Chapter 3 Oral Cavity 3 J.W. Eveson Contents 3.1 Embryonic Rests and Heterotopias . 72 3.5.4 Addison Disease . 88 3.1.1 Fordyce Granules/Spots . 72 3.5.5 Peutz Jeghers Syndrome . 89 3.1.2 Juxtaoral Organ of Chievitz . 72 3.5.6 Racial Pigmentation . 89 3.5.7 Laugier Hunziker Syndrome . 89 3.2. Vesiculo-Bullous Diseases . 72 3.5.8 Smoker’s Melanosis . 89 3.2.1 Herpes Simplex Infections . 72 3.5.9 Drug-Associated Oral Pigmentation . 90 3.2.2 Chickenpox and Herpes Zoster . 73 3.2.3 Hand-Foot-and-Mouth Disease . 73 3.6 Hyperplastic Lesions . 90 3.2.4 Herpangina . 74 3.6.1 Fibrous Hyperplasias . 90 3.2.5 Pemphigus Vulgaris . 74 3.6.2 Papillary Hyperplasia . 90 3.2.6 Pemphigus Vegetans . 74 3.6.3 Generalised Gingival Fibrous Hyperplasia . 91 3.2.7 Paraneoplastic Pemphigus . 75 3.6.4 Crohn’s Disease . 91 3.2.8 Mucous Membrane Pemphigoid . 75 3.6.5 Orofacial Granulomatosis . 92 3.2.9 Dermatitis Herpetiformis . 76 3.6.6 Chronic Marginal Gingivitis 3.2.10 Linear IgA Disease . 76 and Localised Gingival Fibrous Hyperplasia . 92 3.2.11 Erythema Multiforme . 77 3.6.7 Peripheral Giant Cell Granuloma (Giant Cell Epulis) . 93 3.3 Ulcerative Lesions . 77 3.6.8 Pyogenic Granuloma . 93 3.3.1 Aphthous Stomatitis 3.6.9 Pulse (Vegetable) Granuloma . 93 (Recurrent Aphthous Ulceration) . 77 3.3.2 Behçet Disease . 78 3.7 Benign Tumours and Pseudotumours . 94 3.3.3 Reiter Disease . 78 3.7.1 Giant Cell Fibroma . 94 3.3.4 Median Rhomboid Glossitis . 78 3.7.2 Lingual Th yroid . 94 3.3.5 Eosinophilic Ulcer 3.7.3 Verruciform Xanthoma . 95 (Traumatic Ulcerative Granuloma 3.7.4 Haemangiomas . 95 with Stromal Eosinophilia) . 79 3.7.5 Lymphangioma . 95 3.3.6 Acute Necrotising Ulcerative Gingivitis . 79 3.7.6 Benign Nerve Sheath Tumours . 95 3.3.7 Wegener’s Granulomatosis . 80 3.7.6.1 Neurofi broma . 96 3.3.8 Tuberculosis . 81 3.7.6.2 Schwannoma . 96 3.7.6.3 Neurofi bromatosis . 96 3.4 White Lesions . 81 3.7.6.4 Multiple Neuromas 3.4.1 Candidosis . 81 in Endocrine Neoplasia Syndrome . 96 3.4.2 Lichen Planus . 82 3.7.7 Granular Cell Tumour 3.4.3 Lupus Erythematosus . 83 (Granular Cell Myoblastoma) . 96 3.4.4 Oral Epithelial Naevi . 84 3.4.5 Smoker’s Keratosis . 84 3.8 Squamous Cell Carcinoma . 96 3.4.6 Stomatitis Nicotina . 84 3.8.1 Introduction . 96 3.4.7 Hairy Tongue . 85 3.8.2 Clinical Features . 97 3.4.8 Hairy Leukoplakia . 85 3.8.2.1 Buccal Mucosa . 97 3.4.9 Geographic Tongue . 85 3.8.2.2 Tongue . 97 3.4.10 Frictional Keratosis . 86 3.8.2.3 Floor of Mouth . 97 3.8.2.4 Gingiva and Alveolar Ridge . 97 3.5 Pigmentations . 86 3.8.2.5 Hard Palate . 98 3.5.1 Amalgam Tattoo . 86 3.8.2.6 Retromolar Trigone . 98 3.5.2 Localised Melanotic Pigmentation . 86 3.8.3 Staging . 98 3.5.2.1 Oral Melanotic Macules . 86 3.5.2.2 Melanoacanthoma . 87 References . 98 3.5.2.3 Pigmented Naevi . 87 3.5.3 Premalignant Oral Melanoses and Oral Melanoma . 87 72 J.W. Eveson 3.1 Embryonic Rests 3.2 Vesiculo-Bullous Diseases and Heterotopias 3.2.1 Herpes Simplex Infections 3.1.1 Fordyce Granules/Spots Herpes simplex is a common virus that often causes 3 Fordyce granules are ectopic sebaceous glands in the subclinical infections. It is, however, a cause of serious oral mucosa [39, 119]. They appear as soft, creamy white and sometimes fatal illnesses in immunocompromised or yellowish spots or clusters, typically a few millime- patients. In the orofacial tissues, clinically apparent in- tres in diameter. They are symmetrically distributed fections can be primary or recurrent. The majority of and tend to increase in size and number with age. The cases of oral infections are due to Herpes simplex type main site is the buccal mucosa, but they may also involve 1, but an increasing proportion is being attributed to the vermilion border and labial mucosa, particularly in Herpes simplex type 2, which is typically more closely the upper lip. More rarely, the tongue, palatoglossal fold, associated with genital infections. The virus is trans- tonsil and other intraoral sites may be affected, and the mitted by close contact. Although in the past primary condition can then be confused with other lesions. Mi- herpes affected children most frequently, in Western croscopy shows typical sebaceous glands opening di- societies it is seen increasingly in young and middle- rectly onto the surface by short, keratinised ducts with aged adults. no associated hair follicles. Primary herpes infection (primary herpetic gingivo- stomatitis) is characterised by widespread vesicular le- sions of the oral mucosa [183]. Any site may be involved, 3.1.2 Juxtaoral Organ of Chievitz but the hard palate and the dorsum of the tongue are the most common locations. The vesicles quickly rup- Chievitz’s organ, or the bucco-temporal organ, is ture to leave shallow, painful, sharply demarcated ulcers thought to be a vestigial neuroepithelial structure. It has that are 1–2 mm in diameter and have an erythematous also been suggested that the juxtaoral organ is an anlage halo. Ulcers frequently coalesce to form more irregular of the parotid gland, or arises from Schwann cells that lesions. Gingivitis is a very characteristic feature of pri- have undergone squamous metaplasia [132]. It has been mary herpes. The gingivae are swollen and often strik- demonstrated in neonates and children and can persist ingly erythematous, even in the absence of frank ulcer- into adult life [16]. The organ is usually found between ation. There is often conspicuous cervical lymphade- the temporalis muscle and the bucco-temporal fascia or nopathy, together with mild fever and malaise. Oral le- pterygomandibular raphe, and is usually present bilater- sions usually resolve spontaneously within 1–2 weeks. ally. It is seen fortuitously, generally in material taken About a third of patients infected with Herpes simplex, from surgical resections, and is important as it can be either clinically or sub-clinically, are susceptible to re- misinterpreted as a squamous cell carcinoma. Very rare current infections. cases have presented as tumours in the infratemporal It is uncommon for herpetic lesions to be biopsied fossa [83]. It is usually only a few millimetres in size and (Fig 3.1). In the early stages there is intercellular oede- microscopically forms a multilobulated mass of discrete ma and ballooning and vacuolisation of keratinocytes cell nests that resemble squamous epithelium, but do not due to intracellular oedema. This leads to intraepithe- show obvious keratinisation. Occasionally, the cells have lial vesiculation. Nuclei become enlarged, and occasion- clear cytoplasm and form duct-like structures that may ally basophilic or eosinophilic nuclear inclusions with contain mucin-negative colloid. The cell nests are associ- a clear halo ( Lipschutz bodies) can be identified. Cells ated with nerve fibres, particularly at the periphery, and may fuse to form multinucleated epithelial giant cells. this may be mistakenly interpreted as a squamous car- The vesiculation is followed rapidly by epithelial necro- cinoma with perineural involvement, or sometimes mu- sis and breakdown, leading to ulceration and more flor- coepidermoid carcinoma and thyroid carcinoma [103]. id inflammatory infiltration. The central areas of the epithelial cell nests are positive Herpes simplex virus can persist in a latent form in for cytokeratin 19 and most cell nests are positive for the trigeminal ganglion and when re-activated causes vimentin and weakly positive for epithelial membrane recurrent infections. These are typically seen at the antigen. They are negative for S-100 protein, glial acidic mucocutaneous junctions of the mouth or nasal cavi- fibrillary protein, and neuroendocrine markers such ty, and involvement of the lips, the most common site, as chromogranin, synaptophysin and neurone-specific is called herpes labialis. A variety of apparently dis- enolase [132]. A similar appearance to the juxtaoral or- parate factors can trigger re-activation, including the gan has rarely been described elsewhere in the mouth, common cold (“fever blister”), exposure to sunlight, including intraosseous locations [47]. menstruation, stress and others. There is usually a brief prodromal burning or prickling sensation in the Oral Cavity Chapter 3 73 affected area, followed by the formation of a localised cluster of vesicles. These rapidly break down, ulcerate and crust. The lesions usually heal spontaneously in 1–2 weeks. Occasionally there may be intraoral recur- rences, particularly in the hard palate. These may be triggered by local anaesthetic injections. Persistent- ly recurrent intraoral herpes, however, should always raise the possibility of immunosuppression. Atypical and often very severe forms of intraoral herpes infec- tions can be seen in patients who are immunocompro- mised [21]. Fig. 3.1. Primary herpetic stomatitis showing intercellular vacu- 3.2.2 Chickenpox olation and multinucleated epithelial cells and Herpes Zoster Chickenpox is a highly contagious infection caused by the herpes virus Varicella zoster. It is typically seen in cerate and crust over, which may take several weeks, children where it causes crops of pruritic cutaneous especially if there is suppuration and subsequent scar- vesicles. It is usually transmitted by direct contact and ring. In these circumstances a significant number of has an incubation period of 2–3 weeks. The exanthem is patients develop the most unpleasant consequence of frequently preceded by a slight fever, malaise and mild post-herpetic neuralgia. headache. The cutaneous lesions start as an itchy macu- lar rash, which progressively becomes vesicular and pustular before breaking down to form focal crusting 3.2.3 Hand-Foot-and-Mouth Disease lesions.