Oral Leukoplakia

A predominantly white patch or plaque of the oral mucosa that cannot be characterised clinically or pathologically as any other definable disease, and which carries an increased risk of malignant transformation. It is a clinical diagnosis of exclusion, and the term carries no histological meaning by itself.

Epidemiology and risk

Global prevalence around 2 to 3 percent, higher in populations with heavy tobacco and areca nut use.
Malignant transformation rate of approximately 1 to 3 percent per year, with a cumulative rate of around 5 to 12 percent overall, and substantially higher in specific subgroups.
Around 15 to 20 percent already contain dysplasia at first biopsy, and a small proportion contain invasive carcinoma.

Factors predicting malignant transformation, which determine surveillance intensity

Non homogeneous appearance, particularly speckled or erythroleukoplakia, with transformation rates several times higher than homogeneous lesions.
Presence and grade of epithelial dysplasia. Severe dysplasia and carcinoma in situ carry the highest risk, though transformation occurs in non dysplastic lesions too.
Site: the floor of mouth, the ventrolateral tongue and the soft palate complex are high risk. The buccal mucosa and hard palate are lower risk.
Size greater than 200 mm squared.
Female sex.
Non smokers, that is idiopathic leukoplakia, which paradoxically has a higher transformation rate than smoking associated leukoplakia.
Long duration.
Proliferative verrucous leukoplakia.
Candida infection within the lesion.

Aetiological factors

Tobacco in all forms: smoking, smokeless tobacco, and reverse smoking with the lit end in the mouth, which produces palatal lesions with high transformation rates.
Areca nut and betel quid, with or without tobacco, which also causes oral submucous fibrosis.
Alcohol, which acts synergistically with tobacco.
Chronic candidal infection, in hyperplastic candidiasis.
Human papillomavirus, particularly types 16 and 18, in a proportion.
Chronic trauma, though frictional keratosis is a separate entity that resolves when the cause is removed.
Idiopathic in a significant proportion, which is the group with the highest risk.

Clinical subtypes

Homogeneous: uniformly flat, thin, white, with a smooth or finely wrinkled surface and well defined margins. Lower risk.
Non homogeneous, which comprises:
Speckled or erythroleukoplakia: mixed white and red, which is the highest risk pattern.
Nodular: small polypoid white outgrowths.
Verrucous or exophytic: wrinkled or corrugated surface.
Proliferative verrucous leukoplakia: a distinct and dangerous entity occurring predominantly in older women who are often non smokers, characterised by multifocal, progressive, spreading white lesions that become verrucous and are highly resistant to treatment, with a transformation rate of 60 to 100 percent over 10 to 20 years and a strong tendency to recur after excision. It requires lifelong intensive surveillance.

Usually asymptomatic and detected incidentally by a dentist or clinician, which is why routine oral examination matters.
Roughness or a sensation of thickening.
Pain, burning or ulceration, which suggest dysplasia, malignant change or superadded candidal infection, and which are late features.
A patch that cannot be wiped or scraped off, which is the finding that distinguishes it from candidiasis and from debris.

Examination

Systematic examination of the entire oral cavity with good lighting and gauze, including the lateral and ventral tongue lifted with gauze, the floor of mouth, the retromolar trigone, the buccal mucosa stretched flat, and the gingivae. The floor of mouth and ventrolateral tongue are the high risk sites and are the areas most often examined inadequately.
Palpate every lesion. Induration is the single most important finding and indicates invasion until proven otherwise.
Record site, size in millimetres, appearance, whether homogeneous or non homogeneous, and photograph.
Palpate the neck for lymphadenopathy.
Examine for evidence of the causative habit: tobacco staining, betel staining, and dental trauma.

Red flags indicating probable malignancy

Induration on palpation.
Ulceration.
Erythematous component, that is speckled leukoplakia.
Rapid change in size or appearance.
Pain.
Bleeding.
Cervical lymphadenopathy.
Loosening teeth or numbness.
Any of these mandate urgent biopsy and referral on a suspected cancer pathway.

Biopsy is mandatory in every case. Leukoplakia is a clinical term and the management is determined entirely by the histology.
Incisional biopsy from the most clinically suspicious area: the erythematous, nodular, ulcerated or indurated part, since dysplasia is heterogeneous within a lesion and biopsying the homogeneous white area produces false reassurance. Where the lesion is large or multifocal, take multiple biopsies from several sites.
Excisional biopsy for small lesions where complete removal is feasible.
Adjuncts including toluidine blue staining, autofluorescence and brush cytology may help select the biopsy site in a large or multifocal lesion, but none replaces scalpel biopsy and none should be used to avoid biopsy.
Histological grading of dysplasia as mild, moderate or severe, or as low grade and high grade in the binary system, assessing architectural and cytological features: loss of polarity, drop shaped rete pegs, increased and abnormal mitoses, nuclear pleomorphism, hyperchromatism, increased nuclear to cytoplasmic ratio and abnormal keratinisation.
Periodic acid Schiff staining for candidal hyphae, since candidal leukoplakia may partially regress with antifungal treatment and requires re assessment afterwards.
Human papillomavirus testing where the histology suggests it.
Full examination of the upper aerodigestive tract with flexible endoscopy in patients with tobacco and alcohol exposure, given the field change effect and the risk of synchronous primary tumours.
Cross sectional imaging where malignancy is confirmed or strongly suspected.
Full blood count, haematinics and glucose.

Differential diagnosis and the discriminating feature

Frictional keratosis: a clear mechanical cause such as a sharp tooth, denture flange or cheek biting, resolving within 2 to 4 weeks of removing the cause. If it does not resolve, biopsy it.
Candidiasis: pseudomembranous plaques wipe off; hyperplastic candidiasis does not and requires biopsy.
Oral lichen planus: bilateral, symmetrical, with lacy Wickham striae.
Lichenoid reaction: unilateral, adjacent to an amalgam restoration or related to a drug.
Leukoedema: a diffuse greyish white filmy appearance of the buccal mucosa that disappears when the mucosa is stretched, which is a normal variant particularly in darker skinned individuals.
White sponge naevus: a hereditary autosomal dominant condition with diffuse thick white folded mucosa from childhood.
Hairy leukoplakia: vertically corrugated plaques on the lateral tongue, Epstein Barr virus related, strongly associated with HIV.
Smoker keratosis of the palate, that is nicotinic stomatitis: a white palate with red punctate inflamed minor salivary duct openings, which is not premalignant in conventional smokers but is in reverse smokers.
Squamous cell carcinoma.
Chemical burn, and morsicatio buccarum from chronic cheek biting.
Syphilitic leukoplakia of the tongue dorsum in tertiary syphilis.

Management centres on removing the cause, obtaining histology, treating dysplastic lesions, and lifelong surveillance, since transformation occurs both at treated sites and at new sites.

Risk factor elimination, which is the foundation

Complete tobacco cessation in all forms, with structured support including behavioural intervention and pharmacotherapy with nicotine replacement, varenicline or bupropion. Around half of leukoplakias regress or resolve within 6 to 12 months of cessation, so this is genuinely disease modifying rather than merely advisable.
Complete cessation of areca nut and betel quid.
Reduction or cessation of alcohol.
Remove chronic trauma: smooth sharp cusps, adjust dentures, treat sharp restorations.
Treat candidal infection with a systemic antifungal course such as fluconazole 50 mg daily for 2 to 4 weeks, then reassess. Candidal leukoplakia may substantially improve, but the residual lesion must still be biopsied.
Optimise oral hygiene and arrange regular dental care.

Management by histology

No dysplasia: risk factor elimination and observation with review at 3 to 6 months initially, then 6 to 12 monthly. Re biopsy if the appearance changes. Consider excision for high risk sites, non homogeneous appearance or large size even without dysplasia.
Mild dysplasia: risk factor elimination, review at 3 to 6 months, with excision considered particularly at high risk sites or if the lesion is non homogeneous or persists after habit cessation.
Moderate dysplasia: excision is generally recommended, with close surveillance thereafter.
Severe dysplasia and carcinoma in situ: excision with clear margins, followed by intensive surveillance.
Invasive carcinoma: manage on the head and neck cancer pathway.

Treatment modalities

Surgical excision with a scalpel, which provides a complete specimen for histology and remains the standard where the diagnosis or completeness of excision matters. Defects may be left to granulate, closed primarily, or reconstructed with a split skin or buccal fat pad graft depending on size and site.
Carbon dioxide laser excision or ablation, which offers good haemostasis, a clean field and reduced scarring and postoperative pain. Excision is preferable to ablation, since ablation destroys the specimen and precludes histological assessment of the margins.
Cryotherapy and electrocautery, which similarly destroy the specimen and are less favoured.
Photodynamic therapy in selected cases.
Recurrence after excision occurs in 10 to 35 percent, and new lesions arise at other sites because the whole mucosa is at risk from field change. Excision reduces but does not eliminate the risk of transformation, and this must be stated clearly to the patient so that they continue to attend for surveillance rather than assuming they are cured.

Medical treatment

No topical or systemic agent has established efficacy in preventing malignant transformation. Retinoids, both topical and systemic, produce regression in some lesions but with high relapse on cessation and significant toxicity including teratogenicity, hyperlipidaemia and mucocutaneous adverse effects. Beta carotene, vitamin E, lycopene, green tea extract, bleomycin and other agents have been studied without convincing evidence of a reduction in transformation. Patients should not be offered these as an alternative to excision or surveillance.

Proliferative verrucous leukoplakia

Requires an aggressive approach with wide excision of accessible lesions, though recurrence is near universal.
Lifelong surveillance at 3 to 6 monthly intervals with repeated biopsy of any changing area.
Counsel the patient explicitly about the very high transformation rate, since these patients require sustained engagement with follow up over decades.

Surveillance

Every patient with leukoplakia requires long term follow up, including those whose lesion has been excised and those whose lesion resolved after habit cessation.
Interval: 3 monthly for high risk lesions, dysplasia and proliferative verrucous leukoplakia; 6 monthly for intermediate risk; annually for low risk homogeneous lesions with no dysplasia in a patient who has stopped their habit.
At each visit: full oral examination with palpation, measurement and photography, and biopsy of any change in appearance, texture, size or symptoms.
Examine the whole upper aerodigestive tract periodically in patients with tobacco and alcohol exposure.
Teach the patient self examination and give clear instructions to present promptly with any ulcer lasting more than 3 weeks, any lump, any bleeding, or any change in an existing patch.
Discharge is generally not appropriate, since transformation occurs years and sometimes decades after initial presentation.

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Retropharyngeal Abscess

A collection of pus in the retropharyngeal space, between the buccopharyngeal fascia covering the constrictor muscles anteriorly and the alar layer of the deep cervical fascia posteriorly. It is predominantly a disease of children under 6 years, and it is an airway emergency.

Anatomy that determines behaviour and danger

The retropharyngeal space extends from the skull base to the tracheal bifurcation at approximately the level of T1 to T2, where the alar and visceral fascia fuse. Infection here can descend directly into the superior mediastinum.
Posterior to the alar fascia lies the danger space, or space 4, which extends uninterrupted from the skull base to the diaphragm. Infection breaching the alar fascia into this space spreads to the posterior mediastinum with minimal resistance, and this is the anatomical basis of descending necrotising mediastinitis.
Retropharyngeal lymph nodes, that is the nodes of Rouvière, drain the nasopharynx, adenoids, posterior paranasal sinuses, middle ear and Eustachian tube. These nodes are prominent in young children and atrophy by around 5 years. Suppurative adenitis of these nodes is the mechanism of retropharyngeal abscess in children, which is why the condition is a paediatric disease and why it declines sharply after the age of 6.
In adults, retropharyngeal abscess arises from penetrating trauma including foreign bodies such as fish bones, from instrumentation, from vertebral osteomyelitis, from tuberculosis of the cervical spine producing a cold abscess, and from extension of other deep neck infections. An adult with a retropharyngeal abscess and no obvious source requires investigation for tuberculosis, malignancy, immunodeficiency and an occult foreign body.

Microbiology

Polymicrobial. Streptococcus pyogenes, Staphylococcus aureus including methicillin resistant strains, Streptococcus milleri group, Haemophilus influenzae, and anaerobes including Fusobacterium, Prevotella, Peptostreptococcus and Bacteroides.

In children

Preceding upper respiratory infection, pharyngitis or otitis media, typically several days earlier.
Fever, irritability and malaise.
Neck pain and refusal to move the neck, with neck stiffness that may be mistaken for meningitis.
Torticollis, with the head held tilted and rotated, which is a characteristic and readily overlooked sign.
Refusal to feed, drooling and dysphagia.
Muffled voice or a cri du canard, that is a duck like cry.
Neck swelling and cervical lymphadenopathy.
Stridor, respiratory distress and preference for lying supine with the neck extended, which is the opposite of epiglottitis where the child sits forward. A child who insists on lying flat with the neck extended and who resists sitting up has a retropharyngeal collection until proven otherwise.

In adults

Severe odynophagia and dysphagia.
Neck pain and stiffness.
Fever and systemic upset.
Dyspnoea and a sensation of throat obstruction.
A history of foreign body ingestion, instrumentation or recent dental or pharyngeal procedure.

Examination

Bulging of the posterior pharyngeal wall, which may be unilateral since the space is divided by a midline raphe. This may be subtle and is easily missed, particularly in a distressed child.
Restricted and painful neck movement, particularly extension.
Cervical lymphadenopathy.
Trismus, which is less prominent than in peritonsillar and parapharyngeal abscess.
Assess the airway carefully but do not provoke a distressed child.

Critical caution: do not perform vigorous oropharyngeal examination or attempt instrumentation in a child with suspected retropharyngeal abscess and airway compromise, since abscess rupture causes aspiration of pus, and distress can precipitate complete obstruction. Examine the airway in a controlled environment with anaesthetic support available.

Red flags

Stridor, respiratory distress, cyanosis and exhaustion.
Inability to lie flat, or conversely refusal to sit up.
Chest pain, dyspnoea and widening of the mediastinum, indicating mediastinal extension.
Crepitus in the neck, indicating gas forming organisms or oesophageal perforation.
Rapid progression, hypotension and sepsis.
Neurological signs, indicating intracranial extension or vertebral involvement.

Lateral soft tissue neck radiograph taken in true lateral position with the neck extended during inspiration, which is a rapid screening study. Prevertebral soft tissue thickening is abnormal when it exceeds 7 mm at C2 in all ages, or 14 mm at C6 in children and 22 mm at C6 in adults. Air or an air fluid level in the prevertebral space is diagnostic. Films taken in flexion or expiration produce false positive thickening, which is a common source of error.
Contrast enhanced computed tomography of the neck and chest, which is the definitive investigation. It distinguishes cellulitis and phlegmon from a drainable abscess, defines the extent and the spaces involved, identifies mediastinal extension, and shows vascular complications. A rim enhancing hypodense collection with surrounding fat stranding indicates abscess; homogeneous enhancement without a defined collection indicates cellulitis.
Include the chest in the imaging whenever mediastinal extension is possible, which is whenever the collection extends below the level of the hyoid.
Magnetic resonance imaging where vertebral osteomyelitis, discitis or spinal epidural abscess is suspected, which is superior for these.
Full blood count, C reactive protein, blood cultures, glucose.
Pus culture at drainage for aerobic, anaerobic, mycobacterial and fungal organisms.
Tuberculosis testing with an interferon gamma release assay and mycobacterial culture in adults, in the immunocompromised, in those from high prevalence areas, and where the presentation is subacute with a cold abscess and vertebral changes.
HIV testing.

Differential diagnosis

Epiglottitis, in which the child sits forward, drools and has a normal neck, and where the airway obstruction is supraglottic.
Croup, with a barking cough and inspiratory stridor with a normal pharynx.
Meningitis, which shares neck stiffness but not the pharyngeal findings.
Cervical adenitis without abscess.
Parapharyngeal abscess, which produces lateral rather than posterior pharyngeal wall bulging and more marked trismus.
Cervical spine osteomyelitis and Pott disease, with vertebral destruction on imaging.
Foreign body with perforation.
Retropharyngeal haematoma after trauma or in an anticoagulated patient, which can also obstruct the airway.
Neoplasm, including lymphoma and metastatic disease.

Airway first, then imaging, then antibiotics and drainage.

Airway management

Assess airway urgency immediately. Involve senior anaesthetic and, in children, paediatric intensive care support at the point of suspicion, not after imaging.
Keep the child calm and with a parent. Do not distress them with repeated examination, cannulation or lying them flat against their will.
Give humidified oxygen.
Where intubation is required, it should be performed by the most experienced anaesthetist available in theatre with surgical airway equipment and an otolaryngologist present, using an inhalational induction with maintained spontaneous ventilation. Abscess rupture during intubation with aspiration of pus is the specific hazard.
Nebulised adrenaline 1 mg/kg of 1 in 1000 to a maximum of 5 mL, and intravenous dexamethasone 0.6 mg/kg, may be used as temporising measures for airway oedema, though they do not treat the collection.

Antibiotics

Intravenous therapy from the outset, with broad spectrum cover including anaerobes and staphylococci.
Co amoxiclav 30 mg/kg every 8 hours in children, or 1.2 g every 8 hours in adults.
Alternatively ceftriaxone 50 mg/kg every 12 hours in children, or 2 g every 12 hours in adults, plus metronidazole 7.5 mg/kg every 8 hours in children or 500 mg every 8 hours in adults.
Add clindamycin 10 mg/kg every 6 to 8 hours in children, or 600 mg every 6 hours in adults, or vancomycin with a target trough of 15 to 20 mg/L, where methicillin resistant Staphylococcus aureus is prevalent. Clindamycin also suppresses toxin production in streptococcal disease.
Piperacillin with tazobactam 4.5 g every 6 to 8 hours, or a carbapenem, for severe disease, mediastinal extension and immunocompromise.
Narrow to culture as available. Continue intravenously until afebrile and improving, then complete a total of 2 to 3 weeks, and 4 to 6 weeks for osteomyelitis or mediastinitis.

Conservative management

A trial of intravenous antibiotics without drainage is reasonable in a child with a small collection, generally under 2 to 2.5 cm in maximum diameter, without airway compromise, without sepsis, and with the capacity for close monitoring. Around half of such children resolve without surgery. Reassess clinically at 24 and 48 hours, and repeat imaging if there is no improvement. Any deterioration, airway concern or failure to improve within 24 to 48 hours mandates drainage.

Surgical drainage

Indications:

Airway compromise.
Abscess larger than 2 to 2.5 cm.
Failure to improve within 24 to 48 hours of intravenous antibiotics.
Sepsis or systemic deterioration.
Mediastinal extension.
Immunocompromised patient.
Diagnostic uncertainty requiring tissue.

Technique:

Transoral drainage for midline and paramedian collections confined to the retropharyngeal space above the level of the hyoid. Performed under general anaesthesia with a secured airway, using a Boyle Davis gag, with the patient in Trendelenburg position and with suction immediately available so that pus is not aspirated. Make a vertical incision in the posterior pharyngeal wall over the point of maximal bulge, aspirate first with a needle to confirm and to reduce the risk of a sudden gush, then incise and break loculations with forceps. Avoid lateral dissection, since the carotid sheath lies laterally.
External transcervical drainage through an incision along the anterior border of sternocleidomastoid for collections extending laterally into the parapharyngeal space, extending below the hyoid, or descending toward the mediastinum. This approach permits complete drainage and placement of a drain.
Mediastinal extension requires thoracic surgical involvement with thoracotomy or video assisted thoracoscopic drainage, since descending necrotising mediastinitis has a mortality of 20 to 40 percent and cannot be adequately drained from the neck alone.
Repeat imaging and re drainage where the patient fails to improve.

Complications

Airway obstruction and asphyxia.
Abscess rupture with aspiration pneumonia and lung abscess.
Descending necrotising mediastinitis, pericarditis and empyema.
Extension to the parapharyngeal space with carotid sheath involvement, internal jugular vein thrombosis and carotid artery erosion.
Sepsis and multi organ failure.
Cervical vertebral osteomyelitis and spinal epidural abscess with cord compression.
Atlantoaxial subluxation, that is Grisel syndrome, presenting with persistent torticollis after resolution and requiring imaging and orthopaedic or neurosurgical involvement.

Follow up

Repeat imaging where recovery is slow. Investigate adults for an underlying cause including foreign body, tuberculosis, malignancy, diabetes and immunodeficiency. Persistent torticollis after resolution requires cervical spine imaging.

Oral Leukoplakia

Overview

Clinical Features

Diagnosis

Management

Overview

Clinical Features

Diagnosis

Management