Chapter 76. Biology and Pathology of the Oral Cavity

The mouth is the beginning of the aerodigestive tract and an extension of the skin barrier. It plays an important role in mastication, deglutition and digestion, speech, and immunologic defense. The oral mucosa, salivary glands (both major and minor), jawbones, and teeth are frequently the site of primary inflammatory or neoplastic disease. However, the oral cavity may present with manifestations of systemic disease and in some cases, oral findings may precede systemic signs and symptoms by months or years. Lesions in the maxillary sinus and nasal cavity may lead to pain in the upper teeth or may extend inferiorly and present in the maxilla or palate. Metastatic lesions may present as nodules on the gingiva or masses in the jawbones.

This chapter focuses only on the more common mucosal and salivary gland diseases encountered in dermatology practice.

As with evaluation of the skin, obtaining a comprehensive medical and medication history and careful inquiry into current symptoms are essential. The extraoral examination should begin with an examination of the skin of the face and in particular the perioral region, palpation of the submandibular and submental lymph nodes, and palpation of the temporomandibular joints for clicking or pain on opening. Clicking with no pain occurs in 20%–30% of the population and is of no clinical significance but should be noted. Clicking with pain and/or limitation of opening may indicate temporomandibular joint myofascial pain syndrome and requires referral to a dental specialist for management.

The intraoral examination should be directed to the following areas:

1. The mucosal surfaces as outlined above, taking note of where the lesions are located, and in particular, whether they are on the keratinized or nonkeratinized sites.

2. The presence or absence of saliva in the floor of mouth and whether the saliva is of the usual watery consistency or whether it is ropey.

3. The dentition and whether there are grossly carious teeth.

4. The use of a removable prosthesis (upper and/or lower dentures—complete or partial); this is particularly important for some mucosal diseases caused by denture trauma and for the diagnosis and treatment of candidiasis since the denture acts as a fomite.

There are several structures in the oral mucosa that are considered variations of normal. These include:

1. Fordyce granules: These are sebaceous glands that present as painless yellow papules, 1–2 mm in diameter located in a bilateral symmetric fashion on the posterior buccal mucosa, and lips (usually vermilion) (Fig. 76-1). Sebaceous hyperplasia of these glands may form discrete larger yellow papules several millimeters in size.

2. Linea alba: This is a linear keratosis located on the buccal mucosa bilaterally where the upper and lower teeth meet. It is a form of frictional keratosis and exaggeration of this is seen in patients who habitually chew the buccal mucosa, a condition known as morsicatio mucosae oris (MMO) (see below).

3. Palatal and mandibular tori: These are benign, usually symmetric exostoses that are present in the midline of the hard palate or bilaterally on the lingual aspect of the mandible (Fig. 76-2). They may be large and multilobated, but patients are usually unaware of their presence.

Topical Steroids

Topical steroids are the mainstay of treatment for many inflammatory and autoimmune mucosal diseases.1 The only topical steroid that is FDA-approved for intraoral use is Kenalog-in-Orabase dental paste (0.1% triamcinolone; Apethecon, Princeton, NJ). This is a Class IV steroid and is weakly efficacious as an anti-inflammatory agent in the oral cavity, although the Orabase (methylcellulose) is useful and soothing as a covering agent in some conditions. In general, most oral medicine specialists use fluocinolone, fluocinonide, clobetasol, and topical tacrolimus for the management of mucosal disease. Principles applying to use of these medications in the oral cavity regardless of specific diagnosis are found in Table 76-1 and eBox 76-0.1.

Topical Analgesics

Viscous lidocaine (2%) may be used alone or combined with diphenhydramine, Kaopectate (Pfizer, NY), or Maalox (Novartis, NJ) in equal volumes as a swish and spit out preparation for pain control. This is particularly useful for diffuse painful lesions, acute or chronic.

Localized ulcers may be treated with over-the-counter benzocaine preparations, or covering agents such as methylcellulose (Orabase; Colgate-Palmolive, NY).

As with any disease condition, provision of up-to-date information on the disease allays many fears and misconceptions, empowers patients, and helps patients to better understand their condition. Information on the nature, management, and prognosis of common mucosal conditions are available on the Web sites of the American Academy of Oral and Maxillofacial Pathology (www.aaomp.org) and the American Academy of Oral Medicine (www.aaom.com). These can be modified to suit your practice needs.

Systemic diseases often have distinctive presentations in the oral cavity and many skin conditions also have concomitant oral findings. eTable 76-1.1 provides a list of some of the more common systemic diseases and syndromes that present with oral findings. Some are discussed in greater detail below.

The disease entities to be described are those normally treated by the dermatologist and are divided primarily into how the lesions present clinically (e.g., ulcers, nodules, or red and white lesions). However, there is also a section based on lesions that are site-specific. Pathogenetic mechanisms for diseases such as the autoimmune bullous disorders will not be discussed in any detail since they are presented elsewhere in this book.

Ulcerative Conditions

The oral ulcer appears as a yellow–white papule or plaque of fibrin (often referred to as a “pseudomembrane”), usually with a surrounding red rim. It does not appear crusty because of the wet environment. Such lesions are always painful unless the ulcer represents a squamous cell carcinoma (SCC), which is often painless. Several conditions fall into this category and only the most common will be discussed here (eTable 76-1.2).

Recurrent Aphthous Ulcers/Stomatitis (“Canker Sores”)

Recurrent aphthous ulcer (RAU) is a T-cell-mediated disorder and tumor necrosis factor (TNF)-α plays an important role in its occurrence.2 There is usually a family history of aphthous ulcers and there is a significant association with a number of HLA-haplotypes.3 Stress, systemic illness, and local trauma predisposes to their occurrence in susceptible individuals.

Aphtheiform ulcers are aphthous-like in their appearance and history but they may occur sometimes on the dorsum of the tongue if they are a result of hematinic deficiency or inflammatory bowel disease. RAU are seen in all patients with Behçet disease and may precede other findings by years. Behçet disease, a vasculitic disorder, has a predilection for Turkish and Japanese populations and is associated with an increase in HLA-B51.4 In periodic fever-adenopathy, pharyngitis, aphthae (PFAPA) syndrome, ulcers are often so severe that children miss days at school.5,6 Patients with other systemic or skin conditions and aphthous ulcers form part of the “complex aphthosis” syndrome and include those with MAGIC (mouth and genital ulcers with inflamed cartilage) syndrome (eTable 76-1.2). Approximately 3% of patients with RAU have gluten-sensitive enteropathy7 and some show sensitivity to foods and sodium lauryl sulfate.

Clinical Findings

Idiopathic RAU occurs in 15%–20% of the population beginning in the second decade of life and the disease generally becomes less severe over the age of 50. Patients often report the sensation of a small nodule beneath the epithelium before the ulcer appears. The painful yellow–white ulcers are surrounded by an erythematous halo.

There are four clinical forms of RAU and these are always painful:

1. Minor ulcers (<1 cm, 1–10 at each episode lasting 1–2 weeks) (Fig. 76-3A); this is by far the most common form.

2. Major ulcers (>1 cm lasting several weeks and healing with scarring) (Fig. 76-3B).

3. Herpetiform ulcers (<1 cm, usually 0.1–0.5 cm each, >10 clustered ulcers at each episode, lasting 1–2 weeks (Fig. 76-3C).

4. Severe aphthous ulcers where patients have minor ulcers but with continuous ulcerations with minimum or no ulcer-free days for months.

Idiopathic RAU are almost always confined to the nonkeratinized mucosa. They may occur on the nonattached gingiva, but generally do not cross the mucogingival junction onto the attached gingiva, except in some cases of RAU major.

Differential Diagnosis and Laboratory Studies

Traumatic lesions must be considered because the oral cavity is subject daily to mechanical trauma (such as mastication) (eTable 76-1.2). However, traumatic ulcers are not the same as RAU, although patients with RAU readily develop ulcers at sites of trauma. A history of trauma and the nonepisodic nature of the condition help to differentiate between traumatic ulcers and those of RAU. Chemotherapy-associated ulcers are not generally considered aphthous ulcers but rather chemotherapy- and neutropenia-associated (similar to cyclic neutropenia); they also tend to occur on the nonkeratinized mucosa. Herpetic ulcers in healthy patients occur intraorally on the keratinized mucosa of the gingival margin and the palate. However, in immunocompromised patients, they may resemble RAU, especially RAU major in patients with HIV disease. Culture and biopsy (Box 76-1) are indicated in such patients. Lesions of chronic recurrent oral erythema multiforme must also be considered in the differential diagnosis. Oral manifestations of Crohn disease and other gastrointestinal conditions are discussed below.

The biopsy is nonspecific and shows only a fibrin membrane with acute and chronic inflammation and granulation tissue, but may exclude an infectious etiology.

Management and Prognosis

Any positive findings should be followed up. For example, it may be useful to keep a food diary and to change toothpaste to one that does not contain sodium lauryl sulfate. In most cases, the work-up is negative.

The treatment for minor RAU is topical steroids (Table 76-1) or intralesional steroid injection if the ulcers are large and persistent, especially those of aphthous major or in patients with HIV disease. Topical agents that may be useful include cyanoacrylate (Soothe-N-Seal; Colgate Palmolive, NY) and anti-inflammatory agents such as amlexanox 5% paste (Aphthasol, Uluru, Texas), 2 mg amlexanox mucoadhesive disc (Oradisc, Uluru, Texas), or tetracycline oral rinse. Lesions may also be cauterized with 28%–50% sulfuric acid and sulfonated phenolics (Debacterol, Epien Medical Inc.) or with silver nitrate (shaving sticks). Topical anesthetics in paste form are available over-the-counter, in particular benzocaine of varying strengths. Systemic therapy with prednisone for a few weeks and maintenance with pentoxifylline may reduce the number, duration and size of ulcers, and reduce the number of episodes. In appropriate patients, thalidomide therapy is extremely effective, although patients often develop irreversible neuropathy with long-term use. Other agents that are variably efficacious include colchicine and azathioprine.

Oral Ulcerative Lesions Associated with Gastrointestinal Disease

Clinical Findings

The most common bowel diseases associated with oral ulcers are Crohn disease, ulcerative colitis, malabsorption syndromes leading to hematinic deficiency, and celiac disease.8

Oral lesions are seen in up to 20% of patients with Crohn disease if nonspecific mucogingivitis is excluded.9 Ulcers of Crohn disease typically present as linear lesions along the maxillary and mandibular vestibule/sulcus (Fig. 76-4A). In addition, patients often also present with papulous folds of tissues, swelling of the lips (indistinguishable from cheilitis granulomatosa), and cobblestoning of the mucosa.10 Other manifestations of Crohn disease include severe and diffuse erythema and inflammation of the mucosa, sometimes associated with Staphylococcus aureus infection (Fig. 76-4B).11 A reliable finding is a dusky-red firm area of the perivermilion skin that has a slight pitted, “orange peel” appearance.

Pyostomatitis vegetans (oral analog of pyoderma gangrenosum) associated with inflammatory bowel disease presents as “snail-track” ulcers of the oral mucosa.12 Dental enamel defects (enamel hypoplasia) are associated with celiac disease in children.13

Differential Diagnosis and Laboratory Studies

Oral ulcers ultimately associated with inflammatory bowel disease may predate gastrointestinal lesions by years in up to 60% of patients,10 so that absence of gastrointestinal symptoms does not exclude this etiology. Elevated tissue transglutaminase and the presence of endomysial antibodies support the diagnosis of celiac disease.

A biopsy of oral lesions of Crohn disease shows granulomatous inflammation or while pyostomatitis vegetans shows acantholysis.

Management and Prognosis

In the absence of gastrointestinal findings, treatment is with topical steroid therapy and in severe cases, prednisone for rapid control of lesions with maintenance on topical steroids or other anti-inflammatory agents similar to the protocol for management of idiopathic aphthous ulcers.14 If gastrointestinal disease is active, this should be brought under control first and oral ulcers may then resolve.

Oral manifestations generally wax and wane with the severity of systemic disease.

Chemotherapy-Associated Ulcerative Mucositis

Damage from chemotherapy agents is mediated via production of cytokines, cytokine modulators, and stress responders, leading to apoptosis of dividing epithelial cells.15 Ulcers are potential portals for bacteremia and septicemia, particularly because patients are also often neutropenic. Depending on the regimen, 25%–30% of patients develop this complication. Agents often associated with such lesions include cytarabine and cisplatin, especially when combined with radiation.

Clinical Findings

These ulcers are generally located on the nonkeratinized sites and in particular the buccal mucosa and ventral tongue. They begin within 3–5 days of the start of chemotherapy and generally resolve when absolute neutrophil counts recover, usually a course of 7–10 days. Lesions are extremely painful and may measure several centimeters in size.16

Differential Diagnosis and Laboratory Studies

Recrudescent herpes simplex virus (HSV) infection is common in immunocompromised patients such as patients with cancer and, unlike in healthy hosts, often occurs on nonkeratinized sites. Hence, patients who undergo hematopoietic stem cell transplantation, if seropositive for HSV antibodies, are prophylactically placed on antiviral agents during their hospital course. However, a positive culture may represent shedding of HSV in the oral fluids and saliva rather than true recrudescence within the ulcers.

Deep fungal infections and cytomegalovirus infection may all present with large ulcers on the mucosa, but these generally do not heal with recovery of neutrophil counts.

Radiation to the head and neck leads to severe erythema, inflammation, and ulceration (radiation mucositis).17,18

In patients who have received allogenic hematopoietic transplants, persistence of oral ulcers after engraftment may herald the development of acute graft-versus-host disease. In such situations, involvement of the keratinized tissues of the tongue dorsum and hard palate is not uncommon.

Management and Prognosis

Ulcers are self-limiting and therapy is directed toward pain control and prevention of septicemia from bacterial ingress into the oral wounds.19 Patients are often treated with granulocyte-colony-stimulating factor to reduce the period of neutropenia and this has reduced the frequency of such ulcers.

Topical analgesia such as viscous lidocaine and systemic analgesia (especially narcotics) is the mainstay of pain control. Although chlorhexidine is often used for decontamination, its high alcohol content makes patient compliance poor. Other oral decontamination rinses contain nystatin and antibiotics.

Traumatic Ulcerative Granuloma (Traumatic Ulcerative Granuloma with Stromal Eosinophilia, Eosinophilic Ulcer of the Tongue)

Clinical Findings

Laboratory Studies and Differential Diagnosis

Management and Prognosis

Ulcerative Viral Infections

Differential Diagnosis and Laboratory Studies

Management and Prognosis

Deep Fungal Infections

Zygomycosis is a broad term used to describe fungal infections caused by organisms in the phylum Zygomycota. These include infections caused by organisms in the family Mucorales with organisms in the genera Mucor and Rhizopus. These are unusual infections, seen usually in patients who have diabetes mellitus (usually ketoacidotic) or are immunocompromised, and are often life threatening. Organisms are inhaled and spread into the adjacent sinuses, eroding through the bone, sometimes presenting on the palate as a necrotic ulcer, a condition also referred to as rhinocerebral zygomycosis.29 Aspergillus infections are seen in neutropenic patients, especially those with leukemia and tend to present as necrotic soft tissue and bony lesions of the gingiva, while histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis are seen in areas where such infections are endemic such as in South America and in patients with HIV/AIDS.30–33

Clinical Findings

Unlike candidiasis, deep fungal infections usually present as necrotic ulcers because they are angioinvasive organisms that cause vascular thrombosis and ischemia. The most common location for rhinocerebral zygomycosis is the palate, although fungal infections in immunocompromised patients may occur at any site in the mouth.

Differential Diagnosis and Laboratory Studies

Deep fungal infections involving the palate or maxilla are an important differential diagnosis for the clinical entity “midline destructive disease.” Other conditions that fall into this category include NKT-cell lymphoma, other infections such as tertiary syphilis, granulomatosis with polyangiitis (Wegener disease), cocaine use, and epithelial malignancy of surface or salivary gland origin.34 A biopsy readily distinguishes among these entities.

Because these are deep infections, a swab culture may not capture any organisms. A biopsy shows the presence of hyphae. It is useful to submit part of the harvested tissue in saline for speciation in a microbiology laboratory.

A biopsy shows necrosis and inflammation. The morphology of hyphae seen on special stains, together with culture results, confirms the diagnosis.

Management and Prognosis

Treatment is with systemic antifungal agents such as liposomal amphotericin and triazole antifungal agents such as fluconazole, itraconazole, and posaconazole, often with surgical debridement.35 Mortality is often high in poorly controlled infection. Reducing environmental exposures is a particularly important prophylactic measure for immunocompromised patients.

Ulcers from Vascular Compromise and Vasculitides

Clinical Findings

Differential Diagnosis and Laboratory Studies

Management and Prognosis

Granulomatosis with Polyangiitis (Wegener Disease)

Clinical Findings

Differential Diagnosis and Laboratory Findings

Management and Prognosis

Necrotic Bone Conditions

Clinical Findings

Differential Diagnosis and Laboratory Studies

Management and Prognosis

White Lesions

It is important to distinguish truly white lesions from ulcerated or necrotic lesions that usually have a creamy-yellow color.

Many well-recognized oral lesions are white, ranging from developmental lesions such as white sponge nevus, to infections such as candidiasis, to immune-mediated disorders such as lichen planus (LP) and to frictional keratoses such as morsicatio mucosae oris (Table 76-3). Such lesions, with specific clinical and histologic findings, are not properly termed “leukoplakia.”

True leukoplakias tend to be well demarcated at least around part of the lesion, are frequently dysplastic at first biopsy, and carry a significant potential for developing into SCC over time. White sponge nevus and reactive white lesions are discussed online.

White Sponge Nevus

White sponge nevus is an extremely rare condition, inherited in an autosomal dominant fashion. It affects the oral and genital mucosa, usually in a symmetric and often multifocal pattern, due to mutation in keratin K4 or K13 that results in keratin instability and abnormal keratin aggregation.53 Spontaneous mutations have been reported.

Clinical Findings

Patients develop poorly demarcated, diffuse, painless white plaques on the oral mucosa, usually the buccal mucosa and tongue, usually within the first two decades of life.21,54

Differential Diagnosis and Laboratory Studies

Other conditions that may appear similar clinically include hereditary benign intraepithelial dyskeratosis, another rare mucosal disorder that occurs in a racial isolate in South Carolina,55–57 and pachyonychia congenita.58–60 Oral lesions of dyskeratosis congenita are true leukoplakias occurring in approximately 65% of patients and are usually dysplastic.61,62

Biopsy or exfoliative cytology is always indicated and shows perinuclear eosinophilic condensations (representing abnormal keratin aggregation) and distinguishes it from other mucosal disorders discussed below.

Management and Prognosis

There is no treatment for white sponge nevus, although some have reported resolution with antibiotics, in particular tetracycline.63 It is postulated that tetracycline affects the keratinization process and inhibits epithelial proliferation.

Reactive White Lesions

These very common conditions are caused by very mild topical injury caused by smoking or other mild contact injury such as strong toothpastes and alcoholic mouth rinses. The following white lesions are in ascending order of severity of injury beginning with changes caused by intracellular edema and swelling to those resulting in keratoses.

Leukoedema

Many dentists classify leukoedema as a developmental malformation but it is likely a reactive lesion. It occurs in 20%–70% with habits such as using tobacco, coca, or marijuana to >90% of dark-skinned individuals mainly because the whiteness of the lesion shows up more clearly on pigmented mucosa.54,64

Clinical Findings

Lesions are usually bilateral on the buccal mucosa or ventral tongue and consist of painless, fine grayish white, opalescent reticulations. They are not well demarcated, but diffuse. Stretching the mucosa completely eliminates these fine lines since this is not a keratotic lesion, but rather caused by intracellular edema of damaged superficial keratinocytes.21

Differential Diagnosis and Laboratory Findings

Reticular LP may look similar but they are more densely white and do not disappear on stretching the mucosa.

A biopsy shows typical findings of keratinocyte edema or hydropic degeneration.

Management and Prognosis

No treatment is necessary since these lesions are benign although advice on smoking cessation may be warranted.

Contact Desquamation

This is a common oral condition, where the injury to the tissue is slightly more severe than in leukoedema causing actual degeneration and detachment of the superficial keratinocytes. The offending agents are mouthwashes and toothpastes that are caustic [in particular Listerine (Pfizer Pharmaceutical, NY) mouthwash that contains 27% alcohol as well as eucalyptol and menthol].

Clinical Findings

This is generally a condition of adults. Patients will often report that their mouth is “peeling.” Lesions present as painless sloughs of desquamated tissue that lie in thin ribbons on the mucosa and can be removed without pain or discomfort to the patient, with normal-appearing, pink underlying tissue.65 Since the keratinized tissues are somewhat protected from the adverse effects of such topical agents, it is generally the nonkeratinized tissues that are involved. A helpful sign is a background of leukoedema with faint reticulations.

Differential Diagnosis and Laboratory Studies

While some bullosing disorders may form such sloughs, those lesions are almost always painful or sensitive, and may bleed. Lack of symptoms is key to the diagnosis of this condition coupled with the typical history.

A biopsy shows desquamating strips of surface keratinocytes.

Management and Prognosis

Patients should discontinue the use of the offending dentrifrice, or change to a less caustic agent.

Morsicatio Mucosae Oris (Pathominia Mucosae Oris, Chronic Bite Injury)

This is a yet more intense local factitial injury to the oral mucosa, caused by a chewing habit, leading to reactive keratosis and benign epithelial hyperplasia. It occurs in 3% of the population.66 Any other factitial injury either from an unusual habit, or the rough edge of an appliance may lead to a similar lesion.

Clinical Findings

MMO appears as white papules and plaques on either side of the linea alba on the buccal mucosa, lower labial mucosa, or the lateral tongue, usually caused by raking of the teeth over the mucosa.67 Patients may or may not be aware of this habit (especially if this is a nighttime habit). Lesions have a shaggy, rough surface, are poorly demarcated, and occasionally may show evidence of erythema and/or ulceration where the “chewing” has been more intense (eFig. 76-5.3A and 76-5.3B).

Differential Diagnosis and Laboratory Studies

Candidiasis, some lesions of LP, hairy leukoplakia, and some leukoplakias and erythroleukoplakias may look similar but a biopsy will provide a definitive diagnosis. Such factitial injury may be superimposed upon an underlying condition such as dysplasia or LP, making the diagnosis even more challenging.

A biopsy shows varying degrees of parakeratosis with impetiginization and benign epithelial hyperplasia.

Management and Prognosis

No further management is necessary. These lesions are benign and have no malignant potential. The use of night guards or appliances to break the habit has not been shown to be helpful.

Benign Alveolar Ridge Keratosis (Bark, Oral Lichen Simplex Chronicus)

BARK is a very common condition that was recently defined histologically. It occurs primarily on the keratinized mucosa of the gingiva and hard palate as a reaction to frictional trauma. It is the oral equivalent of lichen simplex chronicus.

Clinical Findings

BARK presents as poorly demarcated, painless white papules and plaques, often with a rough surface, usually less than 1 cm in greatest dimension (eFig. 76-5.4). The most common location is the retromolar pad (at the site of previously extracted wisdom teeth) and other areas where teeth have been extracted.68,69 It is not necessary for the opposing teeth to contact the mucosa, since crushing of food against the alveolar ridge that had been previously protected by a tooth is sufficient.

Differential Diagnosis and Laboratory Studies

Leukoplakia, especially verrucous leukoplakia is a very important differential diagnosis and a biopsy should always be performed if the lesion shows signs of sharp demarcation or is extensive. More worrisome, verrucous leukoplakia, a dysplastic lesion, also has a rough surface and is usually greater than 1 cm.

A biopsy shows typical features of lichen simplex chronicus. BARK is closely related to MMO (described above), another frictional keratosis. It is possible that BARK being located on the keratinized mucosa that is closer in histology to the skin, takes on the more typical histologic characteristics of lichen simplex chronicus (LSC).

Management and Prognosis

No treatment is necessary once the histopathologic diagnosis has been established. If a denture is the source of frictional irritation, this should be adjusted accordingly.

Nicotinic Stomatitis

Nicotinic stomatitis is not caused by nicotine as its name suggests but rather by heat, usually from pipe smoking. A similar condition may be seen in patients who reverse smoke, that is, hold the lighted end of the cigarette in the mouth, as is the habit in some South Indian and Southeast Asian populations. It has also been noted in patients who habitually drink very hot beverages.

Clinical Findings

The palate of adult patients is the site most often affected. It is diffusely white with red, punctuate areas representing the openings of salivary ducts. It is usually not a painful lesion although severe cases may be sensitive to hot and spicy foods, and lesions are usually symmetric and diffuse.21,54

Differential Diagnosis and Laboratory Studies

Leukoplakia and candidiasis of the palate may both mimic nicotine stomatitis.

A biopsy shows hyperkeratosis with benign epithelial changes and importantly, inflammation of excretory salivary ducts that exhibit squamous metaplasia. This diagnosis is difficult if the ducts are not included in the biopsy specimen.

Management and Prognosis

Lesions may resolve if the habit is discontinued. The risk for malignant transformation has not been well documented. However, the development of raised, indurated areas should raise suspicion for malignant transformation.

Smokeless Tobacco Keratosis

This is a lesion that results from a combination of direct contact toxicity of the smokeless tobacco on the mucosa (early lesions), and from effects of carcinogens within the snuff, namely tobacco-associated nitrosamines (late lesions that represent true leukoplakias). Not all smokeless tobaccos are alike. Snuff may be moist or dry and in general moist Swedish snuff (“snus”) is lower in nitrosamines than moist and dry snuff from the United States.70 Toombak, snuff from Ethiopia, has the highest levels of nitrosamines of all.71 In many Asian countries, snuff and smokeless tobacco is mixed with other substances such as spices and importantly areca nut, which contains another potent carcinogen, the alkaloid arecoline.72

Over the last 10–15 years, there has been increased interest in using smokeless tobacco as a risk reduction measure in subjects who have difficulty discontinuing cigarette smoking because the risk of developing cancer (oral and other cancers) is reduced.73,74

Clinical Findings

The lesions are located where the snuff is placed, usually the mandibular sulcus/vestibule, between the teeth and the buccal mucosa. The area looks grayish white, opalescent, and wrinkled, often with fissures.21,54

Lesions are generally painless and poorly demarcated (eFig. 76-5.5).

Differential Diagnosis and Laboratory Studies

The diagnosis includes leukoplakia, candidiasis, and BARK. Aspirin is much more caustic and causes necrosis and ulceration, rather than this delicate white lesion.

Biopsy reveals thin parakeratosis, intracellular edema, and devitalization of superficial keratinocytes. Any other agent that is locally irritating and slightly caustic may cause this clinical appearance.

Management and Prognosis

Most early lesions are primarily caused by contact injury and are reversible if the habit is discontinued. However, the development of a dense white plaque or erythema may signal transformation to malignancy and these areas should be biopsied. The rate of malignant transformation is only 1%–2% compared with cigarette smoking.

Infectious Lesions

Candidiasis

Fungal infections are extremely common in the oral cavity and the most common causative agent is Candida albicans. Approximately 20%–30% of the population are carriers. In immumnocompromised hosts, other species such as C. tropicalis, C. dubliniensis, C. glabrata, and C. kruseii should also be considered, as some of these may be resistant to conventional therapy. Predisposing factors include hyposalivation (see Section “Xerostomia” and “Hyposalivation”), immunocompromise, topical steroid therapy (for treatment of oral lesions or as inhalers), and antibiotic therapy.

Clinical Findings

Oral candidiasis may present in various forms (Table 76-4) (Figs. 76-6A–76-6B).1,21 Lesions are almost always painful and dentures act as fomites.75 Although C. albicans is the most common pathogen in denture-associated candidiasis, C. glabrata is found in 30% of cases.76

Differential Diagnosis and Laboratory Studies

An important differential diagnosis is hairy or coated tongue. This is not a candidal infection, although cultures may grow Candida in carriers. These lesions are almost always painless and do not involve mucosa other than tongue dorsum, unusual for candidiasis. It is caused by hyperplasia and hypertrophy of the filiform papillae of the tongue, with retention of keratinaceous debris as a result of hyposalivation and poor oral intake. Patients therefore are often ill, dehydrated, and on antibiotic therapy, further adding to the suspicion that the lesions represent candidiasis.

Culture is not particularly useful for diagnostic purposes since many individuals are carriers. However, culture is important if speciation or sensitivity is required, or to identify carriers prior to the start of long-term steroid therapy. A potassium hydroxide preparation using scrapings from oral lesions is a good way to identify infection. Biopsies show typical candidal organisms.

Management and Prognosis

Patients who have dry mouths from polypharmacy or substantial damage to salivary glands (such as from radiation) are prone to develop recurrent candidiasis and are particularly difficult to manage. Nystatin rinses and clotrimazole troches contain caries-inducing sugars and should be used long-term only with careful monitoring by the dentist. The use of cholinergic agents such as pilocarpine or cevimeline helps to restore some secretory function of salivary glands and may reduce the frequency of candidiasis.

Hairy Leukoplakia

Epstein–Barr virus (EBV) infections in the oral cavity may present as a primary infection (infectious mononucleosis). Hairy leukoplakia is an unusual presentation of recrudescent EBV in the oral cavity, where this normally lymphotropic virus is present within the epithelium.

Clinical Findings

This manifests as a painless, white plaque usually located on the lateral border of the tongue in immunocompromised patients, and in particular, those with HIV/AIDS and after organ transplantation.77,78

Typically, these present as white linear lesions running perpendicular to the long axis of the tongue but when more advanced, may extend onto the dorsum and present as a plaque (Fig. 76-7). Lesions are usually asymptomatic and usually superinfected with Candida. Infrequently, hairy leukoplakia has been reported in healthy individuals.79

Differential Diagnosis and Laboratory Studies

Lesions of MMO and candidiasis often occur on the lateral tongue and may appear similar.

Both cytologic smears and biopsies show characteristic findings and the presence of EBV can be confirmed by in situ hybridization.

Management and Prognosis

The presence of hairy leukoplakia may be the first indication that a patient is infected with HIV. In patients with established HIV/AIDS, hairy leukoplakia is usually associated with a low CD4 count and high viral load.77 Treatment with an antifungal medication (see Section “Candidiasis”) will resolve the associated candidiasis and treatment with antiretroviral therapy results in resolution.

Oral Lichen Planus

Oral LP is an immune-mediated disorder and an interface stomatitis characterized by T-cell destruction of the basal cells of the epithelium, possibly as a result of altered antigen presentation on these cells, mediated by TH1 cytokines. Interferon-α production is thought to mediate lesions involving the oral cavity only while TNF-α may mediate systemic disease.80 Whether this is a disease in and of itself or whether it represents a “final common pathway” of mucosal reaction is unclear at this time. Many local and systemic conditions predispose to the development of such “lichenoid lesions” in the oral cavity. The term “lichenoid” used here to describe reticulated, often erythematous and/or ulcerated lesions, usually bilateral and symmetric. Unfortunately, many erythroleukoplakias that are by definition red and white lesions but usually without significant reticulation are also clinically described as “lichenoid” by some investigators, causing confusion and leading to the concept of LP as a premalignant lesion.

Local lichenoid reactions may develop as a result of contact injury to amalgam restorations or cinnamic aldehyde from chewing gum. Medications implicated in the development of oral LP include antihypertensive agents (especially hydrochlorthiazide), some hypoglycemic agents, allopurinol, sulfasalazine, carbamazepine, and the new biological agents.80–82 It is often impossible to differentiate either clinically or histologically, between lesions of idiopathic LP and lichenoid hypersensitivity reactions.83

Other conditions associated with oral lichenoid lesions include hepatitis C in Mediterranean races and this is associated with HLA-DR684,85; chronic graft-versus-host disease, and lupus erythematosus.86,87

Clinical Findings

Oral LP occurs in 1%–2% of the population in the United States and affects females more than males, usually those in the fifth decade of life and older. Three clinical forms are noted—(1) keratotic/reticular, (2) erythematous/erosive, and (3) ulcerative—and these often occur in combination.21,54 The most recognizable is the keratotic/reticular form (Wickham striae) that is usually not painful. This is symmetric in distribution and reticulations almost always occur on the buccal mucosa and tongue although any oral mucosal site may be affected (Figs. 76-8A and 76-8B). Lesions on the dorsum of tongue tend to be subtle and more papular with atrophy of filiform papillae giving the tongue a white cast and smooth appearance (Fig. 76-8C). The erythematous or erosive form is usually painful and this is particularly common as a primary presentation on the gingiva (clinically desquamative gingivitis).88 LP on the gingiva is also noted in the gingival–genital syndrome.89 Ulcerative LP usually occurs in association with the other two forms. The finding of intact blisters (bullous LP) is rare in the oral cavity because it is a trauma-intense environment. Concomitant skin involvement is noted only in 10%–15% of patients.

A controversial entity is the so-called “plaque-type LP.” If this lesion occurs as a unilateral plaque without reticulations, it should be considered a leukoplakia. If it occurs within an established, typical symmetric oral LP, it should be considered “leukoplakia developing within LP.” In either case, biopsy is indicated to exclude dysplasia or malignancy.

Several scoring systems have been developed for evaluating the severity of disease but none are universally accepted.90–92

Differential Diagnosis and Laboratory Studies

Many conditions may result in the development of LP and lichenoid reactions. However, the most important is erythroleukoplakia. It can be differentiated from oral LP in that it is not usually definitively reticulated (although it may have subtle linear areas), is usually asymmetrically distributed, and often presents at a high-risk site for cancer such as the ventral tongue unilaterally. It is strongly associated with dysplasia and carcinoma (see below). Other lesions include candidiasis and contact stomatitis such as to chewing gum.

Chronic ulcerative stomatitis is an entity that resembles erythematous/erosive LP but is associated with antibodies directed against δNp63α.93 Direct immunofluorescence studies reveal nuclear binding of keratinocytes in the basal and lower one-third of the epithelium. Serum immunoglobulin (Ig) G can be detected using guinea pig esophagus as substrate and an ELISA is now available.94

The reticulated white areas on the buccal mucosa may sometimes resemble MMO. Erythematous LP lesions on the gingiva are often indistinguishable from other diseases presenting as desquamative gingivitis such as mucous membrane pemphigoid, hypersensitivity reaction, or plasma cell gingivitis. Pure ulcerative lesions without reticulations are more likely to be aphthous ulcers.

Diagnostic histopathologic findings for oral LP, are squamatization of basal cells and a lymphocytic band at the interface. Direct immunofluorescence studies show shaggy fibrinogen and often IgM at the interface and IgM staining of colloid bodies.

Management and Prognosis

Management of oral LP and lichenoid lesions involves pain control and treatment with topical steroids and other anti-inflammatory agents (Table 76-1).95 Gingival lesions are effectively treated with topical steroids held in a stent. Systemic therapy with prednisone (at 1 mg/kg for 1 week with a fairly rapid taper) or hydroxychloroquine should be instituted in severe cases and topical therapy started concomitantly.

Localized, unliateral lesions may respond to removal of dental restorations and a short course of topical steroids. Disease remission occurs in <10% of cases.

The rate of malignant transformation (often given as 1% every 5 years) is controversial because some studies do not correct for confounding factors such as smoking, while other included erythroleukoplakias, leukoplakias (diagnosed as “plaque-type” LP), and proliferative leukoplakia in the group of “lichenoid” lesions. Classic, bilaterally symmetric, reticulated LP has a very low malignant potential.96

Leukoplakia and Erythroplakia

This is one of the more challenging diagnostic entities of oral mucosal disease. Leukoplakia is defined as a “white plaque of questionable risk having excluded other (known) diseases or disorders that carry no increased risk for cancer.”97 It is a clinical diagnosis only and modified once the histopathologic diagnosis is known. For example, what may appear to be a provisional diagnosis of leukoplakia on the buccal mucosa may histopathologically prove to be MMO as a final definitive diagnosis. Frictional keratosis is NOT a leukoplakia and the only two histologically well-defined frictional keratoses are (1) MMO and (2) BARK. Because frictional injury is very common in the oral cavity and usually presents as a hyperkeratosis, it is likely that many so-called leukoplakias actually represent nonspecific frictional keratoses that are not MMO or BARK.

Leukoplakias occur in 2%–4% of the population.98 Any lesion that carries a provisional diagnosis of leukoplakia must be biopsied because approximately 20%–50% of these lesions are dysplastic or cancerous at the time of biopsy.99,100

Leukoplakia is strongly associated with smoking and/or alcohol ingestion. Other predisposing factors are similar to those for oral cancer and will be discussed below.

Clinical Findings

Leukoplakia is more common in adult males. It presents as a painless, white plaque that may be homogenous or nonhomogenous.97 It may occur anywhere in the oral cavity and generally shows areas that are sharply demarcated from the surrounding mucosa (Fig. 76-9). Homogenous leukoplakia may show areas of fissuring. Nonhomogenous leukoplakia have areas of erythema (erythroleukoplakia), rough, warty areas (verrucous leukoplakia), or nodular areas; they have a higher association with dysplasia and carcinoma, as do lesions on the floor of mouth, ventral tongue, and soft palate.101,102

Proliferative verrucous leukoplakia (PVL)103,104 tends to occur in middle-aged females and, as its name suggests, tends to spread or proliferate over the mucosa over time, and is usually multifocal (eFigs. 76-9.1A–76-9.1C). It is associated with smoking in less than 30% of cases. Patients are usually diagnosed with this condition one to two decades after the first appearance of the white lesion. Areas of it may become verrucous, although not invariably, and other areas may appear red, in which case the term proliferative erythroleukoplakia may be appropriate. Approximately 70%–100% of cases develop SCC over time.103,105 These lesions are particularly difficult to diagnose because patients often have had multiple biopsies over many years, and each time, the diagnosis is one of “hyperkeratosis” only without evidence of dysplasia.

Oral erythroplakia, although a red lesion, will be discussed here because of its high associated dysplasia. It is an uncommon lesion and in its pure form presents as a painless, red, sometimes velvety plaque of the oral mucosa (eFig. 76-9.2). More than 90% of cases are associated with dysplasia or carcinoma at the time of diagnosis.106,107 It is much more common to see it in combination with leukoplakia (erythroleukoplakia).

Differential Diagnosis and Laboratory Studies

The clinical differential diagnosis list for leukoplakia is long (Table 76-3). However, sharp demarcation at least one border is a helpful finding and usually excludes an inflammatory/reactive lesion. A biopsy should be performed for any white lesion if the etiology cannot be established with confidence on clinical grounds.

Approximately 20%–50% of leukoplakias are dysplasias or carcinoma at the time of biopsy.100,101,106,108 However, 5%–18% of lesions diagnosed as “benign hyperkeratosis,” when followed over time, transform to carcinoma.99,102,108 This is particularly true of lesions of proliferative leukoplakia where multiple biopsies show “benign hyperkeratosis” until many years later when overt dysplasia or carcinoma develops.

Research using microarrays and other techniques to better characterize the genome of these lesions will shed light on this in coming years. The concept of “oral” or “squamous intraepithelial neoplasia” similar to “cervical intraepithelial neoplasia” has not received acceptance although it is likely a useful concept to adopt.

Management, prognosis, and risk of progression to oral SCC are discussed online.

There is controversy as to whether leukoplakias should be excised.109 Some suggest that small leukoplakias should be excised, while extensive lesions could be managed with multistage stripping.110 While some clinicians and pathologists believe that mild dysplasias may just be observed since some of these regress, it is likely that some of these “regressing mild dysplasias” represent only keratotic lesions with reactive atypia. True dysplasias are intraepithelial neoplasias that have not yet become invasive. If such lesions can be removed without excessive morbidity, this seems prudent.

Options for the 50%–80% of cases diagnosed as “benign hyperkeratosis,” include periodic rebiopsy or excision. It is suggested that “benign hyperkeratoses” that are not clearly frictional or reactive in nature and are in high-risk sites be narrowly excised and followed and that recurrent lesions be excised with a margin of several mm. Because leukoplakia is a clinicopathologic entity, it is important that the clinician work with a pathologist who is experienced in the diagnosis of reactive and nonreactive oral keratotic lesions.

Smoking cessation counseling should always be part of the overall management strategy for patients who smoke.

Oral Squamous Cell Carcinoma

Head and neck cancer is the 11th most commonly occurring cancer in the United States, and there are approximately 35,000 cases per year, with one-third of these occurring in the oropharynx.111 Risk factors include smoking cigarettes, excessive use of alcohol, chewing areca nut, a past history of cancer and/or immunosuppression, family history of cancer, exposure to high-risk forms of human papilloma virus (HPV) (especially for carcinomas of the posterior oral cavity and oropharynx), age, and for lip cancer, sunlight.112,113

Clinical Findings

Oral SCC affects males more often than females in a 2:1 ratio and usually affects older adults. Excluding the lip, the most common sites are the ventral tongue, gingiva, and floor of mouth. It may present as a leukoplakia, erythroplakia, proliferative leukoplakia, a nonhealing ulcer or ulcerated nodule, or a mass.112 The tumor may have a verrucous or papillary surface (eFig. 76-9.3). Pain may or may not be present and there may be paresthesia. Advanced lesions infiltrate the underlying bone or muscle and may lead to difficulty with movement of the tongue, adversely affecting speech and eating. Metastases to the submandibular and upper cervical lymph nodes are common, and nodes should be palpated in patients with suspicious lesions.

Differential Diagnosis and Laboratory Studies

The differential diagnose for leukoplakia are presented in Table 76-3. Traumatic ulcerative granuloma (see above) may be mistaken for oral carcinoma because it is often on the lateral/ventral tongue, may not be particularly painful and is often present for weeks. Benign neoplasms of soft tissue or salivary gland origin may be traumatized and present as an ulcerated nodule, raising the suspicion of oral carcinoma.

A biopsy shows a proliferation of malignant epithelial cells infiltrating the stroma as single cells or in a bluntly invasive fashion. The latter is a particular feature of verrucous carcinoma that tends not to metastasize.

Management and Prognosis

Management and prognosis is dependent on the stage. Most Stage I and II lesions are treated with surgical excision (usually en bloc resection) with an objective of obtaining clear margins.114 Some Stage II lesions are treated with a supraomohyoid neck dissection. Studies on sentinel node biopsy have shown metastatic lesions in 20%–30% of patients.115,116 Stage III and IV tumors may be treated with surgery, radiation or chemoradiation (the chemotherapy being a radiation sensitizer) for organ-sparing purposes.117 The use of cetuximab, a monoclonal antibody against the epidermal growth factor receptor, which is highly expressed in many oral cancer, has resulted in improved disease control.

Five-year survival for patients with local disease only, locoregional disease and distant metastases are 81%, 50%, and 14%, respectively.114

Submucous Fibrosis

Clinical Findings

Submucous fibrosis is seen more frequently in males.120 It is better palpated than seen and the teeth show rust-colored staining. Patients may report that they cannot open their mouths wide. The buccal and tongue mucosa are involved and may have a marble-like pallor. Palpation reveals dense fibrosis and rigidity of the tissues and often “piano wire-like” bands. Patients may also report pain and sensitivity of the tissues especially on eating spicy foods.21

Differential Diagnosis and Laboratory Studies

Management and Prognosis

Many autoimmune bullous disorders present as erythematous and/or ulcerative lesions. It is rare for intact bullae to be present in the oral cavity.

Mucous Membrane Pemphigoid

Mucous membrane pemphigoid is a heterogeneous group of disorders characterized by subepithelial blistering and antibodies, usually IgG or IgA, directed against a variety of antigens such as BP230, BP-180, laminin-332, laminin-331, Type XVII collagen, Type VII collagen, or β 1 integrin subunit,121 to name a few.

Clinical Findings

This is a disease of middle aged and older adults with a slight female predisposition. The most common presentation for mucous membrane pemphigoid is desquamative gingivitis. This presents as a band of bright red, painful gingiva, often denuded of epithelium, with areas that are ulcerated or with necrotic epithelium lying on the surface (Fig. 76.10). Patients have difficult eating coarse, acidic, or spicy foods and the gingiva bleed readily on brushing. Oral mucosa lesions rarely cause scarring and most patients who present with oral lesions initially do not usually develop skin lesions. It is uncommon to see lesions on sites other than the gingiva in the oral cavity.

Differential Diagnosis and Laboratory Findings

LP is the most common disease (70%–75%) presenting as desquamative gingivitis, with mucous membrane pemphigoid representing 9%–14% of cases.122,123 Other conditions include hypersensitivity reactions such as plasma cell gingivitis and less commonly other autoimmune bullous disorders such as pemphigus vulgaris, linear IgA disease, and epidermolysis bullosa acquisita. LP may or may not show reticulations on the gingiva or elsewhere in the oral cavity and pemphigus vulgaris almost always involves mucosal sites other than the gingiva. Linear IgA disease and epidermolysis bullosa acquisita always present with concomitant skin lesions. Granulomatosis with polyangiitis (Wegener disease) produces a granular, erythematous gingivitis.

All patients with a clinical diagnosis of desquamative gingivitis should have a biopsy both for routine histology and for direct immunofluorescence studies. The presence of linear IgG, IgA, and/or C3 at the basement membrane zone on direct immunofluorescence testing is strongly suggestive of pemphigoid. The diagnosis of linear IgA disease should not be made in patients with mucosal disease alone. Indirect immunofluorescence using salt-split skin may also be helpful.121

Management and Prognosis

The most effective way to treat mucous membrane pemphigoid presenting as desquamative gingivitis is with a topical steroid gel held in a soft stent (similar to a bleaching or fluoride tray extended over the gingiva) for 30 minutes twice a day. Clobetasol may be used for the first few months, switching to fluocinonide when disease is better controlled. Application may also be reduced to 10–15 minutes once a day for maintenance. Prednisone and dapsone may be used if lesions are recalcitrant.124 Azathioprine and cyclophosphamide are also effective in some cases.121 It is unclear whether patients with IgA on direct immunofluorescence studies have more recalcitrant disease. Some cases may respond to etanercept.125

This disease is chronic and the disease rarely remits completely. Since ocular complications may be severe, all patients with oral lesions are referred for baseline ophthalmologic examination. Long-term topical steroid therapy may lead to hypertension, hyperlipidemia, and poor control of diabetes mellitus, so periodic blood pressure measurements, ACTH and cortisol levels, and lipid and glucose levels are indicated.

Pemphigus

The oral cavity may be involved by pemphigus vulgaris and paraneoplastic pemphigus. There is a predilection for this condition among Ashkenazi Jews and those living around the Mediterranean and South Asia and a strong association with HLA-DR4, Drw14, and DQB1*503.126 The antigen is desmoglein 3.

Clinical Findings

Pemphigus vulgaris is an uncommon condition, most often seen in adults. Patients may present with lesions in the mouth before developing skin lesions. Lesions may present as desquamative gingivitis, but almost invariably, other mucosae are involved, in particular the hard and soft palate. Oral lesions are denuded and erythematous, painful, and slightly depressed. Remnants of the bullae or necrotic debris may overlie the erosion, or be heaped up at the edges (eFig. 76-9.4). Some patients have lesions limited to the oral cavity and never develop skin lesions.

In addition to the erosions and ulcers present intraorally, patients with paraneoplastic pemphigus (also known as paraneoplastic autoimmune multiorgan syndrome) present with hemorrhagic crusting of the lips. It is usually associated with a lymphoid malignancy.127

Differential Diagnosis and Laboratory Findings

Large ulcers of Behçet disease and recurrent aphthae major may look similar to pemphigus vulgaris. Stevens–Johnson syndrome and the more severe toxic epidermal necrolysis may resemble lesions of paraneoplastic pemphigus.

The biopsy for pemphigus vulgaris shows suprabasilar acantholysis and direct immunofluorescence studies show intercellular deposition of IgG. Paraneoplastic pemphigus shows deposition of IgG and C3 both intercellularly and at the basement membrane zone. Patients with only oral lesions of pemphigus usually do not exhibit elevated serum IgG.

Management and Prognosis

Treatment for pemphigus vulgaris is with topical steroids in mild cases with the use of a stent for gingival lesions. More severe cases can be successfully treated with prednisone and mycophenolate mofetil in conjunction with topical steroids.

Lupus Erythematosus

Patients with systemic and discoid lupus erythematosus present with oral findings in up to 25% of cases.128

Clinical Findings

Patients may present with erythematous and eroded mucosa, especially on the buccal mucosa and palate with a hint of white reticulations. Ulcers may be present (Fig. 76-11).

Differential Diagnosis and Laboratory Findings

LP can usually be differentiated by well-formed reticulations of the buccal mucosa. Patients with lupus erythematosus usually have an established diagnosis and present for management of painful oral lesions.

The biopsy shows an interface stomatitis with linear IgG deposition along the basement membrane zone on direct immunofluorescence.

Management and Prognosis

The mainstay of treatment is topical steroid therapy. Symptoms usually wax and wane with systemic and skin disease.

Clinical Features

Differential Diagnosis and Laboratory Findings

Management and Prognosis

Clinical Findings

Differential Diagnosis and Laboratory Studies

Management

Clinical Findings

Differential Diagnosis and Laboratory Studies

Management and Prognosis

Clinical Findings

Differential Diagnosis and Laboratory Studies

Reactive Nodular Lesions

Clinical Findings

Differential Diagnosis and Laboratory Studies

Management and Prognosis

Neoplastic Nodular Lesions

The two most common pigments of exogenous origin are amalgam and graphite from pencil lead. Pigmented lesions of endogenous origin are usually caused by melanin or hemosiderin.

Amalgam Tattoo

Dental amalgam restorations are primarily composed of silver and mercury with smaller amounts of other elements such as tin. The silver particles stain the reticulin fibers leading to the tattoo.165

Clinical Findings

This presents in adults usually, as a discrete, nontender, slate-gray, or black macule of the oral mucosa that is usually less than 1 cm.166–168 The patient is usually unaware of the lesion. When it is noted adjacent to a silver or amalgam restoration because of leaching out of particles, the diagnosis is straightforward. However, if it is located at a site away from the restoration, such as the buccal mucosa, tongue, sulcus, or palate, the diagnosis may not be as obvious (Fig. 76-15).

Differential Diagnosis and Laboratory Findings

Any other dark foreign material such as graphite may look similar. Melanotic lesions especially the oral melanotic macule and postinflammatory hypermelanosis may look similar although in general these are more tan and dark brown rather than dark blue. Dysplastic melanocytic lesions and melanoma usually have less uniform pigmentation and irregular borders. A vascular lesion such as a varix or venous lake may look similar, although those intend to appear as blebs or papules and blanch with pressure.

The histopathology is distinctive. Pigmentation by other materials not containing silver such as graphite does not cause staining of the reticulin fibers.

Management and Prognosis

A biopsy is usually not required if the lesion is adjacent to a restoration. However, if there is any doubt about the diagnosis, a biopsy is recommended.

Physiologic Pigmentation (Racial Pigmentation)

This is very common in dark-skinned individuals of African, South and Southeast Asian, and Mediterranean descent.

Clinical Findings

Physiologic pigmentation presents asymptomatic diffuse, even or patchy, brown-to-black macular pigmentation of the oral mucosa and in particular the attached gingiva (Fig. 76-16). This usually has a symmetric distribution.21

Differential Diagnosis and Laboratory Studies

The patient is usually unaware of this. Postinflammatory hypermelanosis from diffuse and symmetric involvement by oral LP may also have a similar appearance. However, the pigmented areas tend to be located where the obvious white reticulations are present. Cosmetic tattooing of the gingiva is a prevalent practice in some African cultures and this may lead to extensive and symmetric pigmentation.

The biopsy shows the presence of melanin within basal cells in the absence of melanocytic hyperplasia.

Management and Prognosis

Recognition of the condition is sufficient and a biopsy is seldom necessary.

The etiology of the solitary melanotic macule is unclear. It is possible that at some of the lesions may have an inflammatory etiology.

Clinical Findings

The most common sites of involvement are the lower lip vermilion, gingiva, and hard palate.169,170 They are asymptomatic, discrete, tan, brown, or black macules, usually less than 1 cm with even pigmentation (eFig. 76-16.1). Unlike ephelis, they do not darken in summer or lighten in winter. While most lesions are solitary, multiple macules are not uncommon in dark-skinned individuals, and they may proliferate in middle age.

Differential Diagnosis and Laboratory Studies

Multiple oral melanotic macules are seen in idiopathic lenticular mucocutaneous pigmentation (Laugier–Hunziker syndrome) associated with melanonychia.171 Multiple melanotic macules are often seen neurofibromatosis, McCune–Albright syndrome, Peutz–Jeghers syndrome, LAMB (lentigenes, atrial myxoma, blue nevus) syndrome, and the associated Carney syndrome.21

The sudden onset of melanotic macules should raise the possibility of Addison disease and ACTH levels should be measured. History and clinical examination usually exclude the other syndromes.

Multifocal oral melanosis is also associated with postinflammatory conditions such as LP and the so-called “smoker's melanosis” that occurs on the gingiva around the canine teeth (see below).

Biopsy reveals increased melanin pigment in the basal cells in the absence of melanocytic hyperplasia, and many melanophages in the lamina propria.

Management and Prognosis

No treatment is necessary. Laser therapy may be useful in patients who are concerned with the esthetic appearance of the macules.172

These pigmented lesions occur in particular in dark-skinned patients, similar to lesions of postinflammatory hyperpigmentation on the skin. They may be localized or diffuse depending on the underlying inflammatory process.

Clinical Findings

LP is often associated with postinflammatory hypermelanosis and the pigmentation underlies the reticulations of the disease (Fig. 76-17). Smoker's melanosis is often described as a separate entity but likely represents a postinflammatory hypermelanosis occurring in approximately 20% of subjects who smoke. It tends to occur on the buccal gingiva around the canine teeth or on the buccal mucosa.173,174 Resolution of these lesions after smoking cessation supports an inflammatory etiology.175

Differential Diagnosis and Laboratory Findings

Oral melanotic macules may resemble melanoacanthosis, another likely inflammatory reactive disorder in which there is proliferation of dendritic melanocytes throughout acanthotic epithelium.

Biopsy helps exclude a dysplastic melanocytic lesion.

Management and Prognosis

No treatment is necessary unless the patient is concerned about esthetics. Lesions generally fade over time if the inflammation resolves.

The medications most commonly associated with oral pigmentation do so via several different mechanisms.176 Minocycline and tetracycline chelate to apatite crystals in bones and teeth and their metabolic products chelate iron and melanin in the soft tissues.177 The latter mechanism is also seen during therapy with antimalarial drugs. Pegylated interferon used with ribavirin may stimulate melanin production by stimulating production of α-melanocyte stimulating factor.178,179 Heavy metals such as lead is secreted into the gingival fluids and likely chelate with sulfides (usually black) produced by plaque bacteria.180 Bismuth subsalicylate ingestion is also associated with pigmentation of the tongue either from systemic ingestion and tissue deposition, or direct conversion of the compound to bismuth sulfide from oral bacteria.181,182

Clinical Findings

The most common site of pigmentation caused by minocycline and antimalarial medications is the palatal mucosa, which assumes a slate-gray to blue diffuse macular discoloration that is generally bilateral and symmetric. The lesions are asymptomatic.

Tongue pigmentation caused by pegylated interferon accentuates the papillae in a punctate configuration; this has been reported mainly in dark-skinned individuals.178 Heavy metals deposit on the gingiva in linear fashion (Burton line in plumbism).180

Differential Diagnosis and Laboratory Findings

The history of ingestion of the drug followed by the appearance of a diffuse pigmentation of the oral mucosa and sometimes skin after several months or years is diagnostic.

Biopsy shows pigment granules that stain for both iron and melanin.

Management and Prognosis

Depending on the length of exposure, discontinuation of the drug may or may not result in eventual complete resolution of the lesion.

This is an uncommon inflammatory condition of the oral mucosa. Although this condition is also reported under the term “melanoacanthoma,” melanoacanthosis is preferred because this is a macular lesion, may be multifocal and is not a tumor-like lesion. Many cases of multifocal melanoacanthoma and melanoacanthosis reported in the literature represent either multiple melanotic macules or postinflammatory hypermelanosis. This raises the question as to whether oral melanotic macules and melanoacanthosis are just two manifestations of postinflammatory hypermelanosis.

Clinical Findings

Black females in the second to fourth decades are most often affected. The lesion starts as a brown macule, usually on the buccal mucosa, that over days and weeks spreads rapidly, but still in a macular fashion.183,184

Differential Diagnosis and Laboratory Studies

While dysplastic nevi and melanoma may grow rapidly, the rate of expansion of the lesion is so fast that an inflammatory condition is more likely.

A biopsy shows acanthosis with benign melanocytes throughout the full thickness of the epithelium.

Management and Prognosis

No treatment is necessary; this condition regresses over time.

Clinical Findings

The most common is the intramucosal nevus that accounts for two-thirds of cases, followed by the compound nevus and the blue nevus (17%) each; junctional nevus constitute only 3% of lesions.168 The most common location is the palate (40%) followed by the buccal mucosa (19%).185 Most were identified in the third and fourth decades of life.

Intramucosal and compound nevi tend to be nodular, while junctional and blue nevi tend to be macular. Most nevi are pale-tan to dark-brown or black while blue nevi are slate-blue in color. Approximately 15%–20% of intramucosal nevi are nonpigmented clinically.185

Differential Diagnosis and Laboratory Studies

Intramucosal and compound nevi may be mistaken for fibromas or any other benign mesenchymal tumor. Blue nevi resemble melanotic macules, amalgam tattoo, or even a varix. Intraoral Spitz nevi are rare but have been reported.

A biopsy shows the presence of nevomelanocytic cells in nests in the lamina propria and/or the epithelial–connective tissue interface. Blue nevi consist of spindled melanocytes in the lamina propria.

Management and Prognosis

In general, nodular lesions are excised or shaved.

Intraoral melanomas constitute 0.7% of all melanomas and occur on average 20 years later than cutaneous melanomas.186,187 The etiopathogenesis in this UV-protected site is unknown and lesions behave similarly to acral lentiginous melanoma.

Clinical Findings

Oral melanomas are tumors of adults in the fifth to seventh decades of life with a male predilection and usually evolve from preexisting dysplastic melanocytic lesions.188,189 They are more frequent in black and Japanese patients and the most common site is the palate or maxillary gingiva. By the time they are diagnosed, they are fairly large, asymmetric, and unevenly pigmented. Areas of ulceration and bleeding may be present. Approximately 40% are amelanotic.188

Differential Diagnosis and Laboratory Findings

Kaposi sarcoma tends to be purple or bluish-red, while melanomas tend to be brown-to-black. A large pyogenic granuloma or other vascular lesion with a dark coloration may resemble a melanoma, although a surrounding macular dysplastic melanocytic lesion would be absent.

A biopsy shows an invasive proliferation of melanocytes from an intraepithelial component.

Management and Prognosis

Five-year survival is approximately 20%–30%.190,191 Excision with clear margins is the treatment of choice and survival is closely related to the depth of invasion.192 Surgery with radiotherapy greatly reduces local relapse and metastasis to lymph nodes, although it may not improve survival.190,193

Disorders of the lips including actinic cheilitis, orofacial granulomatosis,200,204 angular cheilitis, and lip nodules are discussed online.

Some use the term actinic cheilitis to encompass atrophy of the lips caused by actinic damage without evidence of dysplasia. Here, it will be defined as actinic keratosis of the lip, a dysplastic lesion.

Clinical Findings

Because the etiology is related to sun-damage, patients are generally adults in the sixth decade and beyond.194,195 There is usually a background of chronic actinic damage and atrophy of the lip with blurring of junction of the vermilion and the skin, predominantly involving the lower lip. Actinic cheilitis presents as single or multiple crusted or scabbing, slightly scaly lesions and plaques on the vermilion of the lip, usually several millimeters in size, that heal and then break down. These occur on a whitish, keratotic background. Fissuring and erosions of the vermilion may be present. Discomfort is variable.

Differential Diagnosis and Laboratory Studies

An early SCC, traumatized adnexal or salivary gland tumor, or recrudescent herpes simplex infection should be considered in the differential diagnosis.

A biopsy is diagnostic and shows keratinocytic dysplasia.

Management and Prognosis

Several treatment options are available depending on the size of the lesion and patient preference. Lesions may be surgically excised, treated with cryotherapy or carbon dioxide laser,196 or managed with topical agents such as 5-fluorouracil or 5% imiquimod for 4–6 weeks.197,198 In patients prone to herpes simplex recrudescence, antiviral prophylaxis should be considered. More recently, the use of photodynamic therapy with 5-aminolevulinic acid has shown complete clinical response in two-thirds of cases and partial response in one-third; follow-up revealed recurrence in approximately one-third of cases.199

This is the best known of the noninfectious granulomatous diseases that affects the orofacial region. Like other granulomatous disease, it likely represents a delayed-type hypersensitivity reaction to antigens.200 Elimination diets and removal of amalgam restorations have resulted in complete remission of some cases, but no obvious etiologic agents is identified in many cases. There may be a genetic predilection and the reaction is mediated via Th1 pathways.201,202

Patients with orofacial granulomatosis who present only with lip involvement have cheilitis granulomatosa. The term Melkersson–Rosenthal syndrome refers to the triad of fissured tongue, facial palsy, and cheilitis granulomatosa, but it is rare to see the triad fully expressed clinically. It is also unclear whether fissured tongue, a fairly common condition, is truly part of the syndrome.

Clinical Findings

Most patients are young adults and the presentation is variable. Some present with unilateral, soft (early lesions), or firm-rubbery (more established lesions) painless swelling of the lip, and others present with symmetric swelling of the upper or lower lips or, less frequently, both (eFig. 76-17.1). Periorbital or zygomatic swelling are atypical presentations.203 The swelling is originally relapsing–recurring and then becomes persistent, often with fissuring of the lips. There may also be a history of facial swelling, VII nerve palsy (uncommon), and gingival involvement. The last presents as nodular swellings on the gingiva or a cobblestoning of the buccal mucosa. While some also include linear ulcers in the maxillary and mandibular vestibule/sulcus as part of orofacial granulomatosis, such ulcers are more typical of Crohn disease (see Section “Differential Diagnosis and Laboratory Findings”).

Differential Diagnosis and Laboratory Findings

Early Crohn disease and sarcoidosis are indistinguishable from lesions of orofacial granulomatosis, both clinically and histopathologically. Therefore, patients should be questioned regarding gastrointestinal symptoms such as cramping, diarrhea, and blood in stools. Endoscopy is often uninformative in asymptomatic patients since gastrointestinal manifestations may occur years later. Patient should be made aware that this may represent early Crohn disease so that they can self-monitor for gastrointestinal symptoms. In sarcoidosis, angiotensin-converting enzyme levels are often elevated and hilar lymphadenopathy may be present.

Angioedema is never persistent, but rather shows complete resolution between acute episodes; and patients may show increased levels of C1 esterase inhibitor. Cellulitis from infections of the anterior teeth may lead to lip swelling, but these are acute and painful and the offending tooth is always identified.

Biopsy reveals the presence of nonnecrotizing granulomas without foreign material or identifiable infectious agent.

Management and Prognosis

Topical and intralesional steroid injections are the mainstay of treatment.204 The dose depends on the severity of swelling and usually patients are treated every week for 2–3 weeks.205 Systemic therapy in recalcitrant or severe disease includes the use of prednisone (1 mg/kg), thalidomide, minocycline, and more recently, monoclonal antibodies against TNF-α.206,207

Less than 50% of patients are in remission on follow-up.204 In long-standing cases, fibrosis from the inflammation may lead to cosmetic problems that can only be corrected with cheiloplasty.

Clinical

Differential Diagnosis and Laboratory Studies

Treatment

In most cases, this represents a form of candidiasis (see Section “Candidiasis”) often with concomitant S. aureus infection.21 The prevalence is approximately 1% in the general adult population and 28% in denture wearers.211,212 Drooping of the corners of the mouth with drooling and retention of saliva in the creases leading to candidiasis, often associated with wearing of full dentures that do not provide adequate soft tissue support is a major predisposing factor. Patients with hematinic deficiencies or who are immunocompromised are also prone to developing this condition.213

Clinical Findings

There is painful, usually bilateral maceration of the corners of the mouth with ulceration, crusting, cracking, and, in severe cases, fissuring.214 Lesions may heal and recur within days or weeks. Some patients develop a diffuse cheilitis due to candidiasis.215

Differential Diagnosis and Laboratory Studies

Recrudescent HSV infection in immunocompromised patients may lead to bilateral ulcers and maceration of the corners of the mouth, although usually other intraoral sites are also involved. A culture or direct fluorescent antibody testing will establish the diagnosis.

Patients should have bloodwork to rule out a hematinic deficiency.

Management and Prognosis

Antifungal creams with topical steroid therapy (see Table 76-4) are particularly useful in the treatment of this condition. The usual anticandidal regimens employing nystatin, clotrimazole, and chlorhexidine are also effective.216 If lesions only partially resolve, S. aureus infection should be suspected and treatment with topical erythromycin usually resolves the residual lesion.217,218

If there is a hematinic deficiency, repletion should be undertaken and dentures may need to be relined or remade to better support the soft tissues.

This is a rare inflammatory condition of the lip and some cases are associated with factitial injury and lip licking or picking, sometimes associated with psychological distress; however, many cases are of unknown etiology. It is seen in approximately 25% of patients with HIV infection.219

Clinical Findings

The lip is covered by fine or thick scales and crusts that can be peeled away, leaving an erythematous, raw area (eFig. 76-17.1). Patients will report that within a few hours, a new scale or crust forms.220,221 The lips may also appear cracked, fissured, and chapped. Some patients admit picking at the lesions while others deny this.222 Cultures in patients with HIV disease yield Candida in 50% of cases.219

Differential Diagnosis and Laboratory Studies

Actinic keratosis is an important consideration and this also causes scaly plaques but these do not tend to peel and recur as quickly. Plasma cell cheilitis should be considered although this presents as an erythematous rather than scaly lesion.223,224

A biopsy shows parakeratosis, acanthosis, and chronic inflammation, either somewhat consistent with factitial injury or nonspecific in nature.

Management

Some patients have been at least partially successfully treated with antidepressants, suggesting that factitial injury associated with psychological distress plays a role.221,225 Other treatment modalities include mupirocin and tacrolimus.222

On the lower lip nodules usually result from trauma and include bite or irritation fibromas and mucoceles (both discussed previously under Nodular Lesions). The upper lip is traumatized much less frequently and mucosal nodules at this site usually represent one of the following:

1. Benign salivary gland neoplasm (such as pleomorphic adenoma or canalicular adenoma)

2. Malignant salivary gland neoplasm (such as mucoepidermoid carcinoma)

3. Benign nerve sheath tumor (such as solitary circumscribed neuroma)

4. Benign vascular tumor (such as pyogenic granuloma)

5. Nasolabial cyst, a developmental malformation

All require excisional biopsy. Histopathology is diagnostic for each condition.

Atrophic Glossitis

Atrophy of the filiform and fungiform papillae of the tongue leads to a bald shiny, erythematous tongue dorsum. Such atrophy is often seen in hematinic deficiencies and in patients with prolonged hyposalivation such as those with Sjögren syndrome or after head and neck radiation therapy.213

Clinical Findings

The tongue presents with a smooth, bald appearance and papillae are atrophic (Fig. 76-18). Patients often complain of a burning sensation and experience sensitivity when eating acidic, salty, or crunchy foods.21 They may have associated angular cheilitis if there is a hematinic deficiency. Patients who develop malabsorption after intestinal surgery are prone to developing atrophic glossitis.226

Laboratory Studies and Differential Diagnosis

Patient should have blood work to rule out hematinic deficiencies, in particular iron and vitamins B6 and B12 deficiency. For the last, assay of methyl malonic acid may be more sensitive than just a B12 level alone.

Management and Prognosis

Treatment is with repletion of deficient elements. Topical anesthetics help to control symptoms.

Hairy Tongue (Black Hairy Tongue, Coated Tongue)

This is an extremely common condition that causes much confusion. There is generally an antecedent history of illness and antibiotic use, leading to a common misdiagnosis of candidiasis. There are usually no other lesions on other oral mucosal sites and no pain, which would be highly unusual for candidiasis. To further add to the confusion, a small number of such patients will grow Candida on culture because they are carriers.

Hairy tongue is caused by retention of keratinaceous debris on the tongue dorsum resulting from two factors acting alone or in combination: (1) dehydration (leading to more sticky and mucous rather than serous saliva) and (2) poor oral intake (eating a soft diet or one low in fresh fruits and vegetables).54 Since most patients have an antecedent history of illness or are hospitalized, they often are dehydrated and have poor appetite. Chromogenic bacteria that reside in the tongue produce metabolic by-products that sometimes stain the tongue, as do food dyes.

Clinical Findings

The tongue presents with a matted or coated appearance that is usually symmetric (Fig. 76-19). If located on the posterior midtongue, patients may experience gagging if the “hairs” are long. The thickened matte of keratin on the tongue leads to increased bacterial colonization and their metabolic products (often sulfides) may lead to a foul or stale breath. Such metabolic products may stain the tongue a variety of colors such as brown or black.

Differential Diagnosis and Laboratory Studies

Candidiasis involving the dorsum of the tongue is an important differential diagnosis, but has more patchy distribution of the curdy plaques, associated erythema, a less symmetric distribution, and involvement of other parts of the oral cavity by similar candidal papules and plaques. Ingestion of bismuth subsalicylate may transiently lead to a black tongue.182

There is no test that is useful. Rare cases have been biopsied and show only elongated filiform papillae. Cultures for Candida are positive in 20%–30% of patients and likely indicate carrier status.

Management and Prognosis

Vigorous hydration and return to a normal diet with fresh fruits and vegetables generally resolve the lesions. The tongue may be brushed as part of the daily oral hygiene regimen to help to dislodge loose keratin squames and reduce discoloration. Hairy tongue is not harmful to the patient.

Fissured Tongue

This is a common condition that occurs in 1%–2% of the population and is generally believed to be developmental in etiology.211

Clinical Findings

It is fairly uncommon in the first and second decade of life and usually seen in adults. Some believe that Candida reside within the fissures and cause symptoms.

There are two main patterns. The first consists of a central fissure, either alone or with smaller fissures radiating from it at right angles (Fig. 76-20A). The second pattern is one of short fissures distributed evenly throughout the tongue without the central fissure (Fig. 76-20B). Some patients report some sensitivity of the tongue with spicy or acidic foods, although in general, this condition is asymptomatic.21 Approximately one-third of patients with migratory glossitis (see below) have concomitant fissured tongue.

Differential Diagnosis and Laboratory Studies

The clinical presentation is striking and a biopsy is not useful. The presence of sensitivity should prompt a careful examination for the presence of migratory glossitis, atrophic glossitis, or even candidiasis within the fissures.

Management and Prognosis

Most lesions are noted on routine examination, are asymptomatic and do not require therapy. Some patients who are symptomatic show resolution of symptoms with a short course of antifungal therapy, but predisposing factors for candidiasis must be addressed or the lesions will recur.

In general, fissured tongue is a permanent condition. However, some patients report that fissures are evanescent.

Benign Migratory Glossitis/Stomatitis (Geographic Tongue)

Clinical Findings

This occurs in 1%–2% of the population and is associated with a fissured tongue in about 30% of cases.211,227 There is an area of atrophy of the tongue dorsum leading to loss of filiform papillae and a slightly depressed erythematous area that is usually sensitive or painful, especially when acidic foods come in contact with it (Figs. 76-21 and 76-22A and B). Such demarcated areas rimmed by a raised white border that is circinate or serpiginous are diagnostic.228 Waning lesions are often merely well-demarcated erythematous patches. A history of atopy is often elicited from such patients or from immediate family members.227 Approximately 13% of patients with psoriasis develop this tongue condition.229 Flare-ups are associated with both physical and psychological stress.

Infrequently, other mucosal sites such as the palatal mucosa, floor of mouth or buccal mucosa may be involved. In such cases, the term “migratory stomatitis” should be applied.230

Differential Diagnosis and Laboratory Studies

Erythematous candidiasis may cause depapillation of the tongue dorsum and cause some soreness and sensitivity.231 Identification of candidal hyphae via cytology distinguishes the two. LP and MMO on the lateral tongue are white lesions that are sometimes mistaken for this condition, but biopsy showing a psoriasiform pattern with many spongiotic pustules in the absence of candidal hyphae is diagnostic.

Management and Prognosis

Patients should be reassured that this is not infectious in etiology, a common concern. Diphenhydramine used as a swish and spit preparation or 2% viscous lidocaine may reduce symptoms. If severe, topical steroids (especially dexamethasone) are helpful. However, patients need to realize that this is an evanescent lesion that tends to recur.

Macroglossia, hyperplastic lingual tonsil, papillitis of the tongue, and tongue nodules are discussed online.

Clinical Macroglossia

Macroglossia refers to the diffuse enlargement of the tongue that may be symmetric or asymmetric. Patients report that the tongue seem enlarged and is more readily traumatized by biting since it may now overly the mandibular teeth. Mild symmetric enlargement is usually caused by loss of muscle tone such as in aging or with some systemic conditions such as amyloidosis.

Loss of muscle tone (“flabby tongue”) is particularly obvious in older patients who have lost all their teeth so that there is concomitant loss of bone height in the mandible. The tongue appears to “spread” over the edentulous mandibular ridge and this also makes it difficult for the lower denture to stay in place. Patients with trisomy 21 often have such flabby tongues.

Asymmetric enlargement is usually caused by the presence of a tumor, in particular a vascular malformation of either lymphatic (lymphangioma) or blood vascular origin (venous malformation) that tends to insinuate between the muscle fibers rather than produce an encapsulated mass.

Differential Diagnosis and Laboratory Studies

In cases of amyloid deposits or a neoplasm, a biopsy is diagnostic. An MRI study is usually helpful for soft tissue tumors in the tongue that present with asymptomatic enlargement.

Management and Prognosis

The diagnosis relies on a careful clinical history and examination, with biopsy as necessary. For symmetric lesions, there is no treatment unless the patient resorts to a surgical recontouring of the tongue.

For patients with amyloidosis, a work-up for plasma cell dyscrasia is indicated. For patients with other tumors, excision with/out the use of embolization in the case of vascular tumors is the treatment of choice.

Hyperplastic Lingual Tonsil

The lingual tonsil is located on the posterolateral aspects of the tongue bilaterally and is part of Waldeyer ring. In its healthy form, it lies below the foliate papillae (Fig. 76-23). Inflammation of this tissue from trauma or upper respiratory tract infection leads to hyperplasia. Although the term “foliate papillitis” is often used for this condition, the more accurate term is “hyperplastic lingual tonsil.”

Clinical Findings

The hyperplastic lingual tonsil, when inflamed, protrudes as a fleshy, soft area with a slightly irregular surface (because of the crypts in the overlying foliate papillae), which then becomes more readily traumatized that then makes it even more inflamed and protuberant.21

Differential Diagnosis and Laboratory Findings

This posterolateral tongue is a common site for SCC and the fairly rapid appearance of this lesion may mimic cancer. Lymphomas may also develop in this area.

Biopsy shows benign hyperplasia of lymphoid tissue.

Management and Prognosis

Excision is curative. Intralesional steroid injections may reduce the size of the lesion so that it is no longer traumatized.

Papillitis of Tongue

There are several forms of papillitis and they represent irritation of the tongue papillae either from local trauma, dryness, or a hypersensitivity reaction (possibly to a contactant).

Clinical Findings

One form is transient lingual papillitis that presents as multiple enlarged white papillae scattered over the surface of the tongue that tends to be relapsing–recurring.232–234 Another form presents as reddened and enlarged fungiform papillae on the dorsum of the tongue (Fig. 76-24). A rare form is eruptive papillitis with intrafamilial transmission.235

Management and Prognosis

Dexamethasone mouth rinse reduces inflammation. However, the inciting factor must be addressed to prevent recurrence.

Tongue Nodules

As with the lip, nodules on the lateral tongue tend to have a traumatic etiology and include fibromas (and its variant giant cell fibroma) and traumatic neuroma. More common tumors of the tongue include benign nerve sheath tumors, granular cell tumors, oral lymphoepithelial cyst, vascular lesions such as pyogenic granulomas or venous malformations, and osseous and cartilaginous hamartomas.

All require excisional biopsy and have diagnostic histopathology.

1. Do you feel you have less saliva than you normally do?

2. Does your mouth feel dry when eating a meal?

3. Do you have trouble swallowing food?

4. Do you need to sip water to help you eat dry food?

Clinical Findings

Differential Diagnosis and Laboratory Studies

Management and Prognosis

Clinical Findings

Differential Diagnosis and Laboratory Studies

Management and Prognosis