ReviewCommon Musculoskeletal Tumors of Childhood and Adolescence
Section snippets
Methods
We searched MEDLINE using the terms rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, biology, and humans and limited the search to articles from 2000 to September 2011. Additional references found in these articles were utilized as appropriate, as well as references from the background information in current therapeutic studies of the Children's Oncology Group (COG). The same database and time frame were searched for articles written by leading authorities in the field. Discussion in this review
Epidemiology and Clinical Features
Osteosarcoma is the most common malignant bone tumor in children and adolescents, with an incidence of 4.4 per million.1 The peak age incidence is in the second decade of life, with a smaller peak in older adults. Ewing sarcoma/PNET is the second most common malignant bone tumor, with an incidence of 2.9 per million,2 and it also occurs in soft tissues. Bone tumors commonly manifest with pain and swelling in a bone or joint. Symptoms are often attributed to sports injuries in active
Osteosarcoma
High-grade OS is most likely derived from mesenchymal stem cells with at least partial osteoblastic lineage commitment, although the exact cell of origin is unclear.4 Patients with hereditary retinoblastoma, Rothmund-Thomson syndrome, Li-Fraumeni syndrome, and Werner syndrome are predisposed to development of OS, suggesting that alterations in the genes associated with these disorders (RB1, RECQL4, TP53, and WRN, respectively [for expansion of gene symbols, use search tool at www.genenames.org
Diagnosis and Staging
Ideally, evaluation of the child and adolescent with a suspected bone or soft tissue tumor should be performed at the institution that ultimately will be providing multidisciplinary care for the patient. For bone tumors, the biopsy needle tract or incision should be placed such that it can be incorporated into the final surgical excision if surgery is the ultimate form of local tumor control.28 Planning of the biopsy should be coordinated between the radiologist and the surgeon for patients
Multidisciplinary Therapy and Prognosis
When evaluating a child or teenager newly diagnosed with one of these malignancies, it is important to involve a multidisciplinary team of oncologists, surgeons, and radiation oncologists from the outset so that the treatment planning can progress seamlessly and the timing of local control can be optimized so as not to delay chemotherapy. Because radiation treatments are based on the extent of tumor at the time of diagnosis, the radiation oncologist must see patients with ES/PNET and RMS
Late Effects
Despite the advances in cure rates for children and adolescents with these tumors, the long-term consequences of aggressive chemotherapy, radiotherapy, and surgery can be substantial. Survivors are much more likely than controls to have at least one, and often multiple, chronic medical conditions. Examples are cardiac toxicity from anthracyclines, hearing loss or tinnitus from cisplatin, infertility from alkylator therapy or radiation to the pelvis, endocrine complications usually from
New Directions
Recently, the importance of insulin-like growth factor receptor in promoting tissue growth and the contribution of the insulin-like growth factor system to cellular proliferation and immortality in a wide variety of cancers have been recognized. Overexpression of IGF1 and IGF2 have been reported in ES, OS, and RMS, and high expression of IGF1R has also been reported in these and other cancers. In vitro data have demonstrated the key roles of IGF1R in pediatric sarcomas in particular.97, 98, 99
Conclusion
Recent advances in the multidisciplinary management of musculoskeletal tumors in children and adolescents have enabled most children and adolescents with nonmetastatic disease to be cured; however, late effects are not inconsequential. It is hoped that during the next decade we will discover which patients can have therapy reduced and still have the same good outcome, and new approaches with targeted agents and new surgical and radiotherapeutic techniques will be developed for patients with
Acknowledgments
The authors would like to thank Karen Fasbender for help in manuscript preparation and submission.
References (118)
Pathologic classification of rhabdomyosarcomas and correlations with molecular studies
Mod Pathol
(2001)- et al.
Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass
Am J Pathol
(2000) - et al.
Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall
Mod Pathol
(2008) - et al.
Carbon ion radiation therapy improves the prognosis of unresectable adult bone and soft-tissue sarcoma of the head and neck
Int J Radiat Oncol Biol Phys.
(2012) - et al.
Ewing's sarcoma
Lancet Oncol
(2010) - et al.
Sequential high-dose chemotherapy for children with metastatic rhabdomyosarcoma
Eur J Cancer
(2009) Treatment for childhood rhabdomyosarcoma: the cost of cure
Lancet Oncol
(2005)- et al.
Second cancers in patients with the Ewing sarcoma family of tumours
Eur J Cancer
(2008) - et al.
Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program
Cancer
(2009) - et al.
Changes in incidence and survival of Ewing sarcoma patients over the past 3 decades: Surveillance, Epidemiology, and End Results data
J Pediatr Hematol Oncol
(2008)
Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005
Cancer
Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2
J Pathol
Current concepts on the molecular biology of osteosarcoma
Cancer Treat Res
Soft tissue sarcomas with complex genomic profiles
Virchows Arch
Bone and Soft Tissue Pathology
Periosteal osteosarcoma: a single-institution experience
Cancer
Low-grade intraosseous osteosarcoma
Cancer
Clinical outcome of parosteal osteosarcoma
J Surg Oncol
Parosteal osteosarcoma: a clinicopathological study
J Bone Joint Surg Am
Surface osteosarcoma
Clin Orthop Relat Res
Conventional and dedifferentiated parosteal osteosarcoma: diagnosis, treatment, and outcome
Cancer
Periosteal osteosarcoma: long-term outcome and risk of late recurrence
Clin Orthop Relat Res
Enzinger and Weiss' Soft Tissue Tumors
Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases
Am J Surg Pathol
Ewing sarcoma family of tumors: a model for the new era of integrated laboratory diagnostics
Expert Rev Mol Diagn
Impact of EWS-ETS fusion type on disease progression in Ewing's sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial
J Clin Oncol
Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children's Oncology Group
J Clin Oncol
Correspondence re: Parham DMPathologic classification of rhabdomyosarcomas and correlations with molecular studies
Mod Pathol
Adult sclerosing rhabdomyosarcoma: cytogenetic link with embryonal rhabdomyosarcoma
Virchows Arch
Recurrent t(2;2) and t(2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator family
Genes Chromosomes Cancer
Molecular biology of rhabdomyosarcoma
Clin Transl Oncol
Gene expression profiling for survival prediction in pediatric rhabdomyosarcomas: a report from the Children's Oncology Group
J Clin Oncol
The hazards of biopsy, revisited: for the members of the Musculoskeletal Tumor Society
J Bone Joint Surg Am
Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial
J Clin Oncol
[18F]Fluorodeoxyglucose positron emission tomography predicts outcome for Ewing sarcoma family of tumors
J Clin Oncol
[F-18]-fluorodeoxy-D-glucose-positron emission tomography response is associated with outcome for extremity osteosarcoma in children and young adults
Cancer
Osteosarcoma: the COSS experience
Cancer Treat Res
Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival—a report from the Children's Oncology Group
J Clin Oncol
Treatment and prognosis for synchronous multifocal osteosarcoma in 42 patients
J Bone Joint Surg Br
Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols
J Clin Oncol
Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols
J Clin Oncol
Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the Istituto Ortopedico Rizzoli according to the Istituto Ortopedico Rizzoli/Osteosarcoma-2 Protocol: an updated report
J Clin Oncol
Euramos I Trial
Phase II study of chemotherapy with or without trastuzumab (Herceptin®) in patients with metastatic osteosarcoma
Addition of pamidronate to chemotherapy for the treatment of osteosarcoma
Cancer
Pilot study of zoledronic acid in combination with standard chemotherapy in patients with newly diagnosed metastatic osteosarcomaNational Cancer Institute Web site
Does increased rate of limb-sparing surgery affect survival in osteosarcoma?
Clin Orthop Relat Res
Early multicenter experience with a noninvasive expandable prosthesis
Clin Orthop Relat Res
Allograft reconstruction after sarcoma excision in children younger than 10 years old
Clin Orthop Relat Res
Biological reconstruction after resection of bone tumours around the knee: long-term follow-up
J Bone Joint Surg Br
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