Pediatric malignant

bone tumours

Dr. Cornelius Mukuzunga

Kamuzu Central Hospital
Learning objectives

 Describe the features of common pediatric

bone malignancies
 Outline treatment plan for common
pediatric bone malignancies
Pediatric Malignant Bone Tumors
 Osteosarcoma
 Ewing sarcoma
 Malignant fibrous histiocytoma
 Non-Hodgkin Lymphoma
 Eosinophilic granuloma
Pediatric malignant bone tumors
 6% of all childhood malignancies

 Most often occur in young patients < 25

years
 Most common bone tumors
 Osteosarcoma 56%
 Ewing sarcoma 34%
Osteosarcoma
 Primary malignant tumor of bone
 Derived from primitive bone forming
mesenchyme
 Malignant spindle cells produce immature
neoplastic bone matrix – osteoid
 Can look heterogeneous under the microscope
Epidemiology
 Most common during 2nd decade
 75% between 10 and 20 yrs
 Peak during adolescent growth spurt
 M:F 1.5:1
 African-American: Caucasian 1.4:1
Associations or Risk Factors
 Ionizing radiation
 Hereditary retinoblastoma (Rb mutations)
 Li-Fraumeni syndrome (p53 mutations)
 Rothmund-Thomson syndrome

 No environmental risk factors

Clinical presentation
 Pain: dull, aching, constant, worse at
night, often attributed to trauma
 Average duration of symptoms prior to
diagnosis is three months
 May or may not have a mass
 20% have detectable metastases at
diagnosis – most often (>90%) pulmonary
Location
 Most common in long
bones
 90% are metaphyseal
 May cross growth
plate
 Location:
 #1 distal femur
 #2 proximal tibia
 #3 proximal humerus
Diagnostic Workup
 History and physical Radiologic tests
examination
 Plain films of involved
 Laboratory tests: bone
 Blood tests: include  MRI of entire
LDH, Alkaline involved bone
phosphatase  Whole body Bone
Also CBC, Scan
liver/kidney function  CXR and CT of
tests Chest
 Pathology  PET scan
 Biopsy
Radiographs
 Usually blastic
 May be lytic or mixed
bone destruction and
production
 Poorly marginated
 Cortical destruction
 Soft tissue
ossification
Treatment: Multimodal
 Surgery
 control of bulk disease

 Chemotherapy
 control of micrometastases

 Radiation
 Tumors not very radiosensitive, so this usually
reserved for palliation
Treatment: Chemotherapy
 Most active agents include
 adriamycin, cisplatinum, high-dose
methotrexate, ifosfamide, etoposide
 Best # and schedule of chemotherapy unclear
 Immune modulators under study
Treatment: Surgery
 Removal of all gross tumor with wide (>5cm)
margins en bloc and biopsy site through normal
tissue planes is required
 Type of surgical procedure depends on tumor
location, size, extramedullary extent, presence
of distant metastatic disease, age, skeletal
development, and life-style preference
 limb-sparing
 amputation
 Metastatic sites must also be resected
Ewing Sarcoma (EWS)
 Represents a family of tumors including
 Ewing sarcoma of bone
 extraosseous Ewing sarcoma and
 peripheral neuroectodermal tumor (PNET)
of bone or soft tissue
 2nd most common bone tumor in children
Pathology
 One of many ‘small round
blue cell’ tumors seen in
pediatrics
 Thought to be of neural
origin, derived from
post-ganglionic
parasympathetic
primordial cells
Small, Round, Blue Cell Tumor
Differential Diagnosis
 Lymphoma/Leukemia
 Rhabdomyosarcoma
 Metastatic Carcinoma
 Neuroblastoma
 Ewing
 Tumor without differentiation
 PNET/Ewing Sarcoma
 PNET
 Small Cell Osteosarcoma  Tumor with neural
differentiation
Incidence
 Occurs most commonly in 2nd decade
 80% occur between ages 5 and 25
 Most common bone tumor in children < 10 yrs
 M:F 1.3:1 < 10 yrs
1.6:1 > 10 yrs
Associations or Risk Factors

 Consistent cytogenetic abnormality, t(11;22)

(q24;q12) present in 90-95%
 resultant fusion gene is EWS/FLI-1
Clinical Presentation
 Pain & swelling of affected area
 May also have systemic symptoms:
 Fever
 Anemia
 Weight loss
 Elevated WBC & ESR
 20-25% present with metastatic disease
 Lungs
 Bone
 Bone Marrow
Location
 central axis (47%):
 pelvis,chest wall,
spine, head & neck
 extremities (53%)

#1 Femur
#2 Ilium
#3 Tibia/Fibula
 Location

 Classical presentation is diaphyseal

 Actually more common in metadiaphysis or metaphysis
Diagnostic Work-Up
 History and physical
examination Radiologic tests
 Laboratory tests:  Plain films of primary site
 CBC, liver/kidney function  CT/MRI of primary site
tests, LDH, ESR  CXR/CT of chest
 Urinalysis  Whole body bone scan
 Pathology
 Bone marrow aspirate and
biopsy
 Biopsy
Radiographs
 Destructive
 Poorly Marginated
 Permeative
 Endosteal Cortical
Erosion
 Layered periosteal
new bone- “onion
skinning”
Radiographs
 Radiology

 MRI necessary to
determine
 Soft tissue extent
 Intraosseous extent
Treatment: Multimodal
 Surgery
 local
control where possible
 Amputation

 Radiation
 local control where surgery not possible or incomplete

 Chemotherapy
 control of micrometastases
Treatment: Chemotherapy
 All patients require chemotherapy
 Active agents include
 Vincristine,cyclophosphamide, adriamycin,
dactinomycin,
ifosfamide, etoposide, topotecan, melphalan
 Effective chemotherapy has improved local control
rates achieved with radiation to 85-90%
 Role of SCT for high risk Ewing sarcoma still under
investigation