Review article

Paediatrics Today 2011;7(1):1-9

DOI 10.5457/p2005-114.8

BONE TUMORS IN CHILDREN

Jelena ROGANOVIĆ

Department of Pediatrics Bone tumors in children are rare, accounting for 5% of all childhood
Clinical Hospital Center Rijeka cancer. Although rare, bone cancer deserves a special attention in
& Chair of Pediatrics pediatric oncology. Given an overall 5-year survival rate of approxi-
School of Medicine mately 65% for pediatric patients, malignant bone tumors should be
University of Rijeka diagnosed and treated rapidly and accurately in specialized centers.
Republic of Croatia
Key words: Bone tumors ▪ Child

Introduction
Jelena Roganović
Department of Pediatrics Malignant bone tumors in children occur rarely. Estimated
Clinical Hospital Center Rijeka annual incidence is 7 cases per 1.000.000 children under the
Istarska 43
age of 16. Due to its rare occurrence and often unspecific
HR - 51000 Rijeka
Croatia signs and symptoms, a lot of physicians do not consider
e-mail: [email protected] this diagnosis early enough. Therefore it is not surprising
Tel.: + 385 51 659 103/109 that the majority of patients are referred to the pediatric
Fax: + 385 51 623 126 oncologist when the disease is already in advanced stage.
The aim of this review is to summarize basic facts regar-
ding bone tumors, in order to help primary care pediatrici-
ans and general practitioners to recognize these neoplasms
as soon as possible. Besides malignant, there will be a short
review of benign tumors and tumor-like lesions.
Received: November 11, 2010
Accepted: December 26, 2010 Clinical manifestations
Bone tumors in children could be presented with various
symptoms, depending on the localization, the size and the
Copyright © 2009 by University
nature of the tumor. Predominant symptom is pain, initi-
Clinical Center Tuzla.E-mail
for permission to publish:
ally present during the night or during certain activities, but
[email protected] later the intensity rises. On clinical examination unusually

www.pedijatrijadanas.com 1
 Paediatrics Today 2011;7(1):1-8

swelling can be seen or palpated. Additional surrounding bone, including muscles, tendons,
clinical findings may include limitation of ligaments, nerves and blood vessels. MR can
motion, skin changes, neurological deficits, also demonstrate the possible penetration of
vascular defects or pathological fractures. the tumor through the compact part of the
General symptoms, like fever, fatigue and bone and through the surrounding soft tissue.
weight loss, are more frequent in children Furthermore there is no ionizing radiation.
with metastatic diseases. The main disadvantages are higher cost and li-
mited availability. Ultrasound can be used only
for soft tissue analysis. Radioactively labeled
Diagnostic procedure
technetium scintigraphy shows areas of rapid
Together with thorough history, a complete growth and bone remodeling, and the results
physical examination is very important, inclu- are positive much earlier than radiological. This
ding muscle strength and tendon reflexes asse- method displays whole skeleton and can shows
ssment. First imaging modality should be x-ray. the possible involvement of other bones. The
Radiological images in two directions can reveal final step in the diagnostic process is surgical
the entire affected bone. The method is sim- biopsy and histological analysis of tissue sam-
ple, inexpensive, and available in smaller insti- ple. Needle biopsy or aspiration biopsy may be
tutions, delivers minimal amounts of radiation useful in case of soft tissues involvement (1, 3).
and does not require general anesthesia. Radio-
graphic changes can determine most probable
Malignant bone tumors
tumor type, since many malignant bone tumors
have characteristic radiological findings. Beni- Primary malignant bone tumors are more
gn tumors more often have smooth, straight common in children and adolescents than
line borders, whereas malignant have irregu- in adults. Etiopathology is mostly unknown.
lar ones. Benign tumors mostly grow slowly Tumors may arise in areas of rapid growth.
enough so the bone can separate tumor from Besides accelerated bone growth, possible
the normal bone tissue. In contrast, malignant risk factors include trauma and radiation
tumors are characterized by rapid growth and therapy for other neoplasms. They are more
normal bone tissue cannot limit the proce- common in boys and in the white race. There
ss. Since the symmetry is crucial in assessing are rare hereditary syndromes with an incre-
the findings, it is appropriate to compare the ased risk for bone tumors, such as hereditary
contra lateral bone. In patients with malignant retinoblastoma and Li-Fraumeni syndrome
bone tumors x-ray of the lungs is required to (hereditary gene mutation with a tendency to
reveal possible metastases. Computerized to- develop multiple neoplasms, particularly bre-
mography (CT) is more advanced method and ast cancer, adrenal gland cancer, brain tumor,
can create the three-dimensional view of bone, leukemia and soft tissues sarcomas) (1, 4).
so the tumor can be identified more precisely According to generally accepted ICCC (In-
and provides additional information about its ternational Classification of Childhood Cancer),
size and location. Disadvantages of CT such malignant bone tumors in children are divided
as higher doses of radiation, expensiveness, into osteosarcoma, hondrosarcoma, Ewing tu-
and the need for general anesthesia in young mor and related bone sarcomas, “other speci-
children, are negligible compared to the impor- fied malignant bone tumor” and “unspecified
tance of early diagnosis. Magnetic resonance malignant bone tumor.” Two types of malignant
imaging (MRI) compared to CT provides more bone tumors predominate in children - osteosar-
detailed information regarding the soft tissues coma and Ewing’s sarcoma (5).

2
 J. Roganović  Bone tumors in children

Osteosarcoma is the most common pri- Ewing’s sarcoma is the most aggressi-
mary malignant bone tumor in children and ve bone tumor. The annual incidence is 2.1
adolescents. The annual incidence is 5.6 per 1 per 1 million children. It is more common in
million children under the age of 15. It usu- boys aged between 4 and 15 years, and very
ally occurs in the age group 10-25 years, more rare after 30 years of age (7). The origin of
frequently in boys (4, 6). The greatest risk for this tumor is the subject of numerous discu-
osteosarcoma is during the adolescent growth ssions. Although it was thought to arise from
acceleration, which suggests the association primitive neuroectoderm, there are many in-
of rapid bone growth and malignant transfor- dications that arises from mesenchymal stem
mation. Patients with osteosarcoma are taller cells. It is typically situated at the diaphysis of
than their peers. In almost half of the patients, long bones of arms and legs. Cytogenetic and
osteosarcoma is situated in the area of ​​the knee molecular analysis in 90% of cases shows a
joint, the distal edge of the femur or proximal reciprocal translocation t(11;22) (q24, q12),
edge of the fibula, but also in every other long which results in EWS-FLI1 fusion gene
bone. Tumor process develops in the bone (8). On radiological images it is displayed as
spongiosa, destroying corticalis and gradually symmetrical fusiform thickening of the bone.
expands into the surrounding soft tissue. Pe- Additionally, irregular areas of osteolysis and
riosteum reaction is characteristic radiological sclerosis can be seen. The radiological foota-
sign, with the creation of calcifications radia- ge seems very unclear and blurred, and the
ting from the corticalis to the periphery (Figure bone appears as “eroded by moths” (Figure
1). It can metastasize to other bones, or more 2). Two-thirds of patients have extraosseous
often to the lungs. Prognosis depends on the permeation of the tumor in the soft tissues.
location and size of the primary tumor and At the time of diagnosis 25% of children
the degree of necrosis after neoadjuvant che- have hematogenous metastases in the lungs,
motherapy. Localization on the shoulder girdle, bones, pleura, or bone marrow. Three-year
shoulder blade, collarbone, ribs, vertebrae, pel- survival is around 65%. In children with me-
vic bones and proximal parts of extremities is tastatic disease at the time of diagnosis, the
related with worse outcome. Overall five year prognosis is significantly worse, with 30%
survival is around 65% (6). survival (7, 8).

Figure 1 Osteosarcoma. Osteosclerosis and cortical Figure 2 Ewing sarcoma. Permeative patchy lesion
lytic lesions of the distal femur, with periosteal reac- of the diaphysis of the femur with laminated perioste-
tion and soft tissue swelling al reaction and soft tissue swelling

3
 Paediatrics Today 2011;7(1):1-8

Chondrosarcoma is a rare malignant bone ply limited growth with a base closer to the
tumor in children, more common after 40 ye- epiphyseal part of the bone, which expands
ars of age. It originates from cartilage cells towards the surface (Figure 3). Towards the
and can be either very aggressive or relatively periphery the bony part is covered with lo-
slow in growth. It affects all bones, more of- bulated cartilage. As the cartilage cap is not
ten pelvis and hips more. It can metastasize seen radiologically, the lesion is always larger
to the lungs and lymph nodes. Five-year sur- on palpation. It can be solitary or multiple. It
vival for aggressive forms is only 30%, yet is not recommended to be routinely remo-
90% for slowly growing tumors (9). ved if it does not cause difficulties or start to
Fibrosarcoma is extremely rare in chil- grow rapidly. In 1% of the patients the ma-
dren. It affects predominantly the diaphysis lignant transformation after full growth has
of the long bones. It grows slowly and reo- been described (11).
ccurs late. Radiological findings show blurred
osteolytic area. Clinically, a rigid infiltrate
surrounding the affected bone can be detec-
ted. One third of patients are presented with
pathological fractures (1, 10).
Angiosarcoma is also very rare in children.
This extremely vicious vascular tumor often
involves the long and short tubular bones of
the extremities (usually the femur, tibia and
humerus). On radiologic images multiple
eccentric osteolytic lesions can be seen (10).

Benign bone tumors

In children benign bone lesions are much
more frequent than malignant. However, the-
re is no certain anamnestic data or diagnostic
test that is reliable enough to exclude a ma-
lignant neoplasm. Benign bone tumors may
be painless but also painful, especially in the
Figure 3 Osteochondroma. Broad-based cortical lesi-
case of pathological fracture. Rapid growth
on at the posterior distal femoral diaphysis, without
is common in malignant tumors, but some
adjacent bone changes
benign lesions such as aneurizmatic bone
cysts, can dramatically increase its size (1).
Osteoid osteoma is a small benign tumor
Osteohondroma is the most common be-
of bone. The majority are diagnosed between
nign tumor of the locomotor system. Since
the fifth and twentieth year, more frequently
the majority of them are asymptomatic and
in men. Patients typically feel a constant pain
unrecognized exact incidence is not known.
that intensifies over time, that is stronger du-
The most commonly is discovered in chil-
ring the night and weakens if salicylates are
dren aged 5-15 years when the parents or
used. Radiological sign is the central illumi-
the child notice a painless rigid formation
nation of the sclerotic part of the bone, so
associated with bone. Radiological sign is so-
called. “nest” or “nidus” (Figure 4). In 25%
called osteocartilaginous exostosis – a shar-
of cases osteoid osteoma is not visible on the

4
 J. Roganović  Bone tumors in children

classic radiological images, but it can be visu- ons, the new lesions usually occur within 1-2
alized by CT scan. Treatment is surgical (12). years. Solitary lesions may be asymptoma-
tic, or accompanied with localized pain and
swelling. Pathological fractures are possible.
Radiological image usually displays lytic lesi-
on with or without sclerotic edge (Figure 5),
but it can mimic many benign and malignant
bone lesions. Therefore, biopsy is often ne-
cessary. There are different treatment opti-
ons: observation since the majority of bone
lesions regresses spontaneously and does not
recur, low-dose radiotherapy, local injection
of steroids and surgical treatment (14).

Figure 4 Osteoid osteoma. Subcortical lesion of the

proximal femoral metaphysis with centrally located
radiolucent area (nidus) surrounded by a zone of
uniform bone sclerosis

Figure 5 Eosinophilic granuloma. Solitary osteolytic

Enhondroma is a benign tumor of hya-
lesion in the frontoparietal region of the skull
line cartilage, which usually occurs between
20 and 30 years of age. It is usually asymp-
tomatic and located on the short tubular bo- Timor-like formations
nes of hands and feet. Radiological finding
Timor-like formations are listed in the text
is sharply limited osteolytic lesion in the me-
because they are often confused with genu-
dulla, sometimes with calcifications. Ordina-
ine tumors.
rily it is solitary. Multiple enhondromas with
Solitary bone cyst (juvenile, simple or uni-
a predilection for malignant transformation
cameral bone cyst) occurs at any age but is
occur in Ollier disease (short stature, bone
rare in children younger than 3 years or after
dysplasia, joint deformities, unequal length
completion of growth. The etiology is un-
of limbs) or Maffucci syndrome associated
known. It is located mostly on the edge of
with soft tissue angiomas (13).
the proximal humerus and femur. It may be
Eosinophilic granuloma is a benign form
asymptomatic or presents with pain and pat-
of Langerhans cell histiocytosis. It is charac-
hological fractures. Radiologically, it appears
terized by solitary or multiple bone lesions
as a solitary, centrally located osteolytic lesi-
without extraoseal involvement. It usually
on (Figure 6). It is often treated by aspiration
occurs in the first 3 decades, more common
and injection of corticosteroids with prolon-
in boys between 5 and 10 years of age. Any
ged activity (15).
bone can be affected, but they are more li-
kely to be localized on the skull, mandible,
ribs and femur. When there are multiple lesi-

5
 Paediatrics Today 2011;7(1):1-8

of newly formed bone (Figure 7). Treatment

is surgical. It recurres in 20-30% of patients,
more frequently in younger children and wit-
hin two years after treatment (1, 15).
Fibroma (non-ossifying fibroma, cortical
fibrous defect, metaphyseal fibrous defect) is
a defect of ossification that occurs in 40%
of children older than 2 years. Most of these
fibrotic lesions are asymptomatic and disco-
vered as an incidental finding on X-ray of
the bone after trauma. Pathological fractures
Figure 6 Solitary (unicameral) bone cyst. Sharply are rare. In 50% of cases lesions are bilateral
demarcated osteolytic lesion with cortical thinning or multiple. Radiographical sign is osteolytic
and mild expansion of the bone area in cortical region with a clear sclero-
tic border towards the surrounding healthy
spongiosa. Because of the typical radiologi-
cal findings, biopsy is rarely necessary. After
skeletal maturation spontaneous regression
can be expected (10).
Fibrous dysplasia is a developmental de-
fect characterized by the replacement of
spongious bone by fibrous tissue. The lesion
may be solitary (monostotic form) or mul-
tifocal (poliostotic form). Poliostotic fibrous
dysplasia, premature puberty and skin pi-
gmentation found together are also known
as Allbright syndrome. Most children are
asymptomatic, but pain may be present to-
gether with pathological fractures and skele-
tal deformities. Radiological sign is erasure
of the bone structure with cystic illuminati-
ons, with some septa preserved. Typical sign
is the bending of the upper edges of the fe-
Figure 7 Aneurysmal bone cyst. Expansile osteolytic mur, such as “shepherd’s crook” (16).
lesion of the proximal humeral metaphysis with irre-
gular trabecular pattern and thin sclerotic margins

Aneurismatic bone cyst is a reactive bone Treatment of malignant bone tumors

lesion, characterized with cavernous spaces
Combination of chemotherapy, surgery and
filled with blood. It most commonly affects
radiotherapy is most commonly used the
the femur, tibia and spine. In the children
treatment of children and adolescents with
the course is usually very aggressive because
malignant bone tumors. Close cooperation
of the rapid growth. Radiologically there is
between pediatric oncologists, radiologists,
bone destruction with eccentric expansion
pathologists, orthopedists, physiatrists and
of the affected part, along with the reaction
radiotherapist is required in planning the op-
of the periosteum, which creates a thin layer

6
 J. Roganović  Bone tumors in children

timal therapy. The main goals of treatment healing is best when autotransplant is used,
are longer survival combined with strict con- usually fibula. A special form of biological
trol of malignant disease and a higher life reconstruction is so-called rotational plastics,
quality. when the preserved parts of the limbs are
Neoadjuvant chemotherapy causes preo- used for the rotation, and the tumor is remo-
perative necrosis and control of the possible ved while preserving the blood vessels. An
hematogeneous metastases. Cytotoxic effect example is the use of rotated ankle joint at
is evaluated after surgery by percentage of the knee instead of the resected knee joint.
necrotic tumor cells. A higher percentage of After the successful reconstruction of the
necrosis indicates greater effectiveness of skeleton in children, the most common pro-
chemotherapy. The first grade is tumor ne- blem is limb length difference. For this pur-
crosis less than 50%, which is a bad response, pose so-called growing endoprosthesis are
necrosis of 50% to 90% represents second used, which allow an extension of the limbs
stage, more than 90% necrosis equals the for equalizing the length during the growth
third grade, and fourth grade is 100% necro- After orthopedic surgery and radiotherapy,
sis, which indicates the best response (1, 4). chemotherapy is often re-applied to eradica-
Surgical treatment of bone tumors has te remaining tumor cells, so-called adjuvant
significantly changed during the last quarter chemotherapy. In some malignant tumors of
of century. While amputation has been the the bone it is necessary to apply mega-dosage
standard treatment for many years, limb-sa- therapy with autologous hematopoietic stem
ving surgery is nowadays performed in 85% cell transplantation (1, 4).
of patients. “Salvage surgery” involves re- Risks and side effects exist in each thera-
section of the tumor in the block with the peutic modality. The main risks of orthope-
surrounding healthy tissue, but preserving dic treatment are infections (often following
the affected extremity. The ideal is that the the installation of extrinsic materials), local
operating margins do not contain cancer recurrences and injury of surrounding ti-
cells. There are four ways of tumor resecti- ssues resulting in weakness, loss of sensation
on in relation to the surgical edge, and the or fractures of the remaining bone. Appro-
type of tissue that is removed along with the priate physical therapy improves strength
tumor. Resection trough the tumor itself is and function of the extremities. The most
called intracapsular. Marginal resection is the common side effects of chemotherapy are
surgical removal of tumor through the re- susceptibility to infections, hair loss, nausea,
active zone. Wide resection means that the vomiting, and fatigue. Modern supportive
tumor is removed outside the reactive zone therapy can prevent, alleviate or eliminate a
through the normal bone. Radical resection large number of side effects of chemothe-
means removing the entire affected bone. rapy, which significantly improves the quality
After the orthopedic treatment it is necessary of life of children during treatment and has a
to make the reconstruction of the defect. positive effect on disease outcome. The main
There are various forms of reconstruction, early adverse effect of radiotherapy is dama-
depending on patient age, tumor localizati- ge to the surrounding skin and soft tissue,
on and extent of resection. For the recon- and delayed are effects on physical growth
struction of the bone extrinsic materials can and development of secondary tumors (4).
be used (bone cement, polyethylene or usu- Advance in the understanding and tre-
ally metal prosthesis) or biological materials atment of bone tumors in children and ado-
(autotransplant or homotransplant). Bone lescents has resulted in improved techniques

7
 Paediatrics Today 2011;7(1):1-8

of radiation (three-dimensional conformal rapy for tumors with known genetic aberra-
radiotherapy, beams of variable intensity, tions and so-called targeted therapy, focused
proton therapy), modern combinations of on specific elements of the tumor cells with
chemotherapy and new orthopedic tech- minimal effect on normal cells.
niques. Today’s research is directed towards
establishing or facilitating own reparative Conflict of Interest: The author declare that she
processes using bio-materials that stimulate have no conflict of interest. This study was not
the production of normal bone, gene the- sponsored by any external organisation.

References
1. Arndt CAS. Neoplasms of bone. In: Nathan DG, 10. Vlychou M, Athanasou NA. Radiological and pat-
Orkin SH, Ginsburg D, Look TA, editors. Nathan hological diagnosis of paediatric bone tumours and
and Oski’s Hematology of Infancy and Childho- tumour-like lesions. Pathology. 2008;40(2):196-
od. Philadelphia: W.B. Saunders Company; 2007. p. 216.
2146-51.
11. Kitsoulis P, Galani V, Stefanaki K, Paraskevas G,
2. McCarville MB. The child with bone pain: ma- Karatzias G, Agnantis NJ, et al. Osteochondromas:
lignancies and mimickers. Cancer Imaging. review of the clinical, radiological and pathological
2009;(Spec No A):S115-21. features. In Vivo. 2008;22(5):633-46.
3. Wyers MR. Evaluation of pediatric bone lesions. 12. Lee EH, Shafi M, Hui JH. Osteoid osteoma: a cu-
Pediatr Radiol. 2010; 40(4):468-73. rrent review. J Pediatr Orthop. 2006;26(5):695-700.
4. Heare T, Hensley MA, Dell’Orfano S. Bone tu- 13. Romeo S, Hogendoorn PC, Dei Tos AP. Benign
mors: osteosarcoma and Ewing’s sarcoma. Curr cartilaginous tumors of bone: from morphology to
Opin Pediatr. 2009;21(3):365-72. somatic and germ-line genetics. Adv Anat Pathol.
2009;16(5):307-15.
5. Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch
P. International Classification of Childhood Can- 14. Khan AN, Chandramohan M, Turnbull I, MacDo-
cer, Third Edition. Cancer. 2005;103(7):1457-67. nald S. Eosinophilic granuloma, skeletal; c1994-
2010 [updated 2008 May 14]. Available from:
6. Kim HJ, Chalmers PN, Morris CD. Pediatric osteo-
http://emedicine.medscape.com/article/389350
genic sarcoma. Curr Opin Pediatr. 2010;22(1):61-6.
15. Parman LM, Murphey MD. Alphabet soup: cy-
7. Karosas AO. Ewing’s sarcoma. Am J Health Syst
stic lesions of bone. Semin Musculoskelet Radiol.
Pharm. 2010;67(19):1599-605.
2000;4(1):89-101.
8. Maheshwari AV, Cheng EY. Ewing sarcoma fa-
16. Feller L, Wood NH, Khammissa RA, Lemmer J,
mily of tumors. J Am Acad Orthop Surg. 2010;
Raubenheimer EJ. The nature of fibrous dysplasia.
18(2):94-107.
Head Face Med. 2009;5:22.
9. Gelderblom H, Hogendoorn PC, Dijkstra SD, van
17. Abed R, Grimer R. Surgical modalities in the tre-
Rijswijk CS, Krol AD, Taminiau AH, et al. The cli-
atment of bone sarcomas in children. Cancer Treat
nical approach towards chondrosarcoma. Oncolo-
Rev. 2010;36(4):342-7.
gist. 2008;13(3):320-9.