Benign Neoplasms of the Oral Cavity

Clinical Features

Fibroma is the most common “tumor” encountered in the oral cavity. It occurs more often in women than in men by a 2 : 1 ratio. It usually presents during the fourth to sixth decades of life but may be found across a wide age range that includes children and the elderly. There is no racial predilection. Distribution within the oral cavity, not surprisingly, reflects those sites most prone to trauma. Consequently, fibromas favor the buccal mucosa, specifically along the bite (occlusal) line, and the lateral border of the tongue. They may, however, arise on the lips and gingiva as well. The classic clinical appearance is that of an elevated sessile nodule surfaced by smooth mucosa ( Fig. 8.1 ). Although fibromas are painless, patients tend to report them as a nuisance.

Pathologic Features

Microscopic Findings

The histologic picture is dominated by the nodular deposition of submucosal collagen ( Fig. 8.2 ). Spindled fibroblasts and small blood vessels are dispersed among the pink, dense collagen bundles ( Fig. 8.3 ). The periphery of the nodule may be rounded and sharply demarcated or it may blend imperceptibly with the surrounding fibrous connective tissues. The overlying squamous epithelium may be attenuated with flattening of its rete ridges as if it were being tightly stretched over the nodular mass. Trauma to the nodule may incite secondary changes ranging from friction-induced hyperkeratosis to ulceration.

The fibroblasts of irritation fibromas are spindled and inconspicuous. The presence of larger stellate fibroblasts with large and multiple nuclei is characteristic of the giant cell fibroma ( Fig. 8.4 ). In contrast to the more common irritation fibroma, the giant cell fibroma is not associated with trauma, tends to occur in a younger age group, and favors the tongue and gingiva.

Fibroma—Pathologic Features

Gross Findings

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  Dome-shaped nodule ranging from a few millimeters to 2 cm

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  Smooth surface unless secondarily ulcerated

Microscopic Findings

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  Histologic picture dominated by submucosal collagen

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  Inconspicuous spindled fibroblasts sparsely dispersed among collagen bundles

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  Squamous epithelium is usually unremarkable, but may demonstrate varying degrees of rete atrophy, hyperkeratosis, and/or superficial ulceration

Pathologic Differential Diagnosis

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  Generally obvious, but granular cell tumor, scar, and lobular capillary hemangioma may be considered

Differential Diagnosis

Although fibromas are common and clinically inconsequential, surgical removal with microscopic examination is prudent to rule out various benign and malignant neoplasms that may simulate the clinical appearance of fibromas, such as schwannomas, neurofibromas, granular cell tumors, and salivary gland neoplasms. This broad clinical differential diagnosis, however, is easily resolved by microscopic examination, carefully observing any keloid-like collagen seen in a scar; vascular proliferation, which may be a sign of an organizing lobular capillary hemangioma; or large, polygonal cells with eosinophilic granules seen in granular cell tumor.

Prognosis and Therapy

As a reactive non-neoplastic process, fibromas have no malignant potential. Simple surgical resection is curative. If the source of inciting trauma has not been adequately addressed, the lesion may rarely recur.

Clinical Features

SPs represent the most common benign neoplasm originating from the oral mucosa. They occur across a broad age range, affecting both children and adults. Most lesions, however, are diagnosed in individuals 30 to 50 years of age. Some large studies indicate that males are affected more commonly than females and white more than black patients. They may arise from any intraoral mucosal location, but they show a definite predilection for the hard and soft palate and uvula.

SPs are clinically observed as soft, white pedunculated nodules that usually measure less than 1 cm ( Fig. 8.5 ). Their hallmark frond-like projections give rise to surface irregularities that range from granular, to spiny, to convoluted (i.e., “cauliflower-like”). Most SPs of the oral cavity are solitary and may have a history of being present for years, reflecting the low virulence and infectivity of this lesion. In contrast, verruca vulgaris and condyloma acuminatum frequently present as multiple or clustered lesions reflecting their more infectious nature.

Pathologic Features

Microscopic Findings

The trademark feature of SP, namely its papillary extensions, is histologically characterized by multilayered squamous epithelium supported by a central fibrovascular core ( Fig. 8.6 ). The squamous layer is often thickened, but it demonstrates normal maturation. Hyperplasia of the basal cell layer with increased mitotic figures is not uncommon and should not be interpreted as a precursor (i.e., dysplastic) lesion. HPV-induced cytopathic changes may sometimes be appreciated in cells within the prickle cell layer. These altered cells are referred to as koilocytes, and they are characterized by dark condensed and crenated nuclei surrounded by cleared cytoplasm and prominent cell borders ( Fig. 8.7 , inset ).

Verruca vulgaris demonstrates hyperkeratotic squamous epithelium (church spire appearance) supported by underlying fibrovascular connective cores. Distinguishing findings are a prominent granular cell layer with occasional keratohyaline granules and rete ridges that converge at the base of the lesion ( Fig. 8.8 ). Oral condyloma is characterized by acanthosis with wide rete ridges. The epithelium often displays impressive koilocytic change.

Squamous Papilloma—Pathologic Features

Gross Findings

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  Exophytic, warty, friable, and white to gray

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  Surface irregularities ranging from granular, to spiny, to convoluted

Microscopic Findings

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  Fibrovascular cores lined by mature, stratified squamous epithelium

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  The cells of the prickle layer may show koilocytic change: crenated, hyperchromatic nuclei surrounded by clear cytoplasm (“halos”) and prominent cell borders

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  Hyperplasia of the basal cell layer is common and should not be mistaken as a precursor (i.e., dysplastic) lesion

Pathologic Differential Diagnosis

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  Verruca vulgaris, condyloma acuminatum, multifocal epithelial hyperplasia, reactive papillary hyperplasia, proliferative verrucous leukoplakia, papillary squamous cell carcinoma

Ancillary Studies

In situ hybridization using type-specific HPV probes is a fairly reliable method of documenting the presence of HPV 6 or 11 in oral SPs, but this technique plays no practical role in diagnosing SP, determining treatment, or predicting clinical behavior.

Differential Diagnosis

SPs can be distinguished from other HPV-associated lesions of the oral cavity based on clinical and histopathologic characteristics. Verruca vulgaris usually occurs as warty excrescences located along the vermilion border, labial mucosa, and/or the anterior tongue of children. Histologically, verruca vulgaris will have projections of epithelium that appear to converge at the base. The epithelium demonstrates a prominent granular layer with spires of hyperkeratosis (see Fig. 8.8 ). Oral condyloma, a sexually transmitted disease, is seen most commonly in young adults at sites of sexual contact (e.g., labial mucosa, soft palate), as clusters of pink nodules that coalesce into broad-based exophytic masses. Microscopically, its papillary fronds are broader and more blunted than the papillary projections of SP. Koilocytes are usually more prominent (see Fig. 8.7 ). Multifocal epithelial hyperplasia shows multiple lesions, with acanthosis, and expanded and often fused rete and mitosoid cells.

Other oral lesions that may be considered in the differential diagnosis include reactive papillary hyperplasia , proliferative verrucous leukoplakia (PVL), and papillary squamous cell carcinoma . The distinction between SP and papillary hyperplasia is usually determined clinically. Papillary hyperplasia is a reactive process that is generally seen in association with ill-fitting prostheses, usually dentures. PVL is characterized by multifocal lesions that may appear histologically similar to SPs. This condition represents a varied process that relentlessly spreads and progresses to malignancy. Papillary squamous cell carcinoma may share some of the architectural findings of SP but will have malignant cytology.

Prognosis and Therapy

As a benign neoplasm with a limited growth potential, the oral SP is cured by local excision or laser ablation. Local recurrence is uncommon and malignant transformation is exceedingly rare. Importantly, they do not share with juvenile laryngeal papillomas the penchant for multifocality, widespread growth, and rapid recurrence.

Clinical Features

MFEH is not common, and incidence rates vary widely depending on age and ethnicity. The ethnic incidence of MFEH is broader than initially reported and it has been reported in populations from North, South, and Central America, Africa, and the Middle East, among other groups. Most initial diagnoses involve children and adolescents, and in certain ethnic groups, nearly 40% of children are affected. However, lesions can be seen throughout life. In some ethnic populations, females are affected more frequently than males by a 2 : 1 ratio. MFEH has also been reported among those who are HIV positive and, interestingly, its frequency increases with the introduction of highly active antiretroviral therapy (HAART). This has also been seen with SPs and other HPV-associated lesions of the oral cavity.

MFEH has a distinct clinical appearance. It is seen as multiple clustered flat-topped papules and rounded nodules that have a predilection for the labial, lingual, and buccal mucosae ( Fig. 8.9 ). Individual papules are discrete and small (a few millimeters to 1 cm), but tightly clustered papules may coalesce to form large confluent lesions. Papules tend to be soft and painless.

Pathologic Features

Microscopic Findings

The hallmark histologic feature is acanthosis of the squamous epithelium ( Fig. 8.10 ). The rete ridges are expanded and often fused. The keratinocytes show orderly maturation without atypia. Parakeratosis is a common finding. Virus-induced cellular alterations are sometimes present in the superficial keratinocytes. These alterations include koilocytic changes typical of HPV infection, and a more unique type of alteration characterized by fragmentation of the nuclei in a way that resembles a mitotic figure (the “mitosoid cell”) ( Fig. 8.11 ).

Multifocal Epithelial Hyperplasia—Pathologic Features

Gross Findings

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  Tan, soft nodules with a sessile base and smooth surface

Microscopic Findings

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  Abrupt acanthosis (simple squamous hyperplasia) with orderly maturation

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  Expansion, clubbing, and fusion of the rete ridges

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  Virus-induced alterations include koilocytes and a peculiar form of nuclear fragmentation resembling a mitotic figure (“mitosoid cell”)

Differential Diagnosis

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  Condyloma acuminatum, squamous papilloma

Ancillary Studies

The presence of HPV can be documented using a variety of detection methods ranging from electron microscopy to type-specific DNA in situ hybridization. Viral detection, however, is a matter more of academic interest than of diagnostic relevance and methods of detection are generally not commercially available. Additionally, these techniques do not play any significant role in diagnosing MFEH or predicting its clinical behavior.

Differential Diagnosis

Careful correlation of the clinical and pathologic findings should allow ready distinction of MFEH from other papular eruptions of the oral cavity. Condyloma acuminatum , for example, may clinically present as multifocal coalescent nodules of the oral mucosa. At the microscopic level, however, condyloma acuminatum and its family of HPV-related oral warts are characterized by a papillary growth as opposed to the simple squamous hyperplasia of MFEH. The distinction is important as lesions submitted from children may raise a question of sexual abuse.

Prognosis and Therapy

MFEH is a benign epithelial proliferation that often undergoes spontaneous regression. Removal of individual lesions by surgical excision or laser ablation for cosmetic purposes is feasible when a few lesions are present but impractical when lesions are more numerous and widespread.

Clinical Features

LCH occurs in all age groups. Although it occurs equally in both sexes overall, some have noted an unequal sex distribution across different age groups: Patients younger than 18 years are predominantly male, patients between 18 and 39 years are predominantly female, and patients older than 39 years are more evenly distributed. The proportional increase in females during reproductive years reflects the contribution of hormonally driven lesions that occur during early stages of pregnancy.

The most frequently involved oral sites are the lips, gingiva, cheek, and tongue. Those lesions that arise during pregnancy almost exclusively involve the gingiva and are sometimes referred to as a pregnancy tumor . About one-third develop following minor trauma, whereas others are the result of a reaction to local irritation. Lesions of the oral cavity are almost always solitary. The clinical presentation is that of a nonpainful, purple-red polypoid mass that is friable and bleeds easily; not surprisingly, bleeding is the most common clinical complaint ( Fig. 8.12 ). The surface is often ulcerated and sometimes covered with an exudate. Most lesions range in size from a few millimeters to a few centimeters.