Head and Neck Pathology (2022) 16:1223–1226
https://doi.org/10.1007/s12105-022-01460-7
LETTERS TO THE EDITOR
Peripheral Ossifying Fibroma and Peripheral Odontogenic Fibroma:
Close Relatives or Family?
Fumio Ide1 · Yumi Ito2 · Yuji Miyazaki1 · Michiko Nishimura1 · Shinnichi Sakamoto1 · Takashi Muramatsu3 ·
Kentaro Kikuchi1
Received: 25 February 2022 / Accepted: 25 April 2022 / Published online: 6 May 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022
Dear Editor,
There appears to be little available information on how
peripheral ossifying fibroma (POF) and peripheral odonto-
genic fibroma (POdF) develop [1, 2]. In this context, the
recent paper by Shahrabi-Farahani et al. [2] is of consider-
able interest, as they have provided immunohistochemical
evidence that both POF and POdF express SATB2 intensely
and diffusely, possibly reflecting their osteoblastic differ-
entiation. 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].
It is acknowledged that in fibromatous tumors of the gin-
giva, the term “odontogenic” implies epithelial manifesta-
tion. In 2017, we described an unusual example of POF with
multiple odontogenic epithelium inclusions and discussed
the histogenesis, nosology and terminology of this diagnosti-
cally challenging entity as well as the conceptual evolution
* Fumio Ide
idef@dent.meikai.ac.jp
1
Division of Pathology, Department of Diagnostic
and Therapeutic Sciences, Meikai University School
of Dentistry, 1‑1 Keyakidai, Sakado‑shi, Saitama 350‑0283,
Japan
2 ossifying form accounted for about 10% of cases. The recent
Department of Diagnostic Pathology, Tsurumi
University Dental Hospital, 2‑1‑3 Tsurumi, Tsurumi‑ku,
Yokohama 230‑8501, Japan
3
Department of Operative Dentistry, Cariology and Pulp
Biology, Tokyo Dental College, 2‑9‑18 Kandamisaki‑Cho,
Chiyoda‑ku, Tokyo 101‑0061, Japan
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 com-
posed 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.
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
brief report described three further examples under the diag-
nosis “central cemento-ossifying fibroma with odontogenic
epithelial remnants”, but no consideration was given to the
ossifying variant of central OdF [17]. Before the proposal
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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 Cel-
lular fibroblastic tissue containing trabeculae of woven bone and rests
Fig. 2  A Peripheral odontogenic fibroma in Colyer’s textbook pub-
lished in 1910 [8] (personal collection F.I.). Strands of rounded epi-
thelial 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
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Head and Neck Pathology (2022) 16:1223–1226
of odontogenic epithelium. D Thick bone trabeculae. E Isolated cur-
vilinear trabecula. F Newly formed trabecula. G CK19 expression in
epithelial cell rests. H Stromal xanthomatous change. I CD68 expres-
sion in xanthoma cells
from Hospital Dentistry [Tokyo], Japan). Clusters of odontogenic epi-
thelium 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] (per-
sonal collection F.I.). Radiating bone spicules
Head and Neck Pathology (2022) 16:1223–1226
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 odon-
togenic 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 osteo-
pathica” 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 cel-
lular features of POFs (epulis and semi-ossified tumor surgi-
cally 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 draw-
ings of POF (Fig. 2D). The reported incidence of small epi-
thelial 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 specu-
late 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, con-
tributing 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 quan-
titative degree of bone formation or epithelial proliferation
1225
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.
Funding Not applicable.
Data Availability The data are available upon reasonable request.
Code Availability Not applicable.
Declarations
Conflict of interest All authors declare that there is no conflict of inter-
est to disclose.
Ethical Approval 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.
Consent for Participate Not applicable.
Consent for Publication Not applicable.
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