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Non-Neoplastic Lesions of the Oral Cavity


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Fordyce Granules

Clinical Features

Fordyce granules are considered benign ectopic sebaceous glands (not associated with hair follicles) that occur on the oral mucosa. A normal variant, they are reported in up to 80% of adults, most commonly on the upper and lower lip and the buccal mucosa. They present as multiple, uniform-sized yellow or yellow-white papules ( Fig. 7.1 ), which may coalesce to form plaques. Usually asymptomatic, patients sometimes describe surface roughness.

Fordyce Granules—Disease Fact Sheet

Definition

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    Benign ectopic sebaceous glands, considered to be a normal variant

Incidence and Location

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    Reported in up to 80% of adults

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    Present on the upper and lower lip and the buccal mucosa

Sex and Age Distribution

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    Sexes equally affected

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    Less clinically evident in children and adolescents

Clinical Features

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    Asymptomatic, multiple, small yellow papules

Prognosis and Therapy

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    Considered a normal variant

FIGURE 7.1, Clinical photograph of asymptomatic, multiple, small, yellow papules on the buccal mucosa ( arrows ) in this example of Fordyce granules.

Pathologic Features

Biopsy reveals normal sebaceous glands near the surface epithelium without hair follicles ( Fig. 7.2 ). Usually, multiple acinar lobules are present, although it may consist of one sebaceous lobule. A central duct sometimes connects the sebaceous lobules to the epithelial surface. Along the periphery, the sebaceous cells are basophilic and cuboidal, while the centrally located cells are polygonal in shape with abundant foamy cytoplasm and a centrally placed nucleus.

Fordyce Granules—Pathologic Features

Microscopic Findings

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    Normal sebaceous glands, below the surface, devoid of hair follicles

FIGURE 7.2, Multiple sebaceous glands in the superficial lamina propria.

Differential Diagnosis

Superficial mucoceles, which can present as 1- to 3-mm papules on the lower lip, generally are blue to clear in color and spontaneously resolve.

Prognosis and Therapy

No treatment is indicated, although laser ablation can be offered to patients for cosmesis. Tumors arising from Fordyce granules have been reported but are extremely rare.

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Amalgam Tattoo

Clinical Features

Amalgam tattoo is a common localized area of blue, gray, or black pigmentation caused by amalgam that has been embedded into the oral tissues during dental procedures. Amalgam is a common material used for dental fillings and contains silver, tin, mercury, and other metals. Amalgam tattoos are most commonly located on the buccal mucosa, gingiva, and alveolar ridge ( Fig. 7.3 ), usually presenting as flat macules, anywhere from a few millimeters to larger, more diffuse areas of pigmentation.

FIGURE 7.3, Clinical photograph of a blue-gray pigment present on the maxillary alveolar ridge. The pigmented area is flat with no ulceration or induration, and is asymptomatic.

Radiographic Features

Generally, amalgam tattoos are not visible on dental radiographs. Larger tattoos may be visible on radiographs as densely radio-opaque lesions.

Amalgam Tattoo—Disease Fact Sheet

Definition

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    Localized pigmentation caused by amalgam that has been embedded in the oral tissues due to dental procedures

Incidence and Location

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    Common

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    Most common on the buccal mucosa, the gingiva, and the alveolar ridge

Clinical Features

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    Asymptomatic flat macules ranging from a few millimeters to more diffuse areas of blue, gray, or black pigmentation

Prognosis and Therapy

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    No treatment necessary unless for cosmetic reasons, or if the clinical diagnosis is uncertain and a melanocytic neoplasia needs to be ruled out

Pathologic Features

An amalgam tattoo can demonstrate both discrete, fine, black granules and scattered, irregular, solid fragments ( Fig. 7.4 ). Pigment granules are often arranged along collagen fibers and around blood vessels and nerves. Most cases elicit no tissue reaction, although a foreign body, giant cell reaction has been reported in up to 38% of cases.

FIGURE 7.4, Black pigmented material is seen scattered in the lamina propria along collagen bundles and around blood vessels. The overlying epithelium is normal, and scant inflammatory cells are present. Although unusual, foreign body giant cell reactions can occur ( arrow ).

Differential Diagnosis

Other exogenous pigmentations can mimic an amalgam tattoo, including graphite, coal dust, and intentional tattooing. Melanin may be present in pigmented nevi, oral melanotic macule, oral melanoacanthoma, and melanoma. Further investigation is warranted if amalgam tattoos occur in sites distant from dental work or if the clinical diagnosis is uncertain.

Amalgam Tattoo—Pathologic Features

Microscopic Findings

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    Discrete, black granules, and/or solid fragment findings of pigment arranged along collagen fibers, around blood vessels and nerves

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    Foreign body reaction reported in up to 38% of cases

Pathologic Differential Diagnosis

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    Other exogenous sources of pigmentation including pencil graphite, intentional tattoos, and coal dust

Prognosis and Therapy

No treatment is generally required, unless for cosmetic reasons (surgery or laser treatment) or if the clinical diagnosis is uncertain and a melanocytic neoplasm needs to be ruled out.

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Ectopic Thyroid

Clinical Features

Ectopic thyroid is a result of the abnormal migration of the thyroglossal duct from the foramen cecum located at the junction of the anterior two-thirds and posterior third of the tongue to its normal prelaryngeal location. While uncommon, nearly 90% of all ectopic thyroids are located on the tongue between the foramen cecum and the epiglottis. In > 70% of patients with lingual thyroid, this is the only functioning thyroid tissue. Females are affected four to seven times as frequently as males. Symptoms, including dysphagia, dyspnea, globus sensation, and dysphonia, most often coincide with puberty onset, pregnancy, or menopause corresponding to elevated thyroid-stimulating hormone (TSH). Thyroid function tests should be evaluated as part of the workup. The endoscopic appearance at the base of the tongue is of a hyperemic mass ( Fig. 7.5 ).

FIGURE 7.5, Clinical photograph of a lingual thyroid presenting as a midline nodular mass at the base of the tongue. The surface is smooth and hyperemic.

Radiographic Features

The iodine content of the thyroid tissue results in very high signal attenuation in relation to surrounding soft tissue using computed tomography. Radioisotopic studies ( 131 Iodine and/or 99m Tc: technetium-99m pertechnetate) may be needed to determine size, location, and activity of thyroid tissue.

Ectopic Thyroid—Disease Fact Sheet

Definition

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    Rare developmental anomaly due to the abnormal migration of the thyroid gland from the base of the tongue

Incidence and Location

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    Uncommon, with reported incidence of 1/100,000

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    90% of ectopic thyroids are lingual thyroids

Morbidity and Mortality

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    Larger lesions can cause airway obstruction

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    Rare reports of carcinoma development

Sex and Age Distribution

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    Females > > > males (4-7 : 1)

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    All ages (mean, 44 years)

Clinical Features

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    Dysphagia, dyspnea, dysphonia, globus sensation

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    One-third of patients are hypothyroid

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    In > 70%, ectopic tissue is only functional thyroid tissue

Prognosis and Therapy

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    Euthyroid and asymptomatic patients only require periodic follow-up

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    Suppression therapy with thyroxine to reduce size and symptoms

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    Radioactive 131 I ablation

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    Autotransplantation of lingual thyroid

Pathologic Features

Immediately below the intact surface mucosa, unencapsulated ectopic thyroid follicles containing colloid and lined by cuboidal epithelium are identified, insinuating between the tongue musculature ( Fig. 7.6 ). Lymphocytic thyroiditis and adenomatoid nodules, as well as papillary thyroid carcinoma, have been reported.

Ectopic Thyroid—Pathologic Features

Microscopic Findings

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    Unencapsulated normal thyroid tissue insinuated through skeletal muscle

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    Lymphocytic thyroiditis and adenomatoid nodules may develop

Pathologic Differential Diagnosis

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    Metastatic thyroid carcinoma

Ancillary Studies

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    Positive cytoplasmic staining with thyroglobulin, epithelial membrane antigen, and low-molecular weight cytokeratin

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    Positive nuclear staining with TTF-1

FIGURE 7.6, Normal stratified squamous epithelium overlying a unencapsulated collection of thyroid follicles. Note the minor mucoserous glands adjacent to the thyroid follicles.

Fine Needle Aspiration

Fine needle aspiration biopsy can be used to confirm the diagnosis of ectopic thyroid or to rule out neoplastic changes.

Differential Diagnosis

There are a number of clinical differential diagnostic considerations (hemangioma, lymphangioma, hypertrophic lingual tonsils, abscess, mucus retention cyst, squamous cell carcinoma), but the histologic features of ectopic thyroid are pathognomonic.

Prognosis and Therapy

Thyroxine suppresses TSH with a subsequent reduction in size. Surgery is used if there is uncontrollable hemorrhage, airway obstruction, or inability to eat. Radioablation may be used in nonsurgical candidates. If no “normal” thyroid is identified in the anterior neck, autotransplantation can be performed. Malignancy is a rare complication (< 1%), although it is more common in men.

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Oral Hairy Leukoplakia

Clinical Features

Oral hairy leukoplakia (OHL) is a benign epithelial disease associated with Epstein-Barr virus (EBV) and nearly always identified in human immunodeficiency virus (HIV)-infected and/or immunocompromised patients. The disease correlates with viral load and CD4 counts. OHL usually presents on the lateral border of the tongue as a white plaque, or vertical streaks, or with a corrugated surface ( Fig. 7.7 ). The lesions can become quite extensive, and in some cases cover the entire lateral and dorsal tongue. The lesion is asymptomatic and cannot be rubbed off.

Oral Hairy Leukoplakia—Disease Fact Sheet

Definition

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    Benign, asymptomatic epithelial hyperplasia associated with Epstein-Barr virus nearly always in immunocompromised patients

Incidence and Location

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    Less than 10% of HIV-infected patients who are on highly active antiretroviral therapy

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    Non-HIV associated OHL reported in solid-organ transplant recipients and less commonly in patients with hematologic malignancies, autoimmune diseases, and other systemic inflammatory conditions

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    OHL reported in immunocompetent patients on long-term inhaled, topical, and systemic corticosteroid use

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    Primarily occurs on the lateral tongue, unilaterally or bilaterally

Sex, Race, and Age Distribution

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    Identified particularly in HIV-positive men

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    No racial or age predilection

Clinical Features

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    White patches that can have a corrugated or folded surface that cannot be rubbed off

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    May be quite extensive and bilateral and involve dorsal tongue

Prognosis and Therapy

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    10% improve spontaneously

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    No specific treatment, although secondary Candida may need to be treated

HIV , Human immunodeficiency virus; OHL , oral hairy leukoplakia.

FIGURE 7.7, HIV-positive patient with a white patch on the lateral border of the tongue exhibiting a corrugated appearance in this example of oral hairy leukoplakia.

Pathologic Features

OHL is characterized by marked epithelial acanthosis with elongation of the rete ridges and prominent hyperkeratosis. In the superficial spinous layer, “balloon cells,” characterized by intracellular ballooning degeneration, nuclear clearing, and margination of the chromatin indicative of a viral cytopathic effect, are present ( Fig. 7.8 ). These nonspecific findings require documentation of EBV within the lesion.

Oral Hairy Leukoplakia—Pathologic Features

Microscopic Findings

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    Epithelial hyperplasia, hyperparakeratosis, and acanthosis

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    Balloon cells in the upper spinous layer

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    Viral cytopathic effect can sometimes be seen

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    Little or no inflammation

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    Secondary candidal infection may be identified

Ancillary Studies

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    Markers for Epstein-Barr virus antigens (EBER) show punctate nuclear staining in the balloon cells

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