Central odontogenic fibroma

Central odontogenic fibroma (COF) is a rare benign mesenchymal odontogenic neoplasm arising from odontogenic ectomesenchyme within the jaws.[1][2] It is classified among mesenchymal odontogenic tumors in the current WHO Classification of Head and Neck Tumours.[3][4] The tumor typically presents as a well-defined radiolucent lesion in tooth-bearing areas, with a predilection for the anterior jaws and maxilla, and is solid rather than cystic at surgery.[1][2] Pathogenesis is uncertain; the neoplasm is presumed to originate from the dental papilla, dental follicle, or periodontal ligament, given its intimate relationship with teeth and the consistent presence of odontogenic epithelial remnants within the stroma.[2][5] Conservative enucleation or curettage is the standard treatment, and recurrence is uncommon.[1][2]

Current Classification

The 5th edition WHO Classification of Head and Neck Tumours (2022) lists "odontogenic fibroma" as a single entity under mesenchymal odontogenic tumors, encompassing both central (intraosseous) and peripheral (extraosseous) forms.[4] The central type is the focus of this article.

Accepted Names and Aliases

• Central odontogenic fibroma (COF or COdF) — the standard designation.[1][2]
• Historically subdivided into an "epithelium-poor" (simple) type and an "epithelium-rich" (WHO/complex) type; this separation is no longer considered clinically meaningful because histologic pattern does not correlate with behavior.[2][6]

Obsolete or Confusing Terms

• "Odontogenic fibroma, simple type" and "odontogenic fibroma, WHO type" — older subclassification terms that may still appear in legacy reports.[6][7]
• The amyloid variant was previously misclassified by some authors as the "Langerhans cell variant of calcifying epithelial odontogenic tumor (CEOT)"; current evidence supports its reclassification under COF.[5]

• Frequency: COF is rare, far less common than ameloblastoma, and accounts for roughly 5–10% of odontogenic tumors in most series.[4][8]
• Age: Wide range (8–63 years); mean age approximately 31–34 years, with peak prevalence in the second through fourth decades.[1][9]
• Sex: Most large series report a female predilection (F:M ≈ 1.7–2.3:1). One systematic review of 173 cases found a slight male predominance (M:F 1.13:1), suggesting possible geographic or referral-pattern variation.[1][4][6][9]
• Anatomic distribution:
  • Maxilla and mandible are affected in roughly equal proportions in the largest multicentric study. A systematic review found a slight predilection for the posterior mandible.[1][9]
  • Within the jaws, the anterior region (premolar and anterior teeth) is the most common site, particularly in the maxilla.[1][2][5]
  • Mandibular lesions may be associated with unerupted third molars.[6][8]

Presentation

• Most COFs present as a painless, slow-growing swelling of the alveolar ridge or palate, often discovered incidentally on routine radiographs.[1][2][8]
• Pain is reported occasionally; approximately half of patients in one small series noted discomfort.[8]

Examination Findings

• Buccal or palatal cortical expansion may be palpable.[1][8]
• Palatal depression — a concave remodeling of the hard palate overlying the tumor — is a distinctive clinical sign observed in maxillary COFs; it was noted in 9 of 62 cases in the largest multicentric study and in 6 of 29 cases in a Korean cohort. This finding, while not pathognomonic, should raise suspicion for COF when encountered with a well-defined anterior maxillary radiolucency.[1][10]
• Adjacent teeth are typically vital.[2][11]

Tempo and Complications

• Growth is characteristically indolent; one reported case was present for 25 years before definitive treatment.[12]
• Displacement of adjacent teeth and root resorption are common secondary effects rather than symptoms.[1][2]
• Cortical bone perforation occurs in a subset of cases and has been associated with higher recurrence risk.[9]

Location and Distribution

COF arises centrally within the alveolar process of tooth-bearing areas. The anterior maxilla (premolar–incisor region) is the single most common site, followed by the anterior mandible; posterior mandibular lesions are often associated with unerupted third molars.[1][5][6][8] Lesions are characteristically interradicular, centered between the roots of erupted teeth.[1]

Periphery and Shape

• The hallmark is a well-defined, corticated radiolucent lesion with a smooth or gently lobulated border.[1][12][13]
• Most lesions are unilocular (approximately 70% in the largest series); a multilocular pattern with internal septa is seen in a smaller proportion (roughly 30%).[1][9]
• A scalloped margin has been noted in some cases and may denote a more locally aggressive growth pattern.[2]

Internal Architecture

• The predominant appearance is a homogeneous radiolucency without internal structure, mimicking an odontogenic cyst.[1][13]
• Internal radiopaque foci are uncommon but may be present in the ossifying variant, where metaplastic bone or cementum-like calcifications produce scattered radiopacities within the lucency. When present, these foci create a mixed radiolucent–radiopaque appearance that broadens the differential diagnosis to include calcifying odontogenic tumors and fibro-osseous lesions.[6][14]
• A diffuse sclerotic border surrounding the lesion has been reported rarely.[14]

Effects on Teeth and Adjacent Structures

• Tooth displacement is common, observed in approximately 55% of cases.[1]
• Root resorption of adjacent teeth occurs in roughly 46% of cases, a relatively high rate for a benign odontogenic tumor and an important diagnostic clue.[1][5]
• Association with an unerupted tooth (pericoronal relationship) is seen in a subset of cases, particularly in the posterior mandible.[8]
• Adjacent teeth typically remain vital despite displacement and resorption.[2][11]

Cortical Involvement and Growth Pattern

• Cortical expansion — buccal, lingual/palatal, or both — is frequently observed.[1][8][10]
• Cortical perforation occurs in a minority of cases and is statistically associated with increased recurrence risk.[9]
• In the maxilla, the tumor may thin and depress the palatal cortex, producing the clinically palpable palatal depression that corresponds radiographically to a concave remodeling of the palatal bone.[1][10][12]
• Growth is slow and expansile rather than infiltrative; the lesion displaces structures concentrically from its epicenter.[1][2]

Volumetric Imaging Considerations

CBCT and CT confirm the well-defined borders, allow precise assessment of cortical integrity in all planes, and demonstrate the three-dimensional relationship of the lesion to tooth roots, the nasal floor, and the maxillary sinus.[8] These modalities are particularly valuable for detecting subtle cortical perforation and for surgical planning when the lesion abuts vital structures. The solid nature of the tumor cannot be reliably distinguished from a cystic lesion on cross-sectional imaging alone; this distinction is typically made at surgery.[2][13]

MRI has been reported in a limited number of COF cases and may contribute to lesion characterization when the differential includes vascular lesions or when soft-tissue extent requires clarification. On dynamic contrast-enhanced MRI (DCE-MRI), COF demonstrates a gradual, persistent enhancement pattern consistent with a solid fibrous neoplasm, in contrast to the rapid wash-in and plateau or washout seen in more vascular or aggressive tumors.[13] This enhancement pattern, while not specific, can help differentiate COF from ameloblastoma and odontogenic myxoma when conventional imaging is equivocal.[13] MRI data for COF remain limited to case-level evidence, and the modality is not part of the routine workup.

The imaging appearance of COF — a well-defined, predominantly radiolucent lesion in a tooth-bearing area with tooth displacement and root resorption — overlaps substantially with odontogenic cysts and other benign odontogenic tumors. Definitive diagnosis requires histopathologic examination in virtually all cases.[13][15]

The highest-risk diagnostic pitfall is the amyloid variant of COF being misdiagnosed as CEOT (Pindborg tumor) or, rarely, sclerosing odontogenic carcinoma when amyloid deposits and perineural epithelium are present histologically.[5][12] Immunohistochemistry (CK10/13 positivity, CK7/CK8/18 negativity) and correlation with the indolent clinical and radiographic behavior are essential to avoid overdiagnosis and overtreatment.[5][12]

Diagnostic Microscopic Features

COF is an unencapsulated but well-circumscribed solid neoplasm composed of cellular fibrous or fibromyxoid connective tissue containing scattered nests, cords, and islands of inactive-appearing odontogenic epithelium.[1][2][6] The stromal cellularity ranges from hypocellular and densely collagenous to moderately cellular and myxoid.[6] The epithelial component resembles rests of Malassez; there is no palisading of columnar cells and no stellate reticulum-like organization, distinguishing COF from ameloblastoma.[2]

Histologic Variants

• Epithelium-rich type — the most common pattern; abundant small epithelial islands dispersed throughout the stroma.[1][2]
• Epithelium-poor (simple) type — sparse epithelial component; may be difficult to distinguish from desmoplastic fibroma or dental follicle.[1][6]
• Amyloid variant — juxta-epithelial deposition of amyloid globules, typically without calcification; Langerhans cells are often present within the epithelial nests (S-100 and Langerin positive). This variant should not be classified as CEOT.[1][5]
• Giant cell variant — multinucleated giant cells within the stroma.[1]
• Ossifying variant — foci of metaplastic bone or cementum-like material within the fibrous stroma, producing the mixed radiographic appearance.[1][14]
• Granular cell variant — granular cell change in the stromal or epithelial component; rare.[1]

Immunohistochemistry

The epithelial component is positive for CK10/13 and negative for CK7 and CK8/18, a profile that helps distinguish COF (including the amyloid variant) from CEOT.[5]

Radiologic-Pathologic Correlation

The solid fibrous nature of the tumor accounts for its radiolucent appearance mimicking a cyst on imaging; the distinction is made only at surgery or biopsy.[2][13] Calcified foci in the ossifying variant correspond to internal radiopacities on imaging.[14] Histologic subtype does not reliably predict clinical behavior or recurrence.[2][6]

Treatment

• Conservative enucleation or curettage is the standard of care and is curative in the vast majority of cases.[1][2][6][8]
• Involved teeth may be extracted at the time of surgery, but preservation of contiguous teeth does not appear to significantly affect recurrence rates.[10]

Recurrence

• Recurrence is uncommon. In the largest multicentric study (62 cases), only 1 recurrence was documented. A systematic review of 173 cases identified statistically significant associations between recurrence and three features: maxillary location, multilocular radiographic pattern, and cortical bone perforation.[1][9]
• No correlation between histologic variant and recurrence has been established.[2][6]

Surveillance

• Periodic clinical and radiographic follow-up is recommended, particularly for lesions with risk factors for recurrence (maxillary site, multilocularity, cortical perforation).[9]
• Long-term follow-up of at least 2–5 years is prudent given the slow growth rate of the tumor.[8][10]

Prognosis

Overall prognosis is excellent. Malignant transformation has not been reported.[1][2]

Amyloid Variant and Diagnostic Overlap With CEOT

The amyloid variant of COF poses a specific diagnostic challenge because the presence of amyloid deposits and, occasionally, epithelial cells in perineural or intraneural locations may prompt consideration of the non-calcifying (Langerhans cell–rich) variant of CEOT or sclerosing odontogenic carcinoma.[5][12] Key distinguishing features:

• COF amyloid variant: small, dispersed epithelial nests in a fibrous stroma; CK10/13-positive, CK7/CK8/18-negative epithelium; indolent clinical course; well-corticated radiolucency.[5][12]
• CEOT: sheets of polyhedral epithelial cells with nuclear pleomorphism; calcifications forming Liesegang rings; typically posterior mandible.[2][5]

Previously reported cases of "Langerhans cell variant of CEOT" have been reclassified as the amyloid variant of COF based on shared clinicopathologic and immunohistochemical features.[5] Awareness of this reclassification is essential to prevent overdiagnosis and unnecessarily aggressive treatment.[5][12]