Central ossifying fibroma

Central ossifying fibroma (COF) is a rare benign lesion that typically affects young adults, with the highest incidence occurring between the ages of 20 and 40. It shows a distinct predilection for females, with a reported female-to-male ratio of 2:1.^[5] This fibro-osseous tumor is most commonly found in the mandible, particularly in the posterior regions, such as the molar or premolar areas, although it can also affect the maxilla. The condition has no strong racial or ethnic predisposition, though studies suggest higher prevalence in certain populations, such as those in South Asia.^[6]

The exact etiology of COF is not fully understood, but it is believed to arise from the mesenchymal tissues of the periodontal ligament or adjacent bone. Developmental anomalies, such as metaplastic changes in these tissues, contribute to the formation of the lesion.^[7] Additionally, genetic factors may play a role, with some studies suggesting that mutations or familial predisposition may predispose individuals to fibro-osseous lesions, including COF .^{[citation needed]} Chronic trauma or irritation to the jaw could also lead to the formation of fibrous tissue, which eventually undergoes ossification.^[8] Hormonal influences may further contribute, as evidenced by the higher prevalence of COF in young women, although additional research is needed to establish a definitive link.^[9]

The pathogenesis of COF begins with the proliferation of mesenchymal cells in the periodontal ligament or adjacent bone, leading to fibrous tissue formation that undergoes metaplastic transformation into bone or cementum-like material .^[7] Initially composed of cellular fibrous tissue, the lesion gradually ossifies, resulting in varying amounts of bone and cementum-like deposits .^{[citation needed]} It grows slowly, often causing cortical plate expansion and clinical signs such as facial asymmetry or swelling .^[8] Histologically, COF shows a well-defined fibrous stroma with calcified areas ranging from spongy to compact bone .^[7] Radiographically, it appears as a well-circumscribed radiolucent area with mixed radiopaque features, characteristic of fibro-osseous lesions.^{[citation needed]}

There are four distinct clinicopathologic entities for ossifying fibroma of the craniofacial skeleton: cemento-ossifying fibroma [COF], which is an odontogenic ossifying fibroma; trabecular juvenile ossifying fibroma [TrJOF]; psammomatoid juvenile ossifying fibroma [PsJOF]; and extragnathic adult ossifying fibroma.^[10]

Cemento-ossifying fibroma (COF) typically presents as a painless jaw swelling, often detected incidentally on radiographs. It predominantly affects the mandible more than the maxilla,^[11][12] with the highest incidence in the third and fourth decades of life and a marked female predilection (female-to-male ratio up to 5:1).^[11][12]

Radiographically, COF appears as a well-defined unilocular lesion. In large mandibular cases, it may cause downward bowing of the inferior border.^[13] Tooth displacement is common, while root resorption is less frequently observed.^[13] If untreated, the lesion can grow substantially. Surgically, COF is usually well-demarcated from the surrounding bone and often easily enucleated. Some lesions may also exhibit a distinct capsule.^[11]

Juvenile Ossifying Fibroma (JOF) refers to two distinct clinicopathologic subtypes: Trabecular Juvenile Ossifying Fibroma (TrJOF) and Psammomatoid Juvenile Ossifying Fibroma (PsJOF).^[14] The lesion is also known as juvenile aggressive or juvenile active ossifying fibroma.

TrJOF is histologically characterized by immature trabeculae of woven bone lacking osteoblastic rimming, set within a highly cellular fibrous stroma with strands of immature osteoid.^[14]

The lesion primarily affects children and adolescents, with fewer than 20% of cases occurring after age 15 .^[13][15] The average age range reported in case series is 8.5 to 12 years.^[11] It affects both sexes equally,^[13] with a slightly higher frequency in the maxilla compared to the mandible.^[11] Rare extragnathic cases involve the frontal or ethmoid bones.^[16]

Clinically, TrJOF presents as a painless but progressively enlarging mass. In maxillary cases, symptoms like epistaxis and nasal obstruction may occur. Radiographically, the lesion appears large and may cause cortical thinning or perforation. It may show varying radiolucent to radiopaque patterns depending on the degree of calcification, including a ground-glass or multilocular honeycomb appearance.^[14][16]

PsJOF typically affects a slightly older age group than TrJOF, with average ages ranging from 16 to 33 years, though cases have been reported from 3 months to 72 years.^[14][17]

Most cases originate in the paranasal sinuses, particularly the ethmoid and frontal sinuses ^[14][18][7,13]. Around 10% arise in the calvarium. Mandibular involvement is rare—Makek reported 7% of cases, while a later study found one in three cases involved the mandibular ramus.^[14]

Clinically, PsJOF manifests as bone expansion affecting the sinuses, orbit, or nasal bones. Orbital involvement may result in proptosis, visual disturbances (including blindness), nasal obstruction, ptosis, papilledema, and restricted ocular movement.^[17]

Rarely, ossifying fibromas distinct from the common subtypes may arise in the cranial bones. These lesions lack psammomatoid or cementoid features and are composed of immature and mature bone trabeculae within a fibrous stroma.^[19] Reported locations include the frontal, parietal, temporal, sphenoid, and occipital bones.^[19] There is no gender predilection, and most cases occur in the second or third decades of life. Some tumours have exhibited intracerebral extension.^{[citation needed]}

Clinically, patients may present with localized swelling, pain, headaches, motor disturbances, exophthalmus, diplopia, and mild spastic hemiparesis . The median duration of symptoms is 3.2 years (range: 1–10 years) . Radiographically, these lesions appear as well-defined osteolytic areas with variable degrees of radiopacity.^{[citation needed]}

The radiographic features of central ossifying fibroma can be categorised according to the stages.

In its early stages, central ossifying fibroma (COF) appears as a small, well-defined radiolucent lesion due to its fibrous tissue content. Differential diagnoses at this stage include periapical pathology, central giant cell granuloma, and ameloblastoma.^[22][23] As the lesion matures, it exhibits a mixed radiolucent-radiopaque appearance due to progressive calcification.^[22] At this stage, it should be differentiated from other mixed jaw lesions such as fibrous dysplasia, calcifying epithelial odontogenic tumour, adenomatoid odontogenic tumour, and condensing osteitis.^[22] In its mature form, COF may appear predominantly radiopaque, resembling lesions like odontomas, osteoblastomas, or osteosarcomas radiographically.

COF typically presents with well-defined, smooth, and often corticated borders. As a central lesion, it originates within the medullary bone and expands concentrically in all directions.^[24] With growth, it may cause tooth displacement, root resorption, inferior displacement of the mandibular canal, and loss or alteration of the lamina dura of adjacent teeth.^[25]

In conclusion, COF most commonly occurs in the mandible and expands from a central epicenter. Radiographically, it presents as a well-defined mixed-density lesion,^[26] and Cone Beam CT (CBCT) plays a crucial role in its accurate diagnosis and assessment.

Cemento-ossifying fibroma is a well-demarcated lesion, often encapsulated by a thin fibrous capsule and sharply separated from adjacent normal bone. It shows significant internal variation, with differing amounts of fibrous and mineralized tissue—even within the same lesion. Mineralization is often more prominent centrally and typically includes osteoid, woven to lamellar bone, and dense basophilic cementum-like calcifications. Bony trabeculae may fuse into broad sheets or form thick, anastomosing strands. Osteoblastic rimming is commonly seen around bone trabeculae.^[27]

The stroma is fibroblastic and may exhibit areas of hypercellularity and nuclear hyperchromasia; however, mitotic activity is rare and cellular atypia is minimal .^[28] The mineralized component may include acellular or paucicellular cementum-like spheres along with bone structures .^[28]

Though rare, hemorrhagic cystic degeneration—resembling aneurysmal bone cyst formation—can occur, more commonly in juvenile variants.^[27][29] Histological overlap can exist among subtypes: psammomatoid and trabecular JOF may exhibit features resembling COF, and vice versa. In syndromic cases, such as gnathodiaphyseal dysplasia, COF lesions appear more fibrous with basophilic, acellular bone droplets and spherical ossicles, but histologically resemble nonsyndromic counterparts .^[30]