The differential diagnosis of gingival growths include a variety of lesions such as fibro-osseous lesions like peripheral ossifying fibromas and juvenile ossifying fibromas and connective tissue lesions such as pyogenic granulomas and idiopathic gingival fibromatosis. Due to the age of our patient and the aggressive appearance, aggressive lesions such as osteosarcoma and central juvenile ossifying fibroma were first considered. However, the X-Ray images clearly demonstrated that the lesion was restricted to the gingiva and did not affect the bone besides the rare superficial erosion forming a cupping defect in focal areas. In our case, because of the long evolution and the clinical and radiographic aspects, both osteosarcoma and juvenile ossifying fibroma were excluded. Pyogenic granuloma was never considered because of the abundant presence of mineralization.
Some other alterations were also surveyed. The initial suspect was idiopathic gingival fibromatosis, but the color and consistency of the gum and the histopathological characteristics were not consistent with this diagnosis. A possibility of hereditary gingival fibromatosis was discarded early on in anamneses because there was no family history of this disease. Besides, histopathologically, both idiopathic gingival fibromatosis and hereditary gingival fibromatosis have different characteristics from peripheral ossifying fibroma.
We also suspected plasminogen deficiency, but the patient’s levels of plasminogen were normal. The possibility of mucopolysaccharidosis II (Hunter syndrome) was discussed. However, the patient did not have any of the systemic signs of the accumulation of GAGs, which generally include macrocephaly, dental abnormalities, hyperactivity, hepatosplenomegaly, mental retardation, or chronic diarrhea, among others. Ligneous conjunctivitis can cause periodontal lesions similar to those exhibited by our patient, but it is a serious systemic disease that has other manifestations, such as recurrent chronic conjunctivitis, that were clearly not present. The possibility of exostosis and Gardner syndrome was discarded, as it was clear that the lesions were of gingival origin. Other manifestations of Gardner syndrome such as osteomas in sinuses and epidermoid cysts on the skin were also not present.
The type of mineralized component presented in POF is variable and can consist of bone, cementum-like calcification, or distrophic calcification. Frequently, there is a combination of these mineralized materials [4]. In the present case, in rare areas, bone and cementum-like calcifications were observed, but the position and the pattern of the bone was noted to be quite unusual. Mineralization was always close to the alveolar bone, with the mineralized trabeculae in a parallel pattern starting from the base of the lesion towards its surface. This pattern of explosive mineralization is very common in aggressive lesions such as osteosarcomas, but in the present case, no sign of a malignancy such as cellular atypia or high number of mitosis have been found in any of the recurrences over the years. In addition, this explosive growth pattern was limited to a small area seen in the first biopsy while the majority of the lesion and the recurrences showed a classic peripheral ossifying fibroma histopathological appearance. Therefore, due to the typical histopathological aspect associated with the uncommon multicentric characteristic and frequent recurrences, a diagnosis of peripheral ossifying fibroma-like lesion was established.
Histologically, idiopathic gingival fibromatosis is mainly due to an increase and thickening of mature collagen bundles in the connective tissue stroma. The nodular appearance can be attributed to the thickened para hyperkeratinized epithelium. It can be seen in conjunction with growth hormone deficiency and may exhibit presence of dystrophic calcification. None of our patient’s lesions showed the histopathological aspect of a gingival fibromatosis, as they were mainly formed by robust round cells and showed areas of mineralization as bone and cementum nodules. It did not show collagen accumulation.
The clinical characteristics of the lesion directed us to a possible idiopathic gingival fibromatosis, however, histological characteristics that were repeated in the multiple recurrences pushed us away from that possibility. A variety of histological samples were sent to 3 independent pathologists during the 9 years of the recurrences, and all 3 were definite in the histological diagnosis of POF. Therefore, we chose to nominate this lesion as a peripheral ossifying fibroma-like lesion based on its histopathological aspect.
Nonetheless, it is not possible to discriminate whether ours is a case of idiopathic gingival fibromatosis atypical for the overproduction of bone and cementum or a case of peripheral ossifying fibroma atypical by its numerous recurrences and multicentric nature.
To our knowledge, only one case of a multicentric peripheral ossifying fibroma has been published in the literature to date [7]. This case consisted of recurrent lesions, measuring from 5 mm to 3 cm in diameter, observed in the maxillary and mandibular gingiva of a 49-year-old female who complained of pain and bleeding after palpation. She had her lesions removed by simple excision and electrosurgery over the years with subsequent recurrences. Antibiotic and intra-lesional steroid therapies were also used with no response. Like our patient, this other case of multicentric peripheral ossifying fibroma had many laboratory tests performed with unremarkable results.
The similarities shared between these two cases are the constant recurrences and affection of multiple areas. However, our multicentric recurrent case appears to be more aggressive, since the lesions commonly covered almost all of the teeth from the maxilla and mandible.
The patient’s mother had to be treated with the growth hormone during her infancy. GH is essential for bone formation and remodeling, not only in childhood but also in adulthood. In vitro studies have shown that GH stimulates osteoblast function and proliferation both directly and indirectly by local stimulation of GF induction [9]. Although it is not possible to establish a correlation between this fact and the patient’s condition, a genetic predisposition to bone alterations may be possible. It is important to point out that the levels of GH in our patient were within normal limits. The multiple and recurrent pattern of the condition and the absence of any alteration in the laboratorial and radiographic exams point to a systemic predisposition.
The bacterial plaque must be considered as an etiological factor capable of predisposing to the appearance of the peripheral ossifying fibroma lesions [4]. Therefore, the patient has been under professional care in regards to regular teeth cleaning since the first recurrence, and he was taught how to proceed with buccal hygiene in a correct and careful way. After the beginning of the professional preventive procedures, such as dental plaque removal, the patient still had recurrences, and the lesions were similar to the previous ones, affecting both the maxilla and mandible. Close professional supervision made the prompt identification of the lesions easier, but even in the beginning of their development the recurrences were always multicentric, affecting both the maxilla and mandible.
It has been previously discussed that the surgical technique employed is associated with the probability of recurrences of peripheral ossifying fibroma, and a total excision of the involved periodontal ligament and periosteum is required to minimize it [4]. Moreover, regardless of the surgical technique employed, it is important to eliminate etiological factors including plaque, calculus, and plaque-retention restorations [4]. In our case, despite the careful surgical technique used in all surgeries with the removal of the involved periosteum, the lesion recurred around thirty times.