosinophilic, granular cytoplasm packed with abnormal mitochondria) lining cystic spaces and papillary projections.
  2. A dense, reactive, lymphoid stroma containing active germinal centres.
• Management: Conservative surgical excision (superficial parotidectomy or wide local excision); recurrence is exceptionally rare.

2. Malignant Salivary Neoplasms

Mucoepidermoid Carcinoma

• Epidemiology: The most common primary malignant salivary gland neoplasm in both adults and children. Most common in the parotid gland, followed by the minor glands of the palate.
• Pathogenesis: Driven by a specific chromosomal translocation t(11;19)(q21;p13) creating the CRTC1-MAML2 fusion gene.
• Histopathology: Characterized by an intimate mixture of three distinct cellular phenotypes:
  1. Mucous cells: Mucin-producing cells staining positive with mucicarmine or PAS.
  2. Epidermoid (squamous) cells: Epithelial cells with intercellular bridges.
  3. Intermediate (clear) cells: Progenitor basaloid cells capable of differentiating into mucous or epidermoid lineages.
• Histological Grading: Graded into low, intermediate, and high grade based on the proportion of cystic spaces vs solid cellular sheets, degree of cellular atypia, necrosis, and neural invasion. Low-grade tumours are mostly cystic with abundant mucous cells and carry a >90% five-year survival; high-grade tumours are solid, composed predominantly of atypical epidermoid cells, mimicking metastatic squamous cell carcinoma with poor prognosis.

Adenoid Cystic Carcinoma (ACC)

• Epidemiology: Accounts for ~10% of all salivary malignancies, but represents the most common malignant tumour of the submandibular and minor salivary glands (particularly the hard palate).
• Histopathology: Classic pathognomonic cribriform ("Swiss cheese") pattern, where uniform, basaloid epithelial and myoepithelial cells encircle multiple cylindrical pseudocystic spaces filled with basophilic mucinous material and basement membrane-like hyaline. Tubular and solid variants also occur (solid pattern carries the worst prognosis).
• Clinical Hallmarks:
  1. Perineural Invasion (Neurotropism): ACC has an extraordinary, relentless propensity to invade and track along perineural spaces of cranial nerves (e.g., facial, lingual, or palatine nerves). Consequently, patients characteristically present with intense, unyielding pain, paresthesia, or early facial nerve paralysis, even when the primary tumour mass is deceptively small (<1 cm).
  2. Insidious Infiltration: Infiltrates along nerve sheaths and haversian bone canals centimeters beyond apparent clinical or radiological margins, making complete surgical eradication extremely challenging.
  3. Distant Metastases: Paradoxically, regional cervical lymph node metastasis is uncommon; instead, ACC demonstrates a profound propensity for late, indolent hematogenous distant metastases, especially to the lungs (producing multiple "cannonball" pulmonary metastases) and bones, occurring even 10 to 20 years following initial surgery.
  4. Long-term prognosis is poor: while 5-year survival is ~70%, 15- to 20-year survival drops below 20–30% due to late recurrences.