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Home , Orofacial granulomatosis, Torus mandibularis

Clinical

Oral medicine for the general practitioner: lumps and swellings

Crispian Scully 1

his series of five papers summarises some of the most important problems likely to be Tencountered by practitioners. Some are common, others rare. The practitioner cannot be expected to diagnose all, but has been trained to recognise oral health and disease, and should be competent to recognise normal variants, and common orofacial disorders. In any case of doubt, the practitioner is advised to seek a second opinion from a colleague. The series is not intended to be comprehensive in coverage either of the conditions encountered, or all aspects of Figure 1: . diagnosis or treatment: further details are available in standard texts, in the further reading section, or from the internet. The present article discusses aspects of lumps through fear, perhaps after hearing of someone with and swellings. ‘mouth cancer’. Thus some individuals discover and worry about normal anatomical features such as tori, the parotid Lumps and swellings papilla, foliate papillae on the tongue, or the pterygoid Lumps and swellings in the mouth are common, but of hamulus. The tongue often detects even a very small diverse aetiologies (Table 1), and some represent swelling, or the patient may first notice it because it is sore malignant neoplasms. Therefore, this article will discuss (Figure 1). In contrast, many oral cancers are diagnosed far lumps and swellings in general terms, but later focus on too late, often after being present several months, usually the particular problems of and of orofacial because the patient ignores the swelling. granulomatosis, presentations of which can also include Many different conditions, from benign to malignant, oral ulceration. may present as oral lumps or swellings (see Tables 1 to 5) Most patients have only a passing interest in their mouths including: but some examine their mouths out of idle curiosity, some Developmental Unerupted teeth, and tori are common causes of swellings related to the Inflammatory is one of the most common causes of oral swelling. However, there are a group of 1 Professor Crispian Scully CBE, MD, PhD, MDS, MRCS, BDS, BSc, conditions characterised by chronic inflammation and MB.BS, FDSRCS, FDSRCSE, FDSRCPS, FFDRCSI, FRCPath, FMedSci, , which can present with lumps or swellings. FHEA, FUCL, DSc, DChD, DMed (HC), Dr HC. Emeritus Professor, University College London (UCL); Professor of Oral Medicine, These, which include Crohn’s disease, orofacial University of Bristol; Visiting Professor at Universities of Athens, granulomatosis, and , are discussed below Edinburgh, Granada, Helsinki and Peninsula Neoplasms Oral squamous cell carcinoma (OSCC),

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Table 1: Main conditions which may present as lumps or swellings in the mouth

Kaposi’s sarcoma, and other neoplasms may Normal anatomy Pterygoid hamulus present as swellings, as discussed below. Occasionally Parotid papillae metastatic malignant disease may present as a lump in the mouth or Developmental Unerupted teeth Traumatic Haematoma may cause a swelling at the site Odontogenic cysts of trauma. The flange of a denture impinging on the Eruption cysts vestibular mucosa may stimulate a reactive irregular Developmental cysts (e.g. hyperplasia (denture-induced hyperplasia) thyroglossal, dermoid) Hormonal Pregnancy may result in a gingival swelling Haemangioma (pregnancy ) Lymphangioma Drug-induced A range of drugs can produce gingival Maxillary and mandibular tori swelling - most common are phenytoin, ciclosporin and Hereditary gingival fibromatosis calcium channel blockers (Table 2) Lingual thyroid Viral lesions Papillomas, common (verruca Inflammatory Abscess vulgaris), genital warts (condyloma acuminatum) and Cellulitis focal epithelial hyperplasia (Heck’s disease) are all lumps Crohn’s disease caused by human papillomaviruses Cysts Human papillomavirus-induced Fibro-osseous lesions Fibrous dysplasia and Paget’s lesions (warts etc) disease can result in hard jaw swellings. Insect bites Diagnosis Pyogenic Important features to consider when making the Sarcoidosis provisional diagnosis of the cause of a lump or swelling include: Traumatic Denture granulomata Position The anatomical position should be defined and Epulis the proximity to other structures (e.g. teeth) noted Fibroepithelial polyp • Midline lesions tend to be developmental in origin Haematoma (e.g. ) Mucocele • Bilateral lesions tend to be benign (e.g. sialosis - salivary Surgical emphysema swelling in alcoholism, diabetes or other conditions) Neoplasms Carcinoma • Most neoplastic lumps are unilateral Leukaemia Other similar or relevant changes elsewhere in the oral cavity should be noted Myeloma Size The size should always be measured and recorded. A Odontogenic tumours diagram and photograph may be helpful Others Shape Some swellings have a characteristic shape that Fibro-osseous may suggest the diagnosis: thus a parotid swelling often Fibrous dysplasia fills the space between the posterior border of the Paget’s disease Hormonal Pregnancy epulis/ and the mastoid process Oral contraceptive pill gingivitis Colour Brown or black pigmentation may be due to a Sialosis variety of causes such as a tattoo, naevus or melanoma. Metabolic Amyloidosis Purple or red may be due to a haemangioma, Kaposi’s Other deposits sarcoma or giant-cell lesion Drugs Phenytoin Temperature The skin overlying acute inflammatory Ciclosporin lesions, such as an abscess, or over a haemangioma, is Calcium channel blockers frequently warm Allergic Tenderness Inflammatory swellings such as an abscess

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Table 2: Oral malignant neoplasms

Common Squamous cell carcinoma Less common Salivary gland tumours Malignant melanoma Lymphomas Neoplasms of bone and connective tissue Some odontogenic tumours Maxillary antral carcinoma (or other neoplasms) Metastatic neoplasms (breast, lung, kidney, stomach, liver) Langerhans cell histiocytoses Kaposi’s sarcoma

are characteristically tender, although clearly palpation Ulceration Some swellings may develop superficial must be gentle to avoid excessive discomfort to the ulceration such as squamous cell carcinoma. The character patient of the edge of the ulcer and the appearance of the ulcer Discharge Note any discharge from the lesion (e.g. clear base should also be recorded fluid, pus, or blood), orifice, or sinus Margins Ill-defined margins are frequently associated Movement The swelling should be tested to determine if with malignancy, whereas clearly defined margins are it is fixed to adjacent structures or the overlying suggestive of a benign lesion skin/mucosa such as may be seen with a neoplasm Number of swellings Multiple lesions suggest an Consistency Palpation showing a hard (indurated) infective or occasionally developmental, origin. Some consistency may suggest a carcinoma. Palpation may conditions are associated with multiple swellings of a cause the release of fluid (e.g. pus from an abscess) or similar nature, e.g. neurofibromatosis. cause the lesion to blanch (vascular) or occasionally cause a blister to appear (Nikolsky sign) or to expand. Investigations Sometimes palpation causes the patient pain (suggesting The medical history should be fully reviewed, since an inflammatory lesion). The swelling overlying a bony some systemic disorders may be associated with intra- cyst may crackle (like an eggshell) when palpated or oral or facial swellings (Table 1). The nature of many fluctuation may be elicited by detecting movement of lumps cannot be established without further fluid when the swelling is compressed. Palpation may investigation: disclose an underlying structure (e.g. the crown of a tooth • Any teeth adjacent to a lump involving the jaw should under an eruption cyst) or show that the actual swelling is be tested for vitality, and any caries or suspect in deeper structures (e.g. submandibular calculus) restorations investigated. Surface texture The surface characteristics should be • The periodontal status of any involved teeth should also noted: papillomas have an obvious anemone-like be determined. appearance; carcinomas and other malignant lesions and • Imaging of the full extent of the lesion and possibly deep fungal and other chromic infections tend to have a other areas is required whenever lumps involve the nodular surface and may ulcerate. Abnormal blood vessels jaws. OPT and special radiographs (e.g. of the skull, suggest a neoplasm sinuses, salivary gland function), computerised

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Figure 2: Gingival swelling caused by nifedipine. Figure 3: Oral squamous cell carcinoma.

Figure 4: OFG (orofacial granulomatosis).

tomography (CT scans) or magnetic resonance imaging Oral cancer (MRI), or ultrasound may, on occasions, be indicated. Oral cancer is the most common malignant epithelial Photographs may be useful for future comparison. neoplasm affecting the mouth. More than 90% is oral • Blood tests may be needed, particularly if there is squamous cell carcinoma (OSCC). Cancers of the oral suspicion that a blood dyscrasia or endocrinopathy may cavity are classified according to site: underlie the development of the lump. • (International Classification of Diseases (ICD) 140) • Tongue (ICD 141) Management • Gum (ICD 143) Specialist referral may be indicated if the practitioner • Floor of the mouth (ICD 144) feels: • Unspecified parts of the mouth (ICD 145). • The diagnosis is unclear Other malignant oral neoplasms (Table 2) include: • A serious diagnosis such as cancer is possible • Other epithelial malignancies e.g. melanoma • Systemic disease such as Crohn’s disease, may • Secondary carcinomas be present • Sarcomas e.g. Kaposi’s sarcoma • Unclear as to investigations indicated • Lymphoreticular neoplasms e.g. lymphomas. • Complex investigations are indicated • Unclear as to treatment indicated Oral squamous cell carcinoma • Treatment is complex Oral squamous cell carcinoma (OSCC) is among the ten most • Treatment requires agents not readily available common cancers worldwide and seems to be increasing. The • Unclear as to the prognosis number of new mouth (oral) and oropharyngeal cancers are • The patient would be happier. currently estimated to be 300,000 cases worldwide,

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Table 3: Potentially malignant oral lesions

Lesion Aetiology Features

Erythroplasia Tobacco/alcohol Flat red plaque

Leukoplakia Tobacco/alcohol White or speckled plaque

Proliferative verrucous Tobacco/alcohol/ White or speckled or human papillomavirus (HPV) nodular plaque

Sublingual keratosis Tobacco/alcohol White plaque

Actinic Sunlight White plaque/erosions

Lichen planus Idiopathic White plaque/erosions

Submucous fibrosis Areca nut Immobile mucosa

Discoid Idiopathic White plaque/erosions

Chronic candidosis Candida albicans White or speckled plaque

Syphilitic leukoplakia Syphilis White plaque

Atypia in papillomavirus White or speckled plaque immunocompromised patients

Dyskeratosis congenita Genetic White plaques

Paterson-Kelly syndrome Iron deficiency Post-cricoid web (sideropenic dysphagia; Plummer-Vinson syndrome)

amounting to around 3% of total cancers. OSCC is seen Some other potentially malignant (precancerous) predominantly in males but the male: female differential is conditions include: decreasing. OSCC is seen predominantly in the elderly but is • (mainly seen on the lower lip) increasing in younger adults. • (mainly the non-reticular type) • Submucous fibrosis (mainly in users of areca nut) Potentially malignant states • Rarities such as: Some potentially malignant (precancerous) lesions, which • Dyskeratosis congenita can progress to OSCC, include especially (Table 3): • Discoid lupus erythematosus • Erythroplasia ( (Scully, 2003)), - this is the • Paterson-Kelly syndrome (sideropenic most likely lesion to progress to carcinoma, and is very dysphagia; Plummer-Vinson syndrome). dangerous • Leukoplakias (Scully, 2003), particularly: Predisposing factors (risk factors) • Nodular leukoplakia OSCC is most common in older males, in lower socio- • Speckled leukoplakia economic groups and in ethnic minority groups. In the • Proliferative verrucous leukoplakia developed world, OSCC is seen especially in tobacco and • Sublingual leukoplakia alcohol users. • Candidal leukoplakia Tobacco releases a complex mixture of at least 50 • Syphilitic leukoplakia compounds including polycyclic aromatic hydrocarbons

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Table 4: A TNM classification of malignant neoplasms

Primary tumour size (T) Tx No available information T0 No evidence of primary tumour Tis Only carcinoma in situ T1, T 2, T 3, T 4 Increasing size of tumourb

Regional involvement (N) Nx Nodes could not or were not assessed N0 No clinically positive nodes N1 Single clinically positive homolateral node less than 3cm in diameter N2 Single clinically positive homolateral node 3cm t6 cm in diameter, or multiple clinically positive homolateral nodes, none more than 6cm in diameter N2a Single clinically positive homolateral node 3-6cm in diameter N2b Multiple clinically positive homolateral nodes,none more than 6cm in diameter N3 Massive homolateral nodes (s), bilateral nodes, or contralateral node (s) N3a Clinically positive homolateral node(s), one more than 6cm in diameter N3b Bilateral clinically positive nodes N3c Contralateral clinically positive node(s)

Involvement by distant metastases(M) Mx Distant metastasis was not assessed M0 No evidence of distant metastasis M1, M 2, M 3 Distant metastasis is present. Increasing degrees of metastatic involvement, including distant nodes

a Several other classifications are available, e.g. STNM (S = site). b T 1 maximum diameter 2 cm; T 2 maximum diameter of 4 cm; T 3 maximum diameter over 4cm. T 4 massive tumour greater than 4cm diameter, with involvement of antrum, pterygoid muscles, base of tongue or skin

such as benzpyrene, nitrosamines, aldehydes and Other factors aromatic amines. Neither do all tobacco/alcohol users develop cancer, and Alcohol (ethanol) is metabolised to acetaldehyde, which equally nor do all patients with cancer have these habits. may be carcinogenic. Nitrosamine and urethane The predisposition to OSCC is thus attributed mainly to contaminants may also be found in some alcoholic drinks. specific risk factors such as tobacco and alcohol, but other Betel quid often contains betel vine leaf, betel (areca) factors, which may also play a part, include: nut, catechu, and slaked lime together with tobacco. • Deficiencies of vitamins A, E or C Some 20% of the world’s population use betel. In persons • An impaired ability to metabolise carcinogens and/or from the developing world, OSCC is seen not only in • An impaired ability to repair DNA damaged by tobacco or alcohol users but particularly in betel quid carcinogens and micro-organisms such as candida and users. Various other chewing habits, usually containing human papillomaviruses (HPV). For example, HPV are tobacco, are used in different cultures (e.g. Qat, especially implicated in tonsillar carcinoma. Shammah, Toombak). • Actinic radiation may predispose to lip cancer.

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Table 5: Prognosis for intraoral carcinoma

Stage TNM Approximate % survival at five years 1 T1 N0 M0 85 11 T2 N0 M0 65 111 T3 N0 M0 T1, T2 or T3 N1 M0 40

1V Any T4,N2,N3 or M1 10

Adapted from Sciubba (2001)

• Immune defects may predispose to OSCC, especially lip second primary tumour rather than a recurrence of the cancer, which is increased in, e.g. immunosuppressed initial primary. renal transplant recipients. Diagnosis Pathogenesis Management of early cancers appears to confer survival OSCC arises as a consequence of multiple molecular advantage and is also associated with less morbidity and events causing genetic damage affecting many needs ess mutilating surgery. Thus it is important to be chromosomes and genes, and leading to DNA changes. suspicious of oral lesions - particularly in patients at high The accumulation of genetic changes leads to cell risk, such as older males with habits such as the use of dysregulation to the extent that growth becomes tobacco, alcohol or betel. There should thus be a high autonomous and invasive mechanisms develop - this is index of suspicion, especially of a solitary lesion. Clinicians carcinoma. should be aware that single ulcers, lumps, red patches, or white patches - particularly if any of these are persisting Clinical Features for more than three weeks may be manifestations of Most oral cancer is carcinoma on the lower lip; the other malignancy. main site is the postero-lateral border/ventrum of the Frank tumours should be inspected and palpated to tongue (Table 3). determine extent of spread; for tumours in the posterior OSCC may present as a red lesion (erythroplasia); a tongue, examination under general anaesthetic by a granular ulcer with fissuring or raised exophytic margins; specialist may facilitate this. a white or mixed white and red lesion; a lump sometimes The whole should also be examined as with abnormal supplying blood vessels; an indurated there may be widespread dysplastic mucosa (‘field lump/ulcer i.e. a firm infiltration beneath the mucosa; a change’) or even a second neoplasm, and the cervical non-healing extraction socket; a lesion fixed to deeper lymph nodes and rest of the upper aerodigestive tract tissues or to overlying skin or mucosa; or cervical lymph (mouth, nares, pharynx, larynx, oesophagus) must be node enlargement, especially if there is hardness in a examined. lymph node or fixation. OSCC should be considered where any of these features persist for more than three Investigations weeks. An incisional is invariably required. The biopsy It is important to note that in patients with OSCC, a should be sufficiently large to include enough suspect and second primary neoplasm may be seen elsewhere in the apparently normal tissue to give the pathologist a chance upper aerodigestive tract in up to 25% over three years. to make a diagnosis and not to have to request a further Indeed, many patients treated for OSCC succumb to a specimen. Since red rather than white areas are most

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likely to show dysplasia, a biopsy should be taken of the cancer is suspected. Patient communication and former. Some authorities always take several at information are important. If the patient is to be referred the first visit in order to avoid the delay and aggravation to a specialist for a diagnosis and insists (rightly) on a full resulting from a negative pathology report in a patient explanation as to why there is a need for a second who is strongly suspected as suffering from a malignant opinion, it is probably better say that you are trained more neoplasm. Attempts to clinically highlight probably to be suspicious but hope the lesion is nothing to worry dysplastic areas before biopsy, e.g. by the use of about, though you would be failing in your duty if you did chemiluminescence, toluidine blue dye and other vital not ask for a second opinion. However, you should leave stains, may be of some help where there is widespread discussion of actual diagnosis, treatment and prognosis to ‘field change’. Molecular techniques and DNA ploidy are the specialist concerned, as only they are in a position to being introduced for prognostication in potentially give accurate facts to the patient concerned. malignant lesions and tumours, and to identify nodal Cancer treatment and planning involves a team including metastases. a range of specialities including surgeons, anaesthetists, It is essential to determine whether bone or muscles are oncologists, nursing staff, dental staff, nutritionists, speech involved or if metastases - initially to regional lymph nodes and physiotherapists, and others. Increasingly, Head and and later to liver, bone and brain - are present. Imaging Neck Tumour Boards are being developed along with Cancer may be needed. Another important aspect in planning Networks to facilitate the collaboration of providers of cancer treatment is to determine if there is malignant disease services to provide seamless care based on best practice (see elsewhere, particularly whether other primary tumours are http://www.eastman.ucl.ac.uk/hntb/index.html). Consensus present, and therefore endoscopy may be necessary. guidelines to treatment are now being published. Finally, the specialist also needs to ensure that the OSCC is now treated largely by surgery and/or patient is as prepared as possible for the major surgery radiotherapy to control the primary tumour and required, particularly in terms of general anaesthesia, metastases in cervical lymph nodes. Treatment and potential blood loss and ability to metabolise drugs, and prognosis depend on the TNM classification (Tables 4 & 5). to address any potential medical, dental or oral problems The planning phase includes discussions regarding pre-operatively, to avoid complications. Therefore almost restorative and surgical interventions required before invariably indicated are: cancer treatment, including osseointegrated implants and • Medical examination jaw and occlusal reconstruction and therapy is also • Biopsy of equivocal neck lymph nodes planned to avoid post-operative complications. As much • Jaw and chest radiography oral care as possible should be completed before starting • MRI or CT cancer treatment. • Electrocardiography Oral care is especially important when radiotherapy is to • Blood tests be given, since there is a liability particularly to mucositis, xerostomia and other complications, and a risk of Selected patients may also need: osteonecrosis - the initiating factor for which is often • Bronchoscopy - if chest radiography reveals lesions trauma, such as tooth extraction, or ulceration from an • Endoscopy - if there is a history of tobacco use appliance, or oral infection. • Gastroscopy - if PEG (per-endoscopic gastrostomy) is to be used for feeding post-surgery Orofacial granulomatosis • Liver ultrasound – to exclude metastases Orofacial granulomatosis (OFG) is an uncommon but • Doppler duplex flow studies and angiography: to help increasingly recognised condition seen mainly in in planning free flaps for reconstruction. adolescents and young adults which usually manifests with facial and/or labial swelling, but which can also Management manifest with angular and/or cracked , If you are concerned, phone, email or write for an urgent ulcers, mucosal tags, cobble-stoning, or gingival swelling specialist opinion, which is indicated if you feel a diagnosis (Table 4). A minority of patients with similar features have of cancer is seriously possible or if the diagnosis is unclear. gastrointestinal Crohn’s disease, swelling or have One of the most difficult clinical situations in which sarcoidosis. clinicians find themselves is with the patient in whom The aetiology of OFG is unknown but there may be an

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HLA association (A3, B7, DR2). In some there is a gingiva, hyperplastic folds of the oral mucosa (thickening postulated reaction to food or other (particularly and folding of the mucosa producing a ‘cobblestone-type’ to additives such as benzoates or cinnamon), or metals of appearance, and mucosal tags), ulcers (classically linear such as cobalt. Reactions to , Borrelia vestibular ulcers with flanking granulomatous masses), burgdorferi or mycobacterial stress protein mSP65 have facial swelling and . been hypothesised but not proven. Most patients appear to develop the problem in relation to dietary components Diagnosis such as chocolate, nuts, cheese or food additives. Oral biopsy, haematological, gastrointestinal and other Conditions related to OFG include Miescher’s cheilitis - investigations may be required in suspected Crohn’s where lip swelling is seen in isolation, and Melkersson- disease especially to exclude sarcoidosis. Specialist care is Rosenthal syndrome- where there is facial swelling with usually indicated. Histologically, the epithelium is intact and facial palsy. but thickened, with epithelioid cells and giant cells surrounded by a lymphocytic infiltration. Diagnosis Diagnosis is clinical, supported by blood tests, endoscopy, Management imaging and biopsy to differentiate from Crohn’s disease, Topical or intralesional corticosteroids may effectively sarcoidosis, and foreign body reactions. control the oral lesions but more frequently systemic Specialist care is usually indicated. corticosteroids, azathioprine or salazopyrine are required.

Management Reference Management is to eliminate allergens such as chocolate, Scully C (2003). Oral medicine for the General Practitioner, part four: white nuts, cheese or food additives and treat lesions with colour. Independent Dentistry 8(1) (to be published) intralesional corticosteroids or occasionally systemic clofazimine or sulphasalazine. Further reading Mashberg A and Samit A (1995). Early diagnosis of Crohn’s disease asymptomatic oral and oropharyngeal squamous cancers. Crohn’s disease is a chronic inflammatory idiopathic CA Cancer J Clin 45: 328-351 granulomatous disorder. Many causal factors have been Prince S, Bailey BM (1999). Squamous carcinoma of the hypothesised, one of the most recent being that it may be tongue: review. Br J Oral Maxillofac Surg 37: 164-174 caused by Mycobacterium paratuberculosis. This remains Sciubba JJ (2001). Oral cancer. The importance of early to be proved. Crohn’s disease affects mainly the small diagnosis and treatment. Am J Clin Dermatol 2: 239-251 intestine (ileum) but can affect any part of the Scully, C, Ward-Booth, P (1995). Detection and gastrointestinal tract, including the mouth. There may also treatment of early cancers of the oral cavity. Crit Rev be features of gastrointestinal involvement such as Oncol Hematol 21: 63-75 abnormal bowel movements, pain, or weight loss. Scully C, Porter SR (2000). Orofacial Disease; update for About 10% of patients with Crohn’s disease of the the dental clinical team: 11. . bowel have oral lesions. Oral lesions may be seen in the Dental Update 27: 44-47 absence of any identifiable gut involvement and are the Silverman S (1994). Oral cancer. Semin Dermatol 13: same as those seen in OFG - reddish raised lesions on the 132-137

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