Benign Fibro-Osseous Lesions of the Craniofacial

Area in Children and Adolescents

Доброкачественные фиброзно-костные

поражения краниофациальной зоны у детей и

подростков

Russian Children’s Clinical Hospital, Moscow

Рогожин Дмитрий Викторович.

Москва 2016

Waldron’s Modified Classification of BFOL (1993):

1. Fibrous Dysplasia.

2. Cemento-Osseous Dysplasia (periapical cement-osseous

dysplasia, focal cement-osseous dysplasia, florid

cement-osseous dysplasia).

3. Fibro-Osseous Neoplasm (cementifying fibroma,

ossifying fibroma, cemento-ossifying fibroma).

The classification system of Waldron has suggested that the BFOL originate

from the periodontal ligament which contains multipotent cells which are known

to differentiate into fibrous tissue cells, cementum and bone*.

[Karan Rajpal et al., IOSR Journal of Dental and Medical Sciences. Volume 13, Issue 2 Ver. IV. (Feb. 2014), p. 99-103].

Classification of benign fibro-osseous lesions of the

craniofacial complex (Roy Eversole et al., 2008):

I. Bone dysplasia

a. Fibrous dysplasia (monostotic, polyostotic, polyostotic with endocrinopathy

(McCune-Albright) and osteofibrous dysplasia).

b. Osteitis deformans

c. Pagetoid heritable bone dysplasias of childhood

d. Segmental odontomaxillary dysplasia

II. Cemento-osseous dysplasias

a. Focal cemento-osseous dysplasia

b. Florid cemento-osseous dysplasia

III. Inflammatory/reactive processes

a. Focal sclerosing osteomyelitis

b. Diffuse sclerosing osteomyeliitis

c. Proliferative periostitis

IV. Metabolic Disease: hyperparathyroidism

V. Neoplastic lesions (Ossifying fibromas)

a. Ossifying fibroma NOS

b. Hyperparathyroidism jaw lesion syndrom

c. Juvenile ossifying fibroma (trabecular and psammomatoid type)

d. Gigantiform cementomas

Benign fibro-osseous lesions (BFOLs) of the craniofacial

area are characterized by:

FD – 40 (68.9%)

Juvenile Ossifying Fibroma (JOF) – 15

(25.9%)

BFOL, unclassifiable, with overlapping

features – 3 (5.2%)

Pathologic ossifications and calcifications

A hypercellular fibroblastic marrow element.

Definition: FD is a benign medullary, sporadic fibro-osseous lesion, which may

involve one or more bones (monostotic FD or polyostotic FD)*.

Fibrous Dysplasia:

*Christopher D.M. Fletcher, Julia A. Bridge, Pancras C.W. Hogendoorn, Fredrik Mertens. WHO Classification of Tumors of Soft Tissue and Bone. 4th

Edition, 2013. P. 352-3.

**G. Petur Nielsen, Andrew E. Rosenberg, Vikram Deshpande, Francis J. Hornicek, Susan V. Kattapuram, Daniel I. Rosenthal. Diagnostic Pathology

Bone. 2013, p. 6/2-13.

***K. Krishnan Unni, Carrie Y. Inwards. Dahlin’s Bone Tumors. 2010, p. 317-327.

All forms of FD are associated with a non-germ cell acquired mutation at

codon 201 within exon 8 of the GNAS1 gene located on chromosome 20q**.

Patients with FD were divided into four distinct groups:

1. FD in the jaws,

2. FD in the bones of the skull,

3. FD in the ribs,

4. FD in all other bones.

The largest single group is the last one. Growth in the jawbone accounted for

the second largest group, and of these, the maxilla was involved much more

commonly than the mandible***.

We have analyzed 798 cases of bone tumors

and tumor-like lesions in children and

adolescents from 2009 to 2016.

FD was found in 58 patients (7.2%).

Craniofacial localization was diagnosed in 40

children (68.9%).

Male/Female ratio was 31/27.

Initial diagnoses of all the cases were based on

their clinical, radiological, and histological

features.

Fibrous Dysplasia (FD) in Children and Adolescents.

40

9

2

6

2

Sites of involvement, FD:

Maxilla – 18 cases.

Frontal bone and orbit – 9 cases.

Mandible – 5 cases.

Temporal and occipital bone – 4 cases.

Ethmoid and nasal cavity – 4 cases.

Two patients had multiple

craniofacial lesions (5%).

18

9

5

4

4

The main complaints and symptoms of patients

with FD are:

Painless swelling often leading to facial asymmetry.

Maxillary and mandibular involvement leads to

displacement of teeth and/or malocclusion.

In FD affecting the paranasal sinuses nasal obstruction

occurs.

Sometimes facial pain, headaches or facial numbness

develops.

The time from the appearance of symptoms to

treatment varied from 1 month to 8 years, with a mean

time of 24.7 months.

The size of the lesions varied from 10 to 70 mm.

Imaging findings:

Well-defined margins (can be sclerotic and

have rind-like appearance).

Expanded bone.

Classically produces ground-glass

appearance, and degree of radiolucency or

density is variable.

No prominent periosteal reaction.

Macroscopic findings:

Well-defined margin.

The tissue cuts with a gritty

consistency and is grayish white.

The cortical bone often is thinned

and expanded.

Classic microscopic pathology, FD:

Early formative lesions of FD lay down woven bone trabeculae with extensive

osteoblastic rimming of trabeculae and marked stromal hypercellularity whereas “older

mature” lesions show both woven and lamellar bone with trabecular that lacks osteoblasts*.

*Roy Eversole, Lan Su, Samir ElMoftu. Benign fibro-osseus lesions of the craniofacial complex. A review. Head and Neck Pathol (2008) 2:177-202.

The “maturation” processes in FD:

Differential Diagnosis, overlapping features:

FD

GCRG JPOF

JTOF

Osteomyelitis Low-grade

osteosarcoma

Desmoplasti

c fibroma

In 23 cases we have performed immunohistochemical staining

with CDK4 and MDM2:

All cases were negative for MDM2:

One case was slightly positive for

CDK4 (nuclear reaction):

But: MDM2

cdk4

Juvenile Ossifying Fibroma:

Definition: OF is well-demarcated lesion composed of fibrocellular tissue and

mineralized material of varying appearances.*

According to the WHO Classification (2005) most OFs commonly occurs in

the 2nd to 4th decades and shows a predilection for females*.

The second edition of the WHO classification of odontogenic tumors defines

juvenile (aggressive) ossifying fibroma as an actively growing lesion [**] and

consist of two histologic types:

1. Juvenile trabecular ossifying fibroma (JTOF).

1. Juvenile psammomatoid ossifying fibroma (JPOF).

*Leon Barnes, John W. Eveson, Peter Reichart, David Sidransky. Pathology and Genetics of Head and Neck Tumors. Lyon, 2005. P. 321-2, 323.

**Rashi Bahl, Sumeet Sandhu, Mohita Gupta. Benign fibro-osseus lesions of jaws – a review. International Dental Journal of Student's Research. June-Sep 2012, vol.1, issue 2, p. 56-68.

Image findings:

A round, well-circumscribed expansive mass with a

thick wall of bone density.

Sometimes corticated osteolytic.

Sclerotic changes are evident in the lesion, that show

a ground-glass appearance.

In CT scans set on bone window, the lesion appear

less dense than normal bone and can vary in size

from 2 to 8 cm in diameter.

Areas of low CT density may be noted due to cystic

changes.

Microscopic pathology of JTOF :

JTOF is unencapsulated and shows

infiltration of the surrounding bone.

The stroma is cell-rich, with spindle or

polyhedral cells that produce little

collagen.

The immature cellular osteoid is not

always easily distinguished from the

cellular stroma.

Maturation to lamellar bone is not

observed.

Local aggregates of osteoclastic giant

cells are invariably present in the

stroma*.

Mitoses are present, especially in the

cell-rich areas.

*Roy Eversole, Lan Su, Samir ElMoftu. Benign fibro-osseus lesions of the craniofacial

complex. A review. Head and Neck Pathol (2008) 2:177-202.

Microscopic pathology of JPOF :

The lesion consists of multiple round

uniform small ossicles

(psammomatoid bodies) embedded

in a relatively cellular stroma

composed of uniform, stellate, and

spindle shaped cells.

The psammomatoid bodies are

basophilic and bear superficial

resemblance to dental cementum,

but may have an osteoid rim.

Mitotic activity is extremely rare in

the stromal cells.

Cystic degeneration and aneurismal

bone cyst formation has been

reported in some cases.*

Roy Eversole, Lan Su, Samir ElMoftu. Benign fibro-osseus lesions of the craniofacial complex. A review. Head and Neck Pathol (2008) 2:177-202.

Secondary aneurysmal bone cyst registrated in 2 cases (5%).

Differential Diagnosis:

Psammomatoid meningioma (PM)

Primary extracranial meningiomas are rare and constitute 2% of all

meningiomas.

PM has been reported in the nasal cavity, paranasal sinuses and

nasopharynx, arising from heterotopic rests of arachnoid cells

(meningiocytes, meningothelial cells).

Histopathologically, JPOF and PM may be difficult to distinguish at the time

of intraoperative consultation (frozen sections), or even after obtaining

routine H&E sections*.

*Olga L. Bohn, John R. Kalmar, Carl M. Allen, Claudia Kirsch, Dayna Williams, Marino E. Leon Trabecular and Psammomatoid Juvenile Ossifying Fibroma of the

Skull Base Mimicking Psammomatoid Meningioma. Head and Neck Pathol (2011) 5:71–75.

Certain features favor PM rather

that JPOF, including:

1. The lack of associated osteoclasts

and osteoblasts rimming the

psammoma bodies and

1. The haphazard distribution of

psammoma bodies in PM.

Differential Diagnosis:

Psammomatoid meningioma (PM)

Differential Diagnosis:

EMA S-100 CD10 SMA

JPOF - - +/- +

PM + + +/- -

EMA SMA

JOF JOF

Differential Diagnosis:

Inflammatory/Reactive Processes

(Osteomyelitis)

Poorly circumscribed lesions

Often tooth involvement

May involve angulus mandibulae,

ramus mandibulae and processus

condylaris

Osteomyelitis:

Conclusions:

1. BFOLs are one of the commonest entities reported in the head and

neck region (39,4% among tumors of craniofacial area).

1. Craniofacial FD is the most common benign fibro-osseous lesion in

children and adolescents (67.4%).

2. Histologically we revealed extensive osteoblastic rimming of

trabeculae and marked stromal cellularity in the FD of craniofacial

area in comparison with FD of other sites.

3. FD should be differentiated from low-grade osteosarcoma, juvenile

ossifying fibroma, desmoplastic fibroma and giant cell reparative

granuloma.

4. FD and JOF can be differentiated from one another on the basis of

molecular detection of Gs-alpha mutation in FD of the jaws while

JOFs are negative.

Thank you for your attention!

Спасибо за внимание!

Рогожин Д.В.

Pathol.777@mail.ru

Patanatomia.rdkb@gmail.com

Russian Children's Clinical Hospital,

Moscow (Russian Federation).

Research Center of Pediatric Hematology, Oncology and Immunology,

Moscow (Russian Federation).