Keywords fibrous dysplasia - polyostotic - craniofacial fibrous dysplasia - mandibular osteotomy
- follow-up studies - recurrence - GTP-binding proteins
Introduction
Fibrous dysplasia (FD) is an uncommon skeletal condition in which a normal bone is
replaced by fibrotic tissue, resulting in deformity, fractures, pain, and functional
impairment.[1 ] First reported by Lichtenstein in 1938,[2 ] the disease is classified in two large groups: monostotic (70%) and polyostotic
(30%).[3 ] Clinical onset of the pathology is often observed during childhood or puberty, with
a slow progression that continues into adulthood.[4 ] The etiology of FD is related to a mutation in GNAS gene (20q13) resulting in the overexpression of cAMP reactive units and increased
cell proliferation with inadequate differentiation and disorganized fibrotic bone
matrix.[5 ]
The craniofacial skeleton may be affected in up to 25% of monostotic cases and is
involved in almost 90% of patients with the polyostotic form.[6 ] Clinical presentation in this anatomical area may be variable depending upon the
afflicted bones or the structures adjacent to them. Common complaints include facial
asymmetry, optic nerve compression, nasal obstruction, malocclusion and obstruction
of the auditory canal.[7 ]
[8 ]
Care of patients afflicted with craniofacial fibrous dysplasia (CFD) is complex due
to its functional and aesthetic impact as well as the risk for recurrence. The ongoing
debate includes the ideal surgical techniques for its management and timing for surgery.[1 ]
[9 ] Evidence-based care for this pathology is scarce because the literature is largely
limited to case series or case reports; additionally no information is available from
Latin American countries or other developing nations.
The objective of this work is to present our institution's experience in the characterization,
evaluation, and management of CFD to better understand its clinical manifestations
and help integrate surgical protocols.
Patients and Methods
We conducted a retrospective study that included all individuals with CFD who presented
to the craniofacial surgery clinic from January 2012 to December 2019. Both newly
referred and follow-up patients were included in the series.
The diagnosis was based on clinical evaluation and imaging findings. Data were obtained
from each patient's medical record and entered into a datasheet that included demographic
characteristics, clinical presentation, date of disease onset, afflicted bones, radiological
studies, quantity and type of surgeries performed, recurrence (considered positive
when showing bone growth clinically or on radiological studies), and complications.
Descriptive analysis of the demographic and clinical characteristics of the patients
was performed. Mann–Whitney U test was performed to evaluate recurrence-free years between en bloc resection and
bone burring. Pearson's chi squared test was performed to evaluate association between
the type of surgery and recurrence as well as type of disease and recurrence. Full
approval by the institutional ethics board was received (registration number 05–65–2020).
Results
Eighteen patients were included in the study, 11 females (61%) and 7 males (38%).
The median age was 10.5 years (range: 1 to 38). The most commonly affected age group
was that of patients under 12 years old (9 patients, 50%).
Clinical Presentation
Aesthetic nonconformity was the main cause for consultation (17 patients, 94%). Accompanying
clinical manifestations included headaches in two patients (11%), airway obstruction
due to mass effect in three cases (17%), and visual impairment secondary to compressive
optic neuropathy in three patients (17%). One patient presented Café au Lait spots associated with McCune–Albright syndrome. The mean time from diagnosis to referral
to the clinic was 3 ± 2.1 years.
Radiological and Biological Evaluation
All patients underwent complete skull CT scans with three-dimensional (3D) reconstruction.
Disease was classified as monostotic in 4 patients (22.2%) and polyostotic in 14 (77.7%),
with a total of 50 bones exhibiting signs of FD. The zygoma, frontal, and maxillary
bones were the most commonly affected bones with eight cases each (16%), followed
by the mandible and orbit with six cases each (12%). The remainder of the structures
involved were the ethmoid, the nasal bones, temporal and parietal bones, and the cranial
base. Three patients had extracranial disease affecting the femur.
Bilateral presentation was seen in 8 patients (44%), while 10 patients showed unilateral
presentation (6 right and 4 left) ([Tables 1 ] and [2 ]).
Table 1
Demographic characteristics, clinical features, and surgical management of the patient
population
Patient
Age at first surgery (years)
Gender
Type of involvement
Affected bones
Number of surgeries
Clinical findings
Main surgical procedures
Complications
1
8
Female
Polyostotic
Femur, frontal, ethmoid, nasal, skull base
7
Aesthetic nonconformity
airway obstruction
Resection of tumor and Hip Replacement, burring (3), pericranial flap,
lipoinjection
Nasal obstruction
2
29
Female
Polyostotic
Temporal, parietal
1
Headache, aesthetic nonconformity
Burring
–
3
9
Female
Polyostotic
Frontal, maxilla, malar, temporal, ethmoid, skull base
10
Aesthetic nonconformity, Hemianopsia Malocclusion Angle C, Facial deformity
Intracranial tumor resection (2)
Left hemimaxillectomy
Peroneus flap.
Frontal flap
Loss of orbital integrity. Optic nerve atrophy
4
25
Male
Monostotic
Mandible
3
Aesthetic nonconformity, Pain, Malocclusion
Left hemimandibulectomy
Peroneus flap.
Dental loss, malocclusion.
5
6
Male
Polyostotic
Frontal, Maxilla, mandible, femur
7
Aesthetic nonconformity, Facial deformity, Airway obstruction
Burring (5), Tumor resection
Femur Elongation
–
6
38
Male
Polyostotic
Malar, maxilla
5
Aesthetic nonconformity, Malclusion facial deformity
Maxillectomy
Peroneus flap.
Lower eyelid reconstruction,
canthopexy
Dental loss, malocclusion.
7
16
Male
Monostotic
Malar
1
Aesthetic nonconformity, Facial deformity
Burring
–
8
1
Female
Polyostotic
Frontal, maxilla, orbit, malar, mandible
3
Aesthetic nonconformity, facial deformity, airway obstruction
Burring (2)
Tracheostomy
Repeated airway infections
9
18
Female
Polyostotic
Frontal, malar
10
Facial deformity
Lipoinjection (3)
Frontal abscess drain
Burring
Frontal abscess formation
10
4
Female
Polyostotic
Maxilla, orbit
femur
1
Aesthetic nonconformity, facial deformity,
varus deformity of lower limb Stains café au lait, McCune–Albright syndrome
Burring,
Referred to endocrinologist
Chronic pain
11
8
Male
Polyostotic
Maxilla, Mandible, orbit, frontal
5
Aesthetic nonconformity, facial deformity, dental crowding, orbital compression, recurrent
airway infections
Burring (3)
Frontal craniotomy with tumor resection
and frontal titanium plate placement
–
12
7
Male
Polyostotic
Maxilla, orbit
14
Aesthetic nonconformity, facial deformity, ptosis
Resection (2)
Cranial burring (12)
–
13
17
Male
Polyostotic
Maxilla, Malar, orbit
1
Aesthetic nonconformity, facial deformity,
eye movement limitation
Burring
Eye movement limitation
14
15
Female
Monostotic
Mandible
2
Aesthetic nonconformity, facial deformity
Burring
Tumor resection
–
15
12
Female
Polyostotic
Frontal, ethmoid
6
Aesthetic nonconformity, Facial deformity, Strabismus.
Strabismus correction,
cranial reconstruction,
tumor resection,
nasal reconstruction,
anterolateral thigh flap
–
16
23
Female
Polyostotic
Mandible, orbit, Malar
4
Aesthetic nonconformity, facial deformity, exophthalmos malocclusion angle C
Burring (3)
Tumor resection
–
17
7
Male
Monostotic
Malar
2
Aesthetic nonconformity, facial deformity.
Tumor resection
Burring
–
18
10
Female
Polyostotic
Frontal, nasal, ethmoid
2
Cantal dystopia
Tumor resection
Burring
–
Table 2
Overall view of the afflicted bones
Involved bones
Number of affected bones
Maxilla
8 (16%)
Malar
8 (16%)
Frontal
8 (16%)
Mandible
6 (12%)
Orbit
6 (12%)
Ethmoid
4 (8%)
Nasal
2 (4%)
Skull base
2 (4%)
Temporal
2 (4%)
Parietal
1 (2.2%)
Histopathological analysis was performed in all patients and the diagnosis was confirmed
as fibrous dysplasia. No GNAS mutation test was performed.
Surgical Treatment
A total of 84 surgeries were registered, resulting in an average of 4.6 ± 3.7 procedures
per patient. The most common intervention was bone burring with 36 procedures (42.8%),
followed by 15 cases of en bloc resection (17.8%) ([Figs. 1 ]–[3 ]). The remainder of the surgeries were done for reconstructive or camouflage purposes.
One hemi-mandibulectomy and two maxillectomies were performed and reconstructed with
osteocutaneous free flaps. No patient received bisphosphonates or corticosteroids.
Fig.
1 (A ) Pre and (B ) postoperative images of a 30-year-old female patient with frontal bone CFD.
Fig. 2 (A ) Pre and (B ) postoperative images of a 17-year-old male patient with zygomaticomaxillary complex
CFD.
Fig. 3 (A and B ) Pre and (C and D ) postoperative images of a 17-year-old male patient with polyostotic CFD involving
the zygomaticomaxillary complexes and orbits.
The mean follow-up time after first surgery in our institution was 12.1 ± 8.1 years.
Twenty-six episodes of recurrence were identified in 10 patients. Five cases were
seen after en bloc resection (19.2%), and 21 (80.8%) were identified in the bone burring
group (p = 0.09 odds ratio [OR]: 0.6, confidence interval [CI]: 95%: 0.31–1.18). Two recurrences
occurred in the monostotic group and 24 in the polyostotic group (p = 0.19; OR: 3.17; CI 95%: 0.51–19.6).
Bone burring had an average of 13.6 recurrence-free years and en bloc resection of
15 years, there was no statistical significance regarding one treatment against the
other (p > 0.5).
Posttreatment complications include limitation of eye movements in one patient, chronic
pain in another one, and malocclusion in two cases. No malignant transformation was
identified in any case.
Discussion
Fibrous dysplasia is a rare pathology representing 5 to 7% of all benign bone tumors.
It is estimated to affect one in 30,000 people, but its true prevalence remains difficult
to estimate due to the unknown frequency of asymptomatic lesions.[4 ] CFD is a form of the disease in which the main involvement occurs in the bones of
the craniofacial skeleton. Between 50 and 100% of patients with polyostotic disease
will have craniofacial involvement, while only 10 to 25% of monostotic disease will
affect craniofacial structures[10 ]
Successful clinical management of patients with CFD is complex due to the aesthetic
and functional alterations caused by the disease, its chronicity, and the need for
long-term care.[8 ] Therefore, intervention by a multidisciplinary team is important. Surgery is the
mainstay of treatment in CFD, but the ideal techniques, timing, and indications are
still debated.[1 ]
Large systematic reviews such as those by Wu[11 ] and Yang[12 ] provided us a comprehensive view of the clinical manifestations of the disease.
As a matter of fact clinical presentation in our patients is similar to their descriptions.
For example, the zygomaticomaxillary complex was the most commonly affected structure
and most patients had unilateral presentation in our population. However, some differences
arose in our series, such as the polyostotic form being dominant (77.7%) and having
a higher prevalence of female patients. Differences may be attributed to the small
sample size and selection bias due to our institution being a national referral center.
To this day, no evidence-based guidelines have been established for the surgical management
of CFD. The literature is largely limited to single-institution case series, group
consensus or narrative reviews.[13 ]
[14 ] The broad clinical spectrum of the disease further complicates decision-making,
leading surgical teams to individualize treatment in most cases. Regardless of the
elected procedure reconstructive goals should focus in the prevention of functional
loss, reduction of physical disfigurement, prevention of secondary deformity, and
minimization of long-term morbidity.[13 ]
Bone burring achieves volume reduction and allows for smooth bone contouring. It was
the most commonly performed procedure in our series, mainly due to the high prevalence
of polyostotic disease. The procedure may be technically simple but requires finesse
to avoid under or over-resection, and damage to adjacent structures.[1 ]
En-bloc bone resection was reserved for cases with monostotic disease, severe malocclusion
or severe airway or oral compromise. Bony reconstruction was successfully achieved
with fibula flaps in three cases.
Regrowth is a latent risk for every patient and in some cases may be unpredictable.
A notably higher recurrence rate was seen in the bone burring group when compared
with en bloc resection (80.8 vs. 19.2%). Even though results did not achieve statistical
significance our results coincide with those from Boyce,[7 ] Gabbay,[15 ] and Valentini,[16 ] who report that debulking procedures have a statistically higher risk for recurrence.
Sample size and the greater number of patients with polyostotic disease in our series
may explain our findings.
En-bloc resection of afflicted bone tissue appears to be the ideal surgical approach
for CFD owing to its lower recurrence rate; unfortunately, it is not always feasible
or practical. At our institution, resection is reserved for patients with monostotic
disease or aggressive bone growth that leads to vision loss or airway/oral obstruction.
Bone contouring remains the most popular procedure due to our high prevalence of polyostotic
disease, and is also used to manage small contour defects.
Risk of recurrence and the need for secondary procedures should always be explained
to patients prior to surgery, especially in cases that will submit to debulking, this
can help manage expectations and trace a long-term treatment plan.
Camouflage procedures are also an important tool in the surgical armamentarium for
CFD. Lipofilling is especially useful to achieve smoother contours and symmetry.[17 ] Although not seen in our series, orthognathic surgery with bone debulking may be
indicated in patients with mild-to-moderate malocclusion.[18 ]
Sadly, there are currently no medical therapies capable of altering the disease course
in CFD. Bisphosphonates may be effective in treating bone pain but are unlikely to
impact the bone's quality or lesion expansion.[19 ]
The main limitation of this study is its retrospective nature and the small number
of patients, which generates difficulty for a solid methodological analysis of the
groups. As a strength, it can be mentioned that it is the first and largest Latin
American study of this nature.
Conclusion
CFD is a complex pathology that requires an early diagnosis based on clinical, radiological,
and histopathological findings. Surgery continues to be the cornerstone of its treatment.
Bone burring carries an increased risk for disease recurrence but remains the treatment
of choice for polyostotic disease. An individualized approach should be tailored according
to the anatomical location of the disease, type of FD, behavior of the lesion, and
accompanying clinical complaints.
