Aggressiveness, all sarcomas have (he potential for metastasis.

The degree of malignancy varies, and some are more life threatening than others. Unlike carcinomas that spread through the lymphatics, most sarcomas tend to spread via hematogenous routes, making dissemination more rapid and widespread. Box 91 lists benign and malignant connective tissue neoplasms found in the oral, head, and neck regions. Lesions of the oral connective tissue tend to be more common in some age groups and uncommon or even nonexistent in others (Box 9-2). FIBROUS TISSUE Fibrous proliferations occur as a result of reaction to injury, spontaneous benign neoplastic transformation, and malignant transformation of fibroblastic cells. The reactive hyperplasias are by tar the most common growths encountered in the oral regions. True benign fibroblastic neoplasms or fibromas probably do not occur within the oral submucosa. The benign focal soft tissue growths found within the oral cavity are the result of reactive hyperplasias and are composed primarily of one or more of the following connective tissue components: mature collagen, focal bone formation, endothelial cells, and multinucleated giant cells. When a reactive focal connective tissue proliferation is confined to the gingiva and its exact histologic nature is unknown, it is clinically designated as an epulis. The most common lesions referred to as epuUdes are peripheral fibroma, peripheral ossifying fibroma, pyogenic, granuloma, and peripheral giant cell granuloma (Box 9-3 and Figure 9-1). Although the fibromatoses and fibrous histiocytomas are aggressive fibroblastic proliferations, they are considered by some sources to be reactive in nature instead of neoplastic. This is in spite of the fact that a history of injury to the area is seldom found. In this chapter, fibromatosis, myofibromatosis nodular fasciitis, and benign fibrous histiocytoma are classified as benign neoplasms. The malignant tumor derived from the fibroblast, is fibrosarcoma, an uncommon neoplasm encountered primarily in children and young adults. Most of the fibroblastic lesions arise within the soft tissue, but on occasion lesions are encountered within bone, the mandible being affected more often than the maxilla. Common Reactive Hyperplasia of Gingival Connective Tissue (Epulis) Peripheral fibroma Peripheral ossifying fibroma

Pyogenic granuloma (pregnancy tumor) Peripheral giant cell granuloma

FIGURE 9-1
Distinguishing histologic features of common reactive hyperplasia of gingival connective tissue collectively designated as an epulis. Most lesions are though! to be reactive to a chronic irritant (represented here, as subgingival calculus). A, Peripheral fibroma: hyperplasia of supraperiosteal tissues resulting in overproduction of dense collagen (while double lines). B, Peripheral ossifying fibroma: hyperplasia of periodontal membrane resulting in a ceilular lesion consisting of fibroblasts and collagen (white) and cemental and bone deposits (yellow-green). C, Pyogenic granuloma: hyperplasia of a vascular component of gingival connective tissue resulting in a cellular lesion composed of endothelial cells and small capillaries (light red). D, Peripheral giant cell granuloma: hyperplasia of the periosteum resulting in the overproduction of a vascular component and mononuclear and multinucleated giant cells resembling osteoclasts (pink structure with blue dots).

HYPERPLASIAS Focal Fibrous Hyperplasia (Irritation Fibroma) FOCAL FIBROUS HYPERPLASIA : Hyperplasia of tibrous connective tissue that evolves in response to chronic irritation in which extensive elaboration of collagen resembling scar tissue exists. A focal fibrous hyperplasia is not a true neoplasm of fibroblasts but an exuberant reaction to chronic Injury in which the production of mature bundles of collagen [ire-dominates. Cheek and lip biting, in addition to denture irritation, are the most common contributing factors. The resulting lesion, commonly referred to as irritation fibroma, represents a pathologic overgrowth of both fibroblasts and their collagenous products. It is the most common nodular swelling found within the oral cavity. CLINICAL FEATURES Focal fibrous hyperplasia is most often encountered in adults and is primarily located on the gingiva (figure 9-2), lips, and buccal mucosa (Figure 9-3). Other common sites are the borders of the tongue. These nodular lesions usually occur on the soft tissue in

the plane of the occlusal line. The clinical appearance of irritation fibroma is that of a domelike growth with a smooth mucosal surface of normal coloration. Ulceration is rare yet may occur if the patient continues to irritate the swelling. Surface hyperkeratosis is sometimes encountered and is probably the result of a low-grade chronic irritation of the overlying epithelium. Lesions may remain the same size, for many years. It is of importance that they cannot be positively diagnosed by clinical examination only because other mesenchymal tumors may show similar clinical features. When the irritant is removed, lesions often become slightly smaller as the inflammatory component diminishes, yet they will not completely regress. For this reason it is usually recommended that they be excised and submitted for microscopic examination. When focal fibrous hyperplasia is on the attached gingiva in the area of the gingival sulcus or interdental papilla, it is sometimes termed peripheral fibroma. The term peripheral is used to distinguish this innocuous lesion from the more aggressive fibrous lesion that may occur centrally within the jaws. It is surmised that the gingival reactiveproliferations evolve from an irritant that becomes entrapped within the gingival sulcus. Toothpick fragments, food debris, and calculus are common causative factors. Unfortunately, often at the time of clinical examination, no exogenous irritant is found within the sulcus. By the time the lesion has evolved, the irritant has probably dissolved or has been extruded. HlSTOPATHOLOGY The surface epithelium may be intact, exhibit hyperorthokeratosis, or show foci of ulceration. This epithelium overlies an underlying mass of dense, fibrous connective tissue composed of significant amounts of mature collagen in a scarlike pattern (figure 9-4). The spindle-shaped fibroblasts, common in some of the indeterminate fibrous lesions, are sparse. The fibroblastic nuclei are monomorphic in character, and the overall appearance is one of hypocellularity.

FIGURE 9-2 Focal fibrous hyperplasia. When located on the attached

FIGURE 9-3 Focal fibrous hyperplasia. In nongingival locations, lesions

A histologic variant of focal fibrous hyperplasia, referred to as giant cell fibroma, occurs in the oral mucosa and has a counterpart that is occasionally encountered on the skin and genitalia. The giant cell fibroma is also considered to be a reactive fibrous proliferation. The name given to this variant is based on the presence of binucleated and trinucleated fibroblasts that tend to occur in close proximity to the overlying epithelium. These binucleated and trinucleated cells have oval, monomorphicappearing nuclei with copious eosinophilic cytoplasm. They often assume a stellate appearance, resembling a snanta ray. When ulceration occurs, a mononuclear inflammatory cell infiltration occurs. The peripheral fibroma of the gingiva will usually show histologic features identical to the irritation fibroma located in other oral locations. A hypocellular fibrous reaction is encountered with mature collagen libels TREATMENT Local excision is the treatment of choice, and the lesions seldom recur. They will not involute spontaneously, because the excess collagen found is permanent. The giant cell fibroma variant appears to be no different in behavior from the iocai fibrous hyperplasia. The peripheral fibroma of the gingiva is also treated by local excision but must be accompanied by periodontal root planing to ensure that all sources of irritation are eliminated.

FIGURE 9-4 Focal fibrous hyperplasia. Microscopic appearance consisting of dense bundles of collagen. Because the lesion is usually chronically irritated, hyperorthokeratosis is commonly found on the surface of the epithelium.

Peripheral Ossifying Fibroma PERIPHERAL OSSIFYING FIBROMA A gingival nodule consisting of a reactive hyperplasia of connective tissue containing focal areas of bone. The peripheral ossifying fibroma is a reactive fibrous proliferation; probably of periosteal or periodontal ligament

origin. Because the periosteum and periodontal ligament contain cells that synthesize both bone and cementum, the proliferation includes cells with osteogenic potential. These lesions are related to other reactive gingival swellings, because irritation is considered to play a significant role in the cause.

CLINICAL FEATURES This reactive lesion is more common in women and tends to occur during the reproductive years, especially the third and fourth decades. It is usually not found in children and the elderly. Peripheral ossifying fibroma is an epulis that emanates from the interdental papillae, although occasionally it is seen to arise from the facial 01 lingual attached gingiva (figure 9-5). Invariably, the mass originates from within the periodontal ligament, where an irritant is thought to be responsible for stimulating periodontal ligament fibroblasts that also possess osteogenic and cementogenic potential. The overlying mucosa may be smooth and of normal coloration, or there may be foci of surface ulceration. They are hard to palpate and are fixed to the underlying tissue. Dental radiographs will often disclose radiopacities within the soft tissue swelling.

FIGURE 9-5 Peripheral ossifying fibroma. Lesions frequently become large and interfere with mastication.

HISTOPATHOLOGY Within the connective tissue are diffuse sheets of fibroblasts with plump monomorphic nuclei. The overall picture is one of hypercellularity, with the collagenous component somewhat hyalinized. No true capsule exists; the hypercellular zones slowly merge with mature fibrous and granulation tissues around the periphery (Figure 9-6, A). In focal areas, osteoid deposits can be identified; although some may contain lacunae with TREATMENT Peripheral giant cell granuloma is ireated by surgical excision. Removal must include all the giant cell tissue, because recurrences are common. In the deniulous patient this usually requires removal of one or more teeth and curettage of the socket. Inflammatory hibrous Hyperplasia

Inflammatory fibrous hyperplasia : a proliferation of fibrous connective tissue with an associated chronic inflammation in response to chronic injury. Ill-fitting dentures with overextended flanges or older dentures that irritale vestibular tissue after alveolar ridge resorption may stimulate fibroblastic proliferation and collagen synthesis, ihese hyperplastic processes are most frequently found adjacent to denture flanges and tend to be multilobulated and diffuse. When they result from the impingement of an overextended flange, lesions usually contain an elongated trough with a linear ulcer (fissure) at its base. In the past it was commonly referred to as epulis fissuratum. CLINICAL FEATURES Denture-induced fibrous hyperplasia is usually encountered in the maxillary or mandibular anierior vestibule where it is associated with an ill-fitting denlure that has overextended denture flanges. The hyperplastic tissue is frequently tabulated or in folds and may be fissured where the denture flange impinges on the tissue at the base of the linear troughs (Figure 99). Most of these hyperplastic growths are erythematous because of the areas of ulceration. Occasionally they may be normal in color. They are consistently flabby, soft, and movable and may occur anywhere along the margins of the prosthesis; the anterior locations are most common. HISTOPATHOLOGY The surface stratified squamous epithelium is frequently hyperplastic, demonstrating acanthosis with elongated rete ridges. Occasionally, zones of ulceration are encountered and the ulcerated areas are occupied by fibrin with entrapped leukocytes. The buik of the tissue is composed of mature, fibrous connective tissue that is hypocellular. Spindle-shaped fibroblasts are interposed between dense collagen fibers in a. scarlike pattern (Figure 9-10). When the fibrous hyperplasia extends into the lip and buccal mucosa, minor salivary gland lobules may be identified and will usually show acinar degeneration and ductal dilatation with inflammatory cell infiltration (chronic sclerosing sialadenitis). TREATMENT Diffuse inflammatory fibrous hyperplasia associated with an irritating dental prosthesis will not resolve completely on its own, even if the denture irritation is corrected or the denture is withdrawn. Lesions often become smaller when the denture is withdrawn, altered, or rebased because of the reduction in the

inflammation. The permanently formed fibrous component will remain, resulting in an irregular, unstable area of soft tissue. For new prosthetic appliances to be satisfactory, the residual fibrous masses must be excised in their entirety before fabrication of a new dental prosthesis.

FIGURE 9-9 Inflammatory fibrous hyperplasia. With the denture removed the lesion reveals two linear folds of hyperplastic connective tissue with a central trough that is Irequentiy ulcerated, thus contributing to the often-accornpanying intense inflammation. This lesion is commonly referred to as epulis fissuratum.

FIGURE 9-10 Inflammatory fibrous hyperplasia. Low-power microscopy exhibiting an abundance of dense fibrous connective tissue interspersed with focal accumulations of inflammatory cells and an increase in vascularity, all of which contribute to the excessive tissue.

Inflammatory Papillary Hyperplasia [INFLAMMATORY PAPILLARY HYPERPLASIA: Multiple small nodules that consist of a proliferation of fibrous connective tissue with an associated chronic inflammation found under ill-fitting dentures. Some loose and ill-fitting maxillary dentures will initiate a hyperplastic response on the tissue of the palatal vault. This response is even more intense in dentures that have been made with a socalled palatal relief, whereby negative pressure is placed against the paiate. The palatal tissue responds by producing numerous small areas of erythematous focal fibrous hyperplasia that resemble the surface of a papilloma. CLINICAL FEATURES Inflammatory papillary hyperplasia is confined to the palatal vault, seldom progressing onto the alveolar ridge. This is an important clinical observation, because verrucous carcinoma, an

aggressive epithelial proliferation, usually involves the alveolar ridge and vestibule and may extend to the palate, thereby resembling papillary hyperplasia. Inflammatory papillary hyperplasia is usually encountered under full dentines but occasionally occurs under the palatal coverage of partial dentures. The hyperplastic nodules are characteristically 3 to 4 mm in diameter, with a generalized erythematous "cobblestone" pattern resembling a field of confluent reddish-pink mushrooms (figure 9-11). When probed with a dental instrument, it can be seen thai each polyp is independently attached.

FIGURE 9-11 Inflammatory papillary hyperplasia. The lesion occurred under a denture that had been ill fitting for a prolonged period. The erythematous densely compacted nodules near the midline of the hard palate give the tissues a "cobblestone" appearance.

HISTOPATHOLOGY Tissue section's disclose an obvious polypoid appearance with multiple smooth, round nodules covered with stratified squamous epithelium. Where two papillary projections meet at their base, the epithelium is usually quite hyperplastic and displays acanthosis with elongated, anastomosing rete ridges (pseudoepitheliomatous hyperplasia). The individual epithelial eel's fail to show any atypical cytologic features. The hyperplastic response is not confined to the connective tissue but also involves the overlying epithelium. Supporting each polypoid projection is a dense core of fibrous connective tissue that is traversed by capillaries. Scattered mononuclear inflammatory cells are usually dispersed throughout the connective tissue, this inflammatory component is quite variable and may be minimal in some cases. TREATMENT The hyperplastic tissue should be removed before fabrication of a new maxillary partial or complete denture. This may be achieved with a scalpel, a fluted burr on a rotary instrument, electrocautery, or laser surgery. Hyperplastic Gingivitis

HYPERPLASTIC GINGIVITIS : Focal or generalized fibrous hyperplasia of the marginal gingiva with an associated inflammatory response. Although the gingiva may be edematous and somewhat enlarged in chronic gingivitis and periodontal disease, it rarely becomes conspicuously enlarged. Such an occurrence is referred to as hyperplastic gingivitis and represents an exuberant inflammatory fibrous hyperplastic response (usually to calculus and plaque) that is often intensified by the patient's hormonal status.

CLINICAL FEATURES A predilection exists for this form of gingivitis in females, because it is encountered with increased frequency during puberty and pregnancy (puberty gingivitis, pregnancy gingivitis). Conceptually it is postulated that hyperplastic gingivitis represents an excessive fibrous hyperplasia with an associated inflammatory cell infiltration that occurs in response to elevated estrogen and other hormone metabolites. The enlargements are centered in the interdental papillae where the tissue may be spongy and erythematous with a tendency to bleed with minimal provocation (Figure 9-12). HISTOPATHOLOGY The surface epithelium exhibits parakeratosis with marked acanthosis and epithelial hyperplasia characterized by elongated and anastomosing rete ridges.

FIGURE 9-12 Focal hyperplastic gingivitis, I he lesion is typically an erythematous enlargement of the interdental papilla of the gingiva. Milder degrees of gingivitis may be present in other areas.

Transmigration by neutrophils into the epithelium is common. The submucosal connective tissue accounting for the zones of enlargement are represented by an unremarkable-appearing fibrous connective tissue with prominent vascularity. Disbursed throughout this tissue are mononuclear inflammatory cells mainly plasma cells and lymphocytes. The clinical enlargement is due to both fibrous hyperplasia and mononuclear inflammatory cell infiltration. TREATMENT Dental prophylaxis with scaling and polishing may produce some resolution; however, the fibrotic gingiva usually fails to return completely to normal contour. Attempts to surgically remove the enlarged tissue will result in recurrence as long as the hormonal influences remain. In pregnancy gingivitis, definitive treatment

should not be performed until after delivery. Persistent enlargement that interferes with function can be managed by gingivoplasty. Hereditary Gingival Fibromatosis HEREDITARY GINGIVAL FIBROMATOSIS : A hereditary form of generalized gingival hyperplasia in which the autosomal dominant form may be associated with hypertrichosis, craniofacial deformities, epilepsy, and mental retardation. Diffuse gingival hyperplasia may occur as a hereditary disorder. Although the precise mechanism of the disease is unknown, it appears to be restricted to the fibroblasts that populate the gingiva. The hyperplastic response does not involve the periodontal ligament and occurs peripheral to the alveolar bone within the attached gingiva. There appear to be at least two modes of inheritance : autosomal dominant and autosomal recessive. The affected DNA sequences have been identified. CLINICAL FEATURES The gingiva becomes markedly enlarged and may cover the crowns of the teeth (Figure 9-13). The autosomal dominant form is most often associated with hypertrichosis and other defects, including corneal dystrophy, craniofacial deformities, nail defects, and deafness. In the forms occurring in children, epilepsy and mental retardation are sometimes present. In the autosomal recessive form, facial anomalies with hypertelorism have been observed, but most forms are without defects othei than the gingival enlargement. Consanguinity has been observed in the recessive forms of the disease. In most patients the gingival enlargement begins at puberty and shows progressive proliferation that involves both the interdental papilla and the attached gingiva. Lingual and labial gingiva tissues may be involved. Clinically the gingiva is bulbous, firm, and hard, yet it usually retains its normal coloration. No sex predilection exists. The gingival enlargement is usually minimal but may be massively fibrotic, covering the crowns of the teeth. Eruption of teeth is normal. HlSTOPATHOLOGY The surface epithelium exhibits elongated, thin rete. ridges. The fibrous connective tissue is densely collagenous, with scattered mature spindle-shaped fibroblasts. Significant numbers of mast cells exist that and represent arteriovenous (AV) anastomoses in which an intervening capillary bed is lacking. Lymphatic

malformations of" a similar nature do not occur within the mandible or maxilla.

FIGURE 9-13 Hereditary gingival fibromatosis. The gingiva is firm, normal in color, and exhibits a generalized overgrowth that in some areas exceeds the height of the crowns of the teelh.

HYPERPLASIA Pyogenic Granuloma PYOGENIC GRANULOMA : A fast-growing reactive proliferation of endothelial cells commonly en the gingiva and usually in response to chronic irritation. A focal reactive growth of fibrovascular or granulation tissue with extensive endothelial proliferation is termed a pyogenic granuloma, The term would imply that such lesions react to inlection with pyogenic microorganisms. In fact, no relationship exists between bacteria and the emergence of these reactive proliferations. The tissue is infiltrated with many neutrophils, accounting for the erroneous interpretation of a bacterial cause. Pyogenic granulomas can occur anywhere in the body and are common on the fingers and toes around the nail beds. Within the oral cavity, pyogenic granulomas are frequently localized to the gingiva, where they are included as part of the differential diagnosis of an epulis. An epulis is a collective clinical term for focal growths of the gingiva. Trauma or introduction of foreign material into the gingival sulcus may provide the stimulus for this proliferative hyperplasia. CLINICAL FEATURES Within the oral cavity pyogenic granuloma is most often encountered in the interdental papilla region (Figure 9-56). These lesions may extend from the buccal to the lingual or palatal gingiva; however, they are most often limited to either the buccal or the facial surface. Because they are extremely vascular, they are usually fiery red and will often show a gray pseudornembrane over the surface, secondary- to ulceration of the overlying epithelium. A significant female predilection exists, and lesions

tend to occur more often during the second and third trimesters of pregnancy. These lesions are often referred to as pregnancy tumors. Although the} are benign hyperplastic reactions, they may grow at an alarming rate, reaching i to 2 cm in diameter within 4 to 7 days. Adjacent periodontal inflammation may be identified; however, pyogenic granuloma is unrelated to the regular forms of gingivitis and periodontitis. Pyogenic" granulomas occur as exuberant granulation tissue responses after the removal of teeth, particularly the third molars. As such, the lesion emanates from the exuaciion .sites, usually in response to an irritant tiiat has fallen into the socket such as calculus, food, tooth fragments, or bone spicules. Pyogenic granulomas occur in other mucosal sites unrelated to the gingival sulcus, particularly on the tongue, lips, and buccal mucosa (Figure 9-57). In these locations it is assumed that biting of the tissue serves as the irritation that stimulates the hyperplastic response.

FIGURE 9-56 Pyogenic granuloma. The erythematous exophytic lesion is located in the interdental papilla. In this location, it receives continuous chronic irritation, resulting in an ulcerated surface.

HlSTOPATHOLOGY Pyogenic granuloma is composed of granulation tissue, typified by a plethora of anastomosing endothelial-lined vascular channels engorged with erythrocytes and nodules ol endothelial cells in medullary patterns (Figure 9-58). The endothelial cells are usually plump and vesicular, indicating active proliferation. Often the cells will have a pleomorphic character, and rarely, some of these actively proliferating hyperplasias closely resemble Kaposi sarcoma. Portions of the epithelium overlying the surface are usually ulcerated, leaving a fibrinous exudate with entrapped leukocytes. The loose connective tissue dispersed throughout the fibrovascular tissue and interposed between vascular channels is infiltrated predominantly by neutrophils and histiocytes.

FIGURE 9-57 Pyogenic granuloma. A purplish pedunculated nodular lesion of the commissure.

FIGURE 9-58 Pyogenic granuloma. A. Low-power microscopy demonstrating a raised lobuiai lesion with a thin stalk. B. Medium-power microscopy exhibiting a medullary pattern of endothelial ceils intermingled with small vascular spaces and loose fibrous connective tissue. When ulcerated, lesions will also have acute and chronic inflammatory cells diffusely distributed throughout.

TREATMENT Although these are reactive hyperplasias, they have a relatively high rate of recurrence after simple excision. If the patient is pregnant, recurrence is common. Although many pyogenic granulomas are quite large, gingival lesions usually have a single stalk. After surgical excision the underlying tissue, should be thoroughly curetted and root planing should be undertaken. Recurrence after surgery of pyogenic granulomas in extragineival sites is uncommon. HAMARTOMATOUS AND NEOPLASMS Hemangioma HEMANGIOMA : A proliferation of large (cavernous) or small (capillary) vascular channels occurring commonly in children; individual lesions have variable clinical courses. Hemangiomas are relatively common benign proliferations of vascular channels that may be present at birth or arise during early childhood (Figure 9-59). Some slowly evolve, stabilize in size, and then either remain for life (hamartomatous) or slowly resolve to nor mal. Others may have a gradual but continuous growth pattern (benign). Most are located within the. skin, where diey may be flat or raised. Flat (macular) hemangiomas can be relatively large, covering significant areas of the skin; these lesions are often referred to as birthmarks. Approximately 90% of such hemangiomas spontaneously invo-, lute by the time the patient has finished puberty. The remainder do not and are considered

hamartomas. Vascular lesions of the lips and oral mucosa may arise in adulthood (Figure 9-60) and represent focal venous

FIGURE 9-59 Hemangioma. Congenital hemangioma of the lower lip, exhibiting the usual bluish coloration and nodularity.