Fibrous and gingival nodules

Clinical findings

• Fibroma: This occurs at any age group without sex predilection and consists of a dome-shaped nodule or papule that may be white/keratotic, mucosa-colored, or ulcerated. It is located in areas readily traumatized by biting (i.e., buccal mucosa, lateral tongue, and lower lip mucosa) or on the gingiva where plaque accumulates ( Fig. 5.1 A–D).

  

• Giant cell fibroma: Approximately 60% occur within the first three decades of life with no sex predilection. It often has a papillary surface and 90% are located on the gingiva (50% of cases), tongue (22%), and palatal mucosa (18%), all keratinized sites ( Fig. 5.1 E). A similar histopathologic condition is referred to as the retrocuspid papilla, which occurs on the lingual attached gingiva of the mandibular cuspids, usually bilaterally.

• Multiple fibromas of the gingiva, buccal mucosa, and tongue are often seen in tuberous sclerosis complex (associated with a mutation in TSC1 or TSC2 ), while sclerotic fibromas are seen in PTEN hamartoma tumor (Cowden) syndrome associated with mutation in PTEN ( Fig. 5.1 F).

Etiopathogenesis and histopathologic features

Conventional fibroma is a reactive fibrosis/scar (similar to a hypertrophic scar on the skin) from bite trauma and is not a true neoplasm.

• Fibroma: The nodule consists of a proliferation of fibrocollagenous tissue associated with variable vascularity, neurovascular hyperplasia, parakeratosis or hyperkeratosis, ulceration, inflammation, and epithelial hyperplasia or atrophy ( Figs. 5.2 and 5.3 ); myxoid/mucinous change may be present and may be fairly extensive ( Fig. 5.4 ). Fibromas of the anterior hard palatal mucosa often contain cartilage and branches of the nasopalatine neurovascular bundle ( Fig. 5.5 ).

  
  
  
  

• Giant cell fibroma: Nodules often have a papillary or bosselated surface with acanthosis forming spiky, saw-tooth shaped rete ridges. There are many giant, stellate, bi- and sometimes multinucleate fibroblasts; some of these cells have been shown to be factor XIIIa+; dense collagen and mast cells are often present and this lesion resembles cutaneous angiofibroma (fibrous papule of the nose) ( Figs. 5.6 and 5.7 ).

  
  

• Solitary (sporadic) sclerotic fibroma ( storiform collagenoma ): This paucicellular nodule contains hyalinized bands of dense collagen with a whorled, storiform pattern, usually demarcated from the surrounding soft tissue. There are stellate and fusiform fibroblasts with trailing cytoplasmic processes, and clusters of stellate mononuclear cells giving the appearance of multinucleate cells; clefts between collagen fibers are a distinctive feature and may contain wispy mucinous material; a giant cell version is recognized that contains bizarre, true multinucleate giant cells ( Fig. 5.8 ). Multiple sclerotic fibromas are associated with PTEN hamartoma tumor (Cowden) syndrome . Spindle cells are positive for CD34 and CD99.

  

Differential diagnosis

• Some fibrotic solitary fibrous tumors may resemble sclerotic fibroma but they generally exhibit areas of hypercellularity containing plump cells with larger elongated or ovoid nuclei which are positive for STAT6.

• Desmoplastic fibroblastoma (collagenous fibroma) is a paucicellular tumor that is variably collagenous and that contains spindled and stellate fibroblasts in fibromyxoid stroma. This tumor shows rearrangement in 11q12 leading to deregulated expression of FOSL1 .

Management and prognosis

• Excision is curative although continued irritation and trauma may lead to recurrence.

Etiopathogenesis and histopathologic features

Multipotent cells in the gingival tissues when traumatized or irritated (usually by accumulation of dental calculus or bacterial plaque, rough edges of restorations, or the presence of implants) differentiate toward fibroblasts, endothelial cells, and osteoblasts giving rise to fibromas, pyogenic granulomas (lobular capillary hemangiomas), and peripheral ossifying fibromas or combinations thereof. Estrogen and progesterone causes overexpression of vascular endothelial growth factor in granuloma gravidarum. Oral pyogenic granulomas showed activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway but no RAS or BRAF mutations although some cutaneous pyogenic granulomas exhibit BRAF and RAS mutations. Whether gingival pyogenic granuloma (mass of granulation tissue) have the same etiopathogenesis as non-gingival soft tissue pyogenic granulomas (lobular capillary hemangioma) is unclear.

The peripheral giant cell granuloma derives from monocytes which fuse to form multinucleated giant cells similar to those in the central (intraosseous) lesions. They have been found to harbor KRAS mutations in 50% to 70% of cases.

• See Table 5.1 and Figs. 5.12–5.20 for histopathologic features of the four entities mentioned previously.

  TABLE 5.1

  Reactive Gingival Nodules

  Diagnosis	Histopathology
  Fibroma (inflammatory fibrous hyperplasia)	Nodule of densely collagenous fibrous tissue with scattered vessels and variable edema and inflammation; crevicular epithelium with underlying plasma cells are often seen; when uninflamed, it is indistinguishable from a traumatic fibroma (see Fig. 5.12 A–C)
  Pyogenic granuloma (lobular capillary hemangioma) (see also Chapter 6 )	Lobular or more frequently, nonlobular proliferation of endothelial cells and small, dilated capillaries; often ulcerated and inflamed (see Figs. 5.13 A) Endothelial cells show reactive atypia sometimes with focal “hobnail” pattern and hyperchromatic nuclei (see Fig. 5.13 B–C); mitotic figures are often present May see fibrosis depending on stage of organization ( Fig. 5.13 D–E)
  Peripheral ossifying fibroma (fibroma with osseous metaplasia)	Cellular proliferation of spindled fibroblast-like cells with deposition of osteoid, woven bone with variable osteoblastic rimming, cementum droplets or cementicles (psammoma body–like) (see Figs. 5.14 and 5.15 ); sometimes lamellar bone is present Spindle cells have ovoid nuclei, dispersed chromatin, and inconspicuous nucleoli and the spindle cell proliferation may have a storiform pattern ( Fig. 5.16 ); the amount of calcified material is variable ( Fig. 5.17 ) There may be clusters of multinucleate giant cells similar to peripheral giant cell granuloma (see Fig. 5.18 ) Bone morphogenetic protein has been identified in the spindled fibroblast-like cells
  Peripheral giant cell granuloma	Proliferation of monocytic and multinucleate giant cells (osteoclast-like or foreign body type) usually in sheets; giant cells contain 20–30 evenly distributed nuclei; mitoses may be seen in monocytic cells; fresh hemorrhage and hemosiderin deposits are usually present especially beneath the grenz zone (see Figs. 5.19 and 5.20 ) May see concomitant osseous metaplasia similar to peripheral ossifying fibroma Giant cells are positive for TRAP, RANK, and osteoprotegrin

  
  
  
  
  
  
  
  
  

• A parulis (sinus tract) consists of a mass of edematous granulation tissue with many acute and chronic inflammatory cells and tracts lined by neutrophils that open onto ulcerated epithelium ( Fig. 5.21 ).

  

Differential diagnosis

• A parulis may be mistaken for a mucocele (which does not occur on the attached gingiva because of lack of mucous glands) if the edematous tissue is mistaken for stromal mucin.

• Infantile hemangioma (which is distinct from congenital hemangioma) may look similar to pyogenic granuloma (lobular capillary hemangioma) but it is a developmental malformation and is almost always positive for glucose transporter-1 (GLUT-1) ( Fig. 5.22 ).

  

• Peripheral ossifying fibroma with a storiform pattern and osteoclasts with little calcified material may resemble a benign fibrous histiocytoma. Deeper levels almost always show calcified material (see Fig. 5.16 A–B).

• Peripheral odontogenic fibroma produces dentinoid rather than cementum, and epithelial islands are always present distinguishing this from peripheral ossifying fibroma.

• Aggressive central (intraosseous) giant cell granuloma may erode through bone and the presence of a substantial intraosseous radiolucency on radiograph differentiates it from a peripheral lesion.

Management and prognosis

• Excision is the treatment of choice, although if underlying irritating factors such as dental plaque are not removed the recurrence rate is 10% to 15%; pyogenic granulomas in teenagers may exhibit multiple recurrences.

• Peripheral giant cell granulomas associated with implants have a 30% to 40% recurrence rate, often exhibiting multiple recurrences, but will not recur if the implant is removed, confirming that local noxious stimuli are responsible for their development.

• Older lesions sclerose and become fibrous nodules or fibromas, especially those on the gingiva, and especially postpartum (see Fig. 5.13 D–E).

Clinical findings

• This is seen in patients with poor oral hygiene and/or who are undergoing hormonal changes (e.g., puberty and pregnancy), and in patients on medications such as anticonvulsants (e.g., phenytoin and valproic acid), calcium channel blockers (e.g., nifedipine and amlodipine), cyclosporine, and rarely tacrolimus. It also may develop around dental implants.

• There is a diffuse often slightly nodular enlargement of the gingiva of varying severity ( Fig. 5.23 A–C). However, leukemic infiltrates may have a similar clinical appearance (see Fig. 5.23 D).