E. Staderini, F. Guglielmi, M. Cordaro, P.

Gallenzi Keywords Biopsy, Bone diseases (metabolic), Gingival

abnormalities, Oral diseases, Pseudohypoparathyroidism.
Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma,
Università Cattolica del Sacro Cuore, Institute of Dentistry and
Maxillofacial Surgery, Head: Prof. Massimo Cordaro
Introduction
email: fe.guglielmi@gmail.com
Pseudohypoparathyroidism is a sporadic or inherited
DOI: 10.23804/ejpd.2018.19.03.9 genetic condition characterised by spontaneous bone
formation beneath the skin [Scaramuzzo et al., 2009]; it
may affect both children and adults [Sethuraman et al.,
2006]. Epulis is a general term used to describe a number
Ossifying epulis of reactive gingival lesions with vascular, fibroblastic, and
granulation tissue proliferation [Cohen, 2013]. Primary
in pseudohypo- ossifying epulis (OE) is exceedingly rare, whereas the
secondary type most often develops in association with
parathyroidism: local tissue alteration (inflammatory, traumatic conditions)
or pre-existing calcification disorders, such as Albright’s
a case-based hereditary osteodystrophy (AHO) [Ward et al., 2011].
Disorders caused by impairments in the parathyroid
therapeutic approach hormone (PTH) signaling pathway are historically
classified under the term pseudohypoparathyroidism
(PHP), which encompasses rare, related and highly
heterogeneous diseases with demonstrated (epi)genetic
abstract causes [Thiele et al., 2016]. The aetiopathogenesis of
pseudohypoparathyroidism underlies a metabolic disease
Background The term Pseudohypoparathiroidism caused by a receptor disturbance in the peripheral action
indicates a group of rare conditions characterised of parathormone. From a clinical perspective, the disease
by end-organ resistance to the action of parathyroid is similar to idiopathic hypoparathyroidism.
hormone (PTH). Ossifying epulis (OE) is a exophytic We describe a case of surgical excision of an intraoral
gingival lesion characterised by spontaneous bone miliary ossifying epulis in an 11-year-old girl who had
formation beneath the mucosa, which may affect cutaneous, biochemical and phenotypic features
children and adults: the exophytic, calcified outgrowths of pseudohypoparathyroidism. This is a clinical case
can occur in any bone and generally have favorable reported according to the CARE (CAse REport) guidelines
prognosis. Drug therapy may normalise calcium serum [Gagnier, 2013].
levels, but not completely avoid the occurrence of
peripheral ossifying epulis.
Case report We report a representative case Materials and methods
of a peripheral ossifying epulis in the mouth of a
patient following a drug treatment protocol for Patient information
her pseudohypoparathyroidism and to optimise An 11-year-old girl was referred to the Operative and
serum markers. An 11-year-old girl was referred to Paediatric Dentistry Unit of the Department of Surgical
our department, showing a bulky neoformation Sciences for Head and Neck Diseases, hospital “A. Gemelli,
on the gingival margin of 0.6 mm diameter with Università Cattolica del Sacro Cuore” of Rome (Italy).
sharp margins. The mass was completely excised.
Histological analysis revealed distinctive features of Medical, family and psychosocial history
a chronic and acute inflammatory microenvironment including relevant genetic information
with plasma cells (positivity for CD38, MUM1, Lambda Medical history of the patient revealed that she was
and Kappa chains) and bone tissue fragments with diagnosed pseudohypoparathyroidism and Albright’s
remodeling aspects referable to flogistic osteolysis. hereditary osteodystrophy at the age of 5 years, caused
The biopsy result leads to hypothese a change in the by a frameshift GNAS mutation.
patient’s drug therapy. Multidisciplinary screening and The girl reported to be followed by a dermatologist
individualised pharmacological treatment are strongly for the presence of other benign bone neoformations
recommended in the clinical practice in order to - located in the parasternal and in the right popliteal
improve the therapeutic results. region - which had been surgically removed at the age
of 5 years and 7 years. There was no family history of

218 European Journal of Paediatric Dentistry vol. 19/3-2018

 pharmacological management in paediatric dental patients

fig. 1, 2 Preoperative intraoral aspect of the epulis. fig. 3 Preoperative orthopantomograph.

fig. 4 Surgical treatment and diagnostic methods
Intra- The clinical features of the lesion resemble an osteoma
operative or a central giant cell lesion: the term “giant-cell” refers
intraoral to a group of benign granulomas, which were surgically
image: treated by diagnostic biopsy only and then followed
excision radiographically, and the majority of them did indeed
done. appear to spontaneously resolve over a period of time
fig. 5 [Ficarra et al., 1987]. With the approval of the girl's
Plasma mother, it was decided to keep the lesion under control
cells and and to re-evaluate it monthly. During the first observation,
bone tissue intraoral photographs (Fig. 1, 2) were taken together with
fragments an orthopantomograph (Fig. 3) to evaluate the general
with oral status. After four months, the lesion did not show
remodeling any signs of spontaneous regression; therefore, clinicians
aspects decided to perform a surgical enucleation and a biopsy.
referable The informed consent was obtained, even if the
to flogistic surgical procedure had a minimal risk for the patient
osteolysis. [Ercoli et al., 2015].
Topical antiseptic (chlorhexidine gel 1%) was applied
to the surgical area. Anesthesia was performed with
local infiltration of 2% mepivacain with epinephrine at
the lateral edge of the ossifying epulis and inside the
lesion. The ossifying epulis was easily enucleated using
fig. 6 appropriate forceps (Fig. 4). After peripheral courettage
Post- of the wound, a pressure bandage dressing was applied,
operative and the lesion was left to heal by secondary intention.
intraoral
image. Histological characterisation
The specimen was subjected to decalcification before
fixation and embedding. Histological analysis revealed
some typical features of chronic and acute inflammatory
heterotopic ossification or inherited diseases. microenvironment with plasma cells (positivity for CD38,
MUM1, Lambda and Kappa chains) and bone tissue
Chief complaint fragments with remodeling aspects referable to flogistic
She complained a single subgingival bulky neoformation osteolysis (Fig. 5). To select the most representative
[Biria et al., 2015] of 0,6 cm in diameter and hard- tissues for molecular studies, samples were analysed by
wooden consistency, well-defined margins and sessile- immunohistochemical methods and reviewed by a cancer
based attachment to the underlying bone, covered by pathologist.
non-keratinised ulcerated epithelium, at the level of
tooth 2.1; moreover, a moderate gingival inflammation
was noticed, with no bleeding, pain or tenderness. The Results
extraoral examination revealed a moderately built girl
with no evidence of facial or skeletal abnormalities. The Clinical and radiological follow-ups were scheduled
clinical examination showed a round face with saddle every 6 and 12 months, respectively. Two years after
nose and hypertelorism [Mariani et al., 2015]. Medical excision, no signs of scar or recurrence were noticed (Fig.
records were matched with clinical features, radiological 6). Histological analysis revealed distinctive features of a
and pathological findings for a definitive diagnosis. chronic and acute inflammatory microenvironment with

European Journal of Paediatric Dentistry vol. 19/3-2018 219

Staderini E. et aL.

plasma cells (positivity for CD38, MUM1, Lambda and Exams Results UOM Reference values
Kappa chains) and bone tissue fragments with rehashing Potassium 4.4 mEq/l 3.5 - 5.1
aspects referable to flogistic osteolysis. The biopsy results Sodium 140 mEq/l 136 - 145
suggest a change in the patient’s drug therapy.
Phosphorus 4.8 mEq/dl 4.0 -7.0
Glycemia 87 mEq/dl 70 – 100 Normal
100 – 125 Altered
Discussion > 125 Diabetes
Serum-calcium 9.4 mEq/dl 8.8 – 10.6
We have reported a patient with OE associated
Lactate de- 241 U/I 120 - 245
with POH, in whom an autoimmune thyroiditis has hydrogenase
furthermore developed. According to the available
Gamma GT 33 U/I 0 – 32
literature [Ritchie, 1965; Mantovani, 2011; Altman et al.,
2001], the evidence-based gold standard approach for GOT 35 U/I 0 – 31
this multisystemic disorder is still controversial. There is GPT 36 U/I 0 – 34
a strong evidence supporting the link between thyroid Cholesterol 209 mg/dl <200 200 – 249 slight
hypofunction and the development of benign calcified 250 – 299 moderate
lesions. In accordance with the previously described cases > 300 serious
of the literature, the drug therapy often failed to halt the Triglycerides 154 mg/dl Deficient <10.0
slightly lacking 10 – 30
progression of the disease and to obtain any improvement. Normal 30 – 100
Although hormonal drug therapy (Dibase® 25.000 I.U. Toxicity > 100
/2,5 ml oral solution once a month) yielded a normalisation Urine calcium 120 mg/24h 100 - 300
of serum calcium levels (Table 1), the appearance of a de Vitamin D 15.2 ng/ml
novo calcified formation may suggest the clinicians either
Total bilirubin 0.53 mg/dl 0.3 – 1.1
to change the drug regimen or to explore alternative
pharmacologic therapies [Pippi et al., 2016]. In a minority FT3 2.65 pg/ml 1.88 – 3.18
of cases, clinical features are independent from laboratory FT4 11.76 pmol/l 9.01 – 19.05
parameters. If serum markers offer any additional useful
TSH 1.05 mUI/I 0.35 - 4.94
information, it is worthy to adopt a case-based approach
as a challenging model for a clinical routine workflow in Thyroid anti- 0.29 UI/ml 0.0 – 5.61
peroxidase
rare or unfrequent syndromic disorders.
Anti- 2.29 UI/ml 0.0 – 4.11
tyroglobulin
antibodies
Conclusion Parathyroid 32.3 pg/ml 12 – 57
hormone
The aim of this study is to review and update the
Table 1 Blood analysis of the surgery’s day.
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