Peripheral Ossifying Fibroma and Peripheral Odontogenic Fibroma: Close Relatives or Family?

Dear Editor,

There appears to be little available information on how peripheral ossifying fibroma (POF) and peripheral odontogenic fibroma (POdF) develop [1, 2]. In this context, the recent paper by Shahrabi-Farahani et al. [2] is of considerable interest, as they have provided immunohistochemical evidence that both POF and POdF express SATB2 intensely and diffusely, possibly reflecting their osteoblastic differentiation. Although most classification schemes categorize POF and POdF as separate entities, this pioneering study by Shahrabi-Farahani et al. [2] confirmed that these two lesions might contain cells having osteogenic potential and are most likely derived from the periodontal ligament. Here, presenting a rare composite tumor of the gingiva showing a classical configuration of epithelium-rich POdF, together with a developing POF feature and other areas resembling xanthoma (Fig. 1A–I), we wish to make some comments on their work [2].

Fig. 1.

Peripheral odontogenic fibroma on the buccal gingiva of the left mandibular second molar in a 48-year-old man. A Clinical view. B Survey view of the gingival ossifying fibromatous lesion. C Cellular fibroblastic tissue containing trabeculae of woven bone and rests of odontogenic epithelium. D Thick bone trabeculae. E Isolated curvilinear trabecula. F Newly formed trabecula. G CK19 expression in epithelial cell rests. H Stromal xanthomatous change. I CD68 expression in xanthoma cells

It is acknowledged that in fibromatous tumors of the gingiva, the term “odontogenic” implies epithelial manifestation. In 2017, we described an unusual example of POF with multiple odontogenic epithelium inclusions and discussed the histogenesis, nosology and terminology of this diagnostically challenging entity as well as the conceptual evolution of POF and POdF [3]. Although the present case showed a POF-type proliferation (Fig. 1B–F), our group agree that POdF was the primary pathology on the basis of a mixed fibroepithelial phenotype, especially the abundance and even distribution of epithelium in the whole lesion (Fig. 1G). One of the unexpected findings was the lesional stroma composed of CD63/CD68-positive and S-100 protein-negative xanthoma cells (Fig. 1H, I). Such xanthomatous stromal changes have also been referred to as reactive granular cells [4] and hence are somewhat similar to those seen in granular cell POdF [5–7].

Our centennial review of the relevant literature disclosed that Colyer [8] in 1910 was the first to provide an illustration of POdF in his famous British textbook, using the legend “true fibroma of the gum” (Fig. 2A). Over the years, it has been universally accepted that the histological spectrum of POdF is complex and variable [5, 6, 9, 10]. The reported incidence of bone material has varied widely, one study (151 cases) reporting 49% [9] and another (46 cases) 28% [6]. They did not dominate the fibrous component in any of the cases [11, 12]. However, in a small study of 10 cases from South Africa [13], thick bone trabeculae, similar to those in the present lesion, have been reported to have an incidence of 50%. There was no available data on the degree to which woven bone was present.

Fig. 2.

A Peripheral odontogenic fibroma in Colyer’s textbook published in 1910 [8] (personal collection F.I.). Strands of rounded epithelial cells interspersed between the bundles of fibroblastic tissue (a drawing by Arthur Hopewell-Smith, who was well-known for his work in dental histology and pathology). B Cementifying fibroma in the left maxillary molar area of a 59-year-old man [21] (permission from Hospital Dentistry [Tokyo], Japan). Clusters of odontogenic epithelium with clear cytoplasm and rounded masses of cementum-like tissue. C Key’s peripheral ossifying fibroma springing from bone [26] (personal collection F.I.). D Peripheral ossifying fibroma of the right maxillary lateral incisor and canine in a 45-year-old woman [28] (personal collection F.I.). Radiating bone spicules

Unlike bone-forming POdFs [5, 6, 9, 11–13], central OdFs showing active productions of bone/cementum have been well characterized and are currently referred to as the “ossifying variant” [10, 14–16], a term not approved by the WHO. This nomenclature was coined in 1989 by Jones et al. [14] and popularized by Eversole [10] in 2011. In the largest study of central OdF (62 cases) performed to date [15], the ossifying form accounted for about 10% of cases. The recent brief report described three further examples under the diagnosis “central cemento-ossifying fibroma with odontogenic epithelial remnants”, but no consideration was given to the ossifying variant of central OdF [17]. Before the proposal of this morphological variation, it was also referred to in the literature as “osteofibroma with ectopic epithelium” [18], “unusual composite odontome” [19], “dentinoma” [20] or “cementifying fibroma with marked proliferation of odontogenic epithelium” (Fig. 2B) [21].

With the exception of the old French reports of “épulie osseuse” (for which distinction between POF and exostosis id unclear), the first to make mention of osseous content in epulis was Liston [22] of London in 1837, and soon after, Troschel [23] in Germany coined the term “epulis osteopathica” to describe POF. To our knowledge, the first dental journal reference to POF was an alveolar exostosis, reported in 1843 by Shepherd [24] in the United States. At the same time, Williams [25] of London gave a summary of the cellular features of POFs (epulis and semi-ossified tumor surgically treated by Key), and Key’s case is illustrated with an artistic drawing in the epulis section of the 1872 textbook of surgery [26] (Fig. 2C). In 1848, Tomes [27] (remembered eponymously by the term “Tomes fibers”), published his British textbook, which included a detailed description of the fibro-osseous nature of epulis (POF). Six years later, Salter [28] of London provided gross and microscopic drawings of POF (Fig. 2D). The reported incidence of small epithelial nests in POFs has ranged from 5 to 20% [1, 3, 17, 29], and they were scanty and quiescent in appearance [1, 3, 11, 17]. The epithelium identified in POF is most likely the native odontogenic rests (Malassez or Serres) or sometimes the tangential section of elongated rete ridges of the gingiva. There has been a single report of granular cell POF, but the lesion was devoid of odontogenic epithelium [30].

The present case showed overlap features intermediate or transitional between POdF and POF, suggesting that the two could share a common pathogenesis. Considering the findings of SATB2 expression [2], it is reasonable to speculate that during neoplastic transformation of undifferentiated mesenchymal cells of osteoblastic lineage in the superficial periodontal ligament, if there is concomitant growth of the native epithelial cell rests of Malassez and this eventually suppresses or ceases osteogenesis, the fibroma will take the form of POdF. The resultant POdF usually lacks the ability to mature the intralesional mineralizing product into bone. It seems likely that POF may be the reverse. Unfortunately, the underlying molecular mechanisms through which one form develops and not the other, and generally not both together still remain to be clarified. A piece of data is available for only one case of central OdF [31]; the results suggested that a stem-like subpopulation of the epithelial component may harbor epithelial-mesenchymal transition phenotypes, contributing to the overgrowth of mesenchymal cells.

In conclusion, opinions vary regarding the true nature (odontogenic vs. non-odontogenic) and precise designation (POdF vs. POF) of this debatable entity [3], since the quantitative degree of bone formation or epithelial proliferation that may distinguish between the two is arbitrary. In the context of nomenclature, the compound term “peripheral odontogenic (ossifying) fibroma” adopted in 2000 by Wright [32] is not entirely surprising. We hope that in addition to the insightful research by Shahrabi-Farahani et al. [2], the present communication will encourage further discussion.

Author Contributions

FI contributed to the conception and design of the work. YI conducted a pathological examination. YM & MN were responsible for data interpretation. SS revised the original manuscript. TM conducted a literature review. KK approved the final version of the manuscript. All authors confirm they have meaningfully contributed to the research and read and approved the final manuscript.

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The data are available upon reasonable request.

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All authors declare that there is no conflict of interest to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutions and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of retrospective case report, formal consent is not required.

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