3: Differential diagnosis by site


Differential diagnosis by site


• Few lesions affect only a single oral site: for example, cleft palate affects only the palate.
• Some lesions affect mainly one site; erythema migrans (geographic tongue), for example, almost exclusively affects the dorsum of tongue.
• Other conditions have a predilection for a limited number of sites; pemphigoid, for example, affects mainly the gingivae while burning mouth syndrome affects mainly the anterior tongue.
• Many disorders can affect almost any oral site; lichen planus, for example, can affect most oral sites, and oral pain can appear in any area.

Cervical lymph node disease

Cervical lymph nodes must be examined in every patient. Though most causes of enlargement (lymphadenopathy) are inflammatory (lymphadenitis), especially arising from local infection; others may be caused by malignant disease (Figure 3.1) – either local, distant or systemic – or other serious causes.

Figure 3.1 Neck lesion: lymphoma presenting as upper cervical lymph node enlargement.

Infection (the usual cause) may be:

• local viral or bacterial (dental, face, scalp, ear, nose or throat): including staphylococcal and non-tuberculous mycobacterial lymphadenitis
• systemic

image viral glandular fever syndromes (EBV, CMV, HIV, HHV-6 [human herpesvirus 6]), and rubella
image tuberculosis or other mycobacterial infections, other bacterial infections (brucella, cat-scratch fever, syphilis)
image parasitic, e.g. toxoplasmosis
image others, e.g. Kawasaki disease (mucocutaneous lymph node syndrome; MLNS).

Other inflammatory causes may be:

• granulomatous disorders (e.g. sarcoidosis, Crohn disease, orofacial granulomatosis)
• connective tissue diseases.

Malignant disease may be:

• local (oral, scalp, parotid, ear, nose or throat usually; rarely thyroid)
• systemic: carcinomas, lymphomas, leukaemias, Langerhans cell histiocytosis – especially Letterer–Siwe disease, Wegener granulomatosis.

Drugs – particularly phenytoin – may also be a cause.


• Lymphadenopathy is the term used when one or more lymph nodes enlarge or swell.
• Lymph nodes swell mainly in inflammatory or neoplastic disorders.
• Lymph nodes that swell because of an inflammatory cause are often tender but remain mobile (lymphadenitis).
• Lymph nodes that swell because of malignant involvement may become hard and fixed.

• It is crucial to establish whether only the regional (cervical) lymph nodes alone are involved, or if there is generalized lymphadenopathy.
• Cervical lymph nodes may enlarge in some systemic disorders – when there is typically generalized lymphadenopathy, and there may also be hepato- and/or splenomegaly.

Causes may include:

• Inflammatory causes:

image infection (the usual cause)
image local viral (e.g. herpes simplex infections) or bacterial (dental, scalp, ear, nose or throat) – including cat-scratch fever, staphylococcal lymphadenitis and cervicofacial actinomycosis (Figure 3.2)
Figure 3.2 Neck lesion: actinomycosis showing purplish swelling in the typical location.

image systemic: viral, e.g. infectious mononucleosis, cytomegalovirus, or HIV infection; bacterial, including syphilis, tuberculosis, brucellosis; fungal, rarely; parasitic, toxoplasmosis; Kawasaki disease (mucocutaneous lymph node syndrome)
image others: sarcoidosis, Crohn disease, orofacial granulomatosis, connective tissue diseases
• Malignant disease:

image local (oral, scalp, ear, nose or throat usually; rarely thyroid)
image systemic: leukaemias and lymphomas, carcinomas, Letterer–Siwe disease
• Drugs:

image particularly phenytoin.
Clinical features:

image lymphadenitis: discrete tender, mobile, enlarged firm nodes; rarely suppurate
image metastases: discrete or matted, fixed, enlarged, hard nodes (rubbery in lymphomas); may ulcerate.

image culture and sensitivity testing, if infection is suspected
image search for lesion in drainage area (imaging if necessary)
image blood picture; monospot test or toxoplasma serological profile (TSP)
image fine needle aspiration biopsy (FNAB) or biopsy if neoplasm suspected.
Diagnosis: see above.

image treat cause
image if oral disease is ruled out, then referral to appropriate health provider is needed

Salivary gland disease


• Salivary gland disease may present with swelling, pain or mouth dryness (hyposalivation).
• Swelling may be obstructive, inflammatory, neoplastic or idiopathic (e.g. sialosis).
• Pain may be due to obstructive, inflammatory, or neoplastic conditions.
• Dryness may be iatrogenic – for example after salivary gland irradiation, chemotherapy or graft-versus-host disease, or due to inflammatory disease such as Sjögren syndrome, or sarcoidosis.

Causes may include:

• Swellings:

image ductal obstruction (e.g. by calculus or tumour)
image inflammatory

a. actinomycosis
b. ascending (acute suppurative) sialadenitis
c. HIV salivary gland disease
d. IgG4 syndrome
e. lymphadenitis
f. mumps
g. recurrent sialadenitis
h. sarcoidosis
i. Sjögren syndrome
j. tuberculosis
image neoplasms
image other causes

a. deposits: amyloidosis; haemochromatosis
b. Mikulicz disease (lymphoepithelial lesion and syndrome, now known to be IgG4 syndrome)
c. sialosis (sialadenosis)
d. drug-associated (see also)
• Salivary gland pain:

image duct obstruction (stones or other causes)
image inflammatory

a. acute bacterial sialadenitis

b. viral sialadenitis: HIV sialadenitis; EBV sialadenitis; HCV sialadenitis; mumps
c. recurrent sialadenitis
d. Sjögren syndrome
image neoplastic (salivary gland malignant tumours)
image drug-associated (e.g. chlorhexidine, see also)
• Dryness:

image dehydration
image iatrogenic

graft-versus-host disease
image diseases affecting salivary glands

Sjögren syndrome and IgG4 syndrome
viral infections (e.g. EBV; HCV; HIV).

Acute bacterial (ascending) sialadenitis

Rare, except when following hyposalivation.

Typical orofacial symptoms and signs: painful swelling of one gland only, with red, shiny overlying skin, trismus, and purulent discharge from duct (Figures 3.3, 3.4).
Figure 3.3 Salivary disease: parotitis showing enlarged left parotid gland.
Figure 3.4 Salivary disease: parotitis, intraorally showing purulent discharge from Stensen duct.
Main oral sites affected: parotid gland.
Aetiopathogenesis: usually a bacterial infection ascends the duct of a reduced- or non-functioning salivary gland. Infectious agents include pneumococci, Staphylococcus aureus or viridans streptococci.
Gender predominance: male.
Age predominance: older adults.
Extraoral possible lesions: none.
Main associated conditions: dehydration; poor oral hygiene.
Differential diagnosis: other causes of sialadenitis: mainly mumps.
Investigations: purulent exudate for culture and sensitivities.
Main diagnostic criteria: clinical features.
Main treatments: antimicrobials (flucloxacillin if staphylococcal and not allergic to penicillin); sialogogues (saliva stimulants such as chewing gum or pilocarpine).



Typical orofacial symptoms and signs: dome-shaped, bluish, translucent, fluctuant, painless swelling, usually <10 mm diameter (Figure 3.5) which may rupture. Recur frequently. Deeper mucoceles are less common, more persistent and are often retention cysts (Figure 3.6).
Figure 3.5 Salivary disease: mucocele in a typical location – the lower labial mucosa.
Figure 3.6 Salivary disease: mucocele in the floor of mouth (ranula).
Main oral sites affected: lower lip mainly. Superficial mucoceles are small intra-epithelial lesions (<5 mm diameter) sometimes simulating a vesiculobullous disorder but usually producing a small vesicle only; seen often in the soft palate. Ranula is the term used for the ‘frog belly’ appearance of a large retention mucocele in the floor of the mouth often arising from the sublingual gland and, rarely, burrowing through the mylohyoid muscle (plunging ranula).
Aetiopathogenesis: usually extravasation of mucus from a damaged minor salivary gland duct; rarely retention of mucus within a salivary gland or its duct.
Gender predominance: none.
Age predominance: young people.
Extraoral possible lesions: none except neck swelling and airway obstruction if plunging ranula.
Main associated conditions: superficial mucoceles may be seen in lichen planus or Graft versus host disease.
Differential diagnosis: diagnosis is clear-cut but neoplasm must be excluded, particularly in the upper lip.
Investigations: microscopic features.
Main diagnostic criteria: clinical history and features.
Main treatments: if asymptomatic and small, observe; otherwise, use cryosurgery, laser ablation, micro-marsupialization or excision. Some lesions spontaneously resolve. Systemic gamma linolenic acid (evening primrose oil) has also been used.

Mumps (acute viral sialadenitis)

This is more common in childhood if vaccination with MMR (mumps, measles and rubella vaccine) is not taken.

Typical orofacial symptoms and signs: incubation period 14–21 days. Infections are often subclinical. Malaise, fever, anorexia and sialadenitis – painful, diffuse swelling of one/both parotids and sometimes submandibulars may be seen (Figure 3.7). Saliva is non-purulent but the duct is inflamed. Trismus and occasionally dry mouth may be present.
Figure 3.7 Salivary disease: mumps – bilateral sialadenitis.
Main oral sites affected: parotids bilaterally usually.
Aetiopathogenesis: mumps virus; rarely Coxsackie, ECHO, EBV or HIV infection.
Gender predominance: none.
Age predominance: typically in children.
Extraoral possible lesions: complications are uncommon but may include pancreatitis, encephalitis, orchitis, oophoritis and deafness.
Main associated conditions: as above.
Differential diagnosis: differentiate from obstructive and/or bacterial sialadenitis and recurrent juvenile parotitis mainly.
Investigations: mumps antibody titres (rarely needed); serum amylases or lipases (occasionally); ultrasound.
Main diagnostic criteria: clinical history and features.
Main treatments: symptomatic (reduce fever, pain and malaise with paracetamol, and maintain hydration).

Necrotizing sialometaplasia

(see page 289)

Salivary gland neoplasms

These are uncommon. Classification of the most common salivary neoplasms is:

• Adenomas:

image pleomorphic adenoma (PA: mixed tumour)
image Warthin tumour (adenolymphoma or papillary cystadenoma lymphomatosum)
image ‘monomorphic’: adenolymphoma/oncocytic adenoma/ (canalicular, basal cell, others)
• Others:

image polymorphous low-grade adenocarcinoma
image mucoepidermoid carcinoma
image acinic cell carcinoma
image adenoid cystic and other carcinomas.

Typical orofacial symptoms and signs: asymptomatic, firm and sometimes nodular swelling in one gland (usually parotid) and possible eversion of ear lobe (Figures 3.8). Warthin tumour may be bilateral. No hyposalivation. Malignant neoplasms classically may grow rapidly, may cause pain, may ulcerate and may involve nerves (e.g. facial palsy).
Figure 3.8 Salivary disease: neoplasm; pleomorphic adenoma in tail of parotid.

Main oral sites affected: most tumours involve the parotid (75%), where most are benign pleomorphic adenomas (60%). Most other salivary tumours are in the minor glands, where many are malignant (60%), often arising from palatal glands (Figures 3.93.11). Few tumours are in the submandibular or sublingual glands. Submandibular tumours can be benign or malignant. Most sublingual gland tumours are malignant.
Figure 3.9 Salivary disease: neoplasm in palatal minor glands.
Figure 3.10 Salivary disease: neoplasm – malignant tumour in sublingual gland. Most tumours arising there are malignant.
Figure 3.11 Salivary disease: neoplasm.

Neoplasms in major salivary glands

Aetiopathogenesis: unknown, but age smoking, irradiation and viruses have been implicated; more controversial is the possible effect of mobile telephones.
Gender predominance: none.
Age predominance: middle and old age.
Extraoral possible lesions: none except for enlarged lymph nodes due to metastasis.
Main associated conditions: usually none but a weak association with breast cancer.
Differential diagnosis: differentiate from other neoplasms such as lymphomas or metastases, and from non-neoplastic salivary gland swellings.
Investigations: ultrasound and fine needle aspiration biopsy (FNAB). Microscopy after parotidectomy (open biopsy may allow seeding and recurrence).
Main diagnostic criteria: clinical, advanced imaging and microscopy.
Main treatments: surgical excision; radiotherapy also for some.

Intraoral (minor) salivary gland neoplasms

• Intraoral salivary gland neoplasms are less common than neoplasms in major glands, but a higher proportion are malignant.
• Mucoepidermoid carcinoma is the most common intraoral salivary neoplasm, but adenoid cystic carcinoma and pleomorphic adenoma (PA) are relatively common in the mouth.
• Salivary gland tumours in the tongue are usually malignant – and are especially adenoid cystic carcinoma.
• Salivary gland tumours in the sublingual gland are usually malignant but are rare.
• Salivary gland tumours in the lips are usually seen in the upper lip but are typically benign (pleomorphic or other adenoma).

Typical orofacial symptoms and signs: Pleomorphic adenomas are typically rubbery and often lobulated (Figures 3.12, 3.13); benign neoplasms form painless swellings. Malignant tumours are not initially distinguishable clinically from benign tumours but, in their later stages, are often painful and ulcerate, invade perineurally and they metastasize to upper cervical lymph nodes.
Figure 3.12 Salivary disease: neoplasm presenting as palatal swelling.
Figure 3.13 Salivary disease: neoplasm.
Main oral sites affected: the palate is the intraoral site of predilection.
Aetiopathogenesis: unknown.
Gender predominance: females.
Age predominance: older persons.
Extraoral possible lesions: none.
Main associated conditions: none.
Differential diagnosis: from other causes of lumps or ulcers, particularly:

image lower lip salivary tumours – from mucocele, benign connective tissue tumours
image tongue salivary tumours – from carcinoma, benign connective tissue tumours
image palatal salivary tumours – from oral carcinoma, benign connective tissue tumours, lymphomas, antral carcinoma or necrotizing sialometaplasia.
Main diagnostic criteria: ultrasound, advanced imaging and microscopy.
Main treatments: wide excision; radiation treatment if perineural invasion, and microscopic examination.


Uncommon granulomatous condition.

Typical orofacial symptoms and signs: salivary gland swelling usually painless, bilateral (Figure 3.14). Often hyposalivation is present. May be cervical lymphoadenopathy; mucosal nodules; gingival hyperplasia; or labial swelling.
Figure 3.14 Salivary disease: sarcoidosis presenting with parotid swelling.
Main oral sites affected: lips, palate, major salivary glands.
Aetiopathogenesis: unknown.
Gender predominance: female.
Age predominance: adult.

Extraoral possible lesions: can affect any organ, typically lungs and lymph nodes (e.g. hilar nodes); also ocular (e.g. uveitis) and skin (e.g. erythema nodosum) lesions. The rare combination of parotitis, anterior uveitis, VIIth cranial nerve paralysis and fever is termed uveoparotid fever (Heerfordt–Waldenstrom) syndrome.
Main associated conditions: sometimes autoimmune disorders.
Differential diagnosis: from other causes of salivary gland swelling (particularly sialosis, Sjögren syndrome and IgG4 disease, hyposalivation, metastatic disease, lymphomas, Wegener granulomatosis, rheumatoid nodules, varicella–zoster infection and atypical infections such as Mycobacterium avium complex, cytomegalovirus, and cryptococcosis.
Investigations: lesional biopsy; chest radiograph; gallium scan, raised serum angiotensin-converting enzyme (SACE) and adenosine deaminase. Vitamin D and prolactin levels are often increased.
Main diagnostic criteria: microscopy and SACE.
Main treatments: corticosteroids, methotrexate or other immunosuppressive drugs if lungs or eyes are involved, or if there is hypercalcaemia.


Typical orofacial symptoms and signs: painless, usually bilateral salivary gland swelling (Figure 3.15).
Figure 3.15 Salivary disease: sialosis (sialadenosis) – bilateral painless swellings.
Main oral sites affected: parotids.
Aetiopathogenesis: the common feature is autonomic dysfunction. Frequently idiopathic; known causes include:

image neurogenic: various drugs, such as isoprenaline
image dystrophic-metabolic: anorexia–bulimia, alcoholic cirrhosis, diabetes, malnutrition, thyroid disease, acromegaly and pregnancy.
Gender predominance: male but depends on cause.
Age predominance: older patients.
Extraoral possible lesions: dependent upon aetiopathogenesis.
Main associated conditions: see aetiopathogenesis.
Differential diagnosis: sarcoidosis, Sjögren syndrome, IgG4 disease and Warthin tumour mainly.
Investigations: ultrasound, MRI; blood glucose, liver function tests, immunoglobulins; possibly growth hormone levels.

Main diagnostic criteria: clinical, ultrasound, MRI and exclusion of other diagnoses.
Main treatments: identify and treat predisposing cause.

Sjögren syndrome

Uncommon, the cause is unknown but it is immunological and possibly viral. The common features are dry mouth and dry eyes: joint and other problems may be associated.

Typical orofacial symptoms and signs: saliva is frothy and not pooling; the mucosa may be parchment-like with food debris (Figure 3.16), the lips often dry (Figure 3.17) and the tongue lobulated and depapillated (Figure 3.18). There may be complaints of dry mouth (hyposalivation): difficulty in eating dry foods, disturbed taste, and disturbed speech and swallowing. Rampant caries, candidosis and recurrent sialadenitis may be seen (Figures 3.19 and 3.20). Salivary and lachrymal glands may sometimes swell (Figures 3.21, 3.22). There may be conjunctival dryness and redness (termed injection) (Figure 3.23) and rheumatoid disease (Figure 3.24).
Figure 3.16 Salivary disease: Sjögren syndrome; dry mouth and food residues.
Figure 3.17 Salivary disease: Sjögren syndrome; dry lips.
Figure 3.18 Salivary disease: Sjögren syndrome; dry and lobulated tongue.
Figure 3.19 Salivary disease: Sjögren syndrome; caries.
Figure 3.20 Salivary disease: Sjögren syndrome; candidosis (angular stomatitis).
Figure 3.21 Salivary disease: Sjögren syndrome; salivary gland swelling and ocular involvement.
Figure 3.22 Salivary disease: Sjögren syndrome; salivary gland swelling.
Figure 3.23 Salivary disease: Sjögren syndrome; dry eyes (keratoconjunctivitis sicca).
Figure 3.24 Salivary disease: Sjögren syndrome; rheumatoid arthritis showing finger ulnar deviations.
Aetiopathogenesis: autoimmune inflammatory exocrinopathy.
Gender predominance: women.
Age predominance: middle age or older.
Extraoral possible lesions: dry eyes (keratoconjunctivitis sicca): initially asymptomatic, later gritty sensation, itching, soreness or inability to cry. Swollen lachrymal glands. Extraglandular disease may precede exocrine problems by years, and includes fatiguability, fever and Raynaud phenomenon. Late complications include:

image glomerulonephritis
image lymphoma.
Main associated conditions: there is no connective tissue disease in primary (SS-1, sometimes termed sicca syndrome) but, in secondary Sjögren syndrome (SS-2) there is typically rheumatoid arthritis or less frequently primary biliary cirrhosis, and occasionally other autoimmune disorders. Sjögren syndrome predisposes especially to B cell non-Hodgkin lymphoma (NHL) – a mucosa-associated lymphoid tissue (MALT) malignancy. The risk is greatest in SS-1; affects up to 5% of patients and is seen mainly in mucosal extranodal sites (salivary glands – especially the parotids, mouth, skin, nodes, stomach, lung). Lymphoma is a high risk in those with persistent salivary gland swelling, splenomegaly or lymphadenopathy. Diagnosis of lymphoma is best by:

image ultrasonography
image high-resolution CT
image MRI
image MRI contrast sialography (gadolinium MRI with fat subtraction)
image histology.

Most of these lymphomas are relatively low-grade and require either no treatment apart from regular follow-up or low-dose chemotherapy.

Differential diagnosis: dry mouth can result from many other causes. Similar sicca syndromes may be seen in HCV or HIV disease, IgG4 syndrome, or in graft-versus-host disease (GVHD).
Investigations: salivary flow rates (reduced); auto-antibodies, especially rheumatoid factor, Ro (SS-A) and La (SS-B) antibodies; serum IgG4 levels, and ultrasound. Labial salivary gland biopsy is carried out in some centres and this and IgG4 levels are most helpful in Ro/La negative patients. Sialography and/or scintigraphy are occasionally employed but are largely superseded by ultrasound.
Main diagnostic criteria: clinical features plus Ro (SS-A) and La (SS-B) antibodies, and ultrasound; occasionally labial salivary gland biopsy.
Main treatments: control underlying disease if possible (e.g. ciclosporin, azathioprine, hydroxychloroquine and anti-B cell monoclonals such as the anti-CD20 rituximab)

image dry eyes – methylcellulose eye drops or rarely ligation or cautery of nasolacrimal duct
image dry mouth:

– saliva substitutes (mouth-wetting agents)
– saliva stimulants (sialogogues); sugar-free chewing gum, or drugs (pilocarpine, cevimeline, anetholetrithione or bethanecol) may be used to stimulate salivation
– interferon-alpha
– preventive dental care (oral hygiene, limitation of sucrose and other sugar intake, use of fluorides, amorphous calcium phosphate, chlorhexidine)
– treat infections.

IgG4 syndrome

IgG4 syndrome (‘IgG4 related systemic sclerosing disease’, ‘IgG4-related autoimmune disease’, ‘IgG4-related systemic disease’, ‘IgG4-positive multiorgan lymphoproliferative syndrome’) often manifests with enlarged salivary glands (previously called Mikulicz disease or Kuttner tumour [sclerosing sialadenitis]) and one-third also suffer from dry eyes and dry mouth and arthralgias, so for many years this was considered a subgroup of Sjögren syndrome.

IgG4 syndrome affects mainly middle-aged men. Many other organs and tissues are also involved, including pancreas (the most commonly affected tissue), gall bladder, bile duct, retroperitoneum, kidneys, lung, prostate, lymph nodes, breast, and thyroid and pituitary glands.

Patients have neither anti-Ro/SS-A nor anti-La/SS-B autoantibodies but they have low titres of rheumatoid factor (RF), antinuclear autoantibodies (ANA), and decreased serum complement. Treatment includes systemic corticosteroids or anti-CD20 therapy (rituximab).

Lip lesions


• Lip lesions affecting the vermilion are often termed cheilitis.
• Cheilitis can have a wide range of causes.
• Common forms of cheilitis are traumatic, infective or follow exposure to UV radiation, low humidity, or temperature extremes (cold and heat).
• Blistering of the vermilion is commonly caused by a burn or herpes labialis (‘cold sores’).
• Blistering of the labial mucosa is commonly caused by mucoceles.
• Coloured lesions of the lips are usually brown (labial melanotic macules), red (telangiectasia) or purple/blue (angiomas).
• Bleeding from the lip may be from trauma or a fissure or vesiculobullous disorder such as erythema multiforme or pemphigus.
• Soreness of the lips may be seen in any type of cheilitis, especially factitious, allergic or infective varieties.
• White lesions of the lips are seen in actinic cheilitis, leukoplakia, candidosis and lichen planus.
• Ulceration of the lips can have many causes – systemic, malignant, local irritation, aphthae or drugs, but cancer and pemphigus are the most serious.
• Lumps/swelling of the lips can be seen after trauma, in allergies, in granulomatous disorders, neoplasms and from foreign bodies.

Actinic burns and cheilitis

Mainly seen in fair-skinned individuals exposed in sunny climes or at high altitude.

Typical orofacial symptoms and signs: erythema, oedema, vesiculation and occasionally haemorrhage typify burns (Figures 3.25, 3.26); later whitish lesions or keratosis characterize actinic cheilitis – which is potentially malignant.
Figure 3.25 Lip lesion: actinic cheilitis from severe acute sun-exposure.
Figure 3.26 Lip lesion: actinic cheilitis (solar elastosis) with early carcinoma on the right.
Main oral sites affected: lower lip.
Aetiopathogenesis: shortwave ultraviolet (UV) light (sunlight may also trigger herpes labialis and lupus erythematosus).
Gender predominance: male.
Age predominance: old age.
Extraoral possible lesions: cutaneous cancers on other areas of the face and exposed skin.
Differential diagnosis: from other causes of burns (e.g. friction and heat).
Investigations: biopsy.
Main diagnostic criteria: history and clinical features; biopsy persistent lesions.
Main treatments: prophylaxis – reduce sun exposure; bland or barrier creams (Uvistat); topical bleomycin, or lip shave.

Allergic angioedema

Uncommon: mainly seen in those with allergic (atopic) tendency.

Typical orofacial symptoms and signs: rapid development of oedematous swelling (Figure 3.27).
Figure 3.27 Lip lesion: angioedema causing facial and labial swelling.
Main oral sites affected: lip(s) and tongue; oedema may spread to involve the neck and hazard the airway.
Aetiopathogenesis: type 1 allergic response.
Gender predominance: none.
Age predominance: none.
Extraoral possible lesions: atopy (allergic rhinitis, hayfever or eczema).
Main associated conditions: as above.
Differential diagnosis: from hereditary angioedema (C1 esterase inhibitor deficiency), and other causes of diffuse facial swelling including: oedema from trauma, infection or insect bite; surgical emphysema; Crohn disease, orofacial granulomatosis; sarcoidosis; cheilitis glandularis; lymphangioma; haemangioma.
Investigations: allergy testing, C1 esterase inhibitor levels.
Main diagnostic criteria: history of atopic disease and/or exposure to allergen; allergy testing (prick test).
Main treatments: mild angioedema – antihistamines; severe angioedema – intramuscular adrenaline, and intravenous corticosteroids.

Angioma (haemangioma)

These are fairly common oral lesions.

Typical orofacial symptoms and signs: a painless reddish, bluish or purplish soft vascular lesion which blanches on pressure (diascopy) (Figures 3.28, 3.29).
Figure 3.28 Lip lesion: haemangioma.
Figure 3.29 Lip lesion: haemangioma as in Figure 3.28 after diascopy.
Main oral sites affected: most common on the lip, tongue, or buccal mucosa as painless reddish, or often bluish or purplish soft lesions which usually blanch on pressure, are fluctuant to palpation, are level with the mucosa or have a lobulated or raised surface. Haemangiomas are at risk from trauma and prone to excessive bleeding if damaged (e.g. during tooth extraction). Occasionally, oral haemangiomas calcify (phlebolithiasis).
Aetiopathogenesis: haemangiomas represent hamartomas or vascular anomalies. In children, they are usually congenital and developmental in origin. In adults, they may be acquired.
Gender predominance: female.
Age predominance: many haemangiomas appear in infancy, most by the age of 2 years, grow slowly and, by age 10, the majority have involuted (resolved). In adults, however, haemangiomas rarely involute spontaneously; rather they remain static or slowly enlarge.
Extraoral possible lesions: haemangiomas are typically seen in isolation but a few may be multiple and/or part of a wider syndrome such as:

image Sturge–Weber syndrome (angioma that extends deeply and rarely involves the ipsilateral meninges, producing a facial angioma and seizure disorder, sometimes with learning impairment)

image blue rubber bleb naevus syndrome (BRBNS) – multiple cutaneous venous malformations in association with visceral lesions, most commonly affecting the GI tract
image Maffucci syndrome – multiple angiomas with enchondromas
image Dandy–Walker syndrome – a congenital brain malformation involving the cerebellum, or other posterior cranial fossa malformations.
Main associated conditions: as above.
Differential diagnosis: varicosities, pyogenic granuloma, lymphangioma, Kaposi sarcoma and epithelioid angiomatosis.
Investigations: for large angiomas, angiography may be needed rather than biopsy. After intravenous administration of contrast medium, enhancement is observed in haemangiomas in areas corresponding to those with high signal on T2-weighted MRI.
Main diagnostic criteria: angiomas blanch on pressure (diascopy), or contain blood on aspiration with a needle and syringe.
Main treatments: most angiomas are small, of no consequence and need no treatment but if they do for aesthetic or functional reasons or because of previous episodes of significant bleeding, they respond well to cryosurgery, laser ablation or intralesional injections of corticosteroids, sclerosing agents, interferon alpha, or systemic corticosteroids or propranolol. Very large haemangiomas may need to be treated with ligation or embolization – mainly for cosmetic reasons or if bleeding is troublesome.


Uncommon in England and Wales (600 cases/year) and declining: much more common nearer the Equator, especially in white-skinned people.

Typical orofacial symptoms and signs: thickening, induration, crusting or ulceration, usually at vermilion border of lower lip just to one side of midline (Figures 3.30, 3.31). There is late involvement of the submental and other lymph nodes.
Figure 3.30 Lip lesion: carcinoma. This is a typical location and seen mainly in sun-exposed, older male Caucasian smokers.
Figure 3.31 Lip lesion: advanced carcinoma.
Main oral sites affected: lower lip.
Aetiopathogenesis: predisposing factors include UV irradiation (sun), immunosuppression and tobacco.

Gender predominance: male.
Age predominance: old age.
Extraoral possible lesions: cutaneous cancers on face and other sun-exposed skin.
Main associated conditions: xeroderma pigmentosum and discoid lupus erythematosus predisposed.
Differential diagnosis: from herpes labialis, keratoacanthoma, and (rarely) basal cell carcinoma (on skin), molluscum contagiosum.
Investigations: biopsy. Fibreoptic pharyngolaryngoscopy with autofluorescence (symptom-directed bronchoscopy/oesophagoscopy); ultrasound-guided fine needle aspiration biopsy of any neck mass; staging – supported by MRI (or CT) from skull base to sternoclavicular joints (plus USgFNA and/or FDG-PET if anything equivocal); CT thorax.
Main diagnostic criteria: biopsy is confirmatory.
Main treatments: surgery (wedge resection or lip shave) or irradiation. The prognosis is good: 70% 5-year survival.

Discoid lupus erythematosus (DLE)

Rare. DLE may be categorized as:

• Localized DLE – the head and neck only are involved.
• Widespread DLE – other areas are affected, even if the head and neck are also involved. People with widespread disease may have abnormalities of blood or positive serology, and are more likely to develop SLE (systemic lupus erythematosus).
Typical orofacial symptoms and signs: lesions on vermilion border are scaly and crusting. Intraoral lesions have central atrophic and often indurated red area with border of radiating white striae, and peripheral telangiectasia (Figure 3.32). There is a small predisposition to carcinoma of the lip.
Figure 3.32 Lip lesion: discoid lupus erythematosus. Lesions can mimic lichen planus and can be potentially malignant.
Main oral sites affected: buccal mucosa, palate/alveolar ridges and lips (almost always the lower lip).
Aetiopathogenesis: unclear: drugs, hormones and viruses may contribute in genetically predisposed persons.
Gender predominance: females.

Age predominance: adults.
Extraoral possible lesions: the discoid rash is usually on the face with red patches that are thick and often scaly, appearing red with a whitish, or at least, lighter-coloured, scaly rim. As the patches heal they tend to scar. If discoid lupus occurs on the scalp the hair will be lost, leaving permanent bald areas.
Main associated conditions: none; discoid lupus is a type of lupus that tends to be confined to the skin and mucosa and other organs in the body are not involved.
Differential diagnosis: systemic lupus erythematosus, lichen planus, leukoplakia (keratosis), lichenoid white lesions and carcinoma.
Investigations: biopsy; serology to exclude SLE.
Main diagnostic criteria: histology.
Main treatments: topical corticosteroids (e.g. betamethasone valerate 0.1% or clobetasol cream) or tacrolimus; cryosurgery or excision of localized lesions; follow-up because of increased risk for malignant transformation.

Erythema multiforme


Typical orofacial symptoms and signs: serosanguinous exudate on ulcerated swollen lips, and ulcers (Figures 3.33, 3.34).
Figure 3.33 Lip lesion: erythema multiforme (patient’s fingers).
Figure 3.34 Lip lesion: erythema multiforme in a young boy showing blood-encrusted swollen lips.
Main oral sites affected: lips and oral mucosa.
Aetiopathogenesis: putative reaction to microorganisms (herpes simplex, mycoplasma), to drugs (e.g. NSAIDs, antimicrobials, sulphonamides, beta blockers, dapsone, salicylates, tetracyclines) or to other factors.
Gender predominance: males.
Age predominance: young adult.
Extraoral possible lesions: may affect mouth alone, or skin and/or other mucosa. The minor form affects only one or two mucosal sites and/or the skin. The major form (Stevens–Johnson syndrome) affects more than two mucosal sites and is widespread, with skin rashes, fever and toxicity. Rashes are various but typically ‘target’ lesions or bullae. The most severe form is toxic epidermal necrolysis (TEN) when the lesions affect most of the body surface and the condition is life-threatening.
Main associated conditions: as above.
Differential diagnosis: from other lip lesions, and other causes of mouth ulcers – particularly primary herpes stomatitis and pemphigus.
Investigations: history of exposure to agents and biopsy.
Main diagnostic criteria: clinical picture; biopsy sometimes helpful.
Main treatments: minor form – symptomatic treatment and systemic corticosteroids; major form – systemic corticosteroids or other immunomodulatory drugs.

Exfoliative cheilitis (factitious cheilitis, le tic de lèvres)

An uncommon chronic superficial inflammatory disorder characterized by hyperkeratosis and desquamation of the vermilion epithelium.
Typical orofacial symptoms and signs: persistent scaling of the lips.

Main oral sites affected: often starts in the centre of the lower lip (Figures 3.353.38) and spreads to involve the whole of the lower or of both lips. The patient may complain of irritation or burning and can be observed frequently biting or sucking the lips. Lip scaling and crusting is more or less confined to the vermilion border, persisting in varying severity for months or years. There may be bizarre yellow hyperkeratotic or thick haemorrhagic crusts.
Figure 3.35 Lip lesion: chapping.
Figure 3.36 Lip lesion: cheilitis (factitious or artefactual- self-induced).
Figure 3.37 Lip lesion: cheilitis (the skin erythema beneath the lower lip is from licking).
Figure 3.38 Lip lesion: cheilitis (exfoliative). Note also the crenated tongue, from pressing on the teeth.
Aetiopathogenesis: most patients seem to have a personality disorder. A preoccupation with the lips is prevalent in some individuals. In some cases it appears to start with chapping or with atopic eczema, and develops into a habit tic. Many cases are thus thought to be factitious, caused by repeated self-induced trauma such as repetitive biting, picking, lip sucking, chewing or other manipulation of the lips. Exacerbations have been associated with stress.
Gender predominance: female.
Age predominance: children and young adults.
Extraoral possible lesions: none.
Main associated conditions: none.
Differential diagnosis: actinic cheilitis, contact cheilitis, glandular cheilitis, lupus erythematosus, Candida infections (where it is sometimes termed cheilo-candidosis), and HIV infection.

Investigations: biopsy is sometimes indicated and allergy testing for severe cases.
Main diagnostic criteria: diagnosis is restricted to those few patients whose cheilitis cannot be attributed to other causes, such as contact sensitization or UV light.
Main treatments: some cases resolve spontaneously or with improved oral hygiene. Reassurance and topical corticosteroids may be helpful but often exfoliative cheilitis is refractory to treatment. When a factitial cause is suspected, a psychiatric consultation and care may be beneficial; some improve with psychotherapy and antianxiolytic or antidepressant treatment.

Hereditary angioedema


Typical orofacial symptoms and signs: as in allergic angioedema (above) but precipitated by trauma, e.g. dental treatment. There is high mortality in some families.
Main oral sites affected: lips and tongue.
Aetiopathogenesis: genetic defect of the inhibitor of activated first component of complement C1 (C1 esterase inhibitor); autosomal dominant inheritance generally.
Gender predominance: none.
Age predominance: none.

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Jan 12, 2015 | Posted by in Oral and Maxillofacial Pathology | Comments Off on 3: Differential diagnosis by site
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