Peripheral Cemento-Ossifying Fibroma: Case Series Literature Review

The concept of fibroosseous lesions of bone has evolved over the last several decades and now includes two major entities: fibrous dysplasia and ossifying fibroma. Peripheral cemento-ossifying fibroma is a relatively rare tumour classified between fibroosseous lesions. It predominantly affects adolescents and young adults, with peak prevalence between 10 and 19 yrs. The cemento-ossifying fibroma is a central neoplasm of bone as well as periodontium which has caused considerable controversy because of confusion regarding terminology and the criteria for its diagnosis. The cemento-ossifying fibroma is odontogenic in origin, whereas ossifying fibroma is of bony origin. Lesions histologically similar to peripheral ossifying fibroma have been given various names in existing literature. Therefore, we present and discuss in this paper a series of cases of peripheral cemento-ossifying fibroma emphasizing the differential diagnosis.

Peripheral cemento-ossifying �broma (PCOF) accounts for 3.1% of all oral tumors [4] and for 9.6% of gingival lesions [5]. e pathogenesis of this tumor is uncertain. Due to their clinical and histopathological similarities, some PCOFs are believed to develop �brous maturation and subsequent cal-ci�cation. PCOF is frequently associated with irritant agents such as calculus, bacterial plaque, orthodontic appliances, ill adapted crowns, and irregular restorations. e mineralized product probably originates from periosteal cells or from the periodontal ligament [6]. PCOF affects both genders, but a higher predilection for females has been reported in the literature [4]. With respect to race, there is a predominance in Whites (71%) compared to Blacks (36%) [7]. It may occur at any range, but exhibits a peak incidence between the second [8] and third decades [7]. However, Neville et al. [9] say that it predominantly affects adolescents and young adults, with a peak prevalence between 10 and 19 years. Clinically, PCOF manifests as a pediculate or sessile nodular mass, which usually originates in the interdental papilla. Its color is similar to that of the mucosa unless the lesion is ulcerated. Most tumors measure less than 2 cm in diameter, although lesions larger than 10 cm are occasionally observed. About 60% of the tumors occur in the maxilla and more than 50% of all cases affect the region of the incisors and canines. A potential of tooth migration PCOF has been reported [6]. Hence, the purpose of this paper is to present a series of cases of PCOF lesions and emphasize the importance of discussion of the reasonable differential diagnosis with the patient. Case 2. A healthy 25-year-old male reported to College of Dental Sciences & Hospital, Rau, Indore, India, with a lump in his back teeth. According to the patient, the reddish purple lump has been present for approximately 6 months and the lump was interfering with his bite and felt uncomfortable. Occasionally bleeding occurred when he brushed his teeth. Clinical examination revealed erythematous interdental papilla in relation to maxillary central incisors 11,12 visible from facial aspect with no evidence of lesion palatally. e lesion appeared exophytic and nodular with irregular surface. It measured approximately 10 mm laterally and 8 mm in anterior-posterior direction and 6 mm thick. It was slightly pedunculated with what appeared to be a broad-based attachment. e lesion was neither �uctuant nor did it blanch on pressure, but had a rubbery consistency. It was tender ( Figure 2). Case 3. A 26-year-old male patient was referred by his general dental practitioner for gingival swelling in relation 15 to 16 region. e past dental history revealed presence of swelling since last one and half year duration. On examination, the associated so tissue was slightly swollen but there was no ulceration, on palpation the swelling was so rubbery in consistency, but no tenderness. e lesion was well demarcated and pedunculated measuring approximately 1.5 × 2 cm ( Figure 3).

Case 4. A 31-year-old male reported to the College of Dental
Sciences & Hospital, Rau, Indore, India complaining of inability to chew food since 6 to 8 months. e patient was apparently asymptomatic 18 months back when he developed a small swelling in the mandibular anterior labial region in 31, 41 which gradually increased in size. On examination, a uniform rounded swelling was present in mandibular anterior region due to which the patient could not chew the food. e size of the lesion was 2.5 × 2 cm and the shape was ovoid. e overlying mucosa was pinkish in color and �rm in consistency. e texture was smooth. ere was no compressibility or depressibility ( Figure 4).
Ossifying �bromas elaborate bone, cementum and spheroidal calci�cations, which has given rise to various terms for these benign �broosseous neoplasms. When bone predominates, "ossifying" is the appellation, while the term "cementifying" has been assigned when curvilinear trabeculae or spheroidal calci�cations are encountered �11]. When bone and cementum-like tissues are observed, the lesions have been referred to as cemento-ossifying �broma �11]. Cementifying �bromas may be clinically and radiographically impossible to separate from ossifying �bromas �12]. An attempt has been made by Endo et al. to distinguish cementifying �broma from ossifying �bromas and �brous dysplasias by using immunohistochemical analysis for keratin sulfate and chondrotoin-4 sulfate in which the cementifying �bromas showed signi�cant immunoreactivity for keratan sulfate and ossifying �bromas, and �brous dysplasias showed intensive immunostaining for chondroitin-4-sulfate [12]. e term cemento-ossifying has been referred to as outdated and scienti�cally inaccurate [13] because the clinical presentation and histopathology of cemento-ossifying �broma are the same in areas where there is no cementum, such as the skull, femur, and tibia. ese are all ossifying �bromas� those that happen to occur in the jaws should not be termed cement ossifying �bromas merely because of the presence of teeth. Moreover, there is no histologic or biochemical difference between cementum and bone. Cemento-ossifying �broma is the term given mainly due to presence of dysmorphic round basophilic bone particles within ossifying �broma, which have arbitrarily been called cementicles. However, these so-called cementicles are not from cementum but instead represent a dysmorphic product of this tumour analogous to the keratin pearls, which are a dysmorphic product of squamous cell carcinoma [13].
ough the etiopathogenesis of peripheral ossifying �broma is uncertain, an origin from cells of periodontal ligament has been suggested [10]. e reasons for considering periodontal ligament origin for peripheral ossifying �broma include exclusive occurrence of peripheral ossifying �broma in the gingiva (interdental papilla), the proximity of gingiva to the periodontal ligament, and the presence of oxytalan �bres within the mineralized matrix of some lesions [10]. Excessive proliferation of mature �brous connective tissue is a response to gingival injury, gingival irritation, subgingival calculus, or a foreign body in the gingival sulcus. Chronic irritation of the periosteal and periodontal membrane causes metaplasia of the connective tissue and resultant initiation of formation of bone or dystrophic calci�cation. It has been suggested that the lesion may be caused by �brosis of the granulation tissue [14].
Lesions involving the gingival so tissues are rare compared to the lesions appearing within bone [12]. Mesquita RA found higher numbers of argyrophilic nucleolar organizer regions (AgNORs) and proliferating cell nuclear antigen-(PCNA-) positive cells in ossifying �broma than in peripheral ossifying �broma, indicating higher proliferative activity in ossifying �broma [15]. X-ray diffraction analysis indicated that the mineral phase of both central and peripheral tissues consists of apatite crystals and that the crystallinity of the apatites might improve progressively with the development of the lesion, possibly to the same degree as that of bone apatite [16]. Peripheral ossifying �broma tends to occur in the 2nd and 3rd decades of life, with peak prevalence between the ages of 10 and 19.
Eversole and Rovin [17] stated the similar sex and site predilection of pyogenic granuloma. Gardner [18] stated that peripheral ossifying �broma, cellular connective tissue is so characteristic that a histologic diagnosis can be made with con�dence, regardless of the presence or absence of calci�cation. Buchner and Hansen [19] hypothesized that early POF presents as ulcerated nodules with little calci�cation, allowing easy misdiagnosis as a pyogenic granuloma. Although it is also important to maintain a high index of suspicion, discussion with family members should be tactful to prevent undue distress during the waiting period between differential diagnosis and de�nitive histopathologic diagnosis. Because the clinical appearance of these various lesions can be remarkably similar, classi�cation is based on their distinct histologic differences. e POF must be differentiated from the peripheral odontogenic �broma (PODF) described by the World Health Organization [18,19]. Histologically, the PODF has been de�ned as a �broblastic neoplasm containing odontogenic epithelium [20]. Despite a preponderance of the literature supporting differentiation, some authors continue to argue that the POF (or peripheral cemento-ossifying �broma) is the peripheral counterpart of the central cementoossifying �broma [21]. e POF, as discovered in this case, is a focal, reactive, nonneoplastic tumour-like growth of so tissue oen arising from the interdental papilla [19]. It is a fairly common lesion, comprising nearly 3% of oral lesions biopsied in 1 study 1 approximately 1%-2% in other studies [21]. In 1993, S. Das and A. Das [8] obtained similar results, with 1.6% POFs among 2,370 intraoral biopsies.
POFs are believed to arise from gingival �bers of the periodontal ligament as hyperplastic growth of tissue that is unique to the gingival mucosa [17,18]. is hypothesis is based on the fact that POFs arise exclusively on the gingiva, the subsequent proximity of the gingiva to the periodontal ligament, and the inverse correlation between age distribution of patients presenting with POF and the number of missing teeth with associated periodontal ligament [20]. e POF lesion is generally small and does not require imaging beyond radiographs [18]. Treatment consists of conservative surgical excision [20] and scaling of adjacent teeth [18]. erefore, regular followup is required. Although peripheral ossifying �broma is benign, reactive lesion, the recurrence rate is fairly high. erefore, the patients are still under follow-up period.

Conclusions
POF is a slowly progressing lesion, the growth of which is generally limited. Many cases will progress for long periods before patients seek treatment because of the lack of symptoms associated with the lesion. A slowly growing pink so-tissue nodule in the anterior maxilla of an adolescent should raise suspicion of a POF. Discussion of the differential diagnosis should be done tactfully to prevent unnecessary distress to the patient and family. Zhang and others [16] noted that cancer was included in the differential diagnosis in only 2% of cases. In the current case, the family experienced distress related to the suggestion of squamous cell carcinoma before referral for treatment and de�nitive diagnosis. Treatment consists of surgical excision, including the periosteum and scaling of adjacent teeth. Close postoperative followup is required because of the growth potential of incompletely removed lesions and the 8%-20% recurrence rate.