Lesions of the Oral Cavity

Clinical Features

The irritation fibroma has a 66% female predilection and can occur at almost any age, but is usually biopsied in the fourth through sixth decades of life. It is, however, rare during the first decade. Since it is almost always seen as a single nodule, patients with multiple fibroma-like masses may represent cases of familial fibromatosis, fibrotic papillary hyperplasia of the palate, symmetrical palatal fibromatosis (SPF), chronic lingual papulosis, tuberous sclerosis, Gardner syndrome, multiple hamartoma syndrome (Cowden syndrome), or multiple endocrine neoplasia syndrome 2B (MEN 2B, MEN 3). Those with a generalized fibrous overgrowth of gingival tissues are said to have fibrous gingival hyperplasia or gingival fibromatosis, discussed elsewhere in this chapter.

Buccal mucosa, labial mucosa, and lateral tongue sites are those most likely to be traumatized and so it is not surprising to find that these sites account for 71% of all oral fibromas. The mass is typically pedunculated or sessile with a smooth surface. Usually reaching its maximum size within a few months ( Fig. 4.1A ), it seldom exceeds 1.5 cm in size, and once fully formed, it remains indefinitely without change. It is an asymptomatic, moderately firm, immovable mass with a surface coloration that is most often normal but may show pallor from decreased stromal vascularity, whiteness from thickened surface keratin, or brown discoloration from development in a pigmented portion of mucosa. Occasionally, surface ulceration arises from acute or recurring trauma.

A fibroma beneath a denture has no room to expand uniformly in all directions and so develops as a flat, pancake-shaped mass with small surface irregularities along the outer edges. This leaf-shaped fibroma is often associated with an underlying cupped-out area of bony saucerization, with an associated convexity of palatal bone into the overlying sinus ( Fig. 4. 1B ).

Another unique variant of denture-related fibroma, epulis fissuratum (epulis means “mass on the gingiva”), is an irregular, linear, fibrous hyperplasia occurring in the mucosal vestibule or sulcus, adjacent to the alveolar ridge where the edge of a loose-fitting denture chronically traumatizes the tissue. The mass runs parallel to the edge of the denture ( Fig. 4.1C ). Eventually, three or more “waves” of fibrous redundant tissue may be seen, with deep grooves between them. The superior edges of these masses may have a line of papules or small secondary growths, perhaps explaining why the lesion was first reported in 1858 as mamillated epulis . The lesion accounts for about 3% of submitted oral biopsies and is usually found in persons 40 to 50 years of age.

The most recent variant of the oral fibroma presents not as a single mass but as a cluster of small fibrous masses, often dozens, located on the dorsum of the tongue called chronic lingual papulosis . These patients present with clustered, sometimes generalized, collections of 2 to 4 mm individual masses that appear identical to the irritation fibroma and are usually slightly pedunculated ( Fig. 4.1D ). Occasionally, one mass will be much larger than the others but usually they are rather uniform in size and show no clinical erythema, edema, or ulceration. The masses probably represent fibrous hyperplasia of fusiform papillae, but there is no alteration in taste, and, in fact, there are no symptoms at all unless a secondary candidiasis develops between the masses. The lesion is typically of long duration, presumably lasting indefinitely once formed; it has been reported from childhood to early middle age. Some cases appear to be late-onset developmental anomalies, while others seem to result from dry mouth or a mild, repeating physical irritation.

Pathologic Features and Differential Diagnosis

The irritation fibroma is composed of a dense, minimally cellular stroma of collagen fibers arranged randomly or organized into interlacing fascicles ( Fig. 4.2A and B ). The stromal cells are bipolar fibroblasts with plump nuclei and fibrocytes with thin, elongated nuclei and minimal cytoplasm. As with keloids of the skin, the mucosal fibroma may be remarkably avascular, but areas of degeneration or necrosis are not seen.

Usually, a few scattered mature capillaries are found; perhaps with a few showing dilation. In cases resulting from the slow fibrosis of granulation tissue or pyogenic granuloma, focal areas of edema and neovascularity may be seen in the midportion or lower third of the mass. Occasional lesions may still contain residual granulation tissue, prompting some pathologists to prefer the term fibrotic pyogenic granuloma . Such lesions may be indistinguishable from the angiofibroma of tuberous sclerosis. Occasional fibroma-like masses have surface lobulations and unusually large, stellate-shaped, sometimes multinucleated fibroblasts. These masses represent giant cell fibroma or other giant fibroblast-containing lesions, described in following sections.

Although usually nonencapsulated, some lesions show a pseudoencapsulation and may, therefore, be mistaken for neurofibroma or palisaded encapsulated neuroma. Scattered chronic inflammatory cells are seen in small numbers, typically beneath the epithelium or around blood vessels. Occasional fibromas demonstrate extreme elongation of rete processes and are called fibroepithelial polyps by some, presumably because of their similarity to the dermal lesion of that name. These polyps are seen especially on the tongue in patients with Gorlin syndrome (nevoid basal cell carcinoma syndrome).

The surface epithelium is usually atrophic but may show signs of continued trauma, such as excess keratin, intracellular edema of the superficial layers, or small traumatic ulceration. The hyperkeratinized epithelium is not dysplastic or precancerous and is essentially a frictional keratosis. Rarely, melanin deposition is seen in the basal layer. The latter has no diagnostic significance, but its presence has led some to refer to such a lesion as pigmented fibromas .

Epulis fissuratum is microscopically similar to routine irritation fibroma except that chronic inflammatory cells are more numerous, and the surface epithelium is much more likely to be ulcerated, especially in the base of the clefts between the redundant folds of tissue. The intact surface epithelium is often quite acanthotic, with occasional lesions showing enough elongation of rete processes to justify a secondary diagnosis of pseudoepitheliomatous hyperplasia ( Fig. 4.2C ). The pathologist must be very cautious about misinterpreting this epithelial hyperplasia as well-differentiated squamous cell carcinoma or verrucous carcinoma, especially with samples showing elongated rete processes cut tangentially or at right angles, appearing as separate islands of epithelium deep in the stroma. It is important, in this regard, to understand that carcinoma in association with epulis fissuratum is extremely rare.

Individual masses of chronic lingual papulosis are microscopically identical to the irritation fibroma, except that occasional taste buds may be found in the surface epithelium.

Treatment and Prognosis

Irritation fibroma and other localized fibrous hyperplasias are easily removed by conservative surgical excision, with no need to remove a large margin of surrounding normal mucosa. Recurrence is unlikely unless the inciting trauma/infection continues or is repeated. The bony concavity associated with some leaf-shaped fibromas, under dentures, will recontour to normal after removal of the offending mass. For epulis fissuratum, the treatment includes both surgical removal and reline or remake of the offending denture. If the denture is not corrected, recurrence in much more likely.

Chronic lingual papulosis requires no treatment and will remain indefinitely, once formed. If the affected lingual surface becomes tender or presents with a burning sensation, treatment for secondary candidiasis should be initiated.

Clinical Features

The giant cell fibroma is an asymptomatic fibrous nodule, which usually remains less than 1 cm in size ( Fig. 4.3A ). The base may be broad or pedunculated and the surface can be smooth but is typically lobulated or papillary, mimicking the squamous papilloma. Almost two-thirds of cases occur before age 30 years and there appears to be a slight female predilection. The most common site of occurrence in the mouth, representing approximately half of all cases, is the gingiva, with mandibular gingiva affected twice as often as the maxillary. The tongue and palate are also common sites of occurrence. An uncommon variant occurs on the retromolar pad of the posterior mandible, often bilaterally, and is sometimes called retromolar papule ( Fig. 4.3B ). This is not to be confused with the normal anatomic structure called the retromolar papilla (see later).

A normal anatomic structure, the retrocuspid papilla, has similar histology to the giant cell fibroma but always occurs on the lingual gingiva of the anterior mandible and is typically less than 5 mm in greatest dimension. It is usually bilateral and is located behind the cuspids or lateral incisors. It is very common in the pediatric population and involutes as the patient ages; it is uncommon in adults. The retrocuspid papilla is usually identified clinically and is not biopsied. A similar normal anatomic structure may be located on the retromolar pad of the posterior mandible and is referred to as the retromolar papilla .

Pathologic Features and Differential Diagnosis

The giant cell fibroma, and its look-alike counterparts, the retrocuspid papillae and the retromolar papule, consists almost entirely of avascular, moderately dense fibrous connective tissue, often with regions of fibromyxomatous stroma ( Fig. 4.3C ). The surface epithelium typically has very elongated, thin, and often pointed rete processes, typically with surface papules or bosselations. The “giant” cells required for the diagnosis are not numerous and are mostly concentrated beneath the epithelium. This cell is a stellate fibroblast, which is several times larger than the typical spindle-shaped fibroblast and often has a “smudged” appearance ( Fig. 4.3D ). Nuclei in these cells are enlarged but are not hyperchromatic; frequently a small number will have multiple nuclei. Some of these fibroblasts may contain melanin pigment, but they are not melanocytes.

Treatment and Prognosis

Giant cell fibroma remains small but can be treated by conservative surgical excision. It is unlikely to recur though recurrences have been reported. There is no malignant potential to the lesion. The retrocuspid papule also remains small and most will eventually disappear, therefore no treatment is usually necessary.

Clinical Features

The DF occurs primarily in males (2.5:1 male:female ratio) aged 40 to 70 years (median age = 50 years), presenting as a slow-growing, often bosselated mass, with individual lesions measuring 1 to 20 cm, at the time of diagnosis (average = 3.4 cm.). They have typically been present more than 6 months by the time of diagnosis. The masses may or may not be pedunculated and at least one has presented with pain.

Pathologic Features

DF is firm, well-circumscribed, round or oval, and demonstrates a glistening gray-to-white, obvious fibrous, cut surface. Histologically, it is hypocellular, with few vessels, and consists of dense to moderately dense collagenous or myxocollagenous stroma with scattered larger-than-normal spindle- or stellate-shaped, sometimes multinucleated, fibroblasts. These fibroblasts occasionally will contain melanin. Often, long, thick avascular bands of collagen are noted, and occasional lesions will contain areas of entrapped adipose tissue or smooth muscle.

Chronic inflammatory cells or focal areas of extravasated erythrocytes may be noted, as may occasional mitotic activity near the lesional borders. The overlying surface epithelium is normal, lacking the elongated, pointed rete processes of the giant cell fibroma and symmetrical palatal fibromatosis, and the border is well-demarcated, sometimes appearing encapsulated, but a few examples have shown apparent infiltration into adjacent muscle.

Lesional fibroblasts are diffusely, usually intensely, positive for vimentin and focally positive for smooth muscle actin (both muscle-specific and alpha), and some lesions have been focally and sparsely positive for cytokeratin. Immunostains for desmin, S-100 protein, and CD34 are typically negative. Ultrastructurally, the cells have characteristics of fibroblasts or myofibroblasts.

Treatment and Prognosis

Conservative surgical excision is the treatment of choice, with a small margin of normal surrounding tissue. DF can produce underlying saucerization overlying bone, but this will return to normal after lesion removal; there is no need to remove the periosteum. There is no malignant transformation potential, but some lesions have been misdiagnosed as sarcomas because of the unusual fibroblasts.

Clinical Features

SPF is diagnosed in young adults and has an average duration of more than 7 years; no reported case has been initiated before age 15 years. There is no gender predilection. Each reported example has presented as bilateral and symmetrical, large and sessile, smooth-surfaced, slightly bosselated masses, usually moderately firm to palpation but occasionally soft, and always with normal surface coloration ( Fig. 4.4A and B ). The center of each mass is on the lateral walls of the hard palate in the region where alveolar bone meets palatal bone. Masses often push into and enlarge adjacent gingival tissues or the maxillary tuberosity, a feature which may lead to misdiagnosis as gingival fibromatosis. Underlying bone is unaffected, adjacent teeth are not resorbed or moved, and the lesion is asymptomatic.

Pathologic Features

Masses are comprised entirely of dense, avascular and rather acellular fibrous connective tissue with scattered thick bands of collagen ( Fig. 4.4C ) and occasional slight surface bosselation. Myxoid change may be prominent, so much so that some have been misdiagnosed as a cartilaginous hamartoma. Occasional lymphocytes may be seen, if so, they are typically toward the surface but may occasionally be found in deeper tissues. Significantly, the stroma contained scattered large, angular fibroblasts, these occasionally have multiple nuclei or a “smudged” appearance, identical to those found in giant cell fibromas ( Fig. 4.4D ). The surface stratified squamous epithelium may show occasional long, thin, sometimes pointed rete processes.

Treatment and Prognosis

SPF can enlarge to more than 5 cm in greatest diameter, but even large lesions do not interfere with speech patterns; however, food may become trapped above masses so large that they touch one another. Treatment is conservative surgical excision, with preservation of the underlying periosteum. No recurrence has been reported.

Clinical Features

Fibromatosis occurs primarily in children and young adults but may first be seen in middle-aged individuals as well. There is no gender predilection. This lesion presents as a broad-based, firm, nonmoveable, sessile or slightly pedunculated, painless, slowly enlarging mass with normal surface coloration, perhaps with surface bosselations. ( Fig. 4.5A ). The speed of enlargement is variable and should not be used as a reliable predictor of aggressive future behavior; some lesions grow rapidly for a few months and then very slowly for years thereafter.

Fibromatosis usually develops adjacent to the mandible, where underlying bone may be eroded or destroyed by infiltrating fibrosis (see Fig. 4.5A ). Lesions average 3 to 4 cm in size at diagnosis, but can be as large as 9 cm, and multiple lesions have been reported. Larger lesions may develop secondary surface lobulation. This entity has also been reported to arise from within the medullary spaces of the jawbones.

Pathologic Features

Fibromatosis is characterized by a proliferation of spindle-shaped, somewhat primitive-looking mesenchymal cells arranged in streaming fascicles ( Fig. 4.5B ). Reticulin stains and Masson trichrome stain will confirm the collagenic nature of the stroma. Immunohistochemistry is focally reactive to smooth muscle actin, shows nuclear positivity for beta-catenin and is not reactive for desmin, h-caldesmon, or CD34.

Thin-walled vascular spaces are invariably present but not in large numbers. The lesional periphery is poorly demarcated from surrounding tissues and often appears to be infiltrating those tissues. Erosion or pressure saucerization of underlying bone, or destruction of the cortex, may be seen.

The degree of cellularity is variable, with some cases demonstrating moderate numbers of lesional cells in a background stroma of abundant mature collagen, while others showing minimal stroma with large numbers of active mesenchymal cells. In both types, cellularity is most pronounced at the periphery of the tumor. Hyperchromatic and pleomorphic nuclei are seldom seen, but occasional normal-appearing mitotic figures may be found. If present, the mitotic figures are never numerous. Regions near the periphery may show small numbers of chronic inflammatory cells. Immunostains are reactive to smooth muscle actin and nonreactive for desmin. Additional immunohistochemical features are described in Chapter 9 .

Occasional fibromatoses infiltrating striated muscle will induce atrophy, degeneration, and regeneration of muscle cells, resulting in the presence of osteoclast-like multinucleated giant cells and imparting a giant cell lesion appearance. The presence of dysplastic mesenchymal cells should make the pathologist suspicious for fibrosarcoma, malignant fibrous histiocytoma, or fibroblastic osteosarcoma (if attached to bone). Additional differential diagnoses are described in Chapter 9 .

Treatment and Prognosis

Though some lesions have spontaneously regressed, oral desmoid-type fibromatosis typically continues to enlarge slowly for months and years. It is usually treated by wide excision, including a thin margin of adjacent normal tissues. It has a locally aggressive, often infiltrative behavior. With surgical excision there is a recurrence rate of more than 20%, possibly because microscopically positive margins may be accepted to minimize local morbidity. Overall, this rate is similar to the rate for lesions of the sinonasal area but is far below the rate for lesions found in other extraabdominal locations (40%).

Recurrences are treated by reexcision, although radiotherapy and chemotherapy are often used. Relative to the latter, noncytotoxic and cytotoxic agents have been tried for recurrence prevention, but the literature suggests that certain hormonal drugs, nonsteroidal antiinflammatory drugs (NSAIDs), biologic drugs, and cytotoxic chemotherapeutic drugs are more helpful.

Severe, multicentric lesions with visceral involvement are much more serious and may lead to diarrhea or even respiratory distress. The oral lesions are usually of minimal consequence in such cases.

Clinical Features

Gingival fibromatosis/fibrous hyperplasia presents as a generalized, often irregular enlargement of the facial and lingual aspects of the attached and marginal gingiva ( Fig. 4.6A ). It is often more severe in the anterior maxillary region, crossing the midline, but there can be involvement of one or all quadrants. Enlargement is painless, slowly progressive, and dependent to a great extent on the oral hygiene of the individual. It is not unusual for the fibromatosis to completely cover the teeth. Some syndrome-associated hyperplasias (noted in Table 4.3 ) may have papillary or nodular surface alterations.

Although the hyperplastic tissues are usually firm to palpation, inflammation and edema may make some surface areas spongy, erythematous, and hemorrhagic under palpation. When this change is limited to tissues overlying only one or two teeth, there is often a unique histopathologic presentation, referred to a spongiotic gingival hyperplasia ; this is discussed in the next section.

Pathologic Features and Differential Diagnosis

Gingival fibromatosis is classically composed of dense or moderately dense, rather avascular, bland collagenic connective tissue, with scattered chronic inflammatory cells noted beneath the surface epithelium ( Fig. 4.6B ). The attached gingival epithelium may show elongation of rete processes; in some cases, this is extreme enough for a secondary diagnosis of pseudoepitheliomatous hyperplasia. The crevicular epithelium facing the tooth surfaces usually shows considerable degeneration, subepithelial edema, and extensive chronic inflammatory cell infiltration. Scattered neutrophils may be present; this is caused by the accompanying gingivitis or periodontitis.

Among the drug-induced examples, cyclosporine-induced lesions exhibit much more chronic inflammation than fibrosis, while nifedipine- and phenytoin-induced lesions are highly fibrotic. Such subtypes may also demonstrate a myxoid background.

When evaluating the inflammatory cell infiltrate, the pathologist must be careful to differentiate the polyclonal, mixed infiltrate from a diffuse submucosal infiltration of atypical leukocytes like those seen in leukemia or diffuse extranodal lymphoma (mucosal-associated lymphoid tissue [MALT] lymphoma).

Both chronic and acute leukemia patients may develop a generalized gingival hyperplasia secondary to massive infiltration of neoplastic leukocytes, presumably because these cells retain a certain amount of normal chemotactic ability and are drawn to an area of inflammation, such as with gingivitis. The clinical presentation is often called leukemic gingivitis or leukemic gingival hyperplasia . The criteria used for the determination of leukemia or lymphoid malignancy are the same as those used for leukemic or diffuse extranodal (MALT) lymphoma infiltrations anywhere in the body. These are discussed further in Chapter 13 .

Some cases of generalized gingival hyperplasia show focal collections of histiocytes intermixed with lymphocytes and foreign-body type multinucleated giant cells. This granulomatous gingivitis may be a foreign body reaction to the pastes used in prophylactic dental cleanings, or to other dental products. However, it may also be indicative of a more systemic chronic granulomatous disease, such as sarcoidosis, Crohn disease, or Wegener granulomatosis (granulomatosis with polyangiitis). Other gingival hyperplasias have large numbers of plasma cells scattered throughout the subepithelial stroma. This plasma cell gingivitis is presumed to be an unusual allergic reaction.

Juvenile hyaline fibromatosis, a hereditary condition that may involve the gingiva, can be distinguished from gingival fibromatosis by its prominent periodic acid-Schiff (PAS)–positive background matrix of chondroitin sulfate. Finally, amyloid infiltration of the gingival tissues is not uncommon in primary or secondary amyloidosis. It can be readily identified via Congo red stain under polarized light, thioflavin T stain under fluorescent light, or immunoreactivity with antibodies for immunoglobulin light chains.

Treatment and Prognosis

Gingival fibromatosis is removed by gingivectomy, recurrences are treated in the same fashion or by more conservative removal of local areas of hyperplasia. Improved oral hygiene and topical antibiotics will greatly diminish the risk of recurrence. DIGH may also be treated by gingivectomy and plaque control. Discontinuation of drug use often results in cessation and even regression of the gingival enlargement.

Recently, researchers have had some success with size reduction using antiinflammatory medications systemically. Granulomatous gingivitis and plasma cell gingivitis are treated by addressing the underlying etiologies, but this often will only keep the lesions from becoming more severe; they may last for many more months and, occasionally, for years.

Clinical Features

LJSGH is typically seen in the first two decades of life, with an average patient age of 12 years. There appears to be equal gender predilection and almost all lesions are located on the anterior maxillary gingiva (80%–91% of cases).

The lesion is typically an asymptomatic, well-demarcated, erythematous, slightly elevated mass with a granular or papillary surface, sometimes with slight bosselations. It occurs on the marginal and attached gingiva and reaches its full size in a few months ( Fig. 4.7A ). Individual lesions often have a linear shape and remain less than 1.5 cm in greatest diameter. Multiple synchronous areas of gingival involvement may be present and there is no loss of underlying osseous structures.

Pathologic Features

This lesion exhibits a pronounced epithelial hyperplasia characterized by acanthosis, prominent spongiosis and neutrophilic exocytosis, often with considerable lengthening of rete processes ( Fig. 4.7B and C ). The mass itself is formed by focally edematous and congested fibrovascular stroma with neovascularity and variable numbers of chronic inflammatory cells, primarily, lymphocytes. Neutrophils are often found in the stroma, as well as an abundance of nuclear dust. Cytokeratin 19 (CK19) is strongly and diffusely positive throughout the thickness of the epithelium, similar to the staining pattern of junctional epithelium. In contrast, normal gingival epithelium exhibits CK19 staining limited to the basal cell layer.

The normally dense, avascular fibrous hyperplasia of other forms of gingival hyperplasia is absent and the most likely mistaken diagnosis to be given is pyogenic granuloma (pyogenic granuloma type of hemangioma).

Treatment and Differential Diagnosis.

Conservative surgical excision is the treatment of choice for this entity, with recurrences occurring up to 2 years after treatment. Multiple recurrences have been noted.

Clinical Features

Oral submucous fibrosis typically affects the buccal mucosa, lips, retromolar areas, and soft palate. Occasional involvement of the pharynx and esophagus is seen. Early lesions present as a blanching of the mucosa, imparting a mottled, marble-like appearance ( Fig. 4.8A ). Later lesions demonstrate palpable fibrous bands running vertically in the buccal mucosa and in a circular fashion around the labial mucosa. As the disease progresses, the mucosa becomes stiff, causing difficulty in eating and considerably restricting the patient’s ability to open the mouth (trismus). If the tongue is involved, it becomes stiff and diminishes in size.

Mucosal petechiae are seen in more than 10% of cases. Most patients complain of a burning sensation, often aggravated by spicy foods. Salivary flow is diminished and blotchy melanotic mucosal pigmentation (reactive melanosis) is often seen. Patients can develop extrinsic staining of the oral mucosal tissues or, more commonly, of the teeth. More than one-fourth of affected persons develop precancerous leukoplakia of one or more oral surfaces. Once present, oral submucous fibrosis does not regress, even after cessation of betel quid chewing.

Pathologic Features and Differential Diagnosis

Early cases of oral submucous fibrosis present as chronic inflammatory cell infiltration of subepithelial connective tissues ( Fig. 4.8B ). This otherwise nonspecific infiltrate usually contains a number of eosinophils, cells seldom found in routine oral inflammation. Older lesions demonstrate reduced vascularity, reduced numbers of inflammatory cells, and dense bundles and sheets of collagen immediately beneath the epithelium. The eventual thick band of hyalinized subepithelial collagen shows varying extension into submucosal tissues, typically replacing the fatty or fibrovascular tissues normal to the site.

Minor salivary glands in the area of habitual quid placement often demonstrate a chronic inflammatory infiltrate and replacement of acinar structures by a hyalinized fibrosis. The hyalinized stroma can mimic amyloid deposits, but Congo red and/or thioflavin-T staining can rule this out.

The epithelium is atrophic, with or without excess surface keratin, and demonstrates intracellular edema. One-fourth of the biopsied cases will demonstrate epithelial dysplasia at the time of biopsy. When squamous cell carcinoma is seen, it has the same features of carcinoma as those seen in persons without the betel quid chewing habit.

Treatment and Prognosis

There is no effective treatment for oral submucous fibrosis, and the condition is irreversible once formed. Plastic surgery may be required to allow for improved opening of the mouth. Surface leukoplakias are handled by close follow-up and repeated biopsies of areas of severe involvement. All dysplasias and carcinomas are treated in the routine manner for those entities. Epidemiologic studies have shown that as many as 8% of oral submucous fibrosis patients develop an oral carcinoma. Since the tobacco is the component of the quid most associated with cancer development, cessation of the quid chewing habit or eliminating the tobacco from the quid will reduce the risk of oral cancer, even though the fibrosis is not altered.

Clinical Features

Persons affected by oral/pharyngeal fibrosarcoma are usually 30 to 50 years of age, but there is a wide age range and many patients are less than 20 years of age. Fibrosarcoma has been diagnosed in the oral region of infants. There is no apparent gender predilection and any submucosal site may be involved, although the buccal mucosa and tongue account for three-fourths of cases.

Fibrosarcoma most often presents as a clinically innocuous, lobulated, sessile, usually painless, and nonhemorrhagic submucosal mass of normal coloration. It may, however, be a rapidly enlarging, hemorrhagic mass similar in clinical appearance to an ulcerated pyogenic granuloma, peripheral giant cell granuloma, or peripheral ossifying fibroma, if present on the gingiva or alveolar ridge. Even lesions that do not demonstrate surface ulceration or rapid growth may show destruction of underlying muscle and bone.

Pathologic Features and Differential Diagnosis

Fibrosarcoma is a lesion with a varied microscopic appearance and is a diagnosis of exclusion, used when all other spindle cell sarcomas are ruled out. Lesional cells are spindle-shaped and uniform in size, with pale eosinophilic cytoplasm and spindled nuclei with tapered ends. Cells typically flow in interweaving fascicles or bundles and often produce focal areas with a herringbone pattern, a feature which helps greatly to separate this lesion from fibrous hyperplasias and fibromatoses.

The lesion is typically quite cellular, but moderate amounts of mature collagen may be produced, perhaps with areas of hyalinization. Scattered, histologically normal mitotic figures are seen in small numbers, while cells and nuclei may be very pleomorphic. It is typically categorized into low-grade, intermediate-grade or high-grade fibrosarcoma and aggressive clinical behavior must be taken into account when determining such grades. This chapter is not intended for microscopic detail and differential diagnosis of fibrosarcoma look-alikes; these are presented, along with immunohistochemistry, in Chapter 9 .

The low-grade or well-differentiated variant is usually somewhat circumscribed and consists primarily of fascicles of uniformly shaped spindle cells that often form a “herringbone” pattern. However, most fibrosarcomas of the oral region are not low-grade. High-grade or poorly-differentiated lesions show cellular and nuclear pleomorphism, more frequent mitotic figures and less collagen than do well-differentiated tumors. Focal anaplasia and necrosis may be seen; these are missing from the low-grade lesions. Immunohistochemical reactivity should be negative except for vimentin, a relatively nonspecific marker for mesenchymal intermediate filaments. Scattered or weak positivity for smooth muscle actin may be seen, suggesting myofibroblastic differentiation. Fibrosarcoma of infancy and early childhood demonstrates smaller, more numerous, and more primitive cells than the adult lesion.

The pathologist must take special precautions to distinguish fibrosarcoma from spindle cell carcinoma, a task made more difficult by the existence of an epithelioid variant of fibrosarcoma, the sclerosing epithelioid fibrosarcoma. The latter has a low cellularity, a mildly pleomorphic, sclerotic hyaline matrix, and a deceptively benign initial behavior, although one-third present with pain. It has recently been shown to have FUS-CREB3L1/L2 fusion transcripts, using reverse transcription-polymerase chain reaction, and so may actually be a low-grade fibromyxoid sarcoma.

Treatment and Prognosis

Well-differentiated fibrosarcoma of the oral cavity is treated by wide local excision, whereas more poorly differentiated tumors require radical surgery, including removal of potentially invaded muscle and bone. Fibrosarcoma seldom metastasizes, except late in its clinical course, but when this does occur, the metastatic deposits are usually blood-borne and carried to distant sites, especially the lungs, liver, and bones. Radiotherapy may be used as salvage for recurrences, which occur in almost half of all cases. The 5-year survival rate ranges from 50% to 70%. The epitheliod variant has a somewhat better prognosis.

Clinical Features

The most common location of BFH occurrence is the skin of the extremities, where it usually presents as a small, firm nodule. Oral and perioral lesions have a similar appearance and occur predominantly on the buccal and vestibular mucosa. The oral lesion is typically found in middle-aged and older adults, where it presents as a painless submucosal nodule that can vary in size from a few millimeters to several centimeters. Deeper tumors tend to be larger and much less frequent. Most lesions cannot be easily moved about beneath the epithelium.

Pathologic Features and Differential Diagnosis

Fibrous histiocytoma is characterized by a submucosal, cellular aggregation of spindle-shaped, fibroblast-like cells with relatively pale, oval nuclei; scattered rounded histiocytic cells are also present. Foamy histiocytes and Touton-type multinucleated giant cells may be seen to contain phagocytosed lipid or hemosiderin; these cells sometimes are so numerous that they form xanthomatous aggregates. A background stroma of variably dense collagenic tissue and vascularity is seen.

The spindled cells may be arranged randomly, but usually there are large areas with tumor cells streaming in interlacing fascicles from a central nidus and intersecting with cells from adjacent aggregates, imparting a storiform or crisscross pattern on low-power magnification. Polygonal epithelioid cells may be present in abundance. If they represent more than 50% of lesional cells, a diagnosis of epithelioid fibrous histiocytoma is preferred. The epitheliod cells have plentiful eosinophilic cytosol, vesicular chromatin and a prominent nucleolus. See Chapter 9 for a more detailed microscopic description, including immunohistochemistry, and differential diagnosis for the epithelioid variant.

More cellular BFH lesions, that is, cellular fibrous histiocytomas, tend to present with a more extensive fascicular or storiform pattern. This variant typically is composed of spindled lesional cells with numerous mitotic figures, but none should be atypical. Unlike other forms of BFH, necrosis of central regions may be seen. Angiomatoid fibrous histiocytoma has a dense fibrous capsule surrounded by a lymphocytic infiltrate with germinal centers, and typically contains spaces filled with blood but not lined by endothelium. See Chapter 9 for a more detailed description of this entity.

Treatment and Prognosis

BFH is treated by wide surgical excision, with 5% to 10% of cases recurring locally. Deeper and larger lesions have a higher rate of recurrence. More aggressive examples may show microscopic features of malignancy, such as marked cellularity, mitotic activity, focal necrosis or atypical giant cells. It is sometimes very difficult to predict biologic behavior on the basis of cellular features, as illustrated by the occasional case that metastasizes, despite its bland histopathologic appearance. For this reason, extended follow-up is recommended after surgical removal.

Clinical Features

The oral UPS occurs primarily in adults, especially those 50 to 70 years of age, but rare cases have been described in children. Regardless of the histopathologic subtype, men are affected almost twice as frequently as women.

Within the maxillofacial region, the most common complaint is a moderately firm submucosal mass expanding slowly or moderately fast, with or without pain and surface ulceration. It is usually less than 4 cm in greatest diameter at the time of biopsy, with a bosselated or nodular surface. The lesion is typically attached to surrounding tissues and adjacent structures. The myxoid variant often has quite a soft consistency and the angiomatoid variant is often found in a location more superficial than that of the other variants.

Pathologic Features and Differential Diagnosis

Oral UPS has a wide spectrum of cellular and tissue alterations; the cellular differentiation and density vary markedly, even within the same tumor. The classic histopathologic features include an invasive, interlacing proliferation of spindled fibroblast-like cells that tend to be arranged in short woven fascicles or bundles, with scattered areas showing a storiform pattern. Cellular and nuclear pleomorphism is common and there often appears to be an admixture of fibroblastic and histiocytic elements.

Most lesional cells are spindle cells. They may be long and thin with minimal atypia, but there are usually areas with plump spindle cells containing enlarged, hyperchromatic, and irregular nuclei. Varying numbers of rounded, polygonal, and irregularly shaped histiocyte-like cells may dominate some areas of the tumor, often with very pleomorphic, multinucleated giant cells interspersed.

When the latter cells are numerous, some prefer to call the UPS a giant cell variant or malignant giant cell tumor of soft parts. The histiocytic cells have either abundant eosinophilic cytoplasm or pale foamy cytoplasm, and cell membranes are not easily visualized. Areas with histiocytic predominance usually have a haphazard structural appearance. When more of the lesion shows myxoid change, some prefer to call it myxoid UPS or myxofibrosarcoma. Fibroblasts within myxoid regions may have pleomorphic, hyperchromatic nuclei and can mimic lipoblasts. Myxoid lesions have been shown to have a better prognosis than other forms of UPS.

Immunohistochemistry is required for this diagnosis. The spindle fibroblasts are vimentin-immunopositive, often with bizarre nuclei with high Ki-67 labeling scores. Chronic inflammatory cells are often scattered sparsely throughout the tumor, including foamy histiocytes, lymphocytes, and plasma cells. Mitotic activity varies widely and is directly related to the degree of cellular pleomorphism.

Treatment and Prognosis

The prognosis of UPS of the mouth, or any other part of the body, depends very much on size, rate of enlargement and histologic grade, with larger, high-grade lesions showing a much worse prognosis. Overall, it is usually treated by radical surgical resection, with at least 40% recurring locally and a similar proportion metastasize within 2 years. The 5-year survival rate is less than 30%, although it is somewhat better for the myxoid variant.

Clinical Features

Myofibroma in the mouth is usually diagnosed within the first four decades of life but can present at any age. The average age of 22 years is older than extraoral lesions. There is a slight female predominance in oral cases, in contrast to myofibromas in other parts of the body. Myofibroma is most often found within the mandible; in the oral soft tissues, it typically is seen on the gingivae or tongue, followed by the buccal mucosae. The soft-tissue lesion presents as a painless, slowly enlarging, moderately firm mucosal mass.

Three-fourths of oral myofibromatosis cases are present at birth. Other cases may arise in patients up to 2 years of age; rarely, cases develop in young adulthood. The tongue is, by far, the most common site of origin. Virtually all patients with oral involvement will present with myofibromas of other parts of the body, ranging from a few to a hundred lesions.

Pathologic Features

Myofibromatosis or myofibroma presents with a microscopic appearance similar to that of fibromatosis, but the peripheral cells demonstrate eosinophilic cytoplasm reminiscent of smooth muscle. There is usually a biphasic pattern of lightly staining fibrous areas, separated by regions of pericyte-like vascular cell or smooth muscle-like spindle cell proliferations ( Fig. 4.9A and B ). It is most vascular centrally, where it may mimic a hemangiopericytoma or glomus tumor, with lesional cells proliferating around blood vessels. Collagen is present but seldom abundant and regions of chondroid-like stroma may be seen. The more fibrotic lesions must be differentiated from fibromatosis, irritation fibroma, neurofibroma, angiofibroma, and fibrotic pyogenic granuloma.

Lesional cells show features of both myofibroblastic and fibroblastic cells, with fuchsinophilic and phosphotungstic acid hematoxylin (PTAH)-positive intracellular fibrils. These cells are immunoreactive for vimentin and smooth muscle actin, but not for desmin or S100 protein. Regions with more primitive appearance may show minimal or missing actin reactivity. These stains help demonstrate the smooth muscle nature of the lesion and separate myofibromatosis from neurofibroma and fibrous histiocytoma, although they are less helpful for nodular fasciitis, which also contains myofibroblasts. More detailed immunohistochemistry, genetic and differential diagnosis information may be found in Chapter 9 .

Treatment and Prognosis

Myofibromatosis is much more innocuous than fibromatosis and spontaneous regression may occur. The typical treatment for oral lesions is surgical removal, with occasional recurrence expected. Multifocal involvement may produce serious, even fatal, extragnathic complications for the patient, especially when visceral lesions are present at birth.

Clinical Features

While occurring at all ages, oral nodular fasciitis is most often diagnosed in persons 30 to 40 years of age, with no gender predilection. It is a discrete, adherent, slightly tender, submucosal nodule with occasional surface ulceration. The lesion is typically more superficially located than fibromatosis of the oral region. Unlike true fibromatoses, it rapidly enlarges, taking only 3 to 6 weeks to reach its full-size potential, though occasional cases may be slow growing. Rarely does this lesion becomes greater than 2 cm in diameter.

Pathologic Features and Differential Diagnosis

Nodular fasciitis presents as haphazardly arranged, well-circumscribed, unencapsulated bundles of fibroblasts in a myxoid or mucoid background. The growth pattern is often described as feathery or “tissue culture-like” because of the tears and pools of mucin seen in the stroma. The fascia origin may not be obvious in oral examples. Lesional fibroblasts are typically large and plump, similar to those seen in granulation tissue, but are more crowded or hypercellular. Pleomorphic fibroblasts may be present and numerous, normal mitotic figures may be quite common. A variable amount of collagen and acid mucopolysaccharide are noted in the intercellular matrix, although the latter may not be readily visible without special staining with Alcian blue or colloidal iron.

An important diagnostic feature is a fine capillary network arranged in a radial pattern around a larger central vessel or vessels. Scattered chronic inflammatory cells are typically present in small to moderate numbers, and long-standing lesions may demonstrate foamy histiocytes and osteoclast-like multinucleated giant cells. When striated muscle is involved (intramuscular fasciitis), it is completely replaced by the fibrovascular proliferation, unlike proliferative myositis, which infiltrates between muscle fibers. Proliferative fasciitis is a variant of nodular fasciitis with large, ganglion-like cells with abundant amphophilic or basophilic cytoplasm.

Nodular fasciitis has a characteristic immunohistochemical profile, which includes reactivity for vimentin, smooth muscle actin and muscle-specific actin, indicating its myofibroblastic character. It is nonreactive for keratin, S100 protein and desmin. Additional microscopic and immunohistochemical detail of this lesion can be found in Chapter 9 , as can its histopathological differential diagnosis.

Treatment and Prognosis

Despite its often, aggressive microscopic appearance, nodular fasciitis is a self-limiting lesion that is readily treated by simple local excision. Deeper lesions tend to be somewhat larger and less well demarcated; they require a wider local excision. Recurrence rates vary from 1% to 6%; some lesions have been reported to regress and disappear without treatment or incisional biopsy.

The major prognostic factor here is an accurate diagnosis; recurrences should be evaluated carefully. Earlier studies have shown that as many as one-fourth of all cases were erroneously interpreted as malignant and, conversely, numerous cases of well-differentiated fibrosarcoma have been misdiagnosed as nodular fasciitis.

Clinical Features

Proliferative myositis of the oral region is a rapidly enlarging, immovable, perhaps tender submucosal mass. Children are rarely affected, and the typical patient is 45 to 65 years of age at tumor onset. There is a slight female predilection. The lesion is usually 1.5 to 5.0 cm in greatest dimension at the time of diagnosis and involves the muscle in a diffuse, infiltrative fashion.

Pathologic Features

Proliferative myositis appears almost scar-like on gross examination, with a poorly circumscribed periphery and a grayish-white cut surface. Microscopically, plump fibroblast-like cells are the predominant cell type, though giant ganglion-like cells, with deeply staining basophilic cytoplasm and prominent nucleoli, are the hallmark of proliferative myositis. These cells are also myofibroblasts but are often so bizarre, they impart a strong similarity to rhabdomyosarcoma or other sarcoma. Likewise, atrophic or degenerated muscle cells may contribute to the overall impression of striated muscle malignancy.

Fibrosis is seen to involve the endomysium, perimysium, and epimysium. Lesional cells are immunoreactive for vimentin, actin, smooth muscle actin, Factor XIIIa, and fibronectin and are usually not reactive for desmin or myosin. However, they may occasionally react for desmin and myosin. Ultrastructurally, they appear to be myofibroblasts. Focal ossification or dystrophic calcification may be observed in some cases, but never is it as pronounced as in heterotopic ossification.

Treatment and Prognosis

Treatment of this self-limiting lesion is conservative surgical excision, and recurrence should not be expected. Spontaneous regression and disappearance have been rarely reported. The major prognostic difficulty is arriving at a correct diagnostic interpretation of the tissue; therefore recurrent lesions should be carefully evaluated for an alternative diagnosis.

Clinical Features

This lesion has a strong female predilection (2:1) and occurs primarily in young adults. Most maxillofacial cases are seen on bone-bound, heavily keratinized mucosa. Three-fourths of all cases occur on the gingiva, with most of the remainder occurring on the hard palate, including a bilateral palatal case in a 2-year-old child. The lesion presents as a sessile or pedunculated, soft, painless nodule with normal surface coloration. Some cases are lobulated, even verruciform, and the mucosal surface may show ulceration. Lesions enlarge slowly and typically remain less than 2 cm in greatest dimension.

Pathologic Features and Differential Diagnosis

Oral focal mucinosis consists of a submucosal, well-localized but nonencapsulated nidus of very loose, myxomatous, or “mucinous” connective tissue ( Fig. 4.10A and B ). More superficial lesions may produce atrophy and loss of rete ridges of the overlying squamous epithelium. Fibroblasts are seen in minimal to moderate numbers within the mucinous area, often demonstrating delicate, fibrillar processes. The mucinous zone is much less vascular than surrounding connective tissues, and inflammatory cells are not associated with the lesion, except as a perivascular infiltrate of lymphocytic Tcells at the periphery. The hyaluronic acid of the lesion will stain positive with Alcian-blue (pH 2.5) in frozen sections, but this is not always the case with paraffin-embedded sections.

There are microscopic similarities between oral focal mucinosis and cutaneous mucinosis of infancy, which may represent a localized form of papular mucinosis or lichen myxedematous. Differentiation from another look-alike lesion, the oral mucocele, is usually not difficult. The mucocele is more strongly demarcated from surrounding fibrovascular tissues by a peripheral “encapsulation” of granulation tissue, and it has bloated inflammatory cells floating within the extravasated mucus. Mucicarmine staining will demonstrate mucus in the mucocele and one may find a traumatized salivary duct in the area of the extravasated mucus.

A slight similarity is also seen between mucinosis and the nerve sheath myxoma (neurothekeoma, bizarre neurofibroma, Pacinian neurofibroma), a variant of neurofibroma that rarely affects mucosa of the upper aerodigestive tract. The nerve sheath myxoma, however, is more circumscribed, has fibrous septa between multiple myxoid nodules, and has more plump stromal cells.

Treatment and Prognosis

Oral focal mucinosis is treated by conservative surgical removal. It does not recur with this treatment.

Clinical Features

IPH is seen in middle-aged and older persons and there is a strong female predilection (2:1). The disease occurs on the bone-bound oral mucosa of the hard palate and alveolar ridges. It presents as a cluster of individual papules or nodules that may be erythematous, somewhat translucent, or normal in surface coloration, depending on their duration; they tend to become fibrotic over time ( Fig. 4.11A ). Often the entire vault of the hard palate is involved, with alveolar mucosa being largely spared. White cottage cheese–like colonies of Candida may be seen in clefts between papules. There is seldom pain, but a burning sensation may be produced by a secondary yeast infection.

Pathologic Features and Differential Diagnosis

Connective tissue papillae are greatly enlarged by edematous connective tissue, granulation tissue, densely fibrotic tissue, or a combination thereof, depending on the duration of the lesion ( Fig. 4.11B and C ). Small to moderate numbers of chronic inflammatory cells are present, perhaps admixed with occasional polymorphonuclear leukocytes. Each enlarged papilla produces a surface nodule that may be pedunculated or sessile, with deep clefts between nodules.

Covering epithelium is often atrophic but may be acanthotic, especially near the base of the internodal troughs. Occasional lesions demonstrate extensive pseudoepitheliomatous hyperplasia. And may show p53 immunoreactivity. Basal cell hyperchromatism and basal layer hyperplasia often impart a false appearance of mild epithelial dysplasia. Surface ulceration is surprisingly rare, and deeper tissues show few alterations beyond a mild chronic inflammatory cell infiltration.

Although individual nodules may appear identical to pyogenic granuloma and irritation fibroma, the palatal location and the multinodularity of this process makes the diagnosis of papillary hyperplasia an easy one. In addition to fungal colonies being found in the clefts between nodules, a silver or PAS stain will frequently identify Candida spores and hyphae in the superficial portions of the epithelium, especially in cases with severe acanthosis or pseudoepitheliomatous hyperplasia.

Treatment and Prognosis

The old concern that papillary hyperplasia of the palate held increased risk for cancer is no longer accepted. Even extensive lesions will continue indefinitely, waxing and waning in the early years, but remaining more constant as nodules become more and more fibrotic. Occasional proliferations are so exuberant that clefts between nodules may be more than a centimeter deep.

Early lesions may completely disappear with cessation of denture use for 2 to 4 weeks, perhaps aided by topical antibiotic or antifungal therapies. Persistent lesions must be surgically removed or laser ablated and the patient must be fitted for a properly-fitting denture.

Clinical Features

Pericoronitis typically occurs in teenagers and young adults, presenting shortly after the eruption of the second or third mandibular molars. It presents as an erythematous, tender or painful, sessile swelling of the retromolar pad. The surface may be ulcerated by continuous trauma from the opposing maxillary molars ( Fig. 4.12A ). Pus may be expressed from the tissue-tooth interface, and a foul taste may be present.

Pain is usually intense and may radiate to the external neck, the throat, the ear or the oral floor. The patient often cannot close the jaw because of tenderness; conversely the extreme pain may result in the inability to open the jaws more than a few millimeters (trismus or “lock jaw”). Cervical lymphadenopathy, fever, leukocytosis, and malaise are common signs and symptoms, and the malady may be associated with an ipsilateral tonsillitis or upper respiratory infection.

Pathologic Features

Pericoronitis is usually surgically removed after a course of antibiotic therapy to prevent future painful episodes, so active pus production is seldom seen in biopsy samples. The retromolar mass is composed of an admixture of moderately dense collagenic tissue and edematous granulation tissue, with moderate to large numbers of mixed chronic inflammatory cells throughout ( Fig. 4.12B ). The superior mucosa may be ulcerated, with an ulcer bed of fibrinoid necrotic debris. The epithelium, immediately adjacent to the offending tooth, typically presents with a combination of rete process hyperplasia, degeneration, and necrosis, perhaps with associated neutrophils. Bacterial colonies, dental plaque, and necrotic food debris may be attached to the epithelium. The pathologist should distinguish this lesion from pyogenic granuloma and routine gingivitis, which often requires correlation with clinical features.

Treatment and Prognosis

Acute pericoronitis is treated by local antiseptic lavage and gentle curettage under the flap, with or without systemic antibiotics. Once the acute phase is controlled, the offending molar may be extracted or a wedge of the hyperplastic pad tissue is removed surgically. Recurrence is unlikely with either of these treatments. With or without treatment, patients with pericoronitis are at increased risk of future gingivitis and periodontitis.

Clinical Features

In addition to these special events, pyogenic granuloma can occur at any mucosal location of acute or chronic trauma or infection. In the mouth, the vast majority of these lesions occur on the gingiva ( Fig. 4.13A ), where they may develop as soft masses, usually on facial gingival surfaces. Dumb-bell shaped lesions may occur, with a facial mass extending as a thin isthmus between teeth to create a similar mass on the lingual gingival surface. Other sites of common involvement include the tongue, the lip mucosa and vermilion, and the buccal mucosa. It tends not to push adjacent teeth away, in contrast to other reactive masses of the gingiva, such as the peripheral ossifying fibroma and peripheral giant cell granuloma, discussed elsewhere in this chapter.

All ages and both genders are susceptible to this exuberant inflammatory response. The lesion is usually a pedunculated, bright red mass with or without white areas of surface ulceration; older lesions tend to have a more normal coloration. Rarely does pyogenic granuloma exceed 2.5 cm in size and it usually reaches its full size within weeks or months, remaining indefinitely thereafter. Occasional lesions have presented as conical or horn-like masses, with granulation tissue proliferating around a central vertical vessel. Rare examples have been reported of multiple oral pyogenic granulomas arising acutely and simultaneously.

A rather unique form of a look-alike granulation tissue proliferation is the traumatic ulcerative granuloma with stromal eosinophilia (TUGSE). This trauma-related lesion of young adults and middle-aged individuals has a more aggressive biological behavior; it is discussed in more detail in the “Ulcerative and Blistering Mucosal Lesions” section.

Pathologic Features and Differential Diagnosis

The pyogenic granuloma is characterized by a rich profusion of neovascularity, with anastomosing vascular channels, lined by endothelial cells with plump nuclei, extending into the lumen ( Fig. 4.13B and C ). The background stroma is typically edematous, but fibroplasia is often active and older lesions may have undergone considerable fibrosis (fibrotic pyogenic granuloma, Fig. 4.13D ). The fibroblasts are typically plumb and mitotic activity may be noted in the stromal cells. Older lesions demonstrate fewer and more mature cells, that is, fibrocytes. Bacteria are virtually never found within lesional tissue, even with a Gram stain, but they may occasionally be seen coating ulcerated surface areas.

The blood vessels may show a clustered or medullary pattern with grouped vessels separated by less vascular fibrotic septa. This has led to a recent acceptance of the pyogenic granuloma as a polypoid form of capillary hemangioma, specifically called lobular capillary hemangioma , although some prefer the term granulation tissue-type hemangioma . A mixed chronic and acute inflammatory cell infiltrate is scattered throughout the stroma, with early lesions containing more neutrophils than older lesions. Occasional lesions demonstrate an extreme predominance of plasma cells, prompting some pathologists to call them plasma cell granuloma , a term that is best avoided because of the potential confusion with mucosal solitary plasmacytoma or multiple myeloma .

Rare examples of intravenous pyogenic granuloma have been reported. Occasionally, classical pyogenic granulomas may also exhibit regions identical to intravascular papillary endothelial hyperplasia, with thin-wall dilated vessels and papillary projections of endothelial cells producing vascular channels, which are associated with areas of an organizing thrombus.

The overlying stratified squamous epithelium may be atrophic or hyperplastic and it is usually degenerated or ulcerated in large areas. If the epithelium is very spongiotic, a diagnosis of localized juvenile spongiotic gingival hyperplasia (discussed earlier in this section) should be considered. When ulcerated, the ulcer bed is composed of fibrinoid necrotic debris, and regenerating epithelium at the ulcer edge may have a primitive or dysplastic appearance.

The histopathologic differentiation of pyogenic granuloma from hyperplastic gingival inflammation is sometimes impossible; the pathologist must depend on the surgeon’s description of a distinct clinical mass to make the pyogenic granuloma diagnosis. Usually, however, routine gingivitis has edema confined to the subepithelial regions of crevicular mucosa (facing the teeth) with more exposed epithelium, demonstrating a normal or hyperplastic appearance without ulceration. Quite often, the differentiation of pyogenic granuloma from inflamed capillary hemangioma is also impossible.

Kaposi sarcoma, bacillary angiomatosis, and epithelioid hemangioma must also be distinguished from pyogenic granuloma. Kaposi sarcoma of acquired immunodeficiency syndrome (AIDS) shows proliferation of dysplastic spindle cells, vascular clefts, extravasated erythrocytes, and intracellular hyaline globules, none of which are features of pyogenic granuloma. Bacillary angiomatosis, also AIDS-related, shows dense, extracellular deposits of pale hematoxyphilic granular material representing masses of bacilli that stain positive with the Warthin-Starry stain. Epithelioid hemangioma has a plumper, histiocytoid, endothelial cell proliferation without an acute inflammatory cell infiltrate. These entities are discussed in more detail in Chapter 9 .

Treatment and Prognosis

Pyogenic granuloma is treated by conservative surgical or laser excision with removal of potential traumatic or infective etiologic factors. Recurrence occurs in approximately 15% of cases with gingival cases showing a higher recurrence rate than lesions from other oral mucosal sites. Therefore pyogenic granuloma of the gingiva should not only be excised, but the surgical wound bed should be curetted, and adjacent teeth should be scaled and root-planed. If possible, removal in a pregnant woman should be postponed until after the birth. Lesional shrinkage at that time may make surgery unnecessary; also, pregnant patients show a higher rate of recurrence.

Clinical Features

The usual age at diagnosis is the fourth through sixth decades, but there is no specific age predilection. More than 60% of cases occur in females, and this female predilection is more pronounced in the older age groups. Individual lesions are nodular and pedunculated, frequently with an ulcerated surface, and often have a red, brown, or bluish hue ( Fig. 4.14A and B ). In general, larger than the pyogenic granuloma, the lesion may exceed 5 cm in size, but typically remains less than 2 cm in diameter. Any gingival region may be affected, with radiographs showing either a saucerization of underlying bone, periodontitis of underlying tissues, or an isthmus of soft tissue connecting to an intraosseous central giant cell granuloma.

Pathologic Features and Differential Diagnosis

The PGCG is composed of an unencapsulated aggregation of rather primitive but uniform mesenchymal cells with oval, pale nuclei and with a moderate amount of eosinophilic cytoplasm. Mitotic activity is not unusual and may even be pronounced in lesions developing in children and adolescents. Mitotic activity within the giant cells is, however, not seen and, if present, should be considered to be a sign of sarcomatous change.

Stromal cells may be spindled, with a background of collagenic fibers, or may be rounded with a less fibrotic background. There may be occasional chronic inflammatory cells admixed with the mesenchymal cells or within surrounding fibrovascular tissues. A thin band of routine fibrovascular tissue separates the lesion from the overlying epithelium, often with dilated veins and capillaries. When surface ulceration is present, the ulcer bed consists of routine fibrinoid necrotic debris over granulation tissue.

Admixed throughout the stroma are numerous osteoclast-like multinucleated giant cells containing varying numbers of pale vesicular nuclei, similar to those within the surrounding stromal cells ( Fig. 4.14C ). These cells have eosinophilic cytoplasm, which electron microscopy has shown to contain large numbers of mitochondria.

Blood vessels within the lesional stroma are not obvious but, when seen, show plump endothelial cell nuclei. Scattered extravasation of erythrocytes is almost universally seen and is a strong diagnostic feature. Hemosiderin deposition may be found in areas of old hemorrhage. Metaplastic or osteoblastic new bone formation may be seen if the lesion has affected underlying bone. Dystrophic calcification may be present higher in the mass, but this is not common.

Occasional lesions show an admixture of tissue types compatible with PGCG, peripheral ossifying fibroma, and pyogenic granuloma, presumably because of the common pathoetiology of these lesions. Such lesions are traditionally diagnosed according to the dominant tissue type.

PGCG can be differentiated from osteoblastic osteosarcoma by the uniformity of the stromal cells and by the lack of dysplasia in these cells. In young persons, however, numerous mitotic figures and active proliferation of stromal cells may make this distinction difficult. PGCG may be indistinguishable from the rare extraosseous brown tumor of hyperparathyroidism.

Treatment and Prognosis

PGCG is treated by conservative surgical excision, followed by curettage of any underlying bony defect and careful scaling and root-planning of associated teeth. A recurrence rate of 10% to 18% has been reported, so reexcision may be necessary. Very large or recurring lesions may represent brown tumors of hyperparathyroidism and will require treatment of the underlying endocrine dysfunction prior to surgical removal.

Clinical Features

Granulomatous lesions of the oral and oropharyngeal mucosa usually present as sessile lobulated, moderately firm and relatively nontender nodules and papules with normal coloration and with little or no surrounding inflammatory mucosal erythema. With time, some of the granulomas may ulcerate centrally and present as a deep, painless ulcer with a nonerythematous rolled border, reminiscent of squamous cell carcinoma ( Fig. 4.15 ). The granulomas of tertiary syphilis, tuberculosis, and deep mycotic infections may reach a size of more than 3 cm, but those related to autoimmune phenomena, especially sarcoidosis ( Fig. 4.16B ), cheilitis granulomatosa, and Crohn disease, typically remain smaller and often present as multiple nodules and papules, sometimes clustered together to impart a cobblestone appearance to the mucosa.

Several granulomatous diseases have unique clinical features. The granulomas of deep fungal infections, Langerhans cell disease (eosinophilic granuloma), sarcoidosis, and Wegener granulomatosis (granulomatosis with polyangiitis) may destroy underlying bone when located on gingival or alveolar mucosa ( Fig. 4.16A ). This is also true for palatal lesions of tertiary syphilis and tuberculosis, which have a special affinity for perforating the hard palate. Granulomatous gingivitis is the only granulomatous lesion typically associated with pain and, of course, by definition must occur on gingival mucosa. Extensive involvement of submucosal areas may produce a generalized enlargement of the affected site, especially noticeable on the lips and tongue, as in cheilitis granulomatosa, Melkersson-Rosenthal syndrome, and syphilitic glossitis.

Pathologic Features and Differential Diagnosis

Most granulomatous lesions of the oral region present as small, noncaseating granulomas with peripheral lymphocytes, central epithelioid histiocytes, and usually, multinucleated giant cells (see Fig. 4.16B ). Foreign bodies within the giant cells and histiocytes may polarize and microorganisms may be identified by appropriate acid-fast bacterial and fungal stains (see Table 4.4 ). Wegener granulomatosis (granulomatosis with polyangiitis) may have no granulomas visible but will show a pattern of mixed inflammatory infiltrates around blood vessels, with focal areas of necrosis and areas with heavy neutrophilic infiltration and nuclear dust ( Fig. 4.16C ). The oral epithelium in this disease may demonstrate severe acanthosis or pseudoepitheliomatous hyperplasia, as may granulomatous infection by blastomycosis, and it is the granulomatous disease most likely to be associated with extravasated erythrocytes.

Many of the granulomatous diseases listed in Table 4.4 require physical examination and laboratory evaluation for an appropriate diagnosis. These are beyond the scope of the present chapter, but many such entities are discussed in other chapters.

Treatment and Prognosis

The treatment of orofacial granulomatosis and the various forms of granulomatous mucositis will be subject to the underlying or systemic cause, and the prognosis of oral lesions will depend on the patient’s response to therapies for the systemic disease. Many lesions eventually resolve spontaneously with or without therapy, especially those associated with sarcoidosis, but others continue to progress despite rather aggressive therapy.

Localized lesions without a systemic connection can be treated by conservative surgical removal and plastic surgical reconstruction. Prior to surgery, a host of medications may be used with variable results: intralesional and systemic corticosteroids, low-dose radiotherapy, methotrexate, dapsone, salazosulfapyridine (sulfasalazine), and hydroxychloroquine sulfate, among others. No therapy has proven to be universally effective in such cases.

Clinical Features

These entities are all very site specific. The palatal torus is found only in the midline of the hard palate ( Fig. 4.17A ). The mandibular torus is found only on the lingual surface of the mandible, near the bicuspid and first molar teeth ( Fig. 4.17B ). The buccal exostosis is found only on the facial surface of alveolar bone, directly overlying a tooth under occlusal stress. When a similar reactive cortical prominence develops beneath a fixed prosthesis (dental bridge), it is referred to as subpontic cortical hyperplasia .

Bony surface proliferations found in any other jawbone site are typically given the generic diagnosis of reactive exostosis or osteoma; they are considered to be trauma-induced inflammatory periosteal reactions or true benign neoplasms, respectively. Unless such a bony prominence is specifically located or is associated with an osteoma-producing syndrome, such as Gardner syndrome, there may be no means by which to differentiate an exostosis from an osteoma, especially under the microscope.

As previously stated, these lesions are not present until the late teen and early adult years, and many, if not most, continue to slowly enlarge over time. Fewer than 3% occur in children, but taken as a group, these lesions can be found in up to 50% of adults and, while the torus palatinus is more common in females than in males, the others show no gender bias.

The palatal and mandibular tori may be bosselated or multilobulated and the mandibular masses are usually bilateral and always located on the lingual side of the mandible. Lesions may become 3 to 4 cm in greatest diameter but are usually less than 1.5 cm at biopsy. A definite hereditary basis, usually autosomal dominant, has been established for some cases of tori, and Asians, especially Koreans, have a much higher prevalence rate than do other ethnic groups. Exostoses are typically single and may be pedunculated, but buccal exostoses may be numerous and may be on both jaws.

A recently reported pathologic change in tori has been identified in patients taking bisphosphonates for osteoporosis, Paget disease of bone or metastatic neoplasms in bone. A number of such individuals have presented with chronically exposed alveolar bone after oral surgical procedures or bone trauma. Approximately 10% of cases of this medication-related osteonecrosis of the jaws (MRONJ) occur within tori, typically after traumatic ulceration of the surface mucosa. This entity is more completely discussed later in the present chapter.

Pathologic Features

On cut surface, the torus and exostosis usually show dense bone with a laminated pattern ( Fig. 4.17C ). They are usually composed of dense, mature, lamellar bone with scattered osteocytes and small marrow spaces filled with fatty marrow or a loose fibrovascular stroma. Conversely, some lesions are osteoporotic, having a thin rim of cortical bone overlying inactive cancellous bone with considerable fatty or hematopoietic marrow present. Typically, there is minimal osteoblastic activity, but occasional lesions will show reactive bone beneath the periosteum. Large areas of bone may show enlarged lacunae with missing or pyknotic osteocytes ( Fig. 4.17D ), indicative of ischemic damage to the bone. Ischemic changes, such as marrow fibrosis and dilated marrow capillaries and veins (medullary congestion), may also be found in the marrow, with rare examples showing microinfarctions in the fatty marrow.

Treatment and Prognosis

Neither the torus nor the bony exostosis requires treatment unless it becomes so large that it interferes with function, denture placement, or suffers from recurring traumatic surface ulceration (usually from sharp foods or factitial trauma). With or without bisphosphonate use, the medullary bone beneath an ulcerated torus might be necrotic. When treatment is elected, the lesions may be chiseled off of the cortex or removed via bone burr, cutting through the base of the lesion. It has been suggested that bone chips from an excised bony mass can be used as an autogenous bone graft material for periodontal or other surgical defects.

Slowly enlarging, recurrent lesions are occasionally seen, but there is no malignant transformation potential. The young patient should be evaluated for Gardner syndrome, especially if multiple bony growths are found outside of the classic torus or buccal exostosis locations. Intestinal polyposis and cutaneous cysts or fibromas are other common features of this autosomal dominant syndrome.

Clinical Features

POF presents as a painless, hemorrhagic, and often lobulated mass of the gingiva or alveolar mucosa ( Fig. 4.18A and B ), perhaps with large areas of surface ulceration. Early lesions are quite irregular and red, but older lesions can have a smooth salmon-pink surface and may be indistinguishable clinically from the much more common irritation fibroma. Most POFs are 1 to 2 cm in size, but some may slowly enlarge to more than 5 cm. Early growth is often alarmingly rapid, and occasional examples of multiple synchronous lesions have been documented.

A lesion may vary somewhat in size over time, depending on the amount of superficial inflammation and edema involved. Although this tumor is typically diagnosed in teenagers and young adults, it may occur at any age, especially in individuals with poor oral hygiene, and multiple lesions in a single patient have been reported. Radiographs occasionally show irregular, scattered radiopacities in a POF, but this change is usually not present.

Pathologic Features and Differential Diagnosis

An aggregated submucosal proliferation of primitive oval and bipolar mesenchymal cells is the hallmark of peripheral ossifying fibroma. The POF can be very cellular or may be somewhat fibrotic but scattered throughout are islands and trabeculae of woven or lamellar bone, usually with abundant osteoblastic rimming ( Fig. 4.18C ). Metaplastic bone may also be seen. The calcified tissues can have the dark-staining, acellular, rounded appearance of cementum, in which case the term peripheral cementifying fibroma has traditionally been used ( Fig. 4.18D ).

Many examples show an admixture of bone and cementum, that is, peripheral cementoossifying fibroma, and early lesions may contain only small ovoid areas of dystrophic calcification. Although the lesional stroma may be similar to that of POF, the erythrocyte extravasation of the latter lesion is not a feature of POF and osteoclast-like cells are quite rare in the POF. Osteopontin expression is universal to all POFs.

Surrounding tissues are often edematous, with neovascularity and variable numbers of chronic and acute inflammatory cells. By way of differential diagnosis, the exuberant callus, so common to the long bones, is almost never found at the surface of jawbones and so is not a serious diagnostic distinction from peripheral ossifying fibroma. Some gingival masses, however, contain large areas of classic pyogenic granuloma, irritation fibroma, or peripheral giant cell granuloma, as well as POF. In such cases, the pathologist usually chooses for the appropriate diagnosis the lesional type that predominates. Also individual cells must be carefully examined for dysplastic changes to rule out osteoblastic or juxtacortical osteosarcoma, but frequent mitotic figures of normal configuration are acceptable for the benign diagnosis, especially in POF in the first decade of life.

Treatment and Prognosis

Conservative surgical excision must be followed by diligent curettage of the wound and root-planing of adjacent teeth, if recurrence is to be avoided. With simple removal, the recurrence rate is 10% to 20% and may be higher. Malignant transformation has not been reported for this lesion.

Clinical Features

Heterotopic ossification of the head and neck region typically occurs in the masseter muscle of a young person after a single severe injury. There is no gender predilection. Shortly after the injury, a painful mass begins enlarging to 2 to 4 cm in greatest dimension. The tumor usually reaches its maximum size within 1 to 2 weeks. It is minimally movable beneath the skin or mucous membrane and may be rather firm to palpation. Radiographs of early lesions will reveal feathery opacities caused by ossifications along muscle fibers. Older lesions show more solid opaque masses that may coalesce to appear as one large, irregularly opaque mass, often with a central or acentric zone of radiolucency ( Fig. 4.19A ). The mass is not attached to adjacent bone.

Computed tomograms show the lesion to be well circumscribed, usually with a shell of ossification surrounding a less mineralized core. Conversely, the lesion may appear to be poorly defined and infiltrative on magnetic resonance images.

Myositis ossificans progressiva is rare, slowly progressive, inherited, and associated with a microdactyly or adactyly of the thumbs and great toes, and with the eventual onset of fibroblastic proliferations and calcification during the first decade of life. Sporadic examples have been reported and there is no gender predilection. Diffuse or multinodular, doughy, soft-tissue involvement is seen most commonly on the back, shoulders, and upper arms. Facial and lip involvement have been reported, with masseter muscle involvement sometimes severe enough to interfere with jaw opening. Muscles become progressively stiffened and contraction deformities may occur. Joint ankylosis is a frequent problem, as are exostoses and osteoporosis.

Pathologic Features and Differential Diagnosis

Active, poorly organized fibroblastic proliferation is seen throughout the lesion. The stromal cells are plump and bipolar and may demonstrate considerable mitotic activity, but they never demonstrate cytologic atypia or true dysplasia. The background consists of loosely arranged collagen and reticulin fibers with neovascularity becoming more pronounced toward the lesional periphery. The fibroblasts also form into fascicles toward the periphery, with an admixture of osteoblasts and reactive new bone ( Fig. 4.19B and C ).

The bone is woven or immature in early lesions, but in older lesions it is mature lamellar bone, perhaps with fatty or hematopoietic marrow. Large amounts of cartilage may also be seen, tempting the pathologist to call the tumor soft-tissue chondroma or soft-tissue chondrosarcoma . Those ossifications with very active stromal cells might, likewise, tempt the pathologist to consider a soft-tissue osteosarcoma. Some lesions contain cystic spaces centrally, where the tissues can take on the appearance of aneurysmal bone cyst, a bone lesion with rare examples in soft tissues.

Treatment and Prognosis

Treatment is usually not necessary, as most tumors of heterotopic ossification regress spontaneously. The lesion for which treatment is elected, however, can be removed by conservative surgical excision. Occasional recurrences do occur, often with rapid onset after surgery and with rapid growth after onset. There have been a few reported cases of malignant transformation of heterotopic ossification into extraskeletal osteosarcoma, but there is some concern that these may actually have been misdiagnosed at the outset.

Patients with myositis ossificans progressiva or fibrodysplasia ossificans progressiva will, of course, have more serious, perhaps life-threatening sequelae, such as anorexia from difficult mouth opening and pneumonia or respiratory failure in early life.

Clinical Features

Osseous/cartilaginous choristoma is characteristically diagnosed as a painless, firm nodule in children or young adults, especially in females, and has most frequently been reported on the tongue, although no submucosal site is immune. It seldom reaches a size greater than 1.5 cm, although even small lesions may produce local dysfunction, if located on the lateral border of the tongue. A similar lesion, osteoma cutis, is found beneath the skin of the face and other areas, but is usually considered to be a different entity.

A unique cartilage-producing form of this tissue-level disorder is found on the edentulous alveolar ridge of a denture wearer, especially in the anterior maxilla. Presumably trauma-induced, this self-limiting Cutright tumor (chondroid choristoma, traumatic osseous and chondromatous metaplasia) may produce pressure atrophy of underlying bone, may become tender, and may contain bone in addition to cartilage.

When multiple primary cutaneous ossifications are encountered, it may be part of Albright’s hereditary osteodystrophy, which is associated with congenital or early subcutaneous ossifications of the extremities, trunk, and scalp. Oral mucosal involvement is very rare. The bony spicules in this disease may produce surface ulceration or may extrude from the surface. Pseudohypoparathyroidism and pseudopseudohypoparathyroidism are frequently observed in this condition, which is inherited as an X-linked or autosomal dominant trait.

Pathologic Features and Differential Diagnosis

The osseous/cartilaginous choristoma is composed of a submucosal proliferation of benign and normal (perhaps immature) bone or cartilage. These “abnormal” tissues are embedded within a background stroma of fibrovascular connective tissue, usually without true encapsulation, but often with a pseudoencapsulation. Cartilage may be active and mimic synovial chondromatosis (joint mice) or soft-tissue chondroma ( Fig. 4.20A and B ). Bone maturation often results in lamellar bone, perhaps with hematopoietic or fatty marrow. Choristomas and hamartomas given other specific diagnostic names, such as Fordyce granules (ectopic sebaceous glands) and oral tonsils (benign lymphoid aggregates) , are discussed under those names in this text.

Osseous choristoma may be confused with heterotopic ossification (myositis ossificans), but the latter is typically located in muscle and has more osteoblastic activity than the choristoma. Differentiation of osseous choristoma from peripheral ossifying fibroma is not usually difficult because the latter has a unique cellular stroma of oval, primitive mesenchymal cells and is found exclusively on alveolar bone surfaces. Neither cartilage nor marrow is produced by the peripheral ossifying fibroma and, by tradition, a cartilaginous choristoma of the crest of the alveolar ridge in a denture wearer is called a Cutright tumor .

Osseous choristoma should not be confused with the dystrophic calcification so frequently found in old thrombi, hematomas and keratin-filled soft-tissue cysts. This darkly staining aggregation of precipitated salts does not have a bone-like organization.

Treatment and Prognosis

The choristoma is best treated by conservative surgical excision. Surgery for congenital lesions is often delayed for 6 to 12 months. No recurrences have been reported with this therapy.

Clinical Features

Nearly all reported cases of ECT have occurred on the anterior dorsal tongue. A recent case report and literature review found 74 lingual tumors (56/63 tumors [89%], where location was specified, were located in the anterior tongue and four on the posterior tongue, three were located on tongue dorsum, not otherwise specified [NOS]); only three extralingual tumors were found, two arose in the palate (the diagnosis in one of these has been called into question) and one in the tonsillar bed. No sex predilection was found and a wide age range was noted (7–78 years; mean: 39 years). The tumor size clinically ranges from 0.3 to 5.0 cm. The duration of the lesion varies, with one patient reporting up to a 20-year history, while other patients describe a slow growing mass of only a few months duration. Most patients are asymptomatic. Clinical examination shows a firm, nonmobile, dome-shaped submucosal mass with normal overlying epithelium.

Pathologic Features and Differential Diagnosis

Gross examination reveals a rubbery nodule that on cut surface demonstrates a well-circumscribed mass, which may show foci of hemorrhage or which may have a gelatinous consistency. Microscopic examination shows a multilobulated, well-delineated, but not encapsulated tumor in the submucosa ( Fig. 4.21A ). The overlying epithelium is uninvolved although the epithelial rete ridges may be flattened by tumor extension. Along the periphery of the tumor, vessels and small nerves may be compressed, while entrapped muscle fibers, small nerves and blood vessels can be seen within the tumor. The tumor is composed of spindle- to round-shaped cells with small uniform nuclei ( Fig. 4.21B and C ). The faintly basophilic cytoplasm can be sparse to moderate. Occasional binucleation, nuclear pleomorphism, hypercellularity, focal necrosis, and hyperchromatism can be seen, but mitotic figures are rare and atypical mitoses are not seen.

The background stroma is predominantly myxoid and can have areas of hyalinization or chondroid matrix. The stroma is positive for Alcian blue stains at pH 0.4 and 2.5, and mucicarmine stains are faintly positive in the extracellular matrix. ECT shows strong and diffuse immunoreactivity with both monoclonal and polyclonal GFAP. Variable immunoreactivity has been reported with S100, smooth muscle actin, cytokeratins, CD57, p63, Sox 10, desmin, myogenin, and vimentin ( Fig. 4.21D ).

Differential diagnosis of ECT includes other tumors that have a chondroid or myxoid stroma. Oral focal mucinosis, the oral counterpart of cutaneous focal mucinous, generally occurs on the gingivae or the hard palate, but there have been reported cases in the tongue. However, the histochemical and immunohistochemical features are different from ECT. Oral soft-tissue myxomas are uncommon oral lesions that can be distinguished from ECT by the hypocellular stroma and ill-defined margins. Myxomas show positive immunostaining only with vimentin, unlike ECT.

Another look-alike lesion, ossifying fibromyxoid tumor (OFT) of soft parts, is a fairly well-defined and lobulated tumor composed of small round cells arranged in nests or in a trabecular pattern. Bone formation is present along the periphery of the tumor, which is not a feature of ECT. Approximately two-thirds of OFT exhibit positive immunoreactivity with S100 protein, but electron microscopy favors a Schwann cell origin for this tumor. This is in contrast to the ECT, which likely derives from undifferentiated ectomesenchymal progenitor cells of neural crest origin. Finally, OFT has not been described in the tongue.

Nerve sheath myxoma (myxoid neurothekeoma) can occur on the tongue and microscopically can appear as a well-circumscribed myxoid lesion demonstrating S100 protein immunopositivity, but it is generally negative for cytokeratins and GFAP. Neurothekeoma, unlike ECT, is hyaluronidase sensitive with Alcian blue staining. Lastly, there is significant overlap in the microscopic findings and immunohistochemical profile with myoepitheliomas. Neoplastic myoepithelial cells of salivary gland origin are positive for S100 protein, GFAP, and cytokeratins; they show variable positivity with smooth muscle actin. The dorsal anterior tongue where ECT occurs is devoid of salivary glands; however, myoepithelioma of soft-tissue origin is thought by some authors to be synonymous with ECT. soft-tissue myoepitheliomas have been reported in the upper and lower limbs, scalp, face, and trunk.

Treatment and Prognosis

Complete surgical excision is the treatment of choice. Of the several dozen cases reported, follow-up information is available for fewer than 25. Simple excision is usually curative; three patients had recurrences, one at 3 months, one at 19 months and the other at 41 months. Recurrences are treated with reexcision. Malignant behavior has not been reported.

Clinical Features

Parosteal osteosarcoma and periosteal osteosarcoma present in a similar fashion: an irregular, lobulated or fungating, nonmoveable submucosal mass of the attached gingiva or alveolar mucosa, covering the mandible or maxilla. It is seldom painful, but may present with a dull ache. The malignancy occurs more frequently on the surface of the mandible than the maxilla, and there seems to be a strong predilection for males. The typical patient is 35 years of age at diagnosis, and lesions have been present for 1 to 5 years before diagnosis; the age range, however, is quite broad: 17 to 63 years. Irregular radiopacities are seen on up to 90% of routine radiographs of the lesions. A unique jawbone feature is widening of the periodontal ligament space around the teeth. This occurs as lesional cells infiltrate down into the space. Also teeth are pushed aside by the tumor.

Pathologic Features and Differential Diagnosis

Parosteal osteosarcoma is characterized by a high degree of tissue differentiation, and the bland histology may lead the pathologist to a benign diagnosis, such as osteoblastoma, peripheral ossifying fibroma, or heterotopic ossification. The criteria, however, for intramedullary malignancy are also used for the peripheral lesions, namely, dysplasia or anaplasia of the mesenchymal stroma and the production of bone by that neoplastic stroma. Periosteal osteosarcoma is more poorly differentiated and often has a prominent chondroid component.

The classic parosteal osteosarcoma demonstrates scattered trabeculae of immature or woven bone, which may run parallel one to the other ( Fig. 4.22 ). The bone shows only mild osteoblastic rimming; only occasional lesional cells become incorporated into the new bone. Occasionally, very primitive reticular osteoid is produced. Small foci of chondroid metaplasia may also be seen. The fibrous stroma is usually hypocellular and the cellular dysplasia required for a malignant diagnosis may be rather sparse in the parosteal osteosarcoma, but periosteal version typically has numerous lesional cells that are moderately or poorly differentiated. The latter shows at least some regions where normal or proliferative periosteum can be seen beneath the tumor and the underlying cortex. It may, additionally, have so much cartilage production that there is a strong similarity to the intramedullary chondroblastic osteosarcoma.

The differentiation of juxtacortical osteosarcoma from peripheral ossifying fibroma, reactive cortical exostosis, heterotopic ossification, osseous choristoma, and peripheral giant cell granuloma, with reactive bone, is based predominantly on the identification of pleomorphic or otherwise dysplastic stromal cells producing bone in the osteosarcoma. The other lesions, all of which are discussed elsewhere in this chapter, may show many plump, active stromal cells with moderate mitotic activity, but true dysplasia is lacking. Moreover, heterotopic ossification has its most active stromal proliferation centrally located, while the juxtacortical osteosarcoma has the most active regions toward its periphery. Finally, although some lesions may mimic osteochondroma, that benign lesion has not yet been reported to arise from the surface of the jawbones, except near the mandibular condyle.

Once malignancy has been established, radiographic and clinical information may be required to ensure that the lesion is not an intramedullary osteosarcoma that has perforated through to the periosteal surface. This task is sometimes made impossible by the converse invasion of a juxtacortical lesion into cancellous bone.

Treatment and Prognosis

Lesions are treated by extensive surgical removal. Well-differentiated lesions may be handled more conservatively than poorly differentiated ones, but it is important to remember that different sites within the same tumor may show different tissue grades. Juxtacortical osteosarcoma has a considerably better prognosis than its intraosseous counterpart, although the few jawbone cases reported do not allow for specific commentary to be made for that anatomic site.

Well-differentiated lesions of long bones have an approximate 80% 5-year survival rate, whereas the survival rate of those with poorly differentiated lesions is less than half that. However, only a few deaths have been reported from the juxtacortical osteosarcomas of the jaws.

Pathologic Features

Glial choristoma is composed of an unencapsulated but fairly well-demarcated submucosal aggregation of loose glial fibers, intermixed with a variable number of mononuclear and multinucleated oval and stellate astrocytes, with moderate eosinophilic cytoplasm. Ganglion cells may be numerous. Bands of fibrous tissue may be intermingled with the lesional cells or may surround clusters of cells. There is no evidence of cellular dysplasia or tissue necrosis.

Glial tissues with astrocytic differentiation are immunoreactive for GFAP, S100 protein, and sometimes for vimentin. In general, the number of GFAP-positive cells is proportional to the degree of differentiation, and with glial choristoma, there is enough cellular maturity to provide strong and diffuse reactivity. This diffuse reactivity will help to differentiate the lesion from neurilemoma, which lacks glial filaments, and from lingual metastasis of an anaplastic brain neoplasm. This entity is described in more detail in Chapter 3 .

Treatment and Prognosis

Glial choristoma is removed by conservative surgical excision. No recurrence has been reported, nor has malignant transformation been reported.

Clinical Features

The oral presentation of epignathus is that of a large, focally soft, polypoid, lobulated mass, extending through a cleft palate into the mouth, often partially or completely filling the mouth. Lobules may extend into the oropharynx as well. The lesions are not painful but may interfere severely with breathing, swallowing, or feeding. The teratoma typically remains less than 4 cm in greatest diameter, but huge examples have been reported. Large lesions extend out of the mouth and may be the size of the newborn’s head. The mass is attached to a defect in the skull base via a stalk and magnetic resonance imaging (MRI) may show a considerably larger mass in the pituitary region of the brain.

Pathologic Features

The various tissue types found in a teratoma are, for the most part, mature, although full differentiation is often lacking. The tissues are randomly admixed one with another, showing little or no correlation with their normal anatomic relationships. The lesion is typically encapsulated and well demarcated from the surrounding normal tissues. There may or may not be a fibrovascular background stroma separating the different tissue types.

The keratin-filled dermoid cyst of the oral floor midline has abortive sebaceous glands, perhaps even hair follicles, in its walls. Many authorities consider this to be a teratoma, going so far as to call such a lesion a teratoid cyst and equating it with the ovarian dermoid cyst. It is best, however, to refer to such a lesion as a dermoid cyst , since it contains elements from only two germ cell layers.

Malignant teratomas do occur, usually with only a single component demonstrating dysplastic changes. When a rhabdomyoblastic component is seen, a variety of heterologous or mixed tumors must be ruled out, and when multiple components appear malignant, terms, such as malignant mesenchymoma , malignant ectomesenchymoma , and teratocarcinosarcoma , may be applied.

Treatment and Prognosis

Treatment of a teratoma consists of conservative surgical removal, a procedure that often requires finesse and delicacy because of the close proximity to important anatomic structures of the head and neck region. With conservative removal, occasional recurrence is to be expected, especially when portions of the teratoma must be left in place to preserve normal anatomic structures. Careful and long-term follow-up is recommended. Malignant teratoma is treated according to its most prominent malignant component, usually by radical surgery, with or without radiotherapy. Rarely, a benign teratoma has been reported to transform into malignancy, especially carcinoma.

Clinical Features

Fordyce granules appear as rice-like, white or yellow-white, asymptomatic papules of 1 to 3 mm in greatest dimension ( Fig. 4.23A ). There is no surrounding mucosal change and the granules remain constant throughout life. The most common sites of occurrence are the buccal mucosa (often bilateral), the upper lip vermilion, and the mandibular retromolar pad and tonsillar areas, but any oral surface may be involved. Some patients will have hundreds of granules, while most have only one or two.

There is a rarely reported systemic association with the hereditary nonpolyposis colorectal cancer syndrome (Lynch syndrome), especially the variant called Muir-Torre syndrome . In addition, at least one investigation found the lesions to be more numerous or more pronounced in persons with hyperlipidemia.

A Fordyce granule has been reported on gingival tissues, with pressure saucerization, producing a small underlying radiolucency. Occasionally, several adjacent glands will coalesce into a larger cauliflower-like cluster similar to sebaceous hyperplasia of the skin. In such an instance, it may be difficult to determine whether to diagnose the lesion as sebaceous hyperplasia or sebaceous adenoma. The distinction may be moot because both entities have the same treatment, although the adenoma has a greater growth potential. It should be mentioned that sebaceous carcinoma of the oral cavity has been reported, presumably arising from Fordyce granules or hyperplastic foci of sebaceous glands.

Pathologic Features and Differential Diagnosis

Fordyce granules are usually not biopsied because they are readily diagnosed clinically, but they are often seen as incidental findings of mucosal biopsies of the buccal, labial, and retromolar mucosa. The granules are similar to normal sebaceous glands of the skin but lack hair follicles and almost always lack a ductal communication with the surface ( Fig. 4.23B ). The glands are located just beneath the overlying epithelium and often produce a local elevation of the epithelium. Individual sebaceous cells are large, with central dark nuclei and abundant foamy cytoplasm ( Fig. 4.23C ). The surrounding stroma may contain occasional chronic inflammatory cells because of trauma with adjacent teeth.

Large numbers of lobules coalescing into a definitely elevated mass may be called benign sebaceous hyperplasia , and occasional small keratin-filled pseudocysts may be seen and must be differentiated from epidermoid cyst or dermoid cyst with sebaceous adnexa. The pathologist must be careful to differentiate such lesions from salivary neoplasms with sebaceous cells, such as sebaceous lymphadenoma and sebaceous adenoma, and their malignant counterparts sebaceous lymphadenocarcinoma and sebaceous carcinoma (see Chapter 6 ).

Treatment and Prognosis

No treatment is required for Fordyce granules, except for cosmetic removal of labial lesions. Inflamed glands can be treated topically with clindamycin. When removal is elected, conservative surgical or laser excision is the treatment of choice, with no recurrence expected. Neoplastic transformation is very rare but has been reported.

Clinical Features

Until recently, it was thought that the organ produces no visible or palpable mass; it was an occasional incidental finding in biopsied tissue samples from the region. A few proliferative masses of the lingual aspect of the posterior mandible have, however, now been reported as examples of tumors of the juxtaoral organ. A similar structure has been found within the anterior maxillary bone, but no embryonic explanation has been offered for its presence in that location.

Pathologic Features and Differential Diagnosis

The juxtaoral organ is a multilobulated nest or aggregation of two to 10 discrete islands of moderately large, oval, or angular cells, with a distinct squamoid appearance but with no keratin formation and with few, if any, intercellular bridges ( Fig. 4.24A and B ). Most islands also have smaller, darkly staining basaloid cells, usually aligned at the periphery, and a few show central epithelioid cells with clear cytoplasm. There is a definite glandular or organoid pattern. The background stroma is moderately dense fibrous tissue with no inflammatory infiltrate, no obvious encapsulation, and perhaps with extracellular melanin deposits.

Characteristically, there is a prominent PAS-positive basement membrane around the epithelial islands, and there are numerous small, myelinated, often degenerated nerves admixed with the epithelial islands. Occasional epithelial islands will demonstrate focal areas of dystrophic calcification.

A word of caution is warranted. Because the organ of Chievitz is located so deep in the soft tissues, it may be mistakenly interpreted by the pathologist as well-differentiated squamous cell carcinoma, mucoepidermoid carcinoma, or metastatic deposits from a visceral organ. Neuroepithelial structures similar to the organ have been reported in the posterior tongues of several individuals, in close association with the subepithelial nerve plexus of taste buds. Location should easily rule out an organ of Chievitz in such cases, but immunohistochemistry has been used as well.

Treatment and Prognosis

Although the function of this structure is completely unknown, it is a very innocuous variation of normal anatomy and requires no treatment. The few reported cases of tumorous growth of the organ had no recurrence 8 months after conservative surgical removal.

Clinical Features

Intraoral and pharyngeal lymphoid aggregates are more prominent in younger individuals, reaching their peak size during the adolescent and teenage years. Although they may become especially large in young people, the hyperplastic state may be seen in persons of any age.

Sites of occurrence, in decreasing order of frequency, are the posterior pharyngeal wall, the lateral posterior tongue, the soft palate, and the oral floor. During and for several days after an upper respiratory or other acute infection, benign lymphoid aggregates become enlarged, erythematous or yellowish, and perhaps somewhat tender, but they do not reach a size greater than 1 cm except on the posterior lateral tongue, where reported cases have been 1.5 cm or greater in diameter. Without hyperplasia, the aggregates are 0.1 to 0.4 cm in size and have a pale yellow, semitransparent appearance ( Fig. 4.25A ). They are often mistaken for mucosal cysts because of their apparent transparency. There is no surrounding erythematous or inflammatory halo.

Pathologic Features

The benign lymphoid aggregate is composed predominantly of well-differentiated lymphocytes collected into a single aggregation, usually with one or more germinal centers containing reactive lymphoblasts, predominantly B-cell types ( Fig. 4.25B and C ). Mitotic figures are seen in the germinal centers, as are macrophages containing phagocytized “tingible bodies” of nuclear debris from the surrounding proliferating lymphocytes. Linear streaking, or single filing, of lymphocytes may be seen at the periphery of the aggregate, and scattered lymphocytes are occasionally present in the surrounding fibrovascular stroma. There is no nodal encapsulation and vascular channels are minimally present, perhaps invisible without special staining.

The surface epithelium is often atrophic, but occasional nodules of lymphoid aggregation show deep “tonsillar” clefts from the surface, which may be filled with sloughed keratin. These clefts can crimp off at the surface, resulting in a keratin-filled lymphoepithelial cyst, or they may be considerably widened by the keratin build-up. In the latter case, the keratin may mushroom above the surface and become clinically visible as a tonsillar keratin plug.

The lymphoid cells of a lymphoid aggregate must be carefully evaluated to differentiate it from extranodal lymphoma and to determine whether the aggregate is hyperplastic. Microscopic criteria for hyperplasia and lymphoma are the same as those used for other lymphoid tissues of the body. Differentiation from a simple chronic inflammatory cell infiltrate is usually not difficult because the inflammatory infiltrate is much less abruptly demarcated from surrounding stroma, has many more lymphocytes in the surrounding stroma, has a greater admixture of inflammatory cell types, lacks germinal centers and is not monoclonal with histochemical analysis.

It should be mentioned that certain very chronic inflammatory or immune-related conditions, such as lichen planus or lupus erythematosus, may demonstrate small lymphoid aggregates deep in the submucosal tissues. These never produce surface nodules. Also a large, generalized infiltration of the hard palatal soft tissues, referred to as benign lymphoid hyperplasia of the palate and often found microscopically to be a B-cell lymphoma (see Chapter 13 ), is clinically so different from these small nodules of lymphoid aggregation that they cannot be clinically confused.

Treatment and Prognosis

The benign lymphoid aggregate requires no treatment but may have to be excisionally biopsied to provide an appropriate diagnosis and to rule out cystic lesions and lymphoid or other malignancy.

Clinical Features

The lingual thyroid is four times more common in females than in males. It presents as an asymptomatic nodular mass of the posterior lingual midline, usually less than a centimeter in size but sometimes reaching more than 4 cm ( Fig. 4.26 ). Larger lesions can interfere with swallowing and breathing, but most patients are unaware of the mass at the time of diagnosis, which is usually in the teenage or young adult years. Up to 70% of patients with lingual thyroid have hypothyroidism and 10% suffer from cretinism.

Pathologic Features

The lingual thyroid consists of a nonencapsulated collection of embryonic or mature thyroid follicles, which may extend between muscle bundles, raising suspicions of malignant invasion. The follicular cells, however, are normal or atrophic in appearance. All diseases capable of affecting the normal thyroid gland can, of course, affect the glandular tissue entrapped in the tongue. Thyroid adenoma, goiter, hyperplasia, inflammation, and carcinoma occur in lingual thyroids, and must therefore be evaluated in the same fashion as would any biopsied thyroid gland. Parathyroid tissue may be seen but has not been neoplastic in reported cases.

Treatment and Prognosis

Surgical excision or radioiodine therapy are effective treatments for lingual thyroid, but no treatment should be attempted until an iodine-131 radioisotope scan has determined that there is adequate thyroid tissue in the neck. In those patients lacking thyroid tissue in the neck, the lingual thyroid can be excised and autotransplanted to the muscles of the neck. Most cases require no treatment and biopsy should be considered with caution because of the potential for hemorrhage, infection, or release of large amounts of hormone into the vascular system (thyroid storm). Occasional patients with parathyroid tissue associated with their lingual thyroid have developed tetany after the inadvertent removal of this tissue.

Rare examples of thyroid carcinoma arising in the mass have been reported, almost always in males, but an enlarged lingual thyroid is more likely to reflect a normal compensatory response to thyroid hypofunction. Endocrine evaluation for hypothyroidism should therefore be done in such cases. In this light, it is important to know that three of every four patients with infantile hypothyroidism have ectopic thyroid tissue.

Clinical Features

The congenital epulis is almost exclusively found on the anterior alveolar ridges of newborns, although a few cases have reportedly developed shortly after birth. The earliest reported case was identified by ultrasonography in a 31-week fetus. Approximately 90% of cases occur in girls, and 10% present with multiple lesions.

This mass presents as a 0.5 to 2.0 cm soft, pedunculated, and perhaps lobulated nodule of the alveolar mucosa, especially the mucosa of the maxilla ( Fig. 4.27A ). A few lesions have been as large as 9 cm in size at birth and several cases have had involvement of both jaws. Large lesions obviously interfere with feeding. There is no tenderness or surface change and the lesion does not increase in size after birth. In fact, many of the smaller examples spontaneously regress after birth.

Pathologic Features and Differential Diagnosis

The mucosal mass is composed almost entirely of large, rounded and polyhedral, histiocyte-like cells with small, dark, oval nuclei and abundant eosinophilic granular cytoplasm ( Fig. 4.27B and C ). Lesional cells may be somewhat spindled. There are vascular channels between granular cells, but fibrous stroma is minimally present and often appears to be completely lacking. The tumor cells extend to the overlying epithelium, which is atrophic and never demonstrates the pseudoepitheliomatous hyperplasia so commonly seen in the granular cell tumor of adults.

Lesion cells do not immunoreact for laminin or S100 protein, as do the granular cells of the granular cell tumor. They are also negative for Leu7, neuron-specific enolase, and other neural markers and reactive only to vimentin. These cells are also strongly positive for acid phosphatase.

There is no other congenital alveolar mucosal lesion that is similar to the congenital epulis, but oral involvement by Langerhans cell disease might have enough tissue histiocytes to somewhat mimic the epulis. Occasional odontogenic tumors contain abundant granular cells, but these are almost never congenital and seldom located outside the bone. Conversely, 30% to 50% of cases show odontogenic epithelial rests among the granular cells.

The granular cell tumor has cells that are histopathologically identical to those of the granular cell epulis, but the early onset, unique location, and pedunculated appearance make the epulis easily differentiated from the tumor. The tumor, moreover, is not encapsulated, is S100 positive and infiltrates into underlying tissues, and many of the lesional cells have a spindled appearance, especially at the deep margin of the tumor.

Similar granular cells are found in the connective tissue papillae of verruciform xanthoma, but the association of this lesion with overlying papillomatosis and the older age at onset make it easily distinguished from granular cell epulis.

Treatment and Prognosis

Before birth, the congenital epulis enlarges at a rate similar to that of the growing fetus, but after birth the mass tends to spontaneously regress and disappear over the first 8 to 12 months of life. Residual remnants do not interfere with tooth eruption. There is therefore no need to treat a small congenital lesion. Larger lesions interfering with feeding require conservative excision as soon as the child is large enough to safely undergo surgery. There is no tendency for recurrence and malignant transformation has not been reported.

Clinical Features

Median rhomboid glossitis presents in the posterior midline of the dorsum of the tongue, just anterior to the V-shaped grouping of the circumvallate papillae ( Fig. 4.28A ). The long axis of the rhomboid, diamond-shaped or oval area of red depapillation is in the anterior-posterior direction. Most cases are not diagnosed until the middle age of the affected patient, but the entity is, of course, present in childhood. There appears to be a 3:1 male predilection.

Those lesions with atrophic candidiasis are usually more erythematous but some respond with excess keratin production, and therefore show a white surface change. Infected cases may also demonstrate midline soft-palate erythema in the area of routine contact with the underlying tongue movement; this is euphemistically referred to as a kissing lesion .

Lesions are typically less than 2 cm in greatest dimension, and most demonstrate a smooth, flat surface, although it is not unusual for the surface to be lobulated, sometimes dramatically so. Occasional lesions have surface mamillations raised more than 5 mm above the tongue surface, and rare lesions are located somewhat anterior to the usual location. None have been reported posterior to the circumvallate papillae.

Prior to biopsy, if elected, the clinician should be certain that a lobulated midline lesion does not represent a lingual thyroid, as it may be the only thyroid tissue present in the patient’s body. Additional clinical look-alike lesions include the gumma of tertiary syphilis, the granuloma of tuberculosis, deep fungal infections, and granular cell tumor.

Pathologic Features

Median rhomboid glossitis shows a smooth or nodular surface covered by atrophic stratified squamous epithelium overlying a moderately fibrosed stroma with somewhat dilated capillaries. Fungiform and filiform papillae are not seen, although surface nodules may mimic or perhaps represent anlage of these structures. A mild to moderately intense chronic inflammatory cell infiltrate may be seen within subepithelial and deeper fibrovascular tissues.

Chronic Candida infection may result in excess surface keratin or extreme elongation of rete processes and premature keratin production within individual cells or as epithelial pearls (dyskeratosis) deep in the processes ( Fig. 4.28B and C ). Silver or PAS staining for fungus will reveal Candida hyphae and spores in the superficial layers of the epithelium of such cases. This pseudoepitheliomatous hyperplasia may be quite pronounced, and the tangential cutting of such a specimen may result in the artifactual appearance of cut rete processes as unconnected islands of squamous epithelium, leading to a mistaken diagnosis of well-differentiated squamous cell carcinoma . Because of this difficulty, it is recommended that the patient be treated with topical antifungals before biopsy of a suspected median rhomboid glossitis. It should also be mentioned that the posterior midline region of the oral tongue is a very, very unlikely sight for carcinoma development.

Treatment and Prognosis

No treatment is necessary for median rhomboid glossitis, but nodular cases are often removed or incised for microscopic evaluation. Recurrence after removal is not expected, although those cases with pseudoepitheliomatous hyperplasia should be followed closely for at least a year after biopsy to be certain of the benign diagnosis. Antifungal therapy (topical troches or systemic medication) will reduce clinical erythema and inflammation caused by Candida infection. This therapy, as stated earlier, should ideally be given prior to the biopsy, to reduce the Candida -induced pseudoepitheliomatous hyperplastic features. Some lesions will disappear entirely with antifungal therapy.

Clinical Features

The oral epidermoid cyst occurs primarily on the lateral and ventral tongue, the oral floor and the lateral soft palate, especially above the pharyngeal tonsils. Some refer to soft palate cysts as velar cysts . Most cases are diagnosed during the teen or young adult years. The cyst typically remains less than 1 cm in diameter and may be somewhat movable beneath the surface, except on bone-bound mucosa. The cyst is almost always superficial, producing a sessile nodule with a white or yellow-white; the occasional deeper lesions may show a normal color ( Fig. 4.29A ).

The larger cyst is usually found in the oral floor midline above the mylohyoid muscle. Occasionally, such a lesion is dumbbell-shaped because it has penetrated through a hiatus in the muscle to extend into the submental area, possibly imparting a double chin appearance. In this location, the cyst may reach 6 to 7 cm in greatest diameter, may become infected, and may interfere with swallowing or the proper function of the tongue.

The clinically similar gingival cyst of adult is, by definition, found on the attached alveolar or gingival mucosa and appears as a pink or clear, translucent nodule less than 6 mm in diameter. Larger cysts may eventually impart a downward pressure on the underlying bone, producing a well-demarcated saucerized area of thin cortex, which often is radiolucent on a dental radiograph.

Pathologic Features

The epidermoid cyst is lined by a thin stratified squamous epithelium with few rete processes ( Fig. 4.29B and C ). Quite often, there is no granular cell layer and keratin from the surface of the epithelium can be seen to be sloughing into the cystic lumen, which is usually filled with degenerated and necrotic keratinaceous detritus. Areas of epithelial degeneration or ulceration may be seen, usually associated with a mild to moderately intense chronic inflammatory cell reaction. Inflammation may extend deeply into subepithelial fibrovascular stroma. Occasional cysts have contained fungi, bacteria, or necrotic food debris in their lumina, and darkly hematoxyphilic precipitated salts (dystrophic calcification) may be seen within the necrosed keratin.

When keratin degenerates within an ulcer bed of the cyst wall, cholesterol crystals form elongated, sharp-ended clefts (cholesterol clefts), which are clear spaces in stained tissue sections because of the dissolution of the associated fats by laboratory processing. Foreign-body multinucleated giant cells are frequently seen adjacent to or surrounding such clefts. This cholesterol granuloma will occasionally proliferate into the lumen of the cyst from an area of ulceration, but they are usually seen within the ulcer bed itself.

The dermoid cyst differs from epidermoid cyst only in the presence within its walls of normal or dysmorphic adnexal appendages, usually sebaceous glands or abortive hair follicles. If the cyst wall contains other elements, such as muscle (other than pilar arrector smooth muscle) or bone, the term teratoid cyst is preferred.

The gingival cyst is lined by thin squamous epithelium, occasionally with focal nodular thickenings, and shows a lumen filled with a clear fluid. Occasionally, chronic inflammatory cells are seen in the surrounding stroma or the cystic lumen.

Treatment and Prognosis

Treatment consists of conservative surgical removal, trying not to rupture the cyst, as the luminal contents may act as irritants to fibrovascular tissues, producing postoperative inflammation. The presence or absence of a cholesterol granuloma has no bearing on the prognosis. Recurrence is unlikely after treatment. Malignant transformation of oral cysts has not been reported, although it has occurred in cysts of the skin.

Large oral floor cysts are problematic surgically because a portion is found beneath the floor muscles. The increased difficulty means that recurrence is more likely, so follow-up examination for a year or two is important.

The gingival cyst of adult almost never requires more than surgical excision. If the underlying cortex is saucerized, it will return to normal spontaneously, over the following months.

Clinical Features

Gingival cysts of the newborn typically present as multiple (usually less than six) 1 to 4 mm milia-like yellow-white, sessile mucosal papules of the alveolar processes. Palatal cysts have a similar appearance but are less numerous and are found on the midline of the posterior hard palate, and occasionally of the anterior soft palate. Occasional palatal cysts are located some distance from the midline. The cysts are usually somewhat larger and less numerous than the gingival cysts of the alveolar processes in newborns, but the two entities are otherwise clinically identical. Both types of cyst are so superficial that several may be ruptured at the time of examination.

Pathologic Features

Both gingival and palatal cysts of the newborn show a thin stratified squamous epithelium cyst lining with a routine fibrovascular connective tissue stroma, usually without an inflammatory cell infiltrate. The cystic lumen is filled with degenerated keratin, usually formed into concentric layers or “onion rings,” and the epithelium lacks rete processes. Occasional cysts will demonstrate a communication with the surface.

Treatment and Prognosis

No treatment is required for gingival or palatal cysts of the newborn. The cysts are very superficial and within weeks will rupture to harmlessly spill their contents into the oral or pharyngeal environment. The cyst lining then fuses with the overlying mucosa and becomes part of it. Occasionally, a larger cyst or a cyst situated more deeply in the submucosal stroma will remain for 6 to 8 months before rupturing. These cysts do not interfere with tooth eruption, should they last that long.

Clinical Features

The nasolabial cyst has a strong female predilection (75% occur in women) and appears to occur more frequently in blacks than in whites. It is found near the base of the nostril, just above the periosteum, or in the superior aspect of the upper lip ( Fig. 4.30A ), it is bilateral in approximately 10% of all cases. The cyst usually obliterates the nasolabial fold and may elevate the ala of the nose on the affected side. It also obliterates the maxillary vestibule and frequently extends into the floor of the nasal vestibule, occasionally causing nasal obstruction or pressure erosion of the bone of the nasal floor. When located in the lip, there almost always is a fibrous or epithelial attachment to the nasal mucosa.

Most examples are less than 1.5 cm in greatest diameter, but some have reached much larger sizes. Injection of a radiopaque dye into the lumen will help define the cyst outline, as will ultrasound. It may be somewhat irregular, even bilobed, and it is not unusual to be secondarily inflamed and somewhat tender to palpation. Occasional cysts rupture or drain into the oral cavity or nose.

Pathologic Features and Differential Diagnosis

The nasolabial cyst is lined by respiratory epithelium, stratified squamous epithelium, pseudostratified columnar epithelium, or a combination of these ( Fig. 4.30B ). Mucus-filled goblet cells may be scattered within the epithelium and apocrine change has been reported. Chronic inflammatory cells may be seen in the surrounding fibrovascular stroma. The nasolabial cyst might be confused with epidermoid cyst or eruption cyst. The epidermoid cyst, however, is more superficial, being located immediately beneath the mucosal epithelium, does not extend into nasal sinus region, and lacks the respiratory epithelial features of the nasolabial cyst. The eruption cyst can be radiographically identified by its association with an underlying erupting tooth.

Treatment and Prognosis

This cyst is treated by conservative surgical excision, usually using access from the anterior maxillary vestibule. The surgical procedure may have to be extended deeply into the nasal sinus, and it is sometimes necessary to remove part of the nasal mucosa to remove the entire cyst. Marsupialization from the nasal sinus floor has been successful in numerous cases.