Pleomorphic Adenoma

Epidemiology & Sites

• Bailey and Love's Short Practice of Surgery, 28th Ed.

Clinical Presentation

• Painless, slow-growing, mobile, well-defined solitary mass
• Gradual progression over many years - can grow to enormous proportions if untreated

Fig. Slowly enlarging parotid neoplasm (left) and its yellow-white circumscribed cross-section (right). - Robbins & Kumar Pathologic Basis of Disease

• Firm to soft consistency depending on the stromal component - chondroid/collagenous tumours feel hard; myxoid ones feel almost fluctuant
• No facial nerve involvement (involvement suggests malignancy)
• Red flags for malignant transformation: sudden increase in size, facial nerve palsy, fixation to surrounding structures, pain

Pathogenesis / Molecular Biology

• Thought to be derived from intercalated duct cells and myoepithelial cells that differentiate into both epithelial and connective tissue elements - hence "mixed tumour"
• PLAG1 overexpression (via chromosomal rearrangements) promotes cell growth through growth factor receptor signalling pathways - found in many cases
• HMGA2 gene mutations (encoding a DNA-binding protein) account for most remaining cases lacking PLAG1 overexpression
• All tumour elements - including the apparent mesenchymal components - are believed to be of myoepithelial or ductal reserve (stem) cell origin

Macroscopic Appearance

Fig. Cut surface displaying solid blue/grey hue characteristic of chondromyxoid matrix, with surface bosselations. - Scott-Brown's Otorhinolaryngology

• Rounded/ovoid, well-demarcated mass, rarely exceeds 6 cm
• Bosselated (nodular) surface
• Cut surface is gray-white with myxoid and blue chondroid (cartilage-like) areas
• May show cystic change, calcification, or bone
• Capsule: variably present; in virtually all PSAs the capsule is <20 microns thick in at least one area, and is incomplete in ~50% - especially the myxoid type
• Protuberant peri-capsular nodules may be attached by slender pedicles - these are easily left behind if the tumour is merely enucleated, forming foci for recurrence

Microscopic / Histological Appearance

Fig. Low-power view: well-demarcated tumour surrounded by fibrous capsule with adjacent normal salivary parenchyma. Blue chondromyxoid matrix fills the centre. - Robbins & Kumar Pathologic Basis of Disease

1. Ductal (epithelial) elements - cuboidal to columnar cells lining duct-like structures; express CK7 (strong and diffuse)
2. Myoepithelial cells - oval, plasmacytoid, spindle, or clear morphology; express p63, S-100, SOX10, SMA
3. Chondromyxoid stroma - loose myxoid and hyaline tissue, islands of cartilage, occasionally bone

• Squamous metaplasia with keratinization - common; does not imply malignancy
• Metaplastic changes: lipomatous, osseous, neuroid, angiomatoid
• Degenerative changes: cystic change, infarction, mineralization, hyalinization, elastosis
• No significant epithelial dysplasia or mitotic activity in benign lesions
• Ductal atypia, diffuse fibrosis, and necrosis should raise suspicion for malignant transformation

Imaging

• CT/MRI: well-demarcated, homogeneous or heterogeneous mass in the parotid or other salivary gland
• Calcifications or bone formation on imaging strongly suggest pleomorphic adenoma (no other salivary gland tumour is likely to develop these)
• Deep lobe tumours extend into the parapharyngeal space - "dumbbell" appearance on CT/MRI

Behaviour & Complications

Recurrence

• Simple enucleation carries a recurrence rate approaching 25% due to capsule incompleteness and peri-capsular nodule spillage
• Recurrences after adequate parotidectomy occur in only ~4%
• Recurrence is typically multifocal (seeding pattern), particularly if myxoid capsular rupture occurs intra-operatively

Malignant Transformation - Carcinoma ex Pleomorphic Adenoma

• Present <5 years: ~2% risk of harbouring malignancy
• Present >15 years: ~10% risk
• Overall figure historically cited: ~6% risk of malignant change (some sources cite 1-5% over 10 years)
• Risk factors for transformation: older age, male sex, long tumour duration, multiple recurrences, deep lobe location

Diagnosis

• Fine Needle Aspiration Biopsy (FNAB): first-line investigation; shows characteristic mixed epithelial and myoepithelial cells in chondromyxoid background
  • Note: the tumour's histological heterogeneity can occasionally make diagnosis from limited FNAB samples difficult
• Imaging (CT / MRI / Ultrasound): delineates extent and relationship to facial nerve; identifies deep lobe involvement
• Core biopsy: occasionally required

Treatment

General Principles

1. It provides definitive histological diagnosis
2. Tumours continue to grow if left untreated
3. There is a risk of malignant transformation

Parotid Pleomorphic Adenoma

• Superficial lobe: superficial parotidectomy with facial nerve preservation
• Deep lobe / total parotid: total conservative parotidectomy
• Simple enucleation is contraindicated - risk of capsular rupture, tumour spillage, and multifocal recurrence
• A cuff of surrounding normal tissue should be included wherever possible to account for pseudopods extending beyond the capsule

Submandibular Gland

• Excision of the entire submandibular gland (extra-capsular dissection)

Minor Salivary Glands (Oral Cavity)

• Transoral complete surgical excision; recurrences are rare given the encapsulated nature
• CO₂ laser may be used as a cutting tool

Summary Table

• Robbins & Kumar Pathologic Basis of Disease (Robbins Cotran, p. 697)
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery (Chapter 26, Chapter 9)
• Bailey and Love's Short Practice of Surgery, 28th Ed. (Chapter 54)
• Cummings Otolaryngology Head and Neck Surgery (Chapter 90)

Clinical Presentation: Tail of Parotid vs. Deep Lobe Pleomorphic Adenoma

Anatomy First - Why It Matters

Tail of Parotid Tumour

Presentation

• Presents as a visible and palpable lump in the upper neck, just below and anterior to the ear lobe
• Often mistaken for a cervical lymph node (level II adenopathy) or a submandibular gland tumour - this is a common diagnostic trap
• The swelling is in the superficial/subcutaneous plane; ultrasound is very helpful in distinguishing a tail of parotid mass from an adjacent lymph node
• Slow-growing, painless, mobile - the classic presentation
• No oropharyngeal symptoms - no dysphagia, no change in voice, no snoring
• No facial nerve involvement unless there is malignant transformation

Key Point

Surgery

Deep Lobe Tumour

Presentation

• Externally, the neck may look normal or show only a subtle parotid swelling - because the mass is hidden medial to the mandibular ramus, it is not easily visible or palpable from the outside
• The tumour grows medially into the parapharyngeal space, so the classic presentation is:

  A paratonsillar bulge - the patient (or their dentist) notices a smooth swelling of the lateral oropharyngeal wall, pushing the tonsil and soft palate medially. The patient may complain of:

  • A feeling of fullness in the throat
  • Snoring or obstructive sleep apnoea-like symptoms
  • Muffled voice (hot-potato voice) in large tumours
  • Dysphagia in large tumours

• There is no external neck mass until the tumour is very large
• The facial nerve is at greater risk during surgery for deep lobe tumours

The Dumbbell Tumour (Mixed Superficial + Deep)

Fig. 84.10 Dumbbell pleomorphic adenoma - Cummings Otolaryngology

Fig. 84.11 Pure deep lobe pleomorphic adenoma - Cummings Otolaryngology

Comparison Table

One Practical Point on Imaging

1. Determine whether the tumour is connected to the deep lobe (affects surgical approach)
2. Assess capsule thickness (myxoid tumours are fragile and prone to rupture)
3. Define the relationship to the facial nerve and great vessels

• Cummings Otolaryngology Head and Neck Surgery
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery
• KJ Lee's Essential Otolaryngology

Ranula

Etymology & Definition

Types

Aetiology

• More commonly acquired than congenital
• Caused by:
  • Obstruction of the sublingual gland or its many small ducts (spontaneous or from periductal scarring)
  • Trauma to the sublingual gland ducts - e.g., following floor-of-mouth procedures, dental procedures
  • Rupture of the main duct or of obstructed acini of the sublingual gland
• May be congenital (a developmental defect in the mylohyoid allows natural herniation)
• Increased occurrence noted in HIV-infected individuals - due to blockage from inflammation and periductal fibrosis as part of HIV-associated salivary gland disease
• A congenital predisposition has been suggested based on higher rates in certain ethnic groups and among siblings

Clinical Presentation

Simple Ranula

Fig. 54.3 Ranulas in the floor of mouth, transillumination and excised specimens - Bailey and Love's Surgery

• Smooth, soft, fluctuant, painless swelling in the floor of the mouth
• Located on one side of the frenulum linguae - almost always unilateral
• Characteristic bluish translucent appearance (due to thin mucosa and fluid content)
• The submandibular (Wharton's) duct can sometimes be seen traversing the dome of the swelling
• Usually detected in the second decade of life; slight female predisposition
• A very large ranula may fill the entire floor of the mouth
• If large enough: elevation of the tongue causing difficulty with:
  • Swallowing (dysphagia)
  • Speech (croaking/muffled voice)
  • Mastication
  • Breathing (rarely - respiratory obstruction is rare but reported)
• Painless unless infected (when it becomes red, tender, and indurated)
• Aspiration yields thick, sticky, viscous saliva - this distinguishes it from a lymphangioma (which yields clear lymph fluid) and is both diagnostic and confirmatory

Plunging Ranula

• Usually presents as a painless, persistent, or slowly enlarging swelling in the submandibular/submental triangle of the neck
• There may be no visible intraoral component - the neck swelling is the presenting complaint
• Rarely may spread to the upper chest wall
• On bimanual palpation (one finger intraoral, one hand on neck): cross-fluctuation is demonstrable between the floor of mouth and the neck extension - a key clinical sign
• The mylohyoid defect through which it herniates is called the boutonniere anomaly

Investigations

Simple Ranula

• Imaging is not necessary to confirm the diagnosis - it is clinical
• However, imaging is required if:
  • Previous surgery has been performed
  • There is a cervical component
  • The diagnosis is clinically uncertain

Plunging Ranula / Uncertain Cases

• MRI is preferred - it best defines soft tissue planes and extent
• CT: simple ranula appears as a solitary, low-attenuation, non-enhancing thin-walled mass; plunging ranulas may show some peripheral enhancement (granulation tissue)
• Ultrasound: unilocular, well-defined cystic mass; may contain fine internal echoes from debris (prior inflammation)
• On MRI: low T1 signal, high T2 signal, no contrast enhancement of the cyst wall

Fig. 54.4 MRI scan - ranula in the floor of mouth as a bright T2 lesion - Bailey and Love's Surgery

Fig. 82.6 Plunging ranula on MRI - Cummings Otolaryngology

Differential Diagnosis

Key histological distinction from lymphatic malformation: a ranula is contained by loose connective tissue (pseudocyst), whereas a lymphatic malformation has a simple epithelial lining.

Treatment

Why Simple Aspiration/Drainage Fails

Definitive Treatment: Sublingual Gland Excision

• The definitive treatment for both simple and plunging ranulas is excision of the cyst together with the sublingual gland
• The sublingual gland has multiple small ducts - if the gland is left behind, these continue leaking and the ranula recurs
• Complete sublingual gland excision: recurrence rate as low as 3.6%
• Ranula excision alone (without gland removal): significantly higher recurrence

Surgical Approaches

• Transoral approach: for intraoral (simple) ranulas and for plunging ranulas with a predominantly intraoral component
• External transcervical approach: for plunging ranulas that present predominantly submentally or in the neck
• Combined transoral + transcervical: for large dumbbell-type plunging ranulas
• Important: during any floor-of-mouth dissection, the lingual nerve and Wharton's duct must be identified and preserved - injury risks obstructive sialadenitis and sensory loss

Alternative/Adjunct Treatments

• OK-432 (picibanil) injection: a sclerotherapeutic agent derived from Streptococcus; induces inflammation and fibrosis leading to cyst obliteration; effective especially in paediatric patients though experience is more limited in this group
• Botulinum toxin injection: reported good results but needs further evaluation
• CO₂ or diode laser excision: reported for intraoral ranulas with low recurrence rates
• Oral nickel gluconate: a medical treatment described by Garofalo et al. - nickel at low doses promotes enzymatic tissue-repair in salivary glands; promising early results reported

Summary

• Scott-Brown's Otorhinolaryngology Head & Neck Surgery (Chapter 9 / Chapter 37)
• Bailey and Love's Short Practice of Surgery, 28th Ed. (Chapter 54)
• Cummings Otolaryngology Head and Neck Surgery (Chapter 82)
• S. Das - A Manual on Clinical Surgery, 13th Ed.
• KJ Lee's Essential Otolaryngology